Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

Science.gov (United States)

Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

2016-01-01

Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Bioequivalence study on two brands of 10% enrofloxacin oral ...

African Journals Online (AJOL)

A bioequivalence of two brands of 10% enrofloxacin was tested in broiler chickens using a parallel design at 20 mg/kg bodyweight orally. Blood was sampled before and after drug administration for 24 hours. Plasma enrofloxacin concentrations were analyzed using microbiological assay. Peak plasma concentrations ...

Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

Science.gov (United States)

Cho, Kyung-Jin; Cho, Wonkyung; Cha, Kwang-Ho; Park, Junsung; Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

2010-01-01

In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serum concentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC(0-4h), AUC(0 --> infinity), C(max), T(max) and T1/2 were 865.28 ng x h/ml, 873.04 ng x h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng x h/ml, 830.97 ng x h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC(0 --> infinity) and C(max) were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC(0 --> infinity) and C(max) were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.

Bioequivalence of a new cyclosporine a formulation to Neoral.

Science.gov (United States)

David-Neto, Elias; Kakehashi, Erica; Alves, Cristiane Feres; Pereira, Lilian M; de Castro, Maria Cristina R; de Mattos, Renata Maciel; Sumita, Nairo Massakazu; Romano, Paschoalina; Mendes, Maria Elizabete; Nahas, William Carlos; Ianhez, Luiz Estevam

2004-02-01

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

Science.gov (United States)

Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

2012-04-01

FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

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Ibarra, Manuel; Valiante, Cristian; Sopeña, Patricia; Schiavo, Alejandra; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

2018-06-15

Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®. In silico simulations for Dilatrend® were compared with published results of bioequivalence studies performed in fasting conditions allowing model development through a learning and confirming process. Single-dose pharmacokinetic profiles were then simulated for the brand-name drug and two similar drug products selected according to in vitro observations, in a virtual Caucasian population of 1000 subjects (50% male, aged between 18 and 50 years with standard body-weights). Population bioequivalence ratios were estimated revealing that in vitro differences in drug release would have a major impact in carvedilol maximum plasma concentration, leading to a non-bioequivalence outcome. Predictions support the need to perform in vivo bioequivalence for these products of extensive use. Application of the in vitro-in silico-in vivo approach stands as an interesting alternative to tackle and reduce drug product variability in biopharmaceutical quality. Copyright © 2018 Elsevier B.V. All rights reserved.

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

Science.gov (United States)

Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

2013-11-01

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.

Science.gov (United States)

Slingerland, Marije; Guchelaar, Henk-Jan; Rosing, Hilde; Scheulen, Max E; van Warmerdam, Laurence J C; Beijnen, Jos H; Gelderblom, Hans

2013-12-01

Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties. Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration. Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa. Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia. At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil. © 2013 Elsevier HS Journals, Inc. All rights reserved.

21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

Science.gov (United States)

2010-04-01

... vivo bioavailability study. 320.27 Section 320.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.27...

Large-volume injection of sample diluents not miscible with the mobile phase as an alternative approach in sample preparation for bioanalysis: an application for fenspiride bioequivalence.

Science.gov (United States)

Medvedovici, Andrei; Udrescu, Stefan; Albu, Florin; Tache, Florentin; David, Victor

2011-09-01

Liquid-liquid extraction of target compounds from biological matrices followed by the injection of a large volume from the organic layer into the chromatographic column operated under reversed-phase (RP) conditions would successfully combine the selectivity and the straightforward character of the procedure in order to enhance sensitivity, compared with the usual approach of involving solvent evaporation and residue re-dissolution. Large-volume injection of samples in diluents that are not miscible with the mobile phase was recently introduced in chromatographic practice. The risk of random errors produced during the manipulation of samples is also substantially reduced. A bioanalytical method designed for the bioequivalence of fenspiride containing pharmaceutical formulations was based on a sample preparation procedure involving extraction of the target analyte and the internal standard (trimetazidine) from alkalinized plasma samples in 1-octanol. A volume of 75 µl from the octanol layer was directly injected on a Zorbax SB C18 Rapid Resolution, 50 mm length × 4.6 mm internal diameter × 1.8 µm particle size column, with the RP separation being carried out under gradient elution conditions. Detection was made through positive ESI and MS/MS. Aspects related to method development and validation are discussed. The bioanalytical method was successfully applied to assess bioequivalence of a modified release pharmaceutical formulation containing 80 mg fenspiride hydrochloride during two different studies carried out as single-dose administration under fasting and fed conditions (four arms), and multiple doses administration, respectively. The quality attributes assigned to the bioanalytical method, as resulting from its application to the bioequivalence studies, are highlighted and fully demonstrate that sample preparation based on large-volume injection of immiscible diluents has an increased potential for application in bioanalysis.

Current Challenges in Bioequivalence, Quality, and Novel Assessment Technologies for Topical Products

DEFF Research Database (Denmark)

Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D

2014-01-01

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic...

Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

Directory of Open Access Journals (Sweden)

Zhou X

2015-02-01

Full Text Available Xiao Zhou, Ji Liu Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4% for the area under the plasma concentration–time curve (AUC from time zero to the last measurable concentration, 99.6% (94.2%–102.7% for the AUC from administration to infinite time, and 100.8% (93.1%–106.4% for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules were bioequivalent. Keywords: tramadol hydrochloride, in vitro release, pharmacokinetic, bioequivalence, fluorescence detector

21 CFR 320.38 - Retention of bioavailability samples.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Retention of bioavailability samples. 320.38... (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.38 Retention of bioavailability samples...

Proposing the Use of Partial AUC as an Adjunctive Measure in Establishing Bioequivalence Between Deltoid and Gluteal Administration of Long-Acting Injectable Antipsychotics.

Science.gov (United States)

Lee, Lik Hang N; Choi, Charles; Gershkovich, Pavel; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

2016-12-01

The maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC) are commonly used to establish bioequivalence between two formulations of the same oral medication. Similarly, these pharmacokinetic parameters have also been used to establish bioequivalence between two sites of administration for the same injectable formulation. However, these conventional methods of establishing bioequivalence are of limited use when comparing modified-release formulations of a drug, particularly those with rates of absorption that are amenable to change with the site of injection. Inherent differences in the rate of absorption can result in clinically significant differences in early exposure and drug response. Here, we propose the use of the partial AUC (pAUC) as a measure of early exposure to aid in the assessment of bioequivalence between the gluteal and the deltoid site of administration for long-acting injectable antipsychotics.

Bioequivalence of three florfenicol preparations in broilers

Directory of Open Access Journals (Sweden)

Husamettin Ekici

2014-12-01

Full Text Available This study was aimed to determine the bioequivalence of three different preparations of florfenicol using non-drugged broiler chickens. A total of 28 broiler chickens aging 30-day were divided into four equal groups; these were Group I, II, III, and IV. The birds of Group I (for effective substance were given intravenous (i.v. administration of florfenicol dosed at 40 mg/kg body weight (b.wt.. The birds of Group II (for reference drug, Group III (for test-1 drug, and Group IV (for test-2 drug received florfenicol preparations with water (dosed at 40 mg/kg b.wt. through intracrop administration. Blood samples were collected periodically from the birds of all four groups, and blood plasma was separated. Levels of florfenicol and its metabolite (florfenicol amine in the plasma were measured by High Performance Liquid Chromatography (HPLC. In this study, the limit of detection (LOD for florfenicol and florfenicol amine were recorded as 0.017 and 0.78 µg/mL, respectively. On the other hand, the recovery of florfenicol and florfenicol amine were 83.4-84.6 and 82.2-83.8%, respectively. Based on the values of area under the curve (AUC, maximum concentration (Cmax, and time to maximum concentration (Tmax, test-1 drug was found to be acceptable, whereas test-2 drug was remained below the acceptable limits (80-125% of AUC and Cmax. Thus, it was concluded that test-1 drug was bioequivalent as compared to the reference drug.

[Bioequivalence of dermatological topical medicines:the Brazilian scenario and the challenges for health surveillance].

Science.gov (United States)

Soares, Kelen Carine Costa; Moraes, Marcelo Vogler; Gelfuso, Guilherme Martins; Gratieri, Taís

2015-11-01

The comparative evaluation required for the registration of generic topical medicines in Brazil is conducted by means of a pharmaceutical equivalence study, which merely assesses the physical/chemical and microbiological parameters of the formulations. At the international level, clinical or pharmacodynamic studies are now being required to prove the efficacy and safety of semisolid topical generic formulations. This work presents a comparison of the different requirements for the registration of topical formulations, taking into consideration the various regulatory authorities, and presents a survey of topical medicines registered in Brazil prior to 2013. The survey revealed that in comparison with the USA there were many more copies of these formulations registered in Brazil. This fact, together with the large number of studies in the literature showing the lack of bioequivalence of topical medication, is clear proof of the major importance of the need to realign Brazilian legislation with respect to the technical requirements for the registration of generic and similar medication for dermatological topical application in Brazil.

Bioequivalence of eslicarbazepine acetate from two different sources of its active product ingredient in healthy subjects.

Science.gov (United States)

Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

2013-06-01

To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions--either a single oral tablet of MF or a single oral tablet of TBM--separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90% confidence intervals (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were within the predetermined range of 80-125%. Test/reference GMR (90% CI) for the Cmax and AUC was respectively 100% (94-109%) and 96% (94-98%) following 400 mg ESL and 100% (95-105%) and 100% (97-103%) following 800 mg ESL. Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix® formulation according to the regulatory definition of bioequivalence.

Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

Science.gov (United States)

Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

2015-06-01

Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

Effect of the Wetting Agent Sodium Lauryl Sulfate on the Pharmacokinetics of Alectinib: Results From a Bioequivalence Study in Healthy Subjects.

Science.gov (United States)

Morcos, Peter N; Parrott, Neil; Banken, Ludger; Timpe, Carsten; Lindenberg, Marc; Guerini, Elena; Dall, Georgina; Bogman, Katrijn; Sturm, Carolina; Zeaiter, Ali; Martin-Facklam, Meret; Phipps, Alex

2017-05-01

The anaplastic lymphoma kinase (ALK) inhibitor alectinib is an effective treatment for ALK-positive non-small-cell lung cancer. This bioequivalence study evaluated the in vivo performance of test 3 formulations with the reduced wetting agent sodium lauryl sulfate (SLS) content. This randomized, 4-period, 4-sequence, crossover study compared alectinib (600 mg) as 25%, 12.5%, and 3% SLS hard capsule formulations with the reference 50% SLS clinical formulation in healthy subjects under fasted conditions (n = 49), and following a high-fat meal (n = 48). Geometric mean ratios and 90% confidence intervals (CIs) for C max , AUC 0-last , and AUC 0-∞ of alectinib, its major active metabolite, M4, and alectinib plus M4 were determined for the test formulations versus the reference formulation. Bioequivalence was concluded if the 90%CIs were within the 80% to 125% boundaries. The 25% SLS formulation demonstrated bioequivalence to the reference 50% SLS formulation for C max , AUC 0-last , and AUC 0-∞ of alectinib, M4, and alectinib plus M4 under both fasted and fed conditions. Further reductions in SLS content (12.5% and 3% SLS) did not meet the bioequivalence criteria. Cross-group comparisons showed an approximately 3-fold positive food effect. Reducing SLS to 25% resulted in a formulation that is bioequivalent to the current 50% SLS formulation used in alectinib pivotal trials. © 2016, The American College of Clinical Pharmacology.

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

Science.gov (United States)

Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

2009-01-01

The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

Science.gov (United States)

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

2013-12-01

Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.

Science.gov (United States)

van Gelder, Teun; Gabardi, Steven

2013-08-01

Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

Science.gov (United States)

2012-02-22

... recommendations provide product-specific guidance on the design of BE studies to support abbreviated new drug... the process that would be used to make product-specific BE recommendations available to the public on... ``Bioequivalence Recommendations for Specific Products,'' which explained the process that would be used to make...

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

Science.gov (United States)

Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

Quantitative analysis of valsartan by two-dimensional liquid chromatography (2D-HPLC) and its application in a bioequivalence study in Chinese volunteers
.

Science.gov (United States)

Zhang, Min; Deng, Yang; Cai, Hua-Lin; Fang, Ping-Fei; Yan, Miao; Zhang, Bi-Kui; Wu, Yan-Qin

2017-04-01

To develop a sensitive, two-dimensional liquid chromatography (2D-LC) method for determination of valsartan, applied to investigate bioequivalence of two valsartan tablets in Chinese volunteers under fasting condition. A full automatic 2D-HPLC system was used to quantify valsartan in human plasma. The analytes were extracted by protein precipitation, using telmisartan as internal standard. The analytical method was applied in a randomized, crossover bioequivalence study of valsartan tablets; the study enrolled 18 Chinese volunteers (12 were men and 6 were women). The subjects received a single 160-mg dose of test or reference preparation with 7-days of washout under fasting state. Plasma samples were collected, pharmacokinetic parameters were obtained and the bioequivalence was evaluated. The calibration range was 9.2 - 4213.8 ng×mL-1. Inter- and intraprecision was less than 7.0%, and accuracies ranged from 99.5 to 103.8%. The extraction recovery for valsartan varied between 89.3 and 97.8%, and the stability in all conditions was excellent. The 90% CI of AUC0→36h and Cmax were 96.5 - 109.4% and 94.2 - 108.6%, respectively. The relative bioavailability was 103.9 ± 15.7%. No gender difference was observed in pharmacokinetic parameters. A sensitive 2D-HPLC method was established for the estimation of valsartan in human plasma and successfully applied in a bioequivalence study of valsartan, which suggests that these two formulations can be assumed to be bioequivalent.
.

Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

Science.gov (United States)

Shahiwala, Aliasgar; Zarar, Aisha

2018-01-01

In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

Science.gov (United States)

Helmy, Sally A; El-Bedaiwy, Heba M

2014-11-01

Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

Science.gov (United States)

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

75 FR 33311 - Guidance for Industry on Bioequivalence Recommendations for Specific Products; Availability

Science.gov (United States)

2010-06-11

... available recommendations on how to design product-specific BE studies to support ANDAs. Under this process... thinking on a new process for making available to sponsors FDA guidance on how to design product-specific... ``Bioequivalence Recommendations for Specific Products.'' This guidance describes a new process for making...

46 CFR 67.171 - Deletion; requirement and procedure.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Deletion; requirement and procedure. 67.171 Section 67...; Requirement for Exchange, Replacement, Deletion, Cancellation § 67.171 Deletion; requirement and procedure. (a... provided in § 67.161, and the vessel is subject to deletion from the roll of actively documented vessels...

Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel

DEFF Research Database (Denmark)

Tettey-Amlalo, Ralph Nii Okai; Kanfer, Isadore; Skinner, Michael F

2008-01-01

The purpose was to investigate dermal microdialysis (DMD) for the assessment of the bioavailability of a ketoprofen topical gel formulation and to evaluate this technique as a tool for the determination of bioequivalence. Four microdialysis probes were inserted into the dermis on the volar aspect...

78 FR 66743 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability

Science.gov (United States)

2013-11-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability AGENCY... guidance, FDA recommended an in vivo fasting BE study with pharmacokinetic endpoints and in vitro studies...

Dissolution efficiency and bioequivalence study using urine data from healthy volunteers: a comparison between two tablet formulations of cephalexin

Directory of Open Access Journals (Sweden)

Cristina Helena dos Reis Serra

2015-06-01

Full Text Available The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation. Dissolution efficiency (DE% was calculated for both formulations to evaluate their in vitrobiopharmaceutical features. The oral bioequivalence study was performed in twenty-four healthy volunteers in a crossover design. Single oral dose (tablet containing 500 mg of cephalexin of each product was administered with two weeks of washout period. Urinary concentrations of cephalexin were measured by high-performance liquid chromatography (HPLC method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of cephalexin excreted in the urine, the total amount of cephalexin excreted in the urine and the maximum urinary excretion rate of cephalexin. DE values of immediate-release cephalexin tablets (500 mg were 68.69±4.18% for product A and 71.03±6.63% for product B. Regarding the dissolution test of the two brands (A and B analysed, both were in compliance with the official pharmacopeial specifications, since the dissolution of both formulations was superior to 80% of the amount declared in the label after 45 minutes of test (A=92.09%±1.84; B=92.84%±1.08. The results obtained indicated that the products A and B are pharmaceutical equivalents. Confidence intervals for the pharmacokinetic parameters were in compliance with the international standards, indicating that products A and B can be considered bioequivalents and, therefore, interchangeable.

Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

KAUST Repository

Al-Talla, Zeyad; Akrawi, Sabah H.; Emwas, Abdul-Hamid M.

2011-01-01

Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a

A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

Science.gov (United States)

Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

2011-06-01

The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

Pharmacokinetic comparison and bioequivalence evaluation of losartan/ hydrochlorothiazide tablet between Asian Indian and Japanese volunteers.

Science.gov (United States)

Kumar, Sudershan; Monif, Tausif; Khuroo, Arshad; Reyar, Simrit; Jain, Rakesh; Singla, Ajay K; Kurachi, Kazuya

2014-01-01

To demonstrate the bioequivalence between the test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablet and evaluate the effect of ethnicity on pharmacokinetics properties of losartan, losartan carboxylic acid and hydrochlorothiazide on healthy Asian Indian and Japanese volunteers. Randomized, open-label, crossover, bioavailability studies were conducted separately in healthy Asian Indian and Japanese volunteers. One tablet either of test or of reference product was administered after 10 hours of overnight fasting. After dosing, serial blood samples were collected for a period of 48 hours for both the studies. Plasma samples were analyzed for losartan, losartan carboxylic acid and hydrochlorothiazide by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0-t, AUC0-∞, Cmax, tmax, and other pharmacokinetics parameters were determined from plasma concentration-time profiles for both test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablets. Statistical evaluations were done to evaluate bioequivalence between generic test formulation (EPR0001) and Japanese reference product (Preminent®). Losartan, losartan carboxylic acid and hydrochlorothiazide were well tolerated by subjects in all periods of each study under fasted conditions. No serious adverse events were observed. The ratios of least square means for AUC0-t and Cmax and the affiliated 90% confidence intervals were within acceptance range recommended by PMDA. Marginal differences were observed in pharmacokinetic values of Asian Indian and Japanese volunteers. The results of these bioavailability studies indicate that the test formulation of losartan/hydrochlorothiazide 50 + 12.5 mg (EPR0001) tablets is bioequivalent to marketed Preminent® reference formulation in Asian Indian and Japanese volunteers, when administered under fasting conditions. Both test and reference formulations were well tolerated

Bioequivalence assessment of two formulations of ibuprofen

Directory of Open Access Journals (Sweden)

Al-Talla ZA

2011-10-01

, therefore, Doloraz was considered bioequivalent to Brufen. Keywords: ibuprofen, bioequivalence study, pharmacokinetics

78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

Science.gov (United States)

2013-12-05

... exposure measures is suitable for documenting BE (e.g., transdermal delivery systems and certain rectal and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1464] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted...

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE... test product and the reference material should be administered to subjects in the fasting state, unless...

Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

Science.gov (United States)

Baribeault, David

2011-08-01

Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Pharmacokinetic bioequivalence studies of a fixed-dose combination of tamsulosin and dutasteride in healthy volunteers.

Science.gov (United States)

Fossler, Michael J; Collins, David A; Thompson, Meg M; Nino, Antonio; Bianco, Joseph J; Chetty, Dushen

2014-05-01

The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0.2 mg) fixed-dose combination (FDC) capsules containing a small dutasteride soft gelatin capsule (smaller than commercial Avodart™) and modified-release tamsulosin pellets that have different amounts of enteric coating. These studies compared the test products to commercial Avodart™ (dutasteride 0.5 mg) and two different commercial tamsulosin HCl 0.2 mg products, Harnal™ Capsules or Harnal-D™ Tablets, which are reportedly bioequivalent to each other. All three studies were randomized single-dose studies in healthy male adults. Study 1 [N = 86 (NCT01254071)] was a two-period crossover study of a dutasteride/tamsulosin HCl FDC versus coadministered Avodart™ and Harnal-D™ Tablets. The pharmacokinetics of both dutasteride and tamsulosin were studied. Study 2 [N = 27 (NCT01471678)] was a four-period crossover study of dutasteride/tamsulosin HCl FDC formulations versus Avodart™ and Harnal™ Capsules or Harnal-D™ Tablets. Only the pharmacokinetics of tamsulosin were studied. Study 3 [N = 40 (NCT01495026)] was a two-period study of dutasteride/tamsulosin HCl FDC formulations versus coadministered Avodart™ and Harnal-D™ Tablets. In this study, only the pharmacokinetics of tamsulosin were studied. Study 2 assessed fed-state pharmacokinetics. Studies 1 and 3 assessed fed- and fasted-state pharmacokinetics. All dutasteride/tamsulosin HCl FDC formulations and coadministered treatments were well-tolerated. In Study 1, the FDC dutasteride was bioequivalent to Avodart™ coadministered with tamsulosin under fed and fasted conditions. In Study 1, the FDC tamsulosin had a slower release than commercial Harnal-D™ Tablets coadministered with dutasteride (fed and fasted

Bioequivalence study of two losartan tablet formulations with special emphasis on cardiac safety.

Science.gov (United States)

Khandave, Suhas S; Sawant, Satish V; Sahane, Rakhi V; Murthi, Vivekanand; Dhanure, Shivanand S; Surve, Pradeep G

2012-05-01

To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

Science.gov (United States)

Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

2013-11-01

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

Science.gov (United States)

Padgaonkar, K A; Revankar, S N; Bhatt, A D; Vaz, J A; Desai, N D; D'Sa, S; Shah, V; Gandewar, K

1999-07-01

To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

77 FR 75439 - Guidances for Industry and Investigators on Safety Reporting Requirements for Investigational New...

Science.gov (United States)

2012-12-20

...] Guidances for Industry and Investigators on Safety Reporting Requirements for Investigational New Drug Applications and Bioavailability/Bioequivalence Studies, and a Small Entity Compliance Guide; Availability... Reporting Requirements for INDs and BA/BE Studies'' and ``Safety Reporting Requirements for INDs and BA/BE...

Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

KAUST Repository

Al-Talla, Zeyad

2011-01-01

Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

Development of a new benazepril hydrochloride chewable tablet and evaluation of its bioequivalence for treatment of heart failure in dogs.

Science.gov (United States)

Qian, M; Chen, T; Zhou, D; Zhang, Z; Zhang, Q; Tang, S; Xiao, X

2016-02-01

The aim of the study was to develop a new chewable benazepril hydrochloride(BH) tablet, investigate its physical properties, and evaluate its bioequivalence with the branded formulation (Fortekor). A corrective agent was included in the formula to improve its palatability and convenience for administration to dogs. The tablet remained stable in light, heat, and humidity tests, and its physical properties such as hardness, uniformity of content, and dissolution rate were highly consistent with the technical standards. After single and repeated administrations to eight beagles and single dose to 14 mongrel dogs (0.5 mg/kg p.o.), plasma BH and its active metabolite, benazeprilat (BZ), were detected. There was no significant difference in the major pharmacokinetic parameters (Cmax , Tmax, and AUC₀₋₂₄) between the two formulations. The 90% confidence intervals calculated for the ratios of area under the time-concentration curve (AUC₀₋₂₄) were 92.4-116.3% for BH and 89.9-102.3% for BZ, within the accepted range for bioequivalence of 80-125%. The results showed our new chewable tablet is bioequivalent to the commercial product and suitable for addition to the benazepril product family for the treatment of heart failure in dogs. © 2015 John Wiley & Sons Ltd.

Generic drugs: myths, facts, and limitations

Directory of Open Access Journals (Sweden)

Antonio Marzo

2012-10-01

Full Text Available Bioequivalence (BE has always been an important pharmaceutical area, particularly (but not solely in Mediterranean region, where the use of generic drugs is a relatively recent development. The lack of new therapeutic molecules has concentrated primary research in the hands of a few large pharmaceutical companies. For smaller companies, this has created opportunities for the development of new formulations of existing drugs (orodispersible tablets that dissolve in the mouth, extended-release tablets, transdermal delivery systems, generic drugs. These applications take advantage of the Abridged New Drug Application (ANDA procedure, which exempts them from a series of expensive investigations and limits the requirement for clinical testing to bioequivalence trials. Since 1991, bioequivalence trials have been regulated by US Food and Drug Administration (FDA and European Medicines Agency (EMA guidelines that provide precise indications on the most specific procedures to be adopted. In spite of these guidelines, however, some aspects of the process have not been fully defined, the most important of which regards the management of endogenous substances. Additional problems are how to manage bioequivalence protocols with drugs that have long half-lives and those whose clearance is characterized by high intrinsic variability. The view that bioequivalence data would be more reliable if they were based on studies in target populations is a myth to be discredited. The present paper reviews issues relative to pharmacokinetics (PK, bioavailability (BA, and bioequivalence, also from an historical viewpoint, and includes a stimulating “questions and answers” section on some key aspects of the bioequivalence of generic drugs.

Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

Science.gov (United States)

Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

2010-05-01

To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets
.

Science.gov (United States)

Cho, Hea-Young; Ngo, Lien; Kim, Sang-Ki; Choi, Yoonho; Lee, Yong-Bok

2018-06-01

This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24 hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC0-t, AUC0-∞, and Cmax based on EDI tablets were 110.07 (102.25 - 118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively, for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and 98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated.
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44 CFR 17.630 - Certification requirements and procedures.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Certification requirements and procedures. 17.630 Section 17.630 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE...

Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

Directory of Open Access Journals (Sweden)

K. O. Zupanets

2016-03-01

Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

Science.gov (United States)

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

2015-03-01

RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics

DEFF Research Database (Denmark)

Kreilgaard, Mads; Kemme, M J; Burggraaf, J

2001-01-01

The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method....

Evaluation of two novel tablet formulations of artemether-lumefantrine (Coartem) for bioequivalence in a randomized, open-label, two-period study.

Science.gov (United States)

Lefèvre, Gilbert; Bhad, Prafulla; Jain, Jay Prakash; Kalluri, Sampath; Cheng, Yi; Dave, Hardik; Stein, Daniel S

2013-09-08

Artemether-lumefantrine (Coartem; AL) is a standard of care for malaria treatment as an oral six-dose regimen, given twice daily over three days with one to four tablets (20/120 mg) per dose, depending on patient body weight. In order to reduce the pill burden at each dose and potentially enhance compliance, two novel fixed-dose tablet formulations (80/480 mg and 60/360 mg) have been developed and tested in this study for bioequivalence with their respective number of standard tablets. A randomized, open-label, two-period, single-dose, within formulation crossover bioequivalence study comparing artemether and lumefantrine exposure between the novel 80/480 mg tablet and four standard tablets, and the novel 60/360 mg tablet and three standard tablets, was conducted in 120 healthy subjects under fed conditions. Artemether, dihydroartemisinin, and lumefantrine were measured in plasma by HPLC/UPLC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analyses. Adjusted geometric mean AUClast for artemether were 345 and 364 ng·h/mL (geometric mean ratio (GMR) 0.95; 90% CI 0.89-1.01) and for lumefantrine were 219 and 218 μg·h/mL (GMR 1.00; 90% CI 0.93-1.08) for 80/480 mg tablet versus four standard tablets, respectively. Corresponding Cmax for artemether were 96.8 and 99.7 ng/mL (GMR 0.97; 90% CI 0.89-1.06) and for lumefantrine were 8.42 and 8.71 μg/mL (GMR 0.97; 90% CI 0.89-1.05). For the 60/360 mg tablet versus three standard tablets, adjusted geometric mean AUClast for artemether were 235 and 231 ng·h/mL (GMR 1.02; 90% CI 0.94-1.10), and for lumefantrine were 160 and 180 μg·h/mL (GMR 0.89; 90% CI 0.83-0.96), respectively. Corresponding Cmax for artemether were 75.5 and 71.5 ng/mL (GMR 1.06; 90% CI 0.95-1.18), and for lumefantrine were 6.64 and 7.61 μg/mL (GMR 0.87; 90% CI 0.81-0.94), respectively. GMR for Cmax and AUClast for artemether and lumefantrine for all primary comparisons were within the bioequivalence acceptance criteria (0

Cognition and procedure representational requirements for predictive human performance models

Science.gov (United States)

Corker, K.

1992-01-01

Models and modeling environments for human performance are becoming significant contributors to early system design and analysis procedures. Issues of levels of automation, physical environment, informational environment, and manning requirements are being addressed by such man/machine analysis systems. The research reported here investigates the close interaction between models of human cognition and models that described procedural performance. We describe a methodology for the decomposition of aircrew procedures that supports interaction with models of cognition on the basis of procedures observed; that serves to identify cockpit/avionics information sources and crew information requirements; and that provides the structure to support methods for function allocation among crew and aiding systems. Our approach is to develop an object-oriented, modular, executable software representation of the aircrew, the aircraft, and the procedures necessary to satisfy flight-phase goals. We then encode in a time-based language, taxonomies of the conceptual, relational, and procedural constraints among the cockpit avionics and control system and the aircrew. We have designed and implemented a goals/procedures hierarchic representation sufficient to describe procedural flow in the cockpit. We then execute the procedural representation in simulation software and calculate the values of the flight instruments, aircraft state variables and crew resources using the constraints available from the relationship taxonomies. The system provides a flexible, extensible, manipulative and executable representation of aircrew and procedures that is generally applicable to crew/procedure task-analysis. The representation supports developed methods of intent inference, and is extensible to include issues of information requirements and functional allocation. We are attempting to link the procedural representation to models of cognitive functions to establish several intent inference methods

Risk and safety requirements for diagnostic and therapeutic procedures in allergology

DEFF Research Database (Denmark)

Kowalski, Marek L; Ansotegui, Ignacio; Aberer, Werner

2016-01-01

One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin...... attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk...... associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access...

Bioequivalence of a new liquid formulation of benazepril compared with the reference tablet product.

Science.gov (United States)

Kelers, K; Devi, J L; Anderson, G A; Zahra, P; Vine, J H; Whittem, T

2013-08-01

To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration. Randomised cross-over design, followed by parallel comparison. Twelve mixed-breed dogs were administered either a tablet (Group A) or liquid formulation (Group B) of benazepril orally at 0.45 mg/kg daily for 4 days. With no washout period, the dogs then received the alternative treatment at the same dose for a further 4 days. Blood samples taken prior to treatment and serially after treatment were analysed for plasma concentrations of benazepril and benazeprilat and the activity and concentration of angiotensin-converting enzyme (ACE). The calculated percentage inhibition of ACE was defined as the primary outcome variable. No statistically significant differences were found between groups A and B for any variable evaluated. The mean (± SD) percentage of ACE inhibition was 85.5 ± 7.04% for the liquid formulation and 85.9 ± 6.66% for the tablet formulation. The mean of the ratios was 1.00 (80% confidence interval 0.96-1.04). No evaluated effect term (sequence, formulation or period) had any statistical effect on any outcome variable. This study supports a conclusion that, based on pharmacodynamic response, the liquid formulation of benazepril is bioequivalent to the reference tablet formulation. Further, the lack of a sequence effect supports the switchability of these two formulations. © 2013 Australian Veterinary Association.

The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

Science.gov (United States)

Tsume, Yasuhiro; Amidon, Gordon L

2010-08-02

The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

Science.gov (United States)

Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

2017-02-01

The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
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Advantages of automation in plasma sample preparation prior to HPLC/MS/MS quantification: application to the determination of cilazapril and cilazaprilat in a bioequivalence study.

Science.gov (United States)

Kolocouri, Filomila; Dotsikas, Yannis; Apostolou, Constantinos; Kousoulos, Constantinos; Soumelas, Georgios-Stefanos; Loukas, Yannis L

2011-01-01

An HPLC/MS/MS method characterized by complete automation and high throughput was developed for the determination of cilazapril and its active metabolite cilazaprilat in human plasma. All sample preparation and analysis steps were performed by using 2.2 mL 96 deep-well plates, while robotic liquid handling workstations were utilized for all liquid transfer steps, including liquid-liquid extraction. The whole procedure was very fast compared to a manual procedure with vials and no automation. The method also had a very short chromatographic run time of 1.5 min. Sample analysis was performed by RP-HPLC/MS/MS with positive electrospray ionization using multiple reaction monitoring. The calibration curve was linear in the range of 0.500-300 and 0.250-150 ng/mL for cilazapril and cilazaprilat, respectively. The proposed method was fully validated and proved to be selective, accurate, precise, reproducible, and suitable for the determination of cilazapril and cilazaprilat in human plasma. Therefore, it was applied to a bioequivalence study after per os administration of 2.5 mg tablet formulations of cilazapril.

Licensing procedure and requirements in the FRG

International Nuclear Information System (INIS)

Brosche, D.

1981-01-01

The investigations of the different dynamic stresses of pressure suppression systems after the Wuergassen incident in 1972 and their theoretical and experimental solutions required an extraordinary effort from all participants of the licensing procedures. As a consequence of these new problems a lot of mathematical models and computer codes had been developed and a lot of experimental work had been performed. Numerous highly qualified scientists and engineers had been involved for a long time in the licensing procedures and innumerable discussions had been necessary. These investigations and discussions had a great influence on the licensing procedures and on the project running. Too pessimistic assumptions and wrong interpretations of experiments led to fictitious problems and a lot of time and money was necessary to overcome these difficulties. Finally at 1977 it could be proved that the construction was able to control stresses so that additional investigations were not necessary. (orig./HP)

15 CFR 291.6 - Additional requirements; Federal policies and procedures.

Science.gov (United States)

2010-01-01

... and Foreign Trade NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE NIST... requirements; Federal policies and procedures. Recipients and subrecipients are subject to all Federal laws and Federal and Department of Commerce policies, regulations, and procedures applicable to Federal financial...

Development of procedural requirements for life extension of nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Hun; Son, Moon Kyu [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Ham, Cheol Hun [The Catholic University of Korea, Seoul (Korea, Republic of); Chang, Keun Sun [Sunmoon Univ., Asan (Korea, Republic of); Paek, Won Phil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of); Cheong, Ji Hwan [Baekseok College Cultural Studies, Cheonan (Korea, Republic of)

2001-03-15

Current status of regulatory aspects of life extension and upgrading of NPPs is reviewed for major foreign countries. Most countries require similar technical requirements; however, procedural aspects differ country by country. Regulatory systems suitable for NPP life extension is investigated. The procedure and requirements for reassessment of design life should be established first; then it can be incorporated into the PSR system. The concept of 'Current Licensing Basis (CLB)' can be adopted in Korea, but further elaboration for terms and definitions is needed for common understanding between interested groups. The procedure for maintenance and backfitting should also be improved. The Systems, Structures, and Components (SSCs) that require development of regulatory requirements for life extension are identified based on extensive analysis of foreign experiences. By analyzing the rules and regulations related to life extension. Basic directions are suggested to harmonize or establish regulatory systems for life extension, two-step licensing, PSR, and backfitting.

Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.

Science.gov (United States)

Kurczewski, Renee; Bowen, Chet; Collins, David; Zhu, John; Serbest, Gulyeter; Manyak, Michael

2017-09-01

A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart ® ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (C max ) and area under the serum concentration-time curve (AUC 0-t ) for dutasteride and tamsulosin, and AUC 0-∞ for tamsulosin. The 90% confidence intervals for the ratios of the C max and AUC 0-t (for dutasteride and tamsulosin) and for AUC 0-∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states. © 2017, The American College of Clinical Pharmacology.

Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

Science.gov (United States)

Pai, Amy Barton

2017-11-01

Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

Directory of Open Access Journals (Sweden)

Zhang Y

2017-07-01

Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

Development to requirements for a procedures software tool

International Nuclear Information System (INIS)

Yasutake, J.Y.; Hachiro Isoda

1993-01-01

In 1989, the Electric Power Research Institute (EPRI) and the Central Research Institute of the Electric Power Industry (CRIEPI) in Japan initiated a joint research program to investigate various interventions to reduce personnel errors and inefficiencies in the maintenance of nuclear power plants. This program, consisting of several interrelated projects, was initiated because of the mutual recognition of the importance of the human element in the efficient and safe operation of utilities and the continuing need to enhance personnel performance to sustain plant safety and availability. This paper summarizes one of the projects, jointly funded by EPRI and CRIEPI, to analyze the requirements for, and prepare a functional description of, a procedures software tool (PST). The primary objective of this project was to develop a description of the features and functions of a software tool that would help procedure writers to improve the quality of maintenance and testing procedures, thereby enhancing the performance of both procedure writers and maintenance personnel

Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers.

Science.gov (United States)

Holt, Robert J; Taiwo, Tolu; Kent, Jeffrey D

2015-08-01

Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects. The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods. The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac. The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https

46 CFR 272.42 - Audit requirements and procedures.

Science.gov (United States)

2010-10-01

... procedures. (a) Required audit. In connection with the audit of the Operator's subsidizable expenses, the... of audit results. Upon completion of the audit by the Office of Inspector General, the MARAD Office of Financial Approvals shall notify the Operator of the audit results, including any items disallowed...

Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

Directory of Open Access Journals (Sweden)

2000-03-01

Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

7 CFR 70.110 - Requirements for sanitation, facilities, and operating procedures in official plants.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Requirements for sanitation, facilities, and operating... Requirements for sanitation, facilities, and operating procedures in official plants. (a) The requirements for sanitation, facilities, and operating procedures in official plants shall be the applicable provisions stated...

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

Science.gov (United States)

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Directory of Open Access Journals (Sweden)

Eunice Kazue Kano

2015-03-01

Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

Science.gov (United States)

Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

2016-03-01

Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

Bioequivalence assessment of two formulations of ibuprofen

KAUST Repository

Al-Talla, Zeyad

2011-10-19

Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

A pharmacokinetic and bioequivalence study of Contiflo ICON 400 µg tablets in healthy Indian subjects.

Science.gov (United States)

Monif, T; Arora, V; Madan, S; Arora, R; Balaji, A; Jha, D; Thudi, N R

2010-12-01

Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in human prostate. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of benign prostatic hypertrophy. A new formulation Contiflo ICON 400 µg has been developed by Ranbaxy Laboratories Limited, India similar to Flomaxtra XL 400 µg of Astellas Pharma Limited, United Kingdom. This product is specifically designed to achieve a more consistent plasma concentration over a period of 24-h, a lower maximum plasma concentration (Cmax) and an independence of pharmacokinetics (PKs) on food intake. The objective of the present study was to evaluate the pharmacokinetics and bioequivalence of the new formulation Contiflo ICON 400 µg of Ranbaxy Laboratories Limited, India and Flomaxtra XL 400 µg prolonged release tablets (containing tamsulosin hydrochloride prolonged release 400 µg) of Astellas Pharma Limited, United Kingdom. Study was conducted as an open label, balanced, randomized, two-treatment, two-period, two-sequence, cross over, single-dose bioequivalence study in 32 adult male human subjects under fed conditions. The mean (range) age, weight and height of the study subjects were 27.03 years (19 - 40 years), 57.19 kg (48 - 72 kg) and 166.81 cm (154 - 181 cm) respectively. Blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 20, 24, 36, 48, 72, and 96 h post dose in each period. Plasma samples were analyzed for tamsulosin by using validated liquid chromatographic mass spectrometry (LC-MS/MS) method. The Mean ± SD of pharmacokinetic parameters tmax, Cmax, AUC24, AUClast and AUCinf for Tamsulosin were 11.741 ± 4.7201 and 12.155 ± 6.3077 h, 10.7614 ± 4.76709 and 10.4954 ± 5.08979 ng/ml, 171.4674 ± 77.39695 and 160.6738 ± 77.98628 ng.h/ml, 262.7771 ± 150.21432 and 250.6854 ± 156.75581 ng

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

Science.gov (United States)

Mita, Sachiko; Chitnis, Shripad D; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Zhou, Wei; Suzuki, Hikoe

2016-04-01

To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

16 CFR 1501.4 - Size requirements and test procedure.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Size requirements and test procedure. 1501.4 Section 1501.4 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT.... The metric approximations are included only for convenience.) (b)(1) Place the article, without...

Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

Science.gov (United States)

Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

2008-10-01

Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

Computer-Based Procedures for Field Workers in Nuclear Power Plants: Development of a Model of Procedure Usage and Identification of Requirements

Energy Technology Data Exchange (ETDEWEB)

Katya Le Blanc; Johanna Oxstrand

2012-04-01

The nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. As a step toward the goal of improving procedure use performance, researchers, together with the nuclear industry, have been looking at replacing the current paper-based procedures with computer-based procedure systems. The concept of computer-based procedures is not new by any means; however most research has focused on procedures used in the main control room. Procedures reviewed in these efforts are mainly emergency operating procedures and normal operating procedures. Based on lessons learned for these previous efforts we are now exploring a more unknown application for computer based procedures - field procedures, i.e. procedures used by nuclear equipment operators and maintenance technicians. The Idaho National Laboratory and participants from the U.S. commercial nuclear industry are collaborating in an applied research effort with the objective of developing requirements and specifications for a computer-based procedure system to be used by field workers. The goal is to identify the types of human errors that can be mitigated by using computer-based procedures and how to best design the computer-based procedures to do so. This paper describes the development of a Model of Procedure Use and the qualitative study on which the model is based. The study was conducted in collaboration with four nuclear utilities and five research institutes. During the qualitative study and the model development requirements and for computer-based procedures were identified.

34 CFR 370.43 - What requirement applies to the use of mediation procedures?

Science.gov (United States)

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false What requirement applies to the use of mediation... applies to the use of mediation procedures? (a) Each designated agency shall implement procedures designed to ensure that, to the maximum extent possible, good faith negotiations and mediation procedures are...

Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid.

Science.gov (United States)

Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

2015-07-10

The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

Science.gov (United States)

Brendel, Erich; Weimann, Boris; Dietrich, Hartmut; Froede, Christoph; Thomas, Dirk

2013-09-01

To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs. 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method. Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated. The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.

Guidelines on the facilities required for minor surgical procedures and minimal access interventions.

LENUS (Irish Health Repository)

Humphreys, H

2012-02-01

There have been many changes in healthcare provision in recent years, including the delivery of some surgical services in primary care or in day surgery centres, which were previously provided by acute hospitals. Developments in the fields of interventional radiology and cardiology have further expanded the range and complexity of procedures undertaken in these settings. In the face of these changes there is a need to define from an infection prevention and control perspective the basic physical requirements for facilities in which such surgical procedures may be carried out. Under the auspices of the Healthcare Infection Society, we have developed the following recommendations for those designing new facilities or upgrading existing facilities. These draw upon best practice, available evidence, other guidelines where appropriate, and expert consensus to provide sensible and feasible advice. An attempt is also made to define minimal access interventions and minor surgical procedures. For minimal access interventions, including interventional radiology, new facilities should be mechanically ventilated to achieve 15 air changes per hour but natural ventilation is satisfactory for minor procedures. All procedures should involve a checklist and operators should be appropriately trained. There is also a need for prospective surveillance to accurately determine the post-procedure infection rate. Finally, there is a requirement for appropriate applied research to develop the evidence base required to support subsequent iterations of this guidance.

Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

Science.gov (United States)

Dadey, Eric

Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

Euratom's accounting procedures to comply with IAEA requirements

International Nuclear Information System (INIS)

Kschwendt, H.

1980-01-01

The accounting concept used by the operators for nuclear materials accountancy is different from the evaluation concept used by IAEA. Euratom integrated these two concepts thus allowing for an automatic transformation from the one to the other concept (establishment of reports to IAEA by computer). Particular procedures have been developed to ensure the corrections of the accountancy in both concepts and to perform the retrospective corrections as required by IAEA. 4 refs

Defining System Requirements: a critical assessment of the Niam conceptual design procedure

Directory of Open Access Journals (Sweden)

Peta Darke

1995-05-01

Full Text Available Requirements definition is a fundamental activity within information systems development. Social and organisational issues are at the centre of many of the problems experienced during the development and implementation of information systems, and these need to be explored during requirements definition. The NIAM Conceptual Schema Design Procedure (CSDP is a method for identifying and describing information requirements using fact types. This paper discusses some limitations of the information requirements definition step of the CSDP which result from its lack of focus on the socio-organisational dimension of information systems development. Four different approaches to exploring the socio-organisational contexts of systems are discussed. It is proposed that one of these, viewpoint development, be incorporated into the NIAM CSDP to provide a means of exploring and understanding a system's socio organisational context and to ensure that contextual information is a major input to the requirements definition process. This results in an enhanced design procedure. Future and current research areas are identified.

19 CFR 101.9 - Test programs or procedures; alternate requirements.

Science.gov (United States)

2010-04-01

... basis for selecting participants. (b) NCAP testing. For purposes of conducting an approved test program or procedure designed to evaluate planned components of the National Customs Automation Program (NCAP... publication requirement. For tests affecting the NCAP, notice shall be published in the Federal Register not...

Investigation of Bioequivalence Between Brand-name and Generic Irinotecan Products.

Science.gov (United States)

Saito, Ken-Ichi; Inoue, Yutaka; Ikegami, Yoji; Nanbo, Izumi; Onozuka, Mari; Sano, Kazumi; Yoshida, Hisahiro; Sakamoto, Toshihiro; Tatebayashi, Emi; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Kitazawa, Takaki

2016-11-01

To investigate bioequivalence among generic and brand-name irinotecan products. Products of Yakult and Daiichi-Sankyo (brand-name products), Sandoz, Nippon Kayaku, Taiho, and Sawai were compared with respect to their composition and antitumor activity. High-performance liquid chromatography demonstrated that related substances were within the acceptable range. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed significant differences in cytotoxicity for four cancer cell lines among the products. The concentration of the active compound SN-38 was highest in Yakult's product (23.82 ng/ml) and lowest in Daiichi-Sankyo's product (8.96 ng/ml). MTT assay data were correlated with the SN-38 concentration, suggesting that it influenced differences in cytocidal activity among products. However, the SN-38 concentration was far lower than that of irinotecan (20 mg/ml), suggesting a negligible clinical effect. Metabolism of irinotecan to SN-38 or open-ring forms did not differ significantly among the products. The generic products showed equivalent efficacy and safety to the brand-name products. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

Science.gov (United States)

Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex absorption: methylphenidate.

Science.gov (United States)

Fourie Zirkelbach, Jeanne; Jackson, Andre J; Wang, Yaning; Schuirmann, Donald J

2013-01-01

Methylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products. A two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC. The sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased. PAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted.

Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

Directory of Open Access Journals (Sweden)

Werawath Mahatthanatrakul

2008-05-01

Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

Science.gov (United States)

Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

2009-10-01

Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

Evaluation procedure of software requirements specification for digital I and C of KNGR

International Nuclear Information System (INIS)

Lee, Jang Soo; Park, Jong Kyun; Lee, Ki Young; Kim, Jang Yeol; Cheon, Se Woo

2001-06-01

The accuracy of the specification of requirements of a digital system is of prime importance to the acceptance and success of the system. The development, use, and regulation of computer systems in nuclear reactor Instrumentation and Control (I and C) systems to enhance reliability and safety is a complex issue. This report is one of a series of reports from the Korean Next Generation Reactor (KNGR) Software Safety Verification and Validation (SSVV) Task, Korea Atomic Energy Research Institute, which investigates different aspects of computer software in reactor I and C systems, and describes the engineering procedures for developing such a software. The purpose of this guideline is to give the software safety evaluator the trail map between the code and standards layer and the design methodology and documents layer for the software important to safety in nuclear power plants. Recently, the requirements specification of safety-critical software systems and safety analysis of them are being recognized as one of the important issues in the software life cycle, and being developed new regulatory positions and standards by the regulatory and the standardization organizations such as IAEA, IEC, and IEEE. We presented the procedure for evaluating the software requirements specifications of the KNGR protection systems. We believe it can be useful for both licenser and licensee to conduct an evaluation of the safety in the requirements phase of developing the software. The guideline consists of the requirements engineering for software of KNGR protection systems in chapter 1, the evaluation checklist of software requirements specification in chapter2.3, and the safety evaluation procedure of KNGR software requirements specification in chapter 2.4

Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

Science.gov (United States)

Ramirez, Elena; Laosa, Olga; Guerra, Pedro; Duque, Blanca; Mosquera, Beatriz; Borobia, Alberto M; Lei, Suhua H; Carcas, Antonio J; Frias, Jesus

2010-01-01

AIM The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes. METHODS We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products. RESULTS Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3. CONCLUSIONS Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for Cmax or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies. PMID:21039763

15 CFR 30.35 - Procedure for shipments exempt from filing requirements.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Procedure for shipments exempt from filing requirements. 30.35 Section 30.35 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE FOREIGN TRADE REGULATIONS Exemptions From the...

Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

Science.gov (United States)

Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

2017-08-01

On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Comparison of parametric and bootstrap method in bioequivalence test.

Science.gov (United States)

Ahn, Byung-Jin; Yim, Dong-Seok

2009-10-01

The estimation of 90% parametric confidence intervals (CIs) of mean AUC and Cmax ratios in bioequivalence (BE) tests are based upon the assumption that formulation effects in log-transformed data are normally distributed. To compare the parametric CIs with those obtained from nonparametric methods we performed repeated estimation of bootstrap-resampled datasets. The AUC and Cmax values from 3 archived datasets were used. BE tests on 1,000 resampled datasets from each archived dataset were performed using SAS (Enterprise Guide Ver.3). Bootstrap nonparametric 90% CIs of formulation effects were then compared with the parametric 90% CIs of the original datasets. The 90% CIs of formulation effects estimated from the 3 archived datasets were slightly different from nonparametric 90% CIs obtained from BE tests on resampled datasets. Histograms and density curves of formulation effects obtained from resampled datasets were similar to those of normal distribution. However, in 2 of 3 resampled log (AUC) datasets, the estimates of formulation effects did not follow the Gaussian distribution. Bias-corrected and accelerated (BCa) CIs, one of the nonparametric CIs of formulation effects, shifted outside the parametric 90% CIs of the archived datasets in these 2 non-normally distributed resampled log (AUC) datasets. Currently, the 80~125% rule based upon the parametric 90% CIs is widely accepted under the assumption of normally distributed formulation effects in log-transformed data. However, nonparametric CIs may be a better choice when data do not follow this assumption.

24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

Science.gov (United States)

2010-04-01

... requirements under HUD building products certification program for solid fuel type room heaters and fireplace... Supplementary specific procedural requirements under HUD building products certification program for solid fuel... fireplace stoves certified under the HUD Building Products Certification Program shall be designed...

Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

Science.gov (United States)

Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

2013-03-01

Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

Energy Technology Data Exchange (ETDEWEB)

Szebeni, Janos, E-mail: jszebeni2@gmail.com [Nanomedicine Research and Education Center, Semmelweis University, Budapest & SeroScience Ltd, Budapest (Hungary); Storm, Gert [Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht (Netherlands)

2015-12-18

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

International Nuclear Information System (INIS)

Szebeni, Janos; Storm, Gert

2015-01-01

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement

Directory of Open Access Journals (Sweden)

Marek L. Kowalski

2016-10-01

Full Text Available Abstract One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing, deliberate induction in the office of allergic symptoms to offending compounds (provocation tests or intentional application of potentially dangerous substances (allergy vaccine to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO, representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established

Improved simultaneous quantitation of candesartan and hydrochlorthiazide in human plasma by UPLC–MS/MS and its application in bioequivalence studies

Directory of Open Access Journals (Sweden)

Bhupinder Singh

2014-04-01

Full Text Available A validated ultra-performance liquid chromatography mass spectrometric method (UPLC–MS/MS was used for the simultaneous quantitation of candesartan (CN and hydrochlorothiazide (HCT in human plasma. The analysis was performed on UPLC–MS/MS system using turbo ion spray interface. Negative ions were measured in multiple reaction monitoring (MRM mode. The analytes were extracted using a liquid–liquid extraction (LLE method by using 0.1 mL of plasma volume. The lower limit of quantitation for CN and HCT was 1.00 ng/mL whereas the upper limit of quantitation was 499.15 ng/mL and 601.61 ng/mL for CN and HCT respectively. CN d4 and HCT-13Cd2 were used as the internal standards for CN and HCT respectively. The chromatography was achieved within 2.0 min run time using a C18 Phenomenex, Gemini NX (100 mm×4.6 mm, 5 µm column with organic mixture:buffer solution (80:20, v/v at a flow rate of 0.800 mL/min. The method has been successfully applied to establish the bioequivalence of candesartan cilexetil (CNC and HCT immediate release tablets with reference product in human subjects. Keywords: Candesartan cilexetil, Hydrochlorothiazide, UPLC–MS/MS, Bioequivalence, Candesartan cilexetil-hydrochlorothiazide (ATACAND HCT

Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

Science.gov (United States)

Stavchansky, Salomon

2008-06-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

76 FR 66721 - New Policies and Procedural Requirements for the Electronic Submission of Discretionary Grant...

Science.gov (United States)

2011-10-27

... electronic submission of discretionary grant applications through the government-wide grants application site... Procedural Requirements for the Electronic Submission of Discretionary Grant Applications AGENCY: Division of... requirements for the electronic submission of discretionary grant applications. Overview Information: The...

System Requirements Analysis for a Computer-based Procedure in a Research Reactor Facility

Energy Technology Data Exchange (ETDEWEB)

Park, Jaek Wan; Jang, Gwi Sook; Seo, Sang Moon; Shin, Sung Ki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-10-15

This can address many of the routine problems related to human error in the use of conventional, hard-copy operating procedures. An operating supporting system is also required in a research reactor. A well-made CBP can address the staffing issues of a research reactor and reduce the human errors by minimizing the operator's routine tasks. A CBP for a research reactor has not been proposed yet. Also, CBPs developed for nuclear power plants have powerful and various technical functions to cover complicated plant operation situations. However, many of the functions may not be required for a research reactor. Thus, it is not reasonable to apply the CBP to a research reactor directly. Also, customizing of the CBP is not cost-effective. Therefore, a compact CBP should be developed for a research reactor. This paper introduces high level requirements derived by the system requirements analysis activity as the first stage of system implementation. Operation support tools are under consideration for application to research reactors. In particular, as a full digitalization of the main control room, application of a computer-based procedure system has been required as a part of man-machine interface system because it makes an impact on the operating staffing and human errors of a research reactor. To establish computer-based system requirements for a research reactor, this paper addressed international standards and previous practices on nuclear plants.

Update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures

Directory of Open Access Journals (Sweden)

Mohanad Shukry

2010-03-01

Full Text Available Mohanad Shukry, Jeffrey A MillerUniversity of Oklahoma Health Sciences Center, Department of Anesthesiology, Children’s Hospital of Oklahoma, Oklahoma City, OK, USAAbstract: Dexmedetomidine was introduced two decades ago as a sedative and supplement to sedation in the intensive care unit for patients whose trachea was intubated. However, since that time dexmedetomidine has been commonly used as a sedative and hypnotic for patients undergoing procedures without the need for tracheal intubation. This review focuses on the application of dexmedetomidine as a sedative and/or total anesthetic in patients undergoing procedures without the need for tracheal intubation. Dexmedetomidine was used for sedation in monitored anesthesia care (MAC, airway procedures including fiberoptic bronchoscopy, dental procedures, ophthalmological procedures, head and neck procedures, neurosurgery, and vascular surgery. Additionally, dexmedetomidine was used for the sedation of pediatric patients undergoing different type of procedures such as cardiac catheterization and magnetic resonance imaging. Dexmedetomidine loading dose ranged from 0.5 to 5 μg kg-1, and infusion dose ranged from 0.2 to 10 μg kg-1 h-1. Dexmedetomidine was administered in conjunction with local anesthesia and/or other sedatives. Ketamine was administered with dexmedetomidine and opposed its bradycardiac effects. Dexmedetomidine may by useful in patients needing sedation without tracheal intubation. The literature suggests potential use of dexmedetomidine solely or as an adjunctive agent to other sedation agents. Dexmedetomidine was especially useful when spontaneous breathing was essential such as in procedures on the airway, or when sudden awakening from sedation was required such as for cooperative clinical examination during craniotomies.Keywords: dexmedetomidine, sedation, nonintubated patients

Rapid determination of telmisartan in human plasma by HPLC using a monolithic column with fluorescence detection and its application to a bioequivalence study.

Science.gov (United States)

Zhang, He; Jiang, Yunyun; Wen, Jun; Zhou, Tingting; Fan, Guorong; Wu, Yutian

2009-11-01

A rapid HPLC method using a monolithic column with fluorescence detection has been developed for determination of telmisartan in human plasma. Sample preparation was done by protein precipitation with acetonitrile and naproxen was used as IS. The compounds were detected by fluorescence detection, using an excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high throughput, sensitive and precise, and it was successfully applied to a bioequivalence study of two formulations of telmisartan.

Significance of metabolites in bioequivalence: losartan potassium as a case study.

Science.gov (United States)

Charoo, Naseem Ahmad; Cristofoletti, Rodrigo; Khatri, Aamer Roshanali; Ali, Areeg Anwer

2014-06-01

Estimation of metabolite data as a supportive evidence of comparable therapeutic outcome is recommended by various guidance documents. However, a consensus on using it solely to establish bioequivalence (BE) is lacking as parent drug is believed to detect pharmacokinetic differences between test and reference formulations better. Four BE studies of losartan potassium reported in the literature are reviewed. In all the four studies, 90% confidence intervals (CIs) of geometric mean ratios of the test and reference formulations for maximum blood drug concentration (Cmax ) of losartan potassium were outside the acceptable range of 80%-125%, whereas, 90% CIs for its active metabolite, losartan carboxylic acid (LCA), were within the acceptance criteria. Although BE with respect to area under the plasma concentration versus time profile curve was demonstrated in all the cases, BE with respect to Cmax could not be established. However, marketing authorization in all the four cases was granted based on scientific evidence that LCA is 10-40 times more potent than losartan, LCA exhibited higher plasma concentration levels than losartan, pharmacodynamic effects correlate with LCA, and losartan shows wide therapeutic index. Further, widened CI limits for losartan were accepted. Losartan presents an opportunity in the diligence of the principles of quality risk management for selecting moiety on which BE decision must be based. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

Directory of Open Access Journals (Sweden)

Radicioni M

2017-04-01

Full Text Available Milko Radicioni,1 Chiara Castiglioni,1 Andrea Giori,2 Irma Cupone,3 Valeria Frangione,4 Stefano Rovati4 1CROSS Research S.A., Phase I Unit, Arzo, Switzerland; 2IBSA Farmaceutici Italia, Lodi, Italy; 3Bouty S.p.A., Strada Padana Superiore, Cassina De’ Pecchi, Italy; 4IBSA Institut Biochimique S.A., Pambio-Noranco, Switzerland Abstract: A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra® after single-dose administration to 53 healthy male volunteers (aged 18–51 years in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg

Scientific Perspectives on Extending the Provision for Waivers of In vivo Bioavailability and Bioequivalence Studies for Drug Products Containing High Solubility-Low Permeability Drugs (BCS-Class 3)

OpenAIRE

Stavchansky, Salomon

2008-01-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA–BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility–Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting ...

Requirements for Computer Based-Procedures for Nuclear Power Plant Field Operators. Results from a Qualitative Study

International Nuclear Information System (INIS)

Le Blanc, Katya; Oxstrand, J.H.; Waicosky, T.

2012-01-01

Although computer-based procedures (CBPs) have been investigated as a way to enhance operator performance on procedural tasks in the nuclear industry for almost thirty years, they are not currently widely deployed at United States utilities. One of the barriers to the wide scale deployment of CBPs is the lack of operational experience with CBPs that could serve as a sound basis for justifying the use of CBPs for nuclear utilities. Utilities are hesitant to adopt CBPs because of concern over potential costs of implementation, and concern over regulatory approval. Regulators require a sound technical basis for the use of any procedure at the utilities; without operating experience to support the use CBPs, it is difficult to establish such a technical basis. In an effort to begin the process of developing a technical basis for CBPs, researchers at Idaho National Laboratory are partnering with industry to explore CBPs with the objective of defining requirements for CBPs and developing an industry-wide vision and path forward for the use of CBPs. This paper describes the results from a qualitative study aimed at defining requirements for CBPs to be used by field operators and maintenance technicians. (author)

Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w).

Science.gov (United States)

Mitra, Amitava; Kim, Nanhye; Spark, Darren; Toner, Frank; Craig, Susan; Roper, Clive; Meyer, Thomas A

2016-12-01

The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and validation of a liquid chromatography-tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study.

Science.gov (United States)

Ye, Ling; Shi, Jian; Wan, Shanhe; Yang, Xiaoshan; Wang, Ying; Zhang, Jiajie; Zheng, Dayong; Liu, Zhongqiu

2013-11-01

Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

Determination of levodopa in human plasma by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS: application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Heliana F. Martins

2013-01-01

Full Text Available A sensitive, accurate and simple method using HPLC-MS/MS was developed and validated for levodopa quantitation in human plasma. Analysis was achieved on a pursuit® C18 analytical column (5 µm; 150 x 4.6 mm i.d. using a mobile phase (methanol and water , 90:10, v/v containing formic acid 0.5% v/v, after extracting the samples using a simple protein plasma precipitation with perchloric acid. The developed method was validated in accordance with ANVISA guidelines and was successfully applied to a bioequivalence study in 60 healthy volunteers demonstrating the feasibility and reliability of the proposed method.

Required number of records for ASCE/SEI 7 ground-motion scaling procedure

Science.gov (United States)

Reyes, Juan C.; Kalkan, Erol

2011-01-01

The procedures and criteria in 2006 IBC (International Council of Building Officials, 2006) and 2007 CBC (International Council of Building Officials, 2007) for the selection and scaling ground-motions for use in nonlinear response history analysis (RHA) of structures are based on ASCE/SEI 7 provisions (ASCE, 2005, 2010). According to ASCE/SEI 7, earthquake records should be selected from events of magnitudes, fault distance, and source mechanisms that comply with the maximum considered earthquake, and then scaled so that the average value of the 5-percent-damped response spectra for the set of scaled records is not less than the design response spectrum over the period range from 0.2Tn to 1.5Tn sec (where Tn is the fundamental vibration period of the structure). If at least seven ground-motions are analyzed, the design values of engineering demand parameters (EDPs) are taken as the average of the EDPs determined from the analyses. If fewer than seven ground-motions are analyzed, the design values of EDPs are taken as the maximum values of the EDPs. ASCE/SEI 7 requires a minimum of three ground-motions. These limits on the number of records in the ASCE/SEI 7 procedure are based on engineering experience, rather than on a comprehensive evaluation. This study statistically examines the required number of records for the ASCE/SEI 7 procedure, such that the scaled records provide accurate, efficient, and consistent estimates of" true" structural responses. Based on elastic-perfectly-plastic and bilinear single-degree-of-freedom systems, the ASCE/SEI 7 scaling procedure is applied to 480 sets of ground-motions. The number of records in these sets varies from three to ten. The records in each set were selected either (i) randomly, (ii) considering their spectral shapes, or (iii) considering their spectral shapes and design spectral-acceleration value, A(Tn). As compared to benchmark (that is, "true") responses from unscaled records using a larger catalog of ground

Verification of dissolution test for doxycycline hyclate in capsules to implement into the pharmacopoeial monograph

OpenAIRE

Dobrova, Anna; Golovchenko, Olga; Georgiyants, Victoria

2018-01-01

The study of dissolution profiles is important as a cheap and easy supplement to bioequivalence research, and as a variation to such studies. This method is not outlined in the State Pharmacopoeia of Ukraine for the doxycycline capsules. Therefore, according to the current requirements, it was necessary to verify the procedure recommended by the US Pharmacopeia to confirm that this laboratory test will be reproduced correctly, and to use it in our further studies.The aim of our research was t...

Standardized Procedure Content And Data Structure Based On Human Factors Requirements For Computer-Based Procedures

International Nuclear Information System (INIS)

Bly, Aaron; Oxstrand, Johanna; Le Blanc, Katya L

2015-01-01

Most activities that involve human interaction with systems in a nuclear power plant are guided by procedures. Traditionally, the use of procedures has been a paper-based process that supports safe operation of the nuclear power industry. However, the nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. Advances in digital technology make computer-based procedures (CBPs) a valid option that provides further enhancement of safety by improving human performance related to procedure use. The transition from paper-based procedures (PBPs) to CBPs creates a need for a computer-based procedure system (CBPS). A CBPS needs to have the ability to perform logical operations in order to adjust to the inputs received from either users or real time data from plant status databases. Without the ability for logical operations the procedure is just an electronic copy of the paper-based procedure. In order to provide the CBPS with the information it needs to display the procedure steps to the user, special care is needed in the format used to deliver all data and instructions to create the steps. The procedure should be broken down into basic elements and formatted in a standard method for the CBPS. One way to build the underlying data architecture is to use an Extensible Markup Language (XML) schema, which utilizes basic elements to build each step in the smart procedure. The attributes of each step will determine the type of functionality that the system will generate for that step. The CBPS will provide the context for the step to deliver referential information, request a decision, or accept input from the user. The XML schema needs to provide all data necessary for the system to accurately perform each step without the need for the procedure writer to reprogram the CBPS. The research team at the Idaho National Laboratory has developed a prototype CBPS for field workers as well as the

Standardized Procedure Content And Data Structure Based On Human Factors Requirements For Computer-Based Procedures

Energy Technology Data Exchange (ETDEWEB)

Bly, Aaron; Oxstrand, Johanna; Le Blanc, Katya L

2015-02-01

Most activities that involve human interaction with systems in a nuclear power plant are guided by procedures. Traditionally, the use of procedures has been a paper-based process that supports safe operation of the nuclear power industry. However, the nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. Advances in digital technology make computer-based procedures (CBPs) a valid option that provides further enhancement of safety by improving human performance related to procedure use. The transition from paper-based procedures (PBPs) to CBPs creates a need for a computer-based procedure system (CBPS). A CBPS needs to have the ability to perform logical operations in order to adjust to the inputs received from either users or real time data from plant status databases. Without the ability for logical operations the procedure is just an electronic copy of the paper-based procedure. In order to provide the CBPS with the information it needs to display the procedure steps to the user, special care is needed in the format used to deliver all data and instructions to create the steps. The procedure should be broken down into basic elements and formatted in a standard method for the CBPS. One way to build the underlying data architecture is to use an Extensible Markup Language (XML) schema, which utilizes basic elements to build each step in the smart procedure. The attributes of each step will determine the type of functionality that the system will generate for that step. The CBPS will provide the context for the step to deliver referential information, request a decision, or accept input from the user. The XML schema needs to provide all data necessary for the system to accurately perform each step without the need for the procedure writer to reprogram the CBPS. The research team at the Idaho National Laboratory has developed a prototype CBPS for field workers as well as the

75 FR 76254 - Official Performance and Procedural Requirements for Grain Weighing Equipment and Related Grain...

Science.gov (United States)

2010-12-08

... DEPARTMENT OF AGRICULTURE Grain Inspection, Packers and Stockyards Administration 7 CFR Part 802 [Docket GIPSA-2010-FGIS-0012] RIN 0580-AB19 Official Performance and Procedural Requirements for Grain Weighing Equipment and Related Grain Handling Systems AGENCY: Grain Inspection, Packers and Stockyards...

Definition of Specific Functions and Procedural Skills Required by Cuban Specialists in Intensive Care and Emergency Medicine.

Science.gov (United States)

Véliz, Pedro L; Berra, Esperanza M; Jorna, Ana R

2015-07-01

INTRODUCTION Medical specialties' core curricula should take into account functions to be carried out, positions to be filled and populations to be served. The functions in the professional profile for specialty training of Cuban intensive care and emergency medicine specialists do not include all the activities that they actually perform in professional practice. OBJECTIVE Define the specific functions and procedural skills required of Cuban specialists in intensive care and emergency medicine. METHODS The study was conducted from April 2011 to September 2013. A three-stage methodological strategy was designed using qualitative techniques. By purposive maximum variation sampling, 82 professionals were selected. Documentary analysis and key informant criteria were used in the first stage. Two expert groups were formed in the second stage: one used various group techniques (focus group, oral and written brainstorming) and the second used a three-round Delphi method. In the final stage, a third group of experts was questioned in semistructured in-depth interviews, and a two-round Delphi method was employed to assess priorities. RESULTS Ultimately, 78 specific functions were defined: 47 (60.3%) patient care, 16 (20.5%) managerial, 6 (7.7%) teaching, and 9 (11.5%) research. Thirty-one procedural skills were identified. The specific functions and procedural skills defined relate to the profession's requirements in clinical care of the critically ill, management of patient services, teaching and research at the specialist's different occupational levels. CONCLUSIONS The specific functions and procedural skills required of intensive care and emergency medicine specialists were precisely identified by a scientific method. This product is key to improving the quality of teaching, research, administration and patient care in this specialty in Cuba. The specific functions and procedural skills identified are theoretical, practical, methodological and social contributions to

[Radiation protection in medical research : Licensing requirement for the use of radiation and advice for the application procedure].

Science.gov (United States)

Minkov, V; Klammer, H; Brix, G

2017-07-01

In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. Questions and typical mistakes in the application process were identified and evaluated. The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants.

78 FR 41298 - Children's Products Containing Lead; Procedures and Requirements for Exclusions From Lead Limits...

Science.gov (United States)

2013-07-10

... on materials previously submitted in connection with a petition for exclusion under this section. In... 16 CFR 1500.90 to provide procedures and requirements for evaluating products or materials for... and comment rulemaking, section 553 of the APA provides an exception when the agency, for good cause...

Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment.

Science.gov (United States)

Oishi, Masayo; Chiba, Koji; Fukushima, Takashi; Tomono, Yoshiro; Suwa, Toshio

2012-01-01

In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.

Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

Science.gov (United States)

Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

2012-08-01

A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

21 CFR 111.16 - What are the requirements under this subpart C for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart C for written procedures? 111.16 Section 111.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.103 - What are the requirements under this subpart F for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart F for written procedures? 111.103 Section 111.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.503 - What are the requirements under this subpart N for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart N for written procedures? 111.503 Section 111.503 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.403 - What are the requirements under this subpart L for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart L for written procedures? 111.403 Section 111.403 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.353 - What are the requirements under this subpart K for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart K for written procedures? 111.353 Section 111.353 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.453 - What are the requirements under this subpart for M written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart for M written procedures? 111.453 Section 111.453 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.8 - What are the requirements under this subpart B for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart B for written procedures? 111.8 Section 111.8 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.153 - What are the requirements under this subpart G for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart G for written procedures? 111.153 Section 111.153 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.25 - What are the requirements under this subpart D for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart D for written procedures? 111.25 Section 111.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.553 - What are the requirements under this subpart O for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart O for written procedures? 111.553 Section 111.553 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

21 CFR 111.303 - What are the requirements under this subpart J for written procedures?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements under this subpart J for written procedures? 111.303 Section 111.303 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

Science.gov (United States)

Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

2002-10-01

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

Science.gov (United States)

Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

2017-01-01

A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

Quantification of sibutramine and its two metabolites in human plasma by LC–ESI-MS/MS and its application in a bioequivalence study

Directory of Open Access Journals (Sweden)

Venkata Suresh Ponnuru

2012-08-01

Full Text Available Obesity can be considered as a chronic illness of epidemic proportion and its incidents have increased exponentially in recent years. The use of anti-obesity drugs such as sibutramine is somewhat helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS method for the quantification of sibutramine (SB and its two metabolites N-des methyl sibutramine (DSB and N-di desmethyl sibutramine (DDSB in human plasma. Zorbax SB-C18 (4.6 mm×75 mm, 3.5 μm, 80 Å analytical column and 5 mM ammonium formate:acetonitrile (10:90, v/v mobile phase were used for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM in the positive mode was used to detect SB, DSB and DDSB at m/z 280.3/124.9, 266.3/125.3 and 252.2/124.9, respectively. Liquid–liquid extraction was used for the extraction of analytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0–10,000.0 pg/mL for SB, DSB and DDSB with correlation coefficients (r of ≥0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting condition. Keywords: LC–ESI-MS/MS, Sibutramine, Human plasma, Bioequivalence, Pharmacokinetic study

39 CFR 230.26 - Do these rules affect the service of process requirements of the Federal Rules of Civil Procedure...

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Do these rules affect the service of process....26 Do these rules affect the service of process requirements of the Federal Rules of Civil Procedure... Rules of Civil Procedure regarding service of process. ...

75 FR 31334 - Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's “Required Use...

Science.gov (United States)

2010-06-03

...-A178 Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's ``Required Use... by those in a position to refer settlement business (such as builders, real estate agents, and... referral fees, kickbacks, and unearned fees for real estate settlement services.\\1\\ \\1\\ In July 2008...

Human factoring administrative procedures

International Nuclear Information System (INIS)

Grider, D.A.; Sturdivant, M.H.

1991-01-01

In nonnuclear business, administrative procedures bring to mind such mundane topics as filing correspondence and scheduling vacation time. In the nuclear industry, on the other hand, administrative procedures play a vital role in assuring the safe operation of a facility. For some time now, industry focus has been on improving technical procedures. Significant efforts are under way to produce technical procedure requires that a validated technical, regulatory, and administrative basis be developed and that the technical process be established for each procedure. Producing usable technical procedures requires that procedure presentation be engineered to the same human factors principles used in control room design. The vital safety role of administrative procedures requires that they be just as sound, just a rigorously formulated, and documented as technical procedures. Procedure programs at the Tennessee Valley Authority and at Boston Edison's Pilgrim Station demonstrate that human factors engineering techniques can be applied effectively to technical procedures. With a few modifications, those same techniques can be used to produce more effective administrative procedures. Efforts are under way at the US Department of Energy Nuclear Weapons Complex and at some utilities (Boston Edison, for instance) to apply human factors engineering to administrative procedures: The techniques being adapted include the following

Determination of bioequivalence of lomefloxacin tablets using urinary excretion data.

Science.gov (United States)

Shah, Shailesh A; Rathod, Ishwarsinh S; Savale, Shrinivas S; Patel, Dharmesh B

2002-11-07

The present study describes development of a sensitive and simple HPTLC method for estimation of lomefloxacin (LMF) in human urine. The drug was extracted using chloroform after adjusting the pH of urine to 7.0. Chloroform extract was spotted on silica gel 60 F(254) TLC plate and was developed in a mixture of n-butanol-methanol-ethyl acetate-6 M ammonia (4:2:3:2, v/v/v/v) as the mobile phase and scanned at 290 nm. The peak for LMF resolved at R(F) of 0.40+/-0.02. The method was validated in terms of linearity (50-600 microgram/ml), precision, specificity and accuracy. The limit of detection and limit of quantification for LMF in urine were found to be 20 and 50 microgram/ml, respectively. The average recovery of LMF from urine was 91.93%. The proposed method was applied to generate urinary excretion data for LMF after administration of two market LMF tablet formulations (400 mg, Formulation R and Formulation T) to six healthy human volunteers in a two-treatment, open, crossover design. Various pharmacokinetic parameters like peak excretion rate ((dAU/dt)(max)), time for peak excretion rate (t(max)), AUC(0-48), AUC(0- infinity ), cumulative amount and % cumulative amount of LMF excreted, elimination half-life (t(1/2)), terminal elimination rate constant (k(el)) and overall elimination rate constant (K), were calculated for both the formulations. The average cumulative amounts of LMF excreted in urine after administration of Formulation R and Formulation T were found to be 321.60 mg (80.40% of dose) and 296.51 mg (74.13% of dose), respectively. The urinary excretion profiles of LMF upto 48 h for both the formulations were found to be similar. Statistical comparison (90% confidence intervals of ratio) of various pharmacokinetic parameters of Formulation T with that of Formulation R revealed that Formulation T is bioequivalent with Formulation R.

Estudio de bioequivalencia de clonazepam, tabletas de 2 mg, en voluntarios sanos colombianos Bioequivalence study of clonazepam 2 mg tablets in colombian healthy volunteers

Directory of Open Access Journals (Sweden)

Victoria Eugenia Toro Pareja

2007-08-01

Full Text Available Con el fin de determinar la bioequivalencia de dos formulaciones de tabletas de 2 mg de clonazepam: Sedatril®/Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia como producto de prueba y Rivotril® (Roche Químicos e Farmacéuticas S. A., Río de Janeiro, Brasil, como producto de referencia, se realizó un estudio de bioequivalencia en 26 voluntarios sanos. Los productos de prueba y de referencia se administraron en condiciones de ayuno de acuerdo con un diseño cruzado aleatorio de dosis única, con dos secuencias, dos tratamientos y un período de lavado de 28 días. Las muestras de sangre se obtuvieron desde las 0 hasta las 96 horas después de la administración del medicamento. Los niveles plasmáticos de clonazepam se determinaron con un método validado por cromatografía líquida de alta eficiencia con detección ultravioleta (HPLC/UV, siglas en inglés. Los parámetros farmacocinéticos ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke se determinaron de los perfiles plasmáticos concentración-tiempo por el método no compartimental. El test de bioequivalencia se realizó con los datos transformados a logaritmo natural (ln de ABC0-∞and Cmax. Los intervalos de confianza del 90% para la relación producto de prueba/producto de referencia fueron de 87,9% a 103,6% y 84,4% a 104,0%, respectivamente. Estos resultados estuvieron dentro de los rangos de aceptación del 80,0% al 125%, establecidos por la FDA y se concluyó que ambos productos son bioequivalentes. In order to determine the bioequivalence of two formulations of clonazepam 2 mg tablets: Sedatril®/ Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia as a test product and Rivotril® (Roche Químicos e Farmacêuticas S. A., Rio de Janeiro, Brazil as a reference product, a bioavailability study was performed in 26 healthy volunteers. Test and reference products were administered under fasting conditions following a single dose, two-sequences, two treatments, crossover randomized

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Quantification of strontium in human serum by ICP-MS using alternate analyte-free matrix and its application to a pilot bioequivalence study of two strontium ranelate oral formulations in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Wang, Xiaolin; Liu, Man; Zhang, Lina; Deng, Ming; Liu, Huichen

2015-01-01

A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00-500ng/mL, corresponding to a concentration range of 0.0300-15.0μg/mL in 50μL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate. Copyright © 2014 Elsevier GmbH. All rights reserved.

Determination of itopride in human plasma by liquid chromatography coupled to tandem mass spectrometric detection: application to a bioequivalence study.

Science.gov (United States)

Lee, Heon-Woo; Seo, Ji-Hyung; Choi, Seung-Ki; Lee, Kyung-Tae

2007-01-30

A simple method using a one-step liquid-liquid extraction (LLE) with butyl acetate followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of itopride in human plasma, using sulpiride as an internal standard (IS). Acquisition was performed in multiple reaction monitoring (MRM) mode, by monitoring the transitions: m/z 359.5>166.1 for itopride and m/z 342.3>111.6 for IS, respectively. Analytes were chromatographed on an YMC C18 reverse-phase chromatographic column by isocratic elution with 1 mM ammonium acetate buffer-methanol (20: 80, v/v; pH 4.0 adjusted with acetic acid). Results were linear (r2=0.9999) over the studied range (0.5-1000 ng mL(-1)) with a total analysis time per run of 2 min for LC-MS/MS. The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Operating characteristics of a partial-block randomized crossover bioequivalence study for dutasteride, a drug with a long half-life: investigation through simulation and comparison with final results.

Science.gov (United States)

Cai, Gengqian; Thiessen, Jake J; Baidoo, Charlotte A; Fossler, Michael J

2010-10-01

Studies to establish bioequivalence (BE) of a drug are important elements in support of drug applications. A typical BE study is conducted as a single dose, randomized, 2-period crossover design. For drugs with long half lives (≥ 48 hours) and evaluation of multiple BE objectives in 1 trial, this design may not be adequate. A parallel design may then be a more appropriate choice. However, parallel designs require increased sample size, which can become substantial. One option that is a compromise between the complete randomized block design and the parallel design is a partial-block crossover design. This approach came about during the development of a combination of dutasteride and tamsulosin. Previous experience with performing single-dose dutasteride studies suggested that 28 days of washout is needed between treatments because of its half-life of 7-9 days. Simulations were performed to assess the operating characteristics of this design using a previously developed PK model. Four scenarios were developed, and each scenario was simulated 500 times. The results showed that this design demonstrated acceptable consumer and producer risk. Partial-block crossover designs should be considered for studies when the half-life of the drug is long and there are more than 2 periods.

Current Mobile Payment Procedures on the German Market from the View of Customer Requirements

OpenAIRE

Pousttchi, Key; Zenker, M.

2003-01-01

The key to mobile payment acceptance is in the hands of customers. In this paper we use the results of the mobile payment survey MP1 in order to identify and roughly weigh the most relevant acceptance criteria. The outcome of the paper is an evaluation scheme containing the covered payment scenarios, important main criteria (security, costs and convenience) and additional functionality requirements for each MP procedure. The scheme is based on empirical results and can assess a given MP proce...

Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers.

Science.gov (United States)

Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba; Nemati, Mahboob

2010-01-01

Valsartan (CAS 137862-53-4) is an antihypertensive drug belonging to the family of angiotensin II receptor antagonists acting at the AT1 receptor, which mediates all known effects of angiotensin II on the cardiovascular system. In the present study, the pharmacokinetic parameters of two oral formulations of valsartan tablets were compared in a randomized, single oral dose, two-treatment crossover design in 24 healthy male volunteers under fasting conditions. After an overnight fast, the volunteers received 80 mg valsartan. Blood samples were collected up to 48 h and drug concentrations were determined by a reverse-phase HPLC method with fluorescence detection. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The obtained values for test and reference products were 3067.7 +/- 1,281.7 and 3,304.3 +/- 1,196.4 ng/ml for Cmax; 17,834.4 +/- 7,083.8 and 18,319.1 +/- 7,800.7 ng x h/ml for AUC0-48; 18,825.7 +/- 7,553.2 and 19,172.2 +/- 8,307.2 ng x h/ml for AUC0-infinity, respectively. The 90% confidence intervals obtained by analysis of variance were 86.84-100.87% for Cmax and 93.43-115.54% for AUC0-t, which are within the acceptance range of 80-125%. Therefore it can be concluded that both products are bioequivalent in terms of rate and extent of drug absorption and therefore interchangeable.

Development of utility generic functional requirements for electronic work packages and computer-based procedures

Energy Technology Data Exchange (ETDEWEB)

Oxstrand, Johanna [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2017-06-01

The Nuclear Electronic Work Packages - Enterprise Requirements (NEWPER) initiative is a step toward a vision of implementing an eWP framework that includes many types of eWPs. This will enable immediate paper-related cost savings in work management and provide a path to future labor efficiency gains through enhanced integration and process improvement in support of the Nuclear Promise (Nuclear Energy Institute 2016). The NEWPER initiative was organized by the Nuclear Information Technology Strategic Leadership (NITSL) group, which is an organization that brings together leaders from the nuclear utility industry and regulatory agencies to address issues involved with information technology used in nuclear-power utilities. NITSL strives to maintain awareness of industry information technology-related initiatives and events and communicates those events to its membership. NITSL and LWRS Program researchers have been coordinating activities, including joint organization of NEWPER-related meetings and report development. The main goal of the NEWPER initiative was to develop a set of utility generic functional requirements for eWP systems. This set of requirements will support each utility in their process of identifying plant-specific functional and non-functional requirements. The NEWPER initiative has 140 members where the largest group of members consists of 19 commercial U.S. nuclear utilities and eleven of the most prominent vendors of eWP solutions. Through the NEWPER initiative two sets of functional requirements were developed; functional requirements for electronic work packages and functional requirements for computer-based procedures. This paper will describe the development process as well as a summary of the requirements.

26 CFR 1.852-9 - Special procedural requirements applicable to designation under section 852(b)(3)(D).

Science.gov (United States)

2010-04-01

... notice by the Internal Revenue Service that the regulated investment company has failed to comply with... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Special procedural requirements applicable to designation under section 852(b)(3)(D). 1.852-9 Section 1.852-9 Internal Revenue INTERNAL REVENUE SERVICE...

Liquid chromatography-tandem mass spectrometry for the quantification of flurbiprofen in human plasma and its application in a study of bioequivalence.

Science.gov (United States)

Mei, Chenghan; Li, Bin; Yin, Qiangfeng; Jin, Jing; Xiong, Ting; He, Wenjuan; Gao, Xiujuan; Xu, Rong; Zhou, Piqi; Zheng, Heng; Chen, Hui

2015-07-01

A simple, quick and accurate LC-MS/MS method for the quantification of flurbiprofen in human plasma with indomethacin as internal standard (IS) was developed and validated. Samples were treated with methanol to precipitate proteins, then separated on a Ultimate C18 column (5μm, 2.1×50mm) with a gradient elusion process. Mobile phase A was comprised of water and formic acid, mobile phase B was comprised of acetonitrile and formic acid. Multi reaction monitoring (MRM) signals were saved on a negative ionization electrospray mass spectrometer. The calibration curve showed good linearity in the range of 40.00-10000.00μg/L (r(2)=0.998). Intra-day RE was 0.2-2.2%. Inter-day RE was 0.5-3.4%. The samples showed good stability under the study conditions. No significant matrix effect was observed. The established method was then applied to a bioequivalence study of a flurbiprofen axetil formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Environmental radiation monitoring during visits of nuclear powered warships to Australian ports: requirements, arrangements and procedures

International Nuclear Information System (INIS)

1988-05-01

The Commonwealth Government has determined conditions to be met when nuclear powered warships visit Australian ports. These conditions include a requirement that appropriate State/Territory and Commonwealth authorities provide a radiation monitoring program to determine whether any radioactivity has been discharged or accidently released from a nuclear powered warship in port; to determine actual or potential levels of any consequent exposure to radiation of members of the public; and to provide this information within a timescale that allows remedial action to be taken. Part 1 of this document sets out the requirements of a radiation monitoring program capable of meeting these objectives. The fundamental arrangements and procedures for implementing the requirements are presented at Part 2 and provide a basis for the development of fully detailed, port specific, radiation monitoring programs

Multiple position borehole extensometer procedure: Final draft

International Nuclear Information System (INIS)

1986-08-01

The purpose of the Multiple Position Borehole Extensometer Procedure is to provide detailed information for MPBXs installed at the salt Deaf Smith County ESF. This procedure includes design of equipment, installation, instructions, instrument locations, measurement requirements, support requirements, quality assurance procedures, and data acquisition requirements. Data reduction procedures are also discussed; however, the relevance of the data is discussed elsewhere in the appropriate test plans. Sufficient detail is provided in this procedure to allow for integrating the requirements of this procedure into both the facility construction and overall underground testing programs; identifying necessary equipment for procurement; determining data acquisition requirements as input to Automatic Data Acquisition System (ADAS) design; providing step-by-step procedures for training personnel as well as for directing field operations; establishing quality assurance (QA) checkpoints and implementation methods; and defining data reduction methods and providing the anticipated accuracy of the system. 11 refs., 14 figs

A study on Requirements of Data Base Translator for APR1400 Computerized Procedure System at Shin-Hanul unit 1 and 2

International Nuclear Information System (INIS)

Seong, Nokyu; Lee, Sungjin

2015-01-01

The CPS is one of the Man Machine Interface (MMI) resources and the CPS can directly display plant graphic objects which are in the Digital Control System (DCS). And the CPS can send a request to DCS to provide DCS screen which is called step support display through DCS link button on a computerized procedure. The procedure writers can insert DCS graphic information to computerized procedure through data base which is provided by CPS Editing System (CPSES). The data base which is provided by CPSES conforms to the naming rule of DCS graphic objects. The naming rule of DCS graphic objects is defined by vendor thus status of DCS graphic objects which are in computerized procedure at Shin-Kori plant cannot be displayed on CPS at Shin-Hanul plant. To use computerized procedure which is written by other plant procedure writer, DCS graphic objects shall be translated by its plant data base. This paper introduces requirements of data base translator to reduce translation and re-inserting graphic objects burden. This paper introduces the requirements of data base translator of CPSES for APR1400 CPS at Shin-Hanul unit 1 and 2. The translator algorithms shall be tested to update data base of CPSES effectively. The prototype of translator is implemented and is being tested using real plant DB. This translator can be applied to Shin- Hanul unit1 and 2 through software V and V

A study on Requirements of Data Base Translator for APR1400 Computerized Procedure System at Shin-Hanul unit 1 and 2

Energy Technology Data Exchange (ETDEWEB)

Seong, Nokyu; Lee, Sungjin [KHNP, Daejeon (Korea, Republic of)

2015-05-15

The CPS is one of the Man Machine Interface (MMI) resources and the CPS can directly display plant graphic objects which are in the Digital Control System (DCS). And the CPS can send a request to DCS to provide DCS screen which is called step support display through DCS link button on a computerized procedure. The procedure writers can insert DCS graphic information to computerized procedure through data base which is provided by CPS Editing System (CPSES). The data base which is provided by CPSES conforms to the naming rule of DCS graphic objects. The naming rule of DCS graphic objects is defined by vendor thus status of DCS graphic objects which are in computerized procedure at Shin-Kori plant cannot be displayed on CPS at Shin-Hanul plant. To use computerized procedure which is written by other plant procedure writer, DCS graphic objects shall be translated by its plant data base. This paper introduces requirements of data base translator to reduce translation and re-inserting graphic objects burden. This paper introduces the requirements of data base translator of CPSES for APR1400 CPS at Shin-Hanul unit 1 and 2. The translator algorithms shall be tested to update data base of CPSES effectively. The prototype of translator is implemented and is being tested using real plant DB. This translator can be applied to Shin- Hanul unit1 and 2 through software V and V.

LC–MS/MS assay for olanzapine in human plasma and its application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Dinesh S. Patel

2012-10-01

Full Text Available This paper describes a selective and sensitive assay for the determination of olanzapine (OLZ in human plasma based on liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analyte and quetiapine as internal standard (IS were extracted from 200 μL plasma via solid phase extraction on Waters Oasis HLB cartridges. Chromatographic separation was achieved on an ACE 5C18-300 column (100 mm×4.6 mm, 5 μm under isocratic conditions in a run time of 3.5 min. Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring (MRM of the transitions at m/z 313/256 for OLZ and m/z 384/253 for the IS. The assay was linear in the range 0.10–40.0 ng/mL with a lower limit of quantitation and limit of detection of 0.10 and 0.012 ng/mL, respectively. Intra- and inter-day precision (as coefficient of variation and relative recovery were 90%, respectively. The method was successfully applied to a bioequivalence study of 5 and 10 mg OLZ disintegrating tablets in 40 healthy Indian males with reproducibility by incurred sample reanalysis in the range −7.43 to 8.07%.

Procedural sedation analgesia

Directory of Open Access Journals (Sweden)

Sheta Saad

2010-01-01

Full Text Available The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA. The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interventions. The goals of PSA in four different multidisciplinary practices namely; emergency, dentistry, radiology and gastrointestinal endoscopy are discussed in this review article. Some procedures are painful, others painless. Therefore, goals of PSA vary widely. Sedation management can range from minimal sedation, to the extent of minimal anesthesia. Procedural sedation in emergency department (ED usually requires combinations of multiple agents to reach desired effects of analgesia plus anxiolysis. However, in dental practice, moderate sedation analgesia (known to the dentists as conscious sedation is usually what is required. It is usually most effective with the combined use of local anesthesia. The mainstay of success for painless imaging is absolute immobility. Immobility can be achieved by deep sedation or minimal anesthesia. On the other hand, moderate sedation, deep sedation, minimal anesthesia and conventional general anesthesia can be all utilized for management of gastrointestinal endoscopy.

40 CFR 92.123 - Test procedure; general requirements.

Science.gov (United States)

2010-07-01

... the test. Auxiliary fan(s) may be used to maintain engine cooling during operation on the dynamometer... smoke. (1) In the raw exhaust sampling procedure, sample is collected directly from the exhaust stream... of another raw exhaust sample. The fuel flow rate for each throttle setting is measured. (2) For...

The importance of procedural defects in Atomic Law

International Nuclear Information System (INIS)

Ossenbuehl, F.

1981-01-01

The Muelheim-Kaerlich decision of the Federal Constitutional Court has brought about a 'revaluation' of procedural requirements. This has caused some insecurity in the application of procedural requirements, e.g. whether a license under Nuclear Law, granted without public participation in spite of procedural requirements, can be revolved on the basis of this procedural defect alone. The answer depends on the applicability of Sect. 46 VwVfG (Act on Procedural Rules) in Nuclear Law. (orig.) [de

Procedural sedation analgesia

OpenAIRE

Sheta, Saad A

2010-01-01

The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA). The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interve...

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

Science.gov (United States)

Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

2016-03-01

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

PC based temporary shielding administrative procedure (TSAP)

International Nuclear Information System (INIS)

Olsen, D.E.; Pederson, G.E.; Hamby, P.N.

1995-01-01

A completely new Administrative Procedure for temporary shielding was developed for use at Commonwealth Edison's six nuclear stations. This procedure promotes the use of shielding, and addresses industry requirements for the use and control of temporary shielding. The importance of an effective procedure has increased since more temporary shielding is being used as ALARA goals become more ambitious. To help implement the administrative procedure, a personal computer software program was written to incorporate the procedural requirements. This software incorporates the useability of a Windows graphical user interface with extensive help and database features. This combination of a comprehensive administrative procedure and user friendly software promotes the effective use and management of temporary shielding while ensuring that industry requirements are met

PC based temporary shielding administrative procedure (TSAP)

Energy Technology Data Exchange (ETDEWEB)

Olsen, D.E.; Pederson, G.E. [Sargent & Lundy, Chicago, IL (United States); Hamby, P.N. [Commonwealth Edison Co., Downers Grove, IL (United States)

1995-03-01

A completely new Administrative Procedure for temporary shielding was developed for use at Commonwealth Edison`s six nuclear stations. This procedure promotes the use of shielding, and addresses industry requirements for the use and control of temporary shielding. The importance of an effective procedure has increased since more temporary shielding is being used as ALARA goals become more ambitious. To help implement the administrative procedure, a personal computer software program was written to incorporate the procedural requirements. This software incorporates the useability of a Windows graphical user interface with extensive help and database features. This combination of a comprehensive administrative procedure and user friendly software promotes the effective use and management of temporary shielding while ensuring that industry requirements are met.

CT4 - Cost-Optimum Procedures

DEFF Research Database (Denmark)

Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

This report collects the status in European member states regarding implementation of the cos optimum procedure for setting energy performance requirements to new and existing buildings.......This report collects the status in European member states regarding implementation of the cos optimum procedure for setting energy performance requirements to new and existing buildings....

Development of Small UAS Beyond-Visual-Line-of-Sight (BVLOS Flight Operations: System Requirements and Procedures

Directory of Open Access Journals (Sweden)

Scott Xiang Fang

2018-04-01

Full Text Available Due to safety concerns of integrating small unmanned aircraft systems (UAS into non-segregated airspace, aviation authorities have required a set of detect and avoid (DAA systems to be equipped on small UAS for beyond-visual-line-of-sight (BVLOS flight operations in civil airspace. However, the development of small UAS DAA systems also requires BVLOS flights for testing and validation. To mitigate operational risks for small UAS BVLOS flight operations, this paper proposes to initially test small UAS DAA systems in BVLOS flights in a restricted airspace with additional safety features. Later, this paper further discusses the operating procedures and emergency action plans for small UAS BVLOS flight operations. The testing results show that these safety systems developed can help improve operational safety for small UAS BVLOS flight operations.

Procedures for ground-water investigations

International Nuclear Information System (INIS)

1989-09-01

This manual was developed by the Pacific Northwest Laboratory (PNL) to document the procedures used to carry out and control the technical aspects of ground-water investigations at the PNL. Ground-water investigations are carried out to fulfill the requirements for the US Department of Energy (DOE) to meet the requirements of DOE Orders. Investigations are also performed for various clients to meet the requirements of the Resource Conservation and Recovery Act of 1976 (RCRA) and the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA). National standards including procedures published by the American Society for Testing and Materials (ASTM) and the US Geological Survey were utilized in developing the procedures contained in this manual

Determination of torasemide in human plasma and its bioequivalence study by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Lin Zhang

2016-04-01

Full Text Available A sensitive and selective method using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS to determine the concentration of torasemide in human plasma samples was developed and validated. Tolbutamide was chosen as the internal standard (IS. The chromatography was performed on a Gl Sciences Inertsil ODS-3 column (100 mm×2.1 mm i.d., 5.0 µm within 5 min, using methanol with 10 mM ammonium formate (60:40, v/v as mobile phase at a flow rate of 0.2 mL/min. The targeted compound was detected in negative ionization at m/z 347.00 for torasemide and 269.00 for IS. The linearity range of this method was found to be within the concentration range of 1–2500 ng/mL (r=0.9984 for torasemide in human plasma. The accuracy of this measurement was between 94.05% and 103.86%. The extracted recovery efficiency was from 84.20% to 86.47% at three concentration levels. This method was also successfully applied in pharmacokinetics and bioequivalence studies in Chinese volunteers.

Estudio de bioequivalencia: formulaciones genéricas y comerciales de estaduvine, lamiduvine, zidovudine e indinavir en pacientes cubanos infectados con VIH Bioequivalence study: generic and trade formulations of stavudine, lamivudine, zidovudine and indinavir in Cuban HIV-infected subjects

Directory of Open Access Journals (Sweden)

Alicia Tarinas Reyes

2006-08-01

Full Text Available Objetivo: El presente estudio describe los estudios de bioequivalencia de los genéricos cubanos antirretrovirales estavudina, lamivudina, zidovudina e indinavir con respecto a sus productos innovadores. Diseño: Los estudios de bioequivalencia de cada antirretroviral estudiado (formulación de prueba, P y referencia, R, se realizaron en 13 ó 14 sujetos, según el caso con la utilización de las medias en un estudio aleatorio, cruzado y a dosis única con un período de lavado de 10 días. Métodos: Las concentración de los antirretrovirales en plasma se monitorearon durante un período de 12 h después de la administración de estos, mediante el uso de métodos validados de cromatografía líquida de alta resolución (HPLC. Los parámetros farmacocinéticos se determinaron con el uso el software profesional WinNolin, versión 2.1. La comparación de los parámetros farmacocinéticos se realizó con un intervalo de confianza del 95 % con la utilización del software NCSS 2000 PASS 2000 (hipótesis nula. Para el estudio de bioequivalencia se usó el software Equiv Test de soluciones estadísticas, empleando ANOVA con el 90 % de intervalo de confianza. Resultados: El presente estudio mostró que no se observaron diferencias significativas en las medias de AUC0-12, AUC0-¥, Cmax y Tmax de ambas formulaciones de estavudina, lamivudina, zidovudina e indinavir. Se concluye que los parámetros farmacocinéticos estudiados se encuentran dentro de los rangos establecidos siendo 80-125 % para Cmax, AUC0-12, y AUC0-¥. En el caso de Cmax de la zidovudina el rango fue 70-143 %. Conclusión: Estos resultados avalan que los genéricos antirretrovirales cubanos son bioequivalentes con sus respectivos productos innovadores en términos de velocidad y magnitud de la absorciónObjective: The present study describes the determination of the bioequivalence of the Cuban generic and trade formulations of stavudine, lamivudine, zidovudine, and indinavir. Design: The

32 CFR 635.35 - Procedures.

Science.gov (United States)

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Procedures. 635.35 Section 635.35 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS LAW ENFORCEMENT REPORTING Victim and Witness Assistance Procedures § 635.35 Procedures. (a) As required by Federal law, Army personnel...

Development and validation of an improved method for the quantitation of sertraline in human plasma using LC-MS-MS and its application to bioequivalence studies.

Science.gov (United States)

Zhang, Mengliang; Gao, Feng; Cui, Xiangyong; Zhang, Yunhui; Sun, Yantong; Gu, Jingkai

2011-02-01

A rapid and sensitive LC-MS-MS method for the quantitation of sertraline in human plasma was developed and validated. Sertraline and the internal standard, telmisartan, were cleaned up by protein precipitation from 100 μL of plasma sample, and analyzed on a TC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 70% acetonitrile and 30% 10 mM ammonium acetate (0.1% formic acid) as mobile phase. The method was demonstrated to be linear from 0.1 ng/mL to 50 ng/mL with the lower limit of quantitation of 0.1 ng/mL. Intra- and inter-day precision were below 4.40% and 3.55%. Recoveries of sertraline at low, medium, and high levels were 88.0 ± 2.3%, 88.2 ± 1.9%, and 90.0 ± 2.0%, respectively. The method was successfully applied to a bioequivalence study of sertraline after a single oral administration of 50 mg sertraline hydrochloride tablets.

Electronic Nose Testing Procedure for the Definition of Minimum Performance Requirements for Environmental Odor Monitoring

Directory of Open Access Journals (Sweden)

Lidia Eusebio

2016-09-01

Full Text Available Despite initial enthusiasm towards electronic noses and their possible application in different fields, and quite a lot of promising results, several criticalities emerge from most published research studies, and, as a matter of fact, the diffusion of electronic noses in real-life applications is still very limited. In general, a first step towards large-scale-diffusion of an analysis method, is standardization. The aim of this paper is describing the experimental procedure adopted in order to evaluate electronic nose performances, with the final purpose of establishing minimum performance requirements, which is considered to be a first crucial step towards standardization of the specific case of electronic nose application for environmental odor monitoring at receptors. Based on the experimental results of the performance testing of a commercialized electronic nose type with respect to three criteria (i.e., response invariability to variable atmospheric conditions, instrumental detection limit, and odor classification accuracy, it was possible to hypothesize a logic that could be adopted for the definition of minimum performance requirements, according to the idea that these are technologically achievable.

Automation of the testing procedure

International Nuclear Information System (INIS)

Haas, H.; Fleischer, M.; Bachner, E.

1979-01-01

For the judgement of technologies applied and the testing of specific components of the HTR primary circuit, complex test procedures and data evaluations are required. Extensive automation of these test procedures is indispensable. (orig.) [de

Requirements for Control Room Computer-Based Procedures for use in Hybrid Control Rooms

Energy Technology Data Exchange (ETDEWEB)

Le Blanc, Katya Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna Helene [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey Clark [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-05-01

Many plants in the U.S. are currently undergoing control room modernization. The main drivers for modernization are the aging and obsolescence of existing equipment, which typically results in a like-for-like replacement of analogue equipment with digital systems. However, the modernization efforts present an opportunity to employ advanced technology that would not only extend the life, but enhance the efficiency and cost competitiveness of nuclear power. Computer-based procedures (CBPs) are one example of near-term advanced technology that may provide enhanced efficiencies above and beyond like for like replacements of analog systems. Researchers in the LWRS program are investigating the benefits of advanced technologies such as CBPs, with the goal of assisting utilities in decision making during modernization projects. This report will describe the existing research on CBPs, discuss the unique issues related to using CBPs in hybrid control rooms (i.e., partially modernized analog control rooms), and define the requirements of CBPs for hybrid control rooms.

Deterministic effects of interventional radiology procedures

International Nuclear Information System (INIS)

Shope, Thomas B.

1997-01-01

The purpose of this paper is to describe deterministic radiation injuries reported to the Food and Drug Administration (FDA) that resulted from therapeutic, interventional procedures performed under fluoroscopic guidance, and to investigate the procedure or equipment-related factors that may have contributed to the injury. Reports submitted to the FDA under both mandatory and voluntary reporting requirements which described radiation-induced skin injuries from fluoroscopy were investigated. Serious skin injuries, including moist desquamation and tissues necrosis, have occurred since 1992. These injuries have resulted from a variety of interventional procedures which have required extended periods of fluoroscopy compared to typical diagnostic procedures. Facilities conducting therapeutic interventional procedures need to be aware of the potential for patient radiation injury and take appropriate steps to limit the potential for injury. (author)

Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

Directory of Open Access Journals (Sweden)

Mona Zarifpour

2017-05-01

Full Text Available Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI. Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume, consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.

Science.gov (United States)

Ma, Jing; Yuan, Li-Hua; Ding, Mei-Juan; Zhang, Jun; Zhang, Qing; Xu, Qun-Wei; Zhou, Xue-Min

2009-03-01

A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Os estudos de bioequivalência: Relevância para a medicina veterinária

Directory of Open Access Journals (Sweden)

João Palermo-Neto

2008-12-01

Full Text Available Bioequivalence (BE studies are scientific methods that allow comparison of different medicinal products containing the same active substance, or different batches of the same medicinal products or, in a broad sense, different routes of administration of the same product.Actually, legislation on generic drugs and bioequivalence only exist in Brazil for drugs intended for human purposes. In the field of Veterinary Medicine, BE is being used in many countries as part of the necessary requirements for registration of animal health products, i.e., to provide efficacy and safety animal data and to allow consumers safety; indeed, they also assure the quality of the food derived from treated animals. The present manuscript was designed to review and discuss BE; for that, it was divided into three major parts: 1- understanding bioequivalence: importance of BE studies for animal and human health; 2- type of BE studies included; 3- general consideration on experimental design involved o BE studies

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

Science.gov (United States)

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-06-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

Directory of Open Access Journals (Sweden)

André Daher

2015-06-01

Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

MITG test procedure and results

International Nuclear Information System (INIS)

Eck, M.E.; Mukunda, M.

1983-01-01

Elements and modules for Radioisotope Thermoelectric Generator have been performance tested since the inception of the RTG program. These test articles seldom resembled flight hardware and often lacked adequate diagnostic instrumentation. Because of this, performance problems were not identified in the early stage of program development. The lack of test data in an unexpected area often hampered the development of a problem solution. A procedure for conducting the MITG Test was developed in an effort to obtain data in a systematic, unambiguous manner. This procedure required the development of extensive data acquisition software and test automation. The development of a facility to implement the test procedure, the facility hardware and software requirements, and the results of the MITG testing are the subject of this paper

Anesthesia for radiologic procedures

International Nuclear Information System (INIS)

Forestner, J.E.

1987-01-01

Anesthetic techniques for neurodiagnostic studies and radiation therapy have been recently reviewed, but anesthetic involvement in thoracic and abdominal radiology has received little attention. Patient reactions to radiologic contrast media may be of concern to the anesthesiologist, who is often responsible for injecting these agents during diagnostic procedures, and thus is included in this discussion. Finally, the difficulties of administering anesthesia for magnetic resonance imaging (MRI) scans are outlined, in an effort to help anesthesiologist to anticipate problems with this new technologic development. Although there are very few indications for the use of general anesthesia for diagnostic radiologic studies in adults, most procedures performed with children, the mentally retarded, or the combative adult require either heavy sedation or general anesthesia. In selecting an anesthetic technique for a specific procedure, both the patient's disease process and the requirements of the radiologist must be carefully balanced

Radiological and administrative criteria and procedures required by the Radiation Protection Ordinance for exemption from regulatory control

International Nuclear Information System (INIS)

Birkholz, W.

2000-01-01

The system of required radioactivity measurements and limits as well as methods, based on the 10 μSv concept, constitutes the regulatory regime for exemption of radioactive waste materials from regulatory control according to atomic energy law. The methods and administrative procedures are suitable both for smaller amounts of materials, such as those resulting from the use of radioactive substances in scientific research and medical applications, and for the large waste volumes emanating from the dismantling of nuclear installations. The system provided for in the Radiation Protection Ordinance ensures harmonized administrative action of all public authorities involved. (orig./CB) [de

Evaluation of safeguards procedures: a summary of a methodology

International Nuclear Information System (INIS)

Salisbury, J.D.; Savage, J.W.

1979-01-01

A methodology for the evaluation of safeguards procedures is described. As presently conceptualized, the methodology will consist of the following steps: (1) expansion of the general protection requirements that are contained in the NRC regulations into more detailed but still generic requirements for use at the working level; (2) development of techniques and formats for using the working-level requirements in an evaluation; (3) development of a technique for converting specific facility protection procedures into a format that will allow comparison with the working-level requirements; (4) development of an evaluation technique for comparing the facility protection procedures to determine if they meet the protection requirements

Biosimilars in psoriasis: what can we expect?

Science.gov (United States)

Radtke, Marc Alexander; Augustin, Matthias

2014-04-01

Biosimilars are biotechnologically processed drugs whose amino acid sequence is identical to the original biopharmaceutical. They are of considerable clinical, economical, and health care interest. As patents for biologicals used to treat psoriasis expire, biosimilars will become more and more important within the field of dermatology. The patents for the two top-selling drugs (adalimumab and etanercept) will terminate in the next few years. Applications for biosimilars will presumably be submitted to the EMA and the FDA for all patent-free biologicals. Both regulatory bodies have issued guidelines on the assessment of bioequivalence, as well as the benefits and risks of biosimilars. While the preclinical requirements of the FDA and EMA are largely comparable, the formal requirements for clinical bioequivalence, including clinical efficacy and safety, differ markedly. Therefore, from a medical and health care perspective before biosimilars enter the market, specific evidence-based regulatory conditions need to be created and fulfilled. Only then biosimilars can be a less expensive option for a large number of patients, providing them with substances of the same value. Adequate, unequivocal proof of their bioequivalence, quality, and related patient safety should have priority over any ostensible economic benefits. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

Science.gov (United States)

Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

2017-02-01

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

Quantification of amlodipine and atorvastatin in human plasma by UPLC-MS/MS method and its application to a bioequivalence study.

Science.gov (United States)

Rezk, Mamdouh R; Badr, Kamal A

2018-07-01

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C 18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Model of Procedure Usage – Results from a Qualitative Study to Inform Design of Computer-Based Procedures

Energy Technology Data Exchange (ETDEWEB)

Johanna H Oxstrand; Katya L Le Blanc

2012-07-01

The nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. As a step toward the goal of improving procedure use performance, researchers, together with the nuclear industry, have been looking at replacing the current paper-based procedures with computer-based procedure systems. The concept of computer-based procedures is not new by any means; however most research has focused on procedures used in the main control room. Procedures reviewed in these efforts are mainly emergency operating procedures and normal operating procedures. Based on lessons learned for these previous efforts we are now exploring a more unknown application for computer based procedures - field procedures, i.e. procedures used by nuclear equipment operators and maintenance technicians. The Idaho National Laboratory, the Institute for Energy Technology, and participants from the U.S. commercial nuclear industry are collaborating in an applied research effort with the objective of developing requirements and specifications for a computer-based procedure system to be used by field operators. The goal is to identify the types of human errors that can be mitigated by using computer-based procedures and how to best design the computer-based procedures to do this. The underlying philosophy in the research effort is “Stop – Start – Continue”, i.e. what features from the use of paper-based procedures should we not incorporate (Stop), what should we keep (Continue), and what new features or work processes should be added (Start). One step in identifying the Stop – Start – Continue was to conduct a baseline study where affordances related to the current usage of paper-based procedures were identified. The purpose of the study was to develop a model of paper based procedure use which will help to identify desirable features for computer based procedure prototypes. Affordances such as note taking, markups

Health and Safety Procedures Manual for hazardous waste sites

Energy Technology Data Exchange (ETDEWEB)

Thate, J.E.

1992-09-01

The Oak Ridge National Laboratory Chemical Assessments Team (ORNL/CAT) has developed this Health and Safety Procedures Manual for the guidance, instruction, and protection of ORNL/CAT personnel expected to be involved in hazardous waste site assessments and remedial actions. This manual addresses general and site-specific concerns for protecting personnel, the general public, and the environment from any possible hazardous exposures. The components of this manual include: medical surveillance, guidance for determination and monitoring of hazards, personnel and training requirements, protective clothing and equipment requirements, procedures for controlling work functions, procedures for handling emergency response situations, decontamination procedures for personnel and equipment, associated legal requirements, and safe drilling practices.

Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

International Nuclear Information System (INIS)

Spampinato, P.T.; Tabor, M.A.

1988-01-01

Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

Metadata requirements for results of diagnostic imaging procedures: a BIIF profile to support user applications

Science.gov (United States)

Brown, Nicholas J.; Lloyd, David S.; Reynolds, Melvin I.; Plummer, David L.

2002-05-01

A visible digital image is rendered from a set of digital image data. Medical digital image data can be stored as either: (a) pre-rendered format, corresponding to a photographic print, or (b) un-rendered format, corresponding to a photographic negative. The appropriate image data storage format and associated header data (metadata) required by a user of the results of a diagnostic procedure recorded electronically depends on the task(s) to be performed. The DICOM standard provides a rich set of metadata that supports the needs of complex applications. Many end user applications, such as simple report text viewing and display of a selected image, are not so demanding and generic image formats such as JPEG are sometimes used. However, these are lacking some basic identification requirements. In this paper we make specific proposals for minimal extensions to generic image metadata of value in various domains, which enable safe use in the case of two simple healthcare end user scenarios: (a) viewing of text and a selected JPEG image activated by a hyperlink and (b) viewing of one or more JPEG images together with superimposed text and graphics annotation using a file specified by a profile of the ISO/IEC Basic Image Interchange Format (BIIF).

40 CFR 7.90 - Grievance procedures.

Science.gov (United States)

2010-07-01

...) Exception. Recipients with fewer than fifteen (15) full-time employees need not comply with this section... Recipients § 7.90 Grievance procedures. (a) Requirements. Each recipient shall adopt grievance procedures... significantly impair the recipient's ability to provide benefits or services. ...

Procedure for the determination of gap and base ground surface configurations beneath the bottom plate of storage tanks using neutron gauging inspection techniques : including radiation safety procedure and emergency procedure

International Nuclear Information System (INIS)

Jaafar Abdullah

1993-01-01

The procedure is intended for the neutron gauging inspection of gap between the bottom plate and the foundation of bulk storage tanks, which potentially exhibit uneven sinking of the bottom plate and the foundation. Its describes the requirements for the performance of neutron back scattered inspection techniques (or radiometric non-destructive evaluation techniques), using an isotopic neutron source associated with neutron detecting systems, to detect and size the gap between the bottom plate and the foundations as well as to quantify the presence of hydrogenous materials (e.g. oil or water) underneath the bottom plate. This procedure is not only outline the requirements for the neutron gauging inspection, but also describes the requirements which shall be taken into account in formulating the radiation safety and emergency procedures for the neutron gauging inspection works

Robotic vascular resections during Whipple procedure

OpenAIRE

Allan, Bassan J.; Novak, Stephanie M.; Hogg, Melissa E.; Zeh, Herbert J.

2018-01-01

Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vas...

[Costing nuclear medicine diagnostic procedures].

Science.gov (United States)

Markou, Pavlos

2005-01-01

To the Editor: Referring to a recent special report about the cost analysis of twenty-nine nuclear medicine procedures, I would like to clarify some basic aspects for determining costs of nuclear medicine procedure with various costing methodologies. Activity Based Costing (ABC) method, is a new approach in imaging services costing that can provide the most accurate cost data, but is difficult to perform in nuclear medicine diagnostic procedures. That is because ABC requires determining and analyzing all direct and indirect costs of each procedure, according all its activities. Traditional costing methods, like those for estimating incomes and expenses per procedure or fixed and variable costs per procedure, which are widely used in break-even point analysis and the method of ratio-of-costs-to-charges per procedure may be easily performed in nuclear medicine departments, to evaluate the variability and differences between costs and reimbursement - charges.

25 CFR 225.21 - Negotiation procedures.

Science.gov (United States)

2010-04-01

... setting forth the duration of the minerals agreement; (3) A statement providing indemnification to the... accounting and mineral valuation procedures; (8) Provisions establishing operating and management procedures... refusal by the Indian mineral owner in the event of a proposed assignment; (10) Bond requirements; (11...

Use of performance curves in estimating number of procedures required to achieve proficiency in coronary angiography

DEFF Research Database (Denmark)

Räder, Sune B E W; Jørgensen, Erik; Bech, Bo

2011-01-01

.001 for all parameters. To approach the experts' level of DAP and contrast media use, trainees need 394 and 588 procedures, respectively. Performance curves showed large individual differences in the development of competence. Conclusion: On average, trainees needed 300 procedures to reach sufficient level...... needed for trainees to reach recommended reference levels was estimated as 226 and 353, for DAP and use of contrast media, respectively. After 300 procedures, trainees' procedure time, fluoroscopy time, DAP, and contrast media volume were significantly higher compared with experts' performance, P ...Background: Current guidelines in cardiology training programs recommend 100-300 coronary angiography procedures for certification. We aimed to assess the number of procedures needed to reach sufficient proficiency. Methods: Procedure time, fluoroscopy time, dose area product (DAP), and contrast...

Software quality assurance procedures for radioactive waste risk assessment codes

International Nuclear Information System (INIS)

Hill, I.; Mayer, J.

1990-01-01

This support study for the evaluation of the safety of geological disposal systems is aimed at identifying the requirements for software quality assurance procedures for radioactive waste risk assessment codes, and to recommend appropriate procedures. The research covers: (i) the analysis of existing procedures and definition of requirements; (ii) a case study of the use of some existing procedures; (iii) the definition and the implementation of procedures. The report is supported by appendices that give more detail on the procedures recommended. It is intended to provide ideas on the steps that should be taken to ensure the quality of the programs used for assessment of the safety case for radioactive waste repositories, and does not represent the introduction of wholly new ideas or techniques. The emphasis throughout is on procedures that will be easily implemented, rather than on the fully rigorous procedures that are required for some application areas. The study has concentrated on measures that will increase the confidence in repository performance assessments among the wider scientific/engineering community, and the lay public

Payment Procedures for Electronic Government Services

OpenAIRE

Pousttchi, Key; Wiedemann, Dietmar Georg

2005-01-01

In this paper, we analyse payment procedures for their suitability for electronic government. We provide an overview of the payment procedures currently available on the market, compare the situation in electronic government with the situation in electronic commerce and analyze what we can transfer. Based on functional requirements we propose a scheme that allows public agencies to examine the appropriateness of any given payment procedure for electronic government.

Robotic vascular resections during Whipple procedure.

Science.gov (United States)

Allan, Bassan J; Novak, Stephanie M; Hogg, Melissa E; Zeh, Herbert J

2018-01-01

Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.

22 CFR 226.71 - Closeout procedures.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Closeout procedures. 226.71 Section 226.71 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS After-the-Award Requirements § 226.71 Closeout procedures. (a) Recipients shall...

Inclusion of service robots in the daily lives of frail older users: A step-by-step definition procedure on users' requirements.

Science.gov (United States)

García-Soler, Álvaro; Facal, David; Díaz-Orueta, Unai; Pigini, Lucia; Blasi, Lorenzo; Qiu, Renxi

2018-01-01

The implications for the inclusion of robots in the daily lives of frail older adults, especially in relation to these population needs, have not been extensively studied. The "Multi-Role Shadow Robotic System for Independent Living" (SRS) project has developed a remotely-controlled, semi-autonomous robotic system to be used in domestic environments. The objective of this paper is to document the iterative procedure used to identify, select and prioritize user requirements. Seventy-four requirements were identified by means of focus groups, individual interviews and scenario-based interviews. The list of user requirements, ordered according to impact, number and transnational criteria, revealed a high number of requirements related to basic and instrumental activities of daily living, cognitive and social support and monitorization, and also involving privacy, safety and adaptation issues. Analysing and understanding older users' perceptions and needs when interacting with technological devices adds value to assistive technology and ensures that the systems address currently unmet needs. Copyright © 2017 Elsevier B.V. All rights reserved.

TRUPACT-II procedures and maintenance instructions

International Nuclear Information System (INIS)

1994-01-01

The purpose of this document is to provide the technical requirements for operation, inspection and maintenance of a TRUPACT-II Shipping Package and directly related components. This document shall supply the minimum requirements as specified in the TRUPACT-II Safety Analysis Report for Packaging (SARP) and Certificate of Compliance (C of C) 9218. In the event there is a conflict between this document and the TRUPACT-II SARP (NRC Certificate of Compliance No. 9218), the TRUPACT-II SARP shall govern. This document details the operations, maintenance, repair, replacement of components, as well as the documentation required and the procedures to be followed to maintain the integrity of the TRUPACT-II container. These procedures may be modified for site use, but as a minimum all parameters and format listed herein must be included in any site modified version. For convenience and where applicable steps may be performed out of sequence. Packaging and payload handling equipment and transport trailers have been specifically designed for use with the TRUPACT-II Packaging. This document discusses the minimum required procedures for use of the adjustable center of gravity lift fixture and the TRUPACT-II transport trailer in conjunction with the TRUPACT-II Packaging

78 FR 16779 - Type Certification Procedures for Changed Products

Science.gov (United States)

2013-03-19

...-8994; Amdt. No. 21-96] RIN 2120-AK19 Type Certification Procedures for Changed Products AGENCY: Federal... requirements for the certification of changes to type-certificated products. The revision required the... entitled, ``Type Certification Procedures for Changed Products'' (December 4, 2012, 77 FR 71691). The 2000...

49 CFR 601.45 - Required information.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Required information. 601.45 Section 601.45 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ORGANIZATION, FUNCTIONS, AND PROCEDURES Emergency Procedures for Public Transportation Systems § 601.45 Required...

22 CFR 92.37 - Authentication procedure.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication procedure. 92.37 Section 92.37... Notarial Acts § 92.37 Authentication procedure. (a) The consular officer must compare the foreign official...) Where the State law requires the consular officer's certificate of authentication to show that the...

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

Science.gov (United States)

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

76 FR 44656 - Proposed Collection; Comment Request for Revenue Procedure(s)

Science.gov (United States)

2011-07-26

... disaffililiation and procedure to eliminate impediments to e-filing consolidated returns and reduce reporting... Eliminate Impediments to E-Filing Consolidated Returns and Reduce Reporting Requirements. OMB Number: 1545... eliminate impediments to the electronic filing of Federal income tax returns (e- filing) and to reduce the...

OCRWM procedure for reporting software baseline change information

International Nuclear Information System (INIS)

1994-07-01

The purpose of this procedure is to establish a requirement and method for participant organizations to report software baseline change information to the M ampersand O Configuration Management (CM) organization for inclusion in the OCRWM Configuration Information System (CIS). (The requirements for performing software configuration management (SCM) are found in the OCRWM Quality Assurance Requirements and Description (QARD) document and in applicable DOE orders, and not in this procedure.) This procedure provides a linkage between each participant's SCM system and the CIS, which may be accessed for identification, descriptive, and contact information pertaining to software released by a participant. Such information from the CIS will enable retrieval of details and copies of software code and documentation from the participant SCM system

10 CFR 71.111 - Instructions, procedures, and drawings.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Instructions, procedures, and drawings. 71.111 Section 71... MATERIAL Quality Assurance § 71.111 Instructions, procedures, and drawings. The licensee, certificate..., procedures, or drawings of a type appropriate to the circumstances and shall require that these instructions...

49 CFR 1503.101 - TSA requirements.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false TSA requirements. 1503.101 Section 1503.101... Scope of Investigative and Enforcement Procedures § 1503.101 TSA requirements. (a) The investigative and enforcement procedures in this part apply to TSA's investigation and enforcement of violations of TSA...

W-087 Acceptance test procedure. Revision 1

Energy Technology Data Exchange (ETDEWEB)

Joshi, A.W.

1997-06-10

This Acceptance Test Procedure/Operational Test Procedure (ATP/OTP) has been prepared to demonstrate that the Electrical/Instrumentation and Mechanical systems function as required by project criteria and to verify proper operation of the integrated system including the interlocks.

W-087 Acceptance test procedure. Revision 1

International Nuclear Information System (INIS)

Joshi, A.W.

1997-01-01

This Acceptance Test Procedure/Operational Test Procedure (ATP/OTP) has been prepared to demonstrate that the Electrical/Instrumentation and Mechanical systems function as required by project criteria and to verify proper operation of the integrated system including the interlocks

21 CFR 821.25 - Device tracking system and content requirements: manufacturer requirements.

Science.gov (United States)

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS Tracking... procedure for the collection, maintenance, and auditing of the data specified in paragraphs (a) and (b) of... recording system, and the file maintenance procedures system; and (3) A quality assurance program that...

10 CFR 72.150 - Instructions, procedures, and drawings.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Instructions, procedures, and drawings. 72.150 Section 72... WASTE Quality Assurance § 72.150 Instructions, procedures, and drawings. The licensee, applicant for a... documented instructions, procedures, or drawings of a type appropriate to the circumstances and shall require...

Procedures for sampling radium-contaminated soils

International Nuclear Information System (INIS)

Fleischhauer, H.L.

1985-10-01

Two procedures for sampling the surface layer (0 to 15 centimeters) of radium-contaminated soil are recommended for use in remedial action projects. Both procedures adhere to the philosophy that soil samples should have constant geometry and constant volume in order to ensure uniformity. In the first procedure, a ''cookie cutter'' fashioned from pipe or steel plate, is driven to the desired depth by means of a slide hammer, and the sample extracted as a core or plug. The second procedure requires use of a template to outline the sampling area, from which the sample is obtained using a trowel or spoon. Sampling to the desired depth must then be performed incrementally. Selection of one procedure over the other is governed primarily by soil conditions, the cookie cutter being effective in nongravelly soils, and the template procedure appropriate for use in both gravelly and nongravelly soils. In any event, a minimum sample volume of 1000 cubic centimeters is recommended. The step-by-step procedures are accompanied by a description of the minimum requirements for sample documentation. Transport of the soil samples from the field is then addressed in a discussion of the federal regulations for shipping radioactive materials. Interpretation of those regulations, particularly in light of their application to remedial action soil-sampling programs, is provided in the form of guidance and suggested procedures. Due to the complex nature of the regulations, however, there is no guarantee that our interpretations of them are complete or entirely accurate. Preparation of soil samples for radium-226 analysis by means of gamma-ray spectroscopy is described

75 FR 78804 - Proposed Collection; Comment Request for Revenue Procedure 2003-45 and Revenue Procedure 2004-48

Science.gov (United States)

2010-12-16

... required by the Paperwork Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently... Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election for Late Electing S Corporations. DATES...-45, Late Election Relief for S Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election...

Report on COTECH test procedure and characterization techniques

DEFF Research Database (Denmark)

Islam, Mohammad Aminul

that need to be attained for successful characterization of the planned demonstrators and it deals with the material characterization and prototype testing for the COTECH demonstrators. The summary of this report includes:  General description of COTECH industrial demonstrators  COTECH materials...... and material characterization techniques  Characterization techniques of the COTECH demonstrators  Functionality and lifecycle testing of the COTECH demonstrators Besides the general introduction and conclusion each section of the report is dedicated to the characterization techniques and test procedure.......Characterization techniques and test procedure requirements for innovative self-ligating dental brackets (EO) Section 5.Characterization techniques and test procedure requirements for smart diagnostic chips comprising a microfluidic channel system (GBO) Section 6.Characterization techniques and test procedure...

Rock mass and shaft concrete lining temperature measurement procedure: Final draft

International Nuclear Information System (INIS)

1986-10-01

This procedure document describes the equipment and procedures which will be used to obtain temperature data from within rock-mass and shaft linings at the Deaf Smith Exploratory Shaft Facility. Temperature measurement methods for instrument temperature correction, fluid temperature correction, heated surface monitoring and air temperature monitoring are outside the scope of this procedure, and are covered in the appropriate individual test procedures. Calibration, acceptance testing and the assignment of transducer reference numbers are outside the scope of this procedure. Section 2.0 provides a summary of the temperature measurement methods which will be employed, together with the measurement locations, environmental considerations and measurement requirements. Test layouts, including detailed descriptions of instruments, support requirements and detailed installation procedures are also presented. Section 3.0 describes the requirements for data recording, ADAS monitoring, and data reporting. Section 4.0 defines personnel responsibilities and qualifications. In addition a measurement and installation schedule is provided, and safety and contingency plans are described. Section 5.0 discusses management and quality assurance requirements. Cited references are listed in Section 6.0. 7 refs., 9 figs

77 FR 30241 - Representation Procedures and Rulemaking Authority

Science.gov (United States)

2012-05-22

... the informal rulemaking procedures in the Administrative Procedure Act (APA), 5 U.S.C. 553, and... stricter requirements in sections 556 and 557 of the APA, this hearing will comply with those informal rulemaking procedures under the APA. See, e.g. United States v. Allegheny-Ludlum Steel Corp., 406 US 742...

30 CFR 36.6 - Application procedures and requirements.

Science.gov (United States)

2010-07-01

... diesel engine, including joints and gaskets; the turbulence or precombustion chamber, if applicable; injector assembly and nozzle details; and any surfaces that form the combustion chamber or part thereof..., EVALUATION, AND APPROVAL OF MINING PRODUCTS APPROVAL REQUIREMENTS FOR PERMISSIBLE MOBILE DIESEL-POWERED...

30 CFR 14.4 - Application procedures and requirements.

Science.gov (United States)

2010-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS... conveyor belt for use in underground coal mines must include the information below, except any information...) A technical description of the conveyor belt, which includes: (i) Trade name or identification...

Procedure for taking physical inventories

International Nuclear Information System (INIS)

Anon.

1981-01-01

This session is intended to apprise one of the various aspects of procedures and routines that Exxon Nuclear uses with respect to its nuclear materials physical inventory program. The presentation describes how plant physical inventories are planned and taken. The description includes the planning and preparation for taking the inventory, the clean-out procedures for converting in-process material to measurable items, the administrative procedures for establishing independent inventory teams and for inventorying each inventory area, the verification procedures used to include previously measured tamper-safed items in the inventory, and lastly, procedures used to reconcile the inventory and calculate MUF (materials unaccounted for). The purpose of the session is to enable participants to: (1) understand the planning and pre-inventorty procedures and their importance; (2) understand the need for and the required intensity of clean-out procedures; (3) understand how inventory teams are formed, and how the inventory is conducted; (4) understand the distinction between inventory previously measured tamper-safed items and other materials not so characterized; (5) understand the reconciliation procedures; and (6) calculate a MUF given the book and inventory results

Acceptance test procedure for Project W-280

International Nuclear Information System (INIS)

Stites, C.G.

1994-01-01

This Document is the Acceptance Test Procedure for 200 Area C and SY Tank Farm Lighting Upgrade. This Acceptance Test Procedure has been prepared to demonstrate that the Tank Farm Lighting Systems function correctly as required by project criteria and as intended by design

22 CFR 201.23 - Procurement under private sector procedures.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Procurement under private sector procedures... § 201.23 Procurement under private sector procedures. (a) General requirements. Procurements under private sector procedures will normally be carried out by importers using negotiated procurement...

Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

Science.gov (United States)

Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

2011-12-15

A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

Autonomous Real Time Requirements Tracing

Science.gov (United States)

Plattsmier, George; Stetson, Howard

2014-01-01

One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto- Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner-TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the

INITIATION AND CONDUCT OF ADMINISTRATIVE PROCEDURE

Directory of Open Access Journals (Sweden)

Milan Stipic

2013-12-01

Full Text Available General administrative procedure act contains legal norms that are valid for all identical cases. In addition to the general, there are special administrative procedures, customized to the specific administrative areas. Procedure initiation is regulated. Administrative procedure can be initiated at the request of the proponent and ex officio. When the official determines that the conditions for the conduct of administrative procedure are met, before making a decision, all the facts and circumstances relevant to the resolution of administrative matter have to be identified. When there are no legal requirements for the initiation of procedures, the official shall make a decision to reject the application of the party. The procedure is initiated ex officio when stipulated by law or when protection of public interest requires it. When initiating procedure ex officio, the public authority shall take into consideration the petition or other information that indicate the need to protect the public interest. In such cases the applicant is not a party, and the official is obliged to notify the applicant, if initiation of procedures is not accepted ex officio. Based on the notification, the applicant has a right to complain, including the situation when there is no response within the prescribed period of 30 days. Public authority may, therefore it is not obliged to, initiate administrative procedure by public announcement only in a situation where the parties are unknown, while it is obliged to initiate procedure by public announcement when this method of initiating the procedure is prescribed by law. Initiation of procedure with public announcement occurs in rare cases. Due to the application of efficiency and cost-effectiveness principle, two or more administrative procedures can be merged into one procedure by a conclusion. The condition for this is that the rights or obligations of the parties are based on the same legal basis and on the same or

FFTF reactor plant procedures plan

International Nuclear Information System (INIS)

1972-01-01

The document presented defines the plan to be used to coordinate the preparation, review, approval, and issuance of the operating procedure documents required to ensure safe and efficient operation of FFTF

Specified assurance level sampling procedure

International Nuclear Information System (INIS)

Willner, O.

1980-11-01

In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

48 CFR 32.003 - Simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... procedures financing. 32.003 Section 32.003 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 32.003 Simplified acquisition procedures financing. Unless agency regulations otherwise permit, contract financing shall not be provided for...

48 CFR 1532.003 - Simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... procedures financing. 1532.003 Section 1532.003 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 1532.003 Simplified acquisition procedures financing. (a) Scope. This subpart provides for authorization of advance and interim payments on...

Health Code Number (HCN) Development Procedure

Energy Technology Data Exchange (ETDEWEB)

Petrocchi, Rocky; Craig, Douglas K.; Bond, Jayne-Anne; Trott, Donna M.; Yu, Xiao-Ying

2013-09-01

This report provides the detailed description of health code numbers (HCNs) and the procedure of how each HCN is assigned. It contains many guidelines and rationales of HCNs. HCNs are used in the chemical mixture methodology (CMM), a method recommended by the department of energy (DOE) for assessing health effects as a result of exposures to airborne aerosols in an emergency. The procedure is a useful tool for proficient HCN code developers. Intense training and quality assurance with qualified HCN developers are required before an individual comprehends the procedure to develop HCNs for DOE.

SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women

Directory of Open Access Journals (Sweden)

Pravin G. Vanol

2016-08-01

Full Text Available A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm column using methanol-0.1% formic acid in water (85:15, v/v as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10–100 ng/mL (r2≥0.9990 using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR of 74 subject samples.

MITS Feed and Withdrawal Subsystem: operating procedures

International Nuclear Information System (INIS)

Brown, W.S.

1980-01-01

This procedure details the steps required to provide continuous feed flow and withdrawal of process product and waste flows in support of thruput operation in the cascade or its elements. It particularly requires operator attention to safety considerations

[Availability of generic drugs in the public sector and prices in the private sector in different regions of Brazil].

Science.gov (United States)

Miranda, Elaine Silva; Pinto, Cláudia Du Bocage Santos; dos Reis, André Luis de Almeida; Emmerick, Isabel Cristina Martins; Campos, Mônica Rodrigues; Luiza, Vera Lucia; Osorio-de-Castro, Claudia Garcia Serpa

2009-10-01

A study to identify availability and prices of medicines, according to type of provider, was conducted in the five regions of Brazil. A list of medicines to treat prevalent diseases was investigated, using the medicines price methodology developed by the World Health Organization and Health Action International, adapted for Brazil. In the public sector, bioequivalent (vis-à-vis reference brand) generics are less available than multisource products. For most medicines (71.4%), the availability of bioequivalent generics was less than 10%. In the private sector, the average number of different bioequivalent generic versions in the outlets was far smaller than the number of versions on the market. There was a positive correlation between the number of generics on the market, or those found at outlets, and the price variation in bioequivalent generic products, in relation to the maximum consumer price. It is estimated that price competition is occurring among bioequivalent generic drugs and between them and multisource products for the same substance, but not with reference brands.

48 CFR 432.003 - Simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... procedures financing. 432.003 Section 432.003 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 432.003 Simplified acquisition procedures financing. (a) The chief of the contracting office may approve contract financing on a contract to be...

48 CFR 1332.003 - Simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... procedures financing. 1332.003 Section 1332.003 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 1332.003 Simplified acquisition procedures financing. Contract financing may be provided for purchases made under the authority of FAR Part 13. Contract...

A phase 1 study to evaluate effect of food on veliparib pharmacokinetics and relative bioavailability in subjects with solid tumors.

Science.gov (United States)

Mostafa, Nael M; Chiu, Yi-Lin; Rosen, Lee S; Bessudo, Alberto; Kovacs, Xenia; Giranda, Vincent L

2014-09-01

A phase 1 study was conducted to evaluate the bioavailability and food effect of a new veliparib formulation in subjects with solid tumors. Subjects (planned: Stage I, N = 20; Stage II, N = 16) received four regimens of a single oral dose of veliparib utilizing a group-sequential design. Subjects were administered single doses of 40 mg veliparib supplied as four 10 mg current formulation, four 10 mg new formulation and one 40 mg new formulation under fasting conditions and under non-fasting conditions. Serial blood samples were collected for the determination of veliparib pharmacokinetics. At the end of Stage I, the relative bioavailability between each pair of regimens was assessed by a two one-sided tests procedure from the analyses of the natural logarithms of C(max) and AUC. A 92.7 % confidence interval within the 0.80-1.25 range between each regimen pair determined bioequivalence. Four 10 mg current formulation capsules, four 10 mg new formulation and one 40 mg new formulation were bioequivalent with respect to C(max) and AUC under fasting conditions. The administration of a high-fat meal did not have a significant effect on AUC and only caused a slight decrease in veliparib C(max) (17 %) and a delay of approximately 1 h in T(max). The 40 mg new capsule was bioequivalent to currently used formulation. Food had no effect on the extent of veliparib absorption and only a small (17 %) decrease in peak exposure of veliparib.

PROCEDURAL CONVENTION AND FLEXIBILITY OF THE PROCED URE: THE INFLUENCE OF PRIVATE AUTONOMY ON THE PUBLICIST PARADIGM OF CIVIL PROCEDURE

Directory of Open Access Journals (Sweden)

Marcelo Dias Ponte

2015-12-01

Full Text Available The research aims to analyze the New CPC innovations with regard to the procedural legal business, to assess, carefully, it s possibilities, its limits, requirements and the function of the court and the parties to the flexibility of the procedure. The study approaches the shared management of the procedure, the procedural calendar as materializing institute the principle of efficiency. As a result, it was found that procedural conventions have the power to better protect the substantive rights involved in the dispute, since the litigants may bring the procedural rite to the needs of the conflict, allowing a view democratic demand, able to increase dialogue and interaction between the parties.

Design Procedure for Hybrid Ventilation

DEFF Research Database (Denmark)

Heiselberg, Per; Tjelflaat, Per Olaf

Mechanical and natural ventilation systems have developed separately during many years. The natural next step in this development is development of ventilation concepts that utilises and combines the best features from each system into a new type of ventilation system - Hybrid Ventilation....... Buildings with hybrid ventilation often include other sustainable technologies and an energy optimisation requires an integrated approach in the design of the building and its mechanical systems. Therefore, the hybrid ventilation design procedure differs from the design procedure for conventional HVAC....... The first ideas on a design procedure for hybrid ventilation is presented and the different types of design methods, that is needed in different phases of the design process, is discussed....

TMACS test procedure TP003: Graphics. Revision 5

International Nuclear Information System (INIS)

Scanlan, P.K.

1994-01-01

The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the graphics requirements of the TMACS. The features to be tested are the data display graphics and the graphic elements that provide for operator control and selection of displays

TMACS test procedure TP003: Graphics. Revision 6

International Nuclear Information System (INIS)

Scanlan, P.K.; Washburn, S.

1994-01-01

The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the graphics requirements of the TMACS. The features to be tested are the data display graphics and the graphic elements that provide for operator control and selection of displays

COPMA-III - Intelligent handling of existing procedures

International Nuclear Information System (INIS)

Hulsund, John-Einar; Jung, Yeonsub; Nilsen, Svein

1999-04-01

This report describes how COPMA-III makes it possible to enhance old procedures without having to change much of their original layout. By means of COPMA-III one can insert into the old procedure text tags that describe the 'meaning' of the various textual elements in the procedure. Those tags can be made invisible to the person using the procedure, but the computer is able to inspect the tags and give appropriate assistance in carrying through the procedure. Previous versions of COPMA required a reformulation and most often a re-structuring of the procedures before taking them into use. A fixed set of instructions and a fixed procedure structure made the computerised procedure different from the original procedure (in most cases). This is no more so in COPMA-III. By means of small procedural elements (microelements), it is possible to configure the COPMA-III system to fit the set of instructions and the procedure structure that is being used in the old procedure system. This report describes an example case, starting with an old procedure, goes through a set of working steps and ends up with a procedure having exactly the same appearance as the old procedure, but having assistance from the COPMA-III system in executing the procedure (author) (ml)

Transthoracic Adrenal Biopsy Procedure Using Artificial Carbon Dioxide Pneumothorax as Outpatient Procedure

Energy Technology Data Exchange (ETDEWEB)

Favelier, Sylvain [CHU (University Hospital), Department of Radiology (France); Guiu, Severine [Georges-Francois Leclerc Cancer Center, Department of Oncology (France); Cherblanc, Violaine; Cercueil, Jean-Pierre; Krause, Denis; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr [CHU (University Hospital), Department of Radiology (France)

2013-08-01

Many routes have been described for percutaneous adrenal gland biopsy. They require either a complex non-axial path or a long hydrodissection or even pass through an organ thereby increasing complications. We describe here an approach using an artificially-induced carbon dioxide (CO{sub 2}) pneumothorax, performed as an outpatient procedure in a 57-year-old woman. Under local anaesthesia, 200 ml of CO{sub 2} was injected in the pleural space through a Veress needle under computed tomography fluoroscopy, to clear the lung parenchyma from the biopsy route. Using this technique, transthoracic adrenal biopsy can be performed under simple local anaesthesia as an safely outpatient procedure.

Quantitation of itopride in human serum by high-performance liquid chromatography with fluorescence detection and its application to a bioequivalence study.

Science.gov (United States)

Singh, Sonu Sundd; Jain, Manish; Sharma, Kuldeep; Shah, Bhavin; Vyas, Meghna; Thakkar, Purav; Shah, Ruchy; Singh, Shriprakash; Lohray, Brajbhushan

2005-04-25

A new method was developed for determination of itopride in human serum by reversed phase high-performance liquid chromatography (HPLC) with fluorescence detection (excitation at 291 nm and emission at 342 nm). The method employed one-step extraction of itopride from serum matrix with a mixture of tert-butyl methyl ether and dichloromethane (70:30, v/v) using etoricoxib as an internal standard. Chromatographic separation was obtained within 12.0 min using a reverse phase YMC-Pack AM ODS column (250 mm x 4.6 mm, 5 microm) and an isocratic mobile phase constituting of a mixture of 0.05% tri-fluoro acetic acid in water and acetonitrile (75:25, v/v) flowing at a flow rate of 1.0 ml/min. The method was linear in the range of 14.0 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 14.0 ng/ml. Average recovery of itopride and the internal standard from the biological matrix was more than 66.04 and 64.57%, respectively. The inter-day accuracy of the drug containing serum samples was more than 97.81% with a precision of 2.31-3.68%. The intra-day accuracy was 96.91% or more with a precision of 5.17-9.50%. Serum samples containing itopride were stable for 180.0 days at -70+/-5 degrees C and for 24.0 h at ambient temperature (25+/-5 degrees C). The method was successfully applied to the bioequivalence study of itopride in healthy, male human subjects.

Procedural Due Process and Fairness in Student Discipline. A Legal Memorandum.

Science.gov (United States)

Johnson, T. Page

When the Supreme Court decided that the Constitution requires public school principals to follow procedural due process in suspension and expulsion cases, the Justices recognized a link between procedural due process and the fairness of effective discipline. This report reviews the constitutional due process required when public school officials…

Constraint-Checking Editor for Procedure Tracking (ConCEPT), Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Constructing, maintaining, and adapting operational procedures for manned space operations is a complex task, requiring the procedure author to satisfy constraints...

System requirements and design description for the environmental requirements management interface (ERMI)

International Nuclear Information System (INIS)

Biebesheimer, E.

1997-01-01

This document describes system requirements and the design description for the Environmental Requirements Management Interface (ERMI). The ERMI database assists Tank Farm personnel with scheduling, planning, and documenting procedure compliance, performance verification, and selected corrective action tracking activities for Tank Farm S/RID requirements. The ERMI database was developed by Science Applications International Corporation (SAIC). This document was prepared by SAIC and edited by LMHC

Program Baseline Change Control Procedure

International Nuclear Information System (INIS)

1993-02-01

This procedure establishes the responsibilities and process for approving initial issues of and changes to the technical, cost, and schedule baselines, and selected management documents developed by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System. This procedure implements the OCRWM Baseline Management Plan and DOE Order 4700.1, Chg 1. It streamlines the change control process to enhance integration, accountability, and traceability of Level 0 and Level I decisions through standardized Baseline Change Proposal (BCP) forms to be used by the Level 0, 1, 2, and 3 Baseline Change Control Boards (BCCBs) and to be tracked in the OCRWM-wide Configuration Information System (CIS) Database.This procedure applies to all technical, cost, and schedule baselines controlled by the Energy System Acquisition Advisory Board (ESAAB) BCCB (Level 0) and, OCRWM Program Baseline Control Board (PBCCB) (Level 1). All baseline BCPs initiated by Level 2 or lower BCCBs, which require approval from ESAAB or PBCCB, shall be processed in accordance with this procedure. This procedure also applies to all Program-level management documents controlled by the OCRWM PBCCB

Designing Flightdeck Procedures: Literature Resources

Science.gov (United States)

Feldman, Jolene; Barshi, Immanuel; Degani, Asaf; Loukopoulou, Loukia; Mauro, Robert

2017-01-01

This technical publication contains the titles, abstracts, summaries, descriptions, and/or annotations of available literature sources on procedure design and development, requirements, and guidance. It is designed to provide users with an easy access to available resources on the topic of procedure design, and with a sense of the contents of these sources. This repository of information is organized into the following publication sources: Research (e.g., journal articles, conference proceedings), Manufacturers' (e.g., operation manuals, newsletters), and Regulatory and/or Government (e.g., advisory circulars, reports). An additional section contains synopses of Accident/Incident Reports involving procedures. This work directly supports a comprehensive memorandum by Barshi, Mauro, Degani, & Loukopoulou (2016) that summarizes the results of a multi-year project, partially funded by the FAA, to develop technical reference materials that support guidance on the process of developing cockpit procedures (see "Designing Flightdeck Procedures" https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20160013263.pdf). An extensive treatment of this topic is presented in a forthcoming book by the same authors.

38 CFR 36.4220 - Substantive and procedural requirements; waiver.

Science.gov (United States)

2010-07-01

... OF VETERANS AFFAIRS (CONTINUED) LOAN GUARANTY Guaranty of Loans to Veterans to Purchase Manufactured... default. (5) The requirement in § 36.4280 that a holder give 30 days advance notice of its intention to...

Helicopter Fatigue. A Review of Current Requirements and Substantiation Procedures

Science.gov (United States)

1979-01-01

stress versus cycles to failure (S/N) method of testing and verification. A mi..iimum of six test specimens is required to establish the mean curve with...Approach) A.D. Hall B.Sc., C.Eng., M.R.Ae.S. 4 Chief Stress Engineer (Dynamic Components) Westland Helicopters Limited, Yeovil, Somerset, England...airworthiness requirements concerning the fatifue strength of British milltary nelicopters are embodied in the U.K. Ministry Documents Aviation Publication

47 CFR 1.2112 - Ownership disclosure requirements for applications.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Ownership disclosure requirements for... PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2112 Ownership disclosure requirements for... agreements, management agreements, franchise agreements, spectrum leasing arrangements, spectrum resale...

Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

Science.gov (United States)

Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

2013-10-01

To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

Procedure guideline for thyroid scintigraphy (version 3)

International Nuclear Information System (INIS)

Dietlein, M.; Schicha, H.; Eschner, W.; Deutsche Gesellschaft fuer Medizinische Physik; Koeln Univ.; Leisner, B.; Allgemeines Krankenhaus St. Georg, Hamburg; Reiners, C.; Wuerzburg Univ.

2007-01-01

The version 3 of the procedure guideline for thyroid scintigraphy is an update of the procedure guideline previously published in 2003. The interpretation of the scintigraphy requires the knowledge of the patients' history, the palpation of the neck, the laboratory parameters and of the sonography. The interpretation of the technetium-99m uptake requires the knowledge of the TSH-level. As a consequence of the improved alimentary iodine supply the 99m Tc-uptake has decreased; 100 000 counts per scintigraphy should be acquired. For this, an imaging time of 10 minutes is generally needed using a high resolution collimator for thyroid imaging. (orig.)

Procedural violation in the licensing procedure and possible legal consequences; Verfahrensmaengel im Konzessionierungsverfahren und etwaige Rechtsfolgen

Energy Technology Data Exchange (ETDEWEB)

Meyer-Hetling, Astrid; Probst, Matthias Ernst; Wolkenhauer, Soeren [Kanzlei Becker Buettner Held (BBH), Berlin (Germany)

2012-07-15

With respect to paragraph 46 sect. 2 to 4 EnWG (Energy Economy Law) communities are required to provide a publication procedure and competition procedure ('licensing procedure') for the new assignment of easement agreements for the establishment of local power supply systems and natural gas supply systems. The specific design of the selection process legally is regulated only rudimentary. Nevertheless old concessionaires increasingly deny the statutory grid transfer to the new concessionaires relying on supposed errors in the selection process. The unclear legal situation and the inconsistent, sometimes unreasonably strict jurisdiction and jurisprudence of antitrust as well as regulatory authorities resulted to a considerable legal certainty in communities and grid operators. Unless the legislature establishes the necessary legal clarity, the competent courts and authorities are invoked to act moderately in the examination of licensing procedures.

On anti-earthquake design procedure of equipment and pipings in near future

International Nuclear Information System (INIS)

Shibata, H.

1981-01-01

The requirement of anti-earthquake design of nuclear power plants is getting severe year by year. The author will try to discuss how to control its severity and how to find a proper design procedure for licensing of new plants under such severe requirements. On the other hand we suffered from the enormous volumes of documents. To decrease such volumes, the format of documents should be standardized as well as the design procedure standardization. Starting from this point, we need the research and development on the following subjects: i) Standardization of design procedure. ii) Standardization of document. iii) Establishment of standard review procedure using computer. iv) Standardization of earthquake-resistant designed equipment. v) Standardization of anti-earthquake design procedure of piping systems. vi) Introducing margin evaluation procedure to design procedure. vii) Introducing proving test procedure of active component to design procedure. viii) Establishment of evaluation of human reliability in design, fabrication, inspection procedures. ix) Establishment of the proper relation of seismic trigger level and post-earthquake design procedures. (orig./HP)

76 FR 31013 - Proposed Collection; Comment Request for Revenue Procedure 99-17

Science.gov (United States)

2011-05-27

... Revenue Procedure 99-17 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... information collection requirements related to Revenue Procedure 99-17, Mark to Market Election for.... OMB Number: 1545-1641. Revenue Procedure Number: Revenue Procedure 99-17. Abstract: This revenue...

Licensing procedures for Low-Level Waste disposal facilities

International Nuclear Information System (INIS)

Roop, R.D.; Van Dyke, J.W.

1985-09-01

This report describes the procedures applicable to siting and licensing of disposal facilities for low-level radioactive wastes. Primary emphasis is placed on those procedures which are required by regulations, but to the extent possible, non-mandatory activities which will facilitate siting and licensing are also considered. The report provides an overview of how the procedural and technical requirements for a low-level waste (LLW) disposal facility (as defined by the Nuclear Regulatory Commission's Rules 10 CFR Parts 2, 51, and 61) may be integrated with activities to reduce and resolve conflict generated by the proposed siting of a facility. General procedures are described for site screening and selection, site characterization, site evaluation, and preparation of the license application; specific procedures for several individual states are discussed. The report also examines the steps involved in the formal licensing process, including docketing and initial processing, preparation of an environmental impact statement, technical review, hearings, and decisions. It is concluded that development of effective communication between parties in conflict and the utilization of techniques to manage and resolve conflicts represent perhaps the most significant challenge for the people involved in LLW disposal in the next decade. 18 refs., 6 figs

Inservice inspection procedures and training according to the ASME code

International Nuclear Information System (INIS)

Greenwald, S.M.; Chockie, L.J.

1987-01-01

Mandatory training of the technical staff at a nuclear power plant is of paramount importance if we are to avoid costly plant shutdowns. This training should include the requirements for both Preservice and Inservice Inspection, in addition to Quality Assurance procedures as required by the American Society of Mechanical Engineers (ASME) Code. The training is best accomplished by utilizing instructors who are thoroughly familiar with plant operations and the ASME Code, as well as serving on one of the Code committees. This paper focuses on the Inservice Inspection procedures and the results of an intensive training effort to implement such procedures. (author)

Space Geodesy Project Information and Configuration Management Procedure

Science.gov (United States)

Merkowitz, Stephen M.

2016-01-01

This plan defines the Space Geodesy Project (SGP) policies, procedures, and requirements for Information and Configuration Management (CM). This procedure describes a process that is intended to ensure that all proposed and approved technical and programmatic baselines and changes to the SGP hardware, software, support systems, and equipment are documented.

21 CFR 314.530 - Withdrawal procedures.

Science.gov (United States)

2010-04-01

... Serious or Life-Threatening Illnesses § 314.530 Withdrawal procedures. (a) For new drugs approved under... benefit; (2) The applicant fails to perform the required postmarketing study with due diligence; (3) Use...

Small Optics Laser Damage Test Procedure

Energy Technology Data Exchange (ETDEWEB)

Wolfe, Justin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-10-19

This specification defines the requirements and procedure for laser damage testing of coatings and bare surfaces designated for small optics in the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL).

38 CFR 39.10 - Application requirements.

Science.gov (United States)

2010-07-01

...-10) Grant Requirements and Procedures § 39.10 Application requirements. (a) For a project to be..., etc., (10) Economic activities, (11) Cultural resources, (12) Aesthetics, (13) Residential population...

7 CFR 1735.94 - Final approval and closing procedure.

Science.gov (United States)

2010-01-01

..., DEPARTMENT OF AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Requirements for All Acquisitions and Mergers § 1735.94 Final approval and closing procedure. (a) Legal documents relating to the acquisition or merger, including copies of required franchises, commission orders...

Safety analysis procedures for PHWR

International Nuclear Information System (INIS)

Min, Byung Joo; Kim, Hyoung Tae; Yoo, Kun Joong

2004-03-01

The methodology of safety analyses for CANDU reactors in Canada, a vendor country, uses a combination of best-estimate physical models and conservative input parameters so as to minimize the uncertainty of the plant behavior predictions. As using the conservative input parameters, the results of the safety analyses are assured the regulatory requirements such as the public dose, the integrity of fuel and fuel channel, the integrity of containment and reactor structures, etc. However, there is not the comprehensive and systematic procedures for safety analyses for CANDU reactors in Korea. In this regard, the development of the safety analyses procedures for CANDU reactors is being conducted not only to establish the safety analyses system, but also to enhance the quality assurance of the safety assessment. In the first phase of this study, the general procedures of the deterministic safety analyses are developed. The general safety procedures are covered the specification of the initial event, selection of the methodology and accident sequences, computer codes, safety analysis procedures, verification of errors and uncertainties, etc. Finally, These general procedures of the safety analyses are applied to the Large Break Loss Of Coolant Accident (LBLOCA) in Final Safety Analysis Report (FSAR) for Wolsong units 2, 3, 4

48 CFR 432.006-4 - Procedures.

Science.gov (United States)

2010-10-01

... REQUIREMENTS CONTRACT FINANCING 432.006-4 Procedures. (a) Immediately upon submittal of the referral described... decision making process. (c) The OIG will determine the need for and the extent of an investigation. (d...

23 CFR 630.1008 - State-level processes and procedures.

Science.gov (United States)

2010-04-01

..., data and information resources, training, and periodic evaluation enable a systematic approach for... management procedures. States should develop and implement systematic procedures to assess work zone impacts... resources that are necessary to support these activities. (d) Training. States shall require that personnel...

Safety and application of procedures or: how do ''they'' have to use operating procedures in nuclear power plants

International Nuclear Information System (INIS)

Dien, Y.

1993-03-01

Emergency procedures are inescapable aspects of safety. They can be seen as the laws to be respected in an accident situation. But as for all laws, there remains the problem of their application: should strict adherence to the procedure be imposed under all circumstances. Is this possible. Are there any potential risks with such a requirement. Or, on the contrary, should application be more ''open'', more flexible, allowing for adaptation to the actual situation. But what are the potential risks involved in this approach. Are these two approaches to the application of procedures mutually exclusive, or are they complementary. This paper analyzes the nature of the problem of application of procedures and proposes orientations for further thought on the matter. (author). 11 refs

7 CFR 1753.8 - Contract construction procedures.

Science.gov (United States)

2010-01-01

... of all bids including “Buy American” evaluations, if any, and all other evaluations required by law... Contract construction procedures. (a) Sealed, competitive bidding—(1) Bid opening date. The borrower is responsible for scheduling the bid opening date. If RUS review of P&S is required by § 1753.7, the borrower...

Pre-procedural antibiotics for endoscopic urological procedures: Initial experience in individuals with spinal cord injury and asymptomatic bacteriuria.

Science.gov (United States)

Chong, Julio T; Klausner, Adam P; Petrossian, Albert; Byrne, Michael D; Moore, Jewel R; Goetz, Lance L; Gater, David R; Grob, B Mayer

2015-03-01

The objective of this study was to compare the safety, efficacy, quality-of-life impact, and costs of a single dose or a longer course of pre-procedural antibiotics prior to elective endoscopic urological procedures in individuals with spinal cord injury and disorders (SCI/D) and asymptomatic bacteriuria. A prospective observational study. Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA. Sixty persons with SCI/D and asymptomatic bacteriuria scheduled to undergo elective endoscopic urological procedures. A single pre-procedural dose of antibiotics vs. a 3-5-day course of pre-procedural antibiotics. Objective and subjective measures of health, costs, and quality of life. There were no significant differences in vital signs, leukocytosis, adverse events, and overall satisfaction in individuals who received short-course vs. long-course antibiotics. There was a significant decrease in antibiotic cost (33.1 ± 47.6 vs. 3.6 ± 6.1 US$, P = 0.01) for individuals in the short-course group. In addition, there was greater pre-procedural anxiety (18 vs. 0%, P antibiotics. SCI/D individuals with asymptomatic bacteriuria may be able to safely undergo most endoscopic urological procedures with a single dose of pre-procedural antibiotics. However, further research is required and even appropriate pre-procedural antibiotics may not prevent severe infections.

Modification of the Nuss Procedure: The Single-incision Technique

Directory of Open Access Journals (Sweden)

Tetsushi Aizawa, MD

2014-11-01

Full Text Available Summary: The Nuss procedure is a prevalent minimally invasive surgery for pectus excavatum. Although the Nuss procedure has the advantage of leaving less obtrusive scars, the standard technique requires at least 3 skin incisions to insert several instruments. We experienced 7 cases of the modified Nuss procedure using a single incision during a 7-year period. To facilitate passing of the bar, a traction guide was created according to our unique method. There was no need for a bar stabilizer, and no severe intraoperative complications occurred. All patients exhibited satisfactory short-term results; however, 1 patient suffered from bar rotation and required repeat surgery for fixation. Two patients underwent bar removal via the same single incision without any difficulties.

49 CFR 383.111 - Required knowledge.

Science.gov (United States)

2010-10-01

... importance of proper visual search, and proper visual search methods. (6) Communication. The principles and procedures for proper communications and the hazards of failure to signal properly. (7) Speed management. The... STANDARDS; REQUIREMENTS AND PENALTIES Required Knowledge and Skills § 383.111 Required knowledge. All...

EMP protection procedure for electrical/electronic systems

International Nuclear Information System (INIS)

Latorre, V.R.

1976-01-01

This paper presents a procedure for the protection engineer to follow in assessing a system with respect to its susceptibility to an electromagnetic pulse (EMP), and in determining whether the system requires protection. If the system is determined to be vulnerable to EMP, the procedure also indicates how to decide upon the most suitable protection scheme. The discussion centers on two flow charts, which illustrate the step-by-step procedure which utilizes the necessary ingredients of EMP protection engineering discussed in a previous paper. The description of the protection procedure is divided into two parts: the first dealing with issues on the macroscopic or large-scale system level, while the second is concerned with operations on the subsystem level or lower

Licensing procedures for Low-Level Waste disposal facilities

Energy Technology Data Exchange (ETDEWEB)

Roop, R.D.; Van Dyke, J.W.

1985-09-01

This report describes the procedures applicable to siting and licensing of disposal facilities for low-level radioactive wastes. Primary emphasis is placed on those procedures which are required by regulations, but to the extent possible, non-mandatory activities which will facilitate siting and licensing are also considered. The report provides an overview of how the procedural and technical requirements for a low-level waste (LLW) disposal facility (as defined by the Nuclear Regulatory Commission's Rules 10 CFR Parts 2, 51, and 61) may be integrated with activities to reduce and resolve conflict generated by the proposed siting of a facility. General procedures are described for site screening and selection, site characterization, site evaluation, and preparation of the license application; specific procedures for several individual states are discussed. The report also examines the steps involved in the formal licensing process, including docketing and initial processing, preparation of an environmental impact statement, technical review, hearings, and decisions. It is concluded that development of effective communication between parties in conflict and the utilization of techniques to manage and resolve conflicts represent perhaps the most significant challenge for the people involved in LLW disposal in the next decade. 18 refs., 6 figs.

47 CFR 80.319 - Radiotelegraph distress call and message transmission procedure.

Science.gov (United States)

2010-10-01

...) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Distress, Alarm, Urgency and Safety Procedures § 80.319 Radiotelegraph distress call and message...

48 CFR 17.403 - Procedures.

Science.gov (United States)

2010-10-01

... CONTRACT TYPES SPECIAL CONTRACTING METHODS Leader Company Contracting 17.403 Procedures. (a) The contracting officer may award a prime contract to a— (1) Leader company, obligating it to subcontract a designated portion of the required end items to a specified follower company and to assist it to produce the...

Pharmacology of biosimilar candidate drugs in rheumatology: a literature review.

Science.gov (United States)

Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E

2014-01-01

To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.

Chromatographic monitoring procedures in laboratory practice

Energy Technology Data Exchange (ETDEWEB)

Kaplina, E G; Belova, O I; Lasunina, N A

1976-01-01

The Moscow Coke and Chemical Works consist of three plants in combination, viz., the coking plant, the synthetic ammonia plant using coke-oven-gas hydrogen and the oxygen plant. The plant requirements include daily analyses not only of the coke-oven gas but also of a rich gas and an ethylene fraction. The analyses are carried out in VTI-2 apparatus. The analytical data are used to calculate the calorific values and densities of the gases. The time requirements are very considerable and the laboratory has long been engaged in developing and introducing chromatographic procedures for the major constituents of coke-oven gas, rich gas and ethylene fraction. The procedure developed for the coke-oven and rich gases uses two parallel columns, one packed with molecular sieves and the other with grade KSM silica gel. Hydrogen was determined with argon as the carrier gas, and all other constituents with helium. The procedure was time-consuming and complicated. An attempt was made to separate the gases in an LKhM-7a chromatograph with a programme-controlled 50 to 250/sup 0/C heating cycle, but the procedure still had a number of serious defects and could not be recommended for regular quality control. The final variant involved two parallel columns and a procedure based on that in GOST 14920 (''Dry gas. Proximate analysis''). The chromatograph was a type KhL-69 with a 6-way cock in the gas line so that each of the columns could be brought on stream in succession. The analytical column packings were zeolite (in a 2 m column) and diatomaceous brick with 25% n-hexadecane (in a 6 m column).

PENILE ENHANCEMENT PROCEDURES: UROLOGICAL AND ETHICOLEGAL ISSUES

OpenAIRE

Marco Vella

2012-01-01

Phalloplasty procedures for most men requiring penile augmentation surgery are cosmetic procedures; generally the patients have a normal-sized and fully functional penis but they think that their penis is too small. There are not well defined indications for penile enhancement surgery and, except for the treatment of “micropenis”, there are not established guidelines and the outcome measures for success are still unclear. All penile enhancement techniques often do not reach the...

Robot-assisted procedures in pediatric neurosurgery.

Science.gov (United States)

De Benedictis, Alessandro; Trezza, Andrea; Carai, Andrea; Genovese, Elisabetta; Procaccini, Emidio; Messina, Raffaella; Randi, Franco; Cossu, Silvia; Esposito, Giacomo; Palma, Paolo; Amante, Paolina; Rizzi, Michele; Marras, Carlo Efisio

2017-05-01

OBJECTIVE During the last 3 decades, robotic technology has rapidly spread across several surgical fields due to the continuous evolution of its versatility, stability, dexterity, and haptic properties. Neurosurgery pioneered the development of robotics, with the aim of improving the quality of several procedures requiring a high degree of accuracy and safety. Moreover, robot-guided approaches are of special interest in pediatric patients, who often have altered anatomy and challenging relationships between the diseased and eloquent structures. Nevertheless, the use of robots has been rarely reported in children. In this work, the authors describe their experience using the ROSA device (Robotized Stereotactic Assistant) in the neurosurgical management of a pediatric population. METHODS Between 2011 and 2016, 116 children underwent ROSA-assisted procedures for a variety of diseases (epilepsy, brain tumors, intra- or extraventricular and tumor cysts, obstructive hydrocephalus, and movement and behavioral disorders). Each patient received accurate preoperative planning of optimal trajectories, intraoperative frameless registration, surgical treatment using specific instruments held by the robotic arm, and postoperative CT or MR imaging. RESULTS The authors performed 128 consecutive surgeries, including implantation of 386 electrodes for stereo-electroencephalography (36 procedures), neuroendoscopy (42 procedures), stereotactic biopsy (26 procedures), pallidotomy (12 procedures), shunt placement (6 procedures), deep brain stimulation procedures (3 procedures), and stereotactic cyst aspiration (3 procedures). For each procedure, the authors analyzed and discussed accuracy, timing, and complications. CONCLUSIONS To the best their knowledge, the authors present the largest reported series of pediatric neurosurgical cases assisted by robotic support. The ROSA system provided improved safety and feasibility of minimally invasive approaches, thus optimizing the surgical

FREY’S PROCEDURE- TO ANALYSE THE OUTCOME OF THIS PROCEDURE IN CHRONIC PANCREATITIS

Directory of Open Access Journals (Sweden)

Shilpa Mariappa Casaba

2017-04-01

Full Text Available BACKGROUND Chronic Pancreatitis (CP is a progressive inflammatory disease characterised by debilitating pain and pancreatic insufficiency. There is enormous personal and socio-economic impact on impairment of quality of life, inability to work and even shortening of life expectancy. Although, pancreaticoduodenectomy had been considered the standard surgical procedure for patients with CP because of its high post-op complications with exocrine and endocrine insufficiency, it is not preferred. This has led to a hybrid procedure described by Frey’s, which is used in our study for CP. We aim to analyse the short-term and long-term outcomes of Frey’s procedure at a tertiary care center in patients with chronic pancreatitis. MATERIALS AND METHODS A retrospective review of all CP patients who underwent Frey procedure were reviewed from January 2007-January 2016. Perioperative variables, short-term (30 days and long-term (3 years outcomes were reviewed. Data are frequency (% or mean. RESULTS A total of 97 patients underwent Frey’s procedure. A total of 72 (70.7% were men and 25 (29.3% were women. Mean age was 38 years (range 14-66 years. Indications for surgery included intractable pain (n=97, 100% and obstructive jaundice (n=4, 4.3%. 9 patients (32.6% were diabetic preoperatively. Concomitant procedures include biliary drainage procedure was done for 4 patients (4.3%, i.e. choledochojejunostomy and splenectomy for 2 patients (2.1%, cholecystectomy (n=6, 6%. Short-term outcomes include surgical site infection (n=10, 10%, pancreatic leak (n=6, 5.82% and 2 patients required reoperation for bleeding and no mortality (30 days, diabetic ketoacidosis (n=2, 2%. Pancreatic carcinoma was detected in 3 (2.1% patients. Long-term outcomes include pain free status (n=80, 86.9%, median follow-up of 3 years. Redo pancreatic procedure was performed in 1 (4.3% for anastomotic leak. CONCLUSION Frey’s procedure is a safe and effective pain palliative option for CP

Knowledge of Legally Sanctioned Discipline Procedures by School Personnel.

Science.gov (United States)

Hillman, Susan J.

Principals, teachers, and counselors in 15 Indiana high schools were interviewed to determine what procedures they believed were required in various disciplinary actions, and what authority they believed had sanctioned these procedures. The interviewees came from small, medium, and large schools in rural and urban settings. Nearly 71 percent of…

22 CFR 226.44 - Procurement procedures.

Science.gov (United States)

2010-04-01

... Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.44 Procurement procedures. (a... and assistance, as appropriate, of such organizations as the Small Business Administration and the...

Application of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of bumetanide in human plasma for a bioequivalence study.

Science.gov (United States)

Patel, Dinesh S; Sharma, Naveen; Patel, Mukesh C; Patel, Bhavin N; Shrivastav, Pranav S; Sanyal, Mallika

2012-07-01

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of bumetanide in human plasma using tamsulosin as internal standard (IS). The analyte and IS were extracted from 200 μL of human plasma via solid phase extraction and the chromatographic separation was achieved on Peerless Basic C18 (100 mm × 4.6 mm, 3 μm) column under isocratic conditions. Detection of bumetanide and IS was done by tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for bumetanide and IS were m/z 365.2→240.2 and 409.2→228.2 respectively. The method was fully validated as per the US FDA guidelines. The limit of detection and lower limit of quantitation of the method were 0.03 and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for bumetanide. The intra-batch and inter-batch precision (% CV) was ≤6.9% while the mean extraction recovery was >90% across quality control levels. The method is selective in presence of four diuretic drugs and some commonly used medications by healthy volunteers. It was successfully applied to a bioequivalence study of 2mg bumetanide tablet formulation in 10 healthy Indian male subjects under fasting condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 42 incurred samples. Copyright © 2012 Elsevier B.V. All rights reserved.

28 CFR 80.12 - Accounting requirements.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Accounting requirements. 80.12 Section 80... PROCEDURE § 80.12 Accounting requirements. Neither the submission of a request for an FCPA Opinion, its... comply with the accounting requirements of 15 U.S.C. 78m(b)(2) and (3). ...

TMACS test procedure TP001: Alarm management. Revision 6

International Nuclear Information System (INIS)

Scanlan, P.K.

1994-01-01

The TMACS Software Project Test Procedures translate the project's acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure addresses the Alarm Management requirements of the TMACS. The features to be tested are: real-time alarming on high and low level and discrete alarms, equipment alarms, dead-band filtering, alarm display color coding, alarm acknowledgement, and alarm logging

Surface Environmental Surveillance Procedures Manual

International Nuclear Information System (INIS)

Hanf, Robert W.; Poston, Ted M.

2000-01-01

Shows and explains certain procedures needed for surface environmental surveillance. Hanford Site environmental surveillance is conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE) under the Surface Environmental Surveillance Project (SESP). The basic requirements for site surveillance are set fourth in DOE Order 5400.1, General Environmental Protection Program Requirements. Guidance for the SESP is provided in DOE Order 5484.1, Environmental Protection, Safety, and Health Protection Information Reporting Requirements and DOE Order 5400.5, Radiation Protection of the Public and Environment. Guidelines for environmental surveillance activities are provided in DOE/EH-0173T, Environmental Regulatory Guide for Radiological Effluent Monitoring and Environmental Surveillance. An environmental monitoring plan for the Hanford Site is outlined in DOE/RL 91-50 Rev. 2, Environmental Monitoring Plan, United States Department of Energy, Richland Operations Office. Environmental surveillance data are used in assessing the impact of current and past site operations on human health and the environment, demonstrating compliance with applicable local, state, and federal environmental regulations, and verifying the adequacy of containment and effluent controls. SESP sampling schedules are reviewed, revised, and published each calendar year in the Hanford Site Environmental Surveillance Master Sampling Schedule. Environmental samples are collected by SESP staff in accordance with the approved sample collection procedures documented in this manual. Personnel training requirements are documented in SESP-TP-01 Rev.2, Surface Environmental Surveillance Project Training Program.

Inspection procedure and essential parameters in NDT qualification

International Nuclear Information System (INIS)

Sarkimo, M.

2000-06-01

The objective of the inspection qualification is to ensure that applied non-destructive methods (NDT) have the required performance. The approach of the qualification process is systematic and carefully documented and therefore some new requirements can be seen concerning the composition of the documentation. There are also new document types, that only application of the inspection qualification requires. The most important of these is the technical justification, that includes the documented evidences concerning the performance of the inspection system. This publication includes two reports: 'Compilation of the inspection procedure' and 'Essential/influential parameters in NDT qualification'. The former of these discusses the issues to be considered in an inspection procedure especially from the point of view of the mechanised ultrasonic testing. The later report explains the parameters formulated to analyse in the technical justification all aspects of the inspection application. (orig.)

Environmental impact statement requirements for CNEA

International Nuclear Information System (INIS)

Ciurciolo, Melisa N.; Mender, J. A.

2009-01-01

The purpose of this paper is to describe the legal framework on Environmental Impact Assessment (EIA) regarding the activities of the National Atomic Energy Commission (Comision Nacional de Energia Atomica, CNEA), and particularly, the Procedure for Internal Management of Environmental Impact Statements of CNEA (PN-PR-027). According to the distribution of powers stated in article 41 of the National Constitution, the environmental legal framework is constituted by National minimum standards for environmental protection and complementary provincial and municipal regulations. As a result, the EIA legal framework is not uniform across the Nation, and therefore, it differs according to the jurisdiction in which the activity subject to EIA is developed. Notwithstanding, the General Statute of the Environment (25.675) requires EIA for any project or activity developed in the National territory, which may cause a significant degradation to the environment, any of its components, or affect the populations' quality of life in a significant way. Since CNEA develops activities along the National territory, it is not possible to determine a uniform legal EIA framework for the entire Institution. Consequently, the binding requirements for Environmental Impact Statements (EISs) of CNEA activities differ among the activities developed in the different locations and atomic centers. In order to achieve a uniform environmental performance in CNEA, it has been considered necessary to uniform, in the internal sphere, the binding requirements for EIS, by means of a procedure written within the framework of the Environmental Management System of the Institution. The purpose of the Procedure for Internal Management of Environmental Impact Statements is to determine the requirements to be complied by the atomic centers, locations and enterprises associated with CNEA, regarding EIS Management. This Procedure shall apply to those projects and activities subjected to EIA, according to a

40 CFR 745.326 - Renovation: State and Tribal program requirements.

Science.gov (United States)

2010-07-01

... sampling technician training programs. (ii) Procedures and requirements for the certification of renovators and dust sampling technicians. (iii) Procedures and requirements for the certification of individuals..., 2010. For the convenience of the user, the added text is set forth as follows: § 745.326 Renovation...

12 CFR 219.6 - Payment procedures.

Science.gov (United States)

2010-01-01

... obtain payment of costs incurred prior to the time the financial institution receives this notice. [Reg... PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S) Reimbursement to Financial Institutions for Providing Financial Records § 219.6 Payment procedures. (a) Notice...

PENILE ENHANCEMENT PROCEDURES: UROLOGICAL AND ETHICOLEGAL ISSUES

Directory of Open Access Journals (Sweden)

Marco Vella

2012-04-01

Full Text Available Phalloplasty procedures for most men requiring penile augmentation surgery are cosmetic procedures; generally the patients have a normal-sized and fully functional penis but they think that their penis is too small. There are not well defined indications for penile enhancement surgery and, except for the treatment of “micropenis”, there are not established guidelines and the outcome measures for success are still unclear. All penile enhancement techniques often do not reach the expected result and the grade of patient’s satisfaction is frequently poor. Phalloplasty procedures for psychological dysmorfism are not approved by any scientific society and the majority of these procedures are performed in private settings. The ethical and medicolegal problems resulting from a penis enhancement can be various and numerous, but few of them are reported in literature. After phalloplasty an attribution of professional responsibility and request of reimbursement is not rare. In this contribution the authors summarize a panorama of several urological and medico-legal aspects related to phalloplasty procedures.

Sup(99m)Tc(Sn)-sucralfate; development of an instant labelling kit

International Nuclear Information System (INIS)

Grouls, R.J.E.; Ackerman, E.W.; Weegh, G. op de

1988-01-01

An instant labelling kit for the preparation of 99m Tc(Sn)-sucralfate has been developed containing 500 mg sucralfate and 1 mg SnCl 2 · 2 H 2 O. The labelling yield, in vitro stability and biodistribution indicate (bio)equivalence of 99m Tc(Sn)-sucralfate and 99m Tc(HSA)-sucralfate. The percentages of labelling obtained with the kit during a period of 8 months always exceeded 95%. The preparation kit is inexpensive and the labelling procedure fast and easy. (author)

Waste segregation procedures and benefits

International Nuclear Information System (INIS)

Fish, J.D.; Massey, C.D.; Ward, S.J.

1990-01-01

Segregation is a critical first step in handling hazardous and radioactive materials to minimize the generation of regulated wastes. In addition, segregation can significantly reduce the complexity and the total cost of managing waste. Procedures at Sandia National Laboratories, Albuquerque require that wastes be segregated, first, by waste type (acids, solvents, low level radioactive, mixed, classified, etc.). Higher level segregation requirements, currently under development, are aimed at enhancing the possibilities for recovery, recycle and reapplication; reducing waste volumes; reducing waste disposal costs, and facilitating packaging storage, shipping and disposal. 2 tabs

Procedures Manual: A Guide to Uniform Grant and Contract Management Standards and The Common Rule for Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments.

Science.gov (United States)

Conable, Sharon R.

This manual has been compiled to provide consistent grant application and administrative procedures for state agencies which award grants or contracts to local governments. It provides a conceptual framework of information concerning the reporting, financial, contractual, and auditing requirements for recipients of Texas State Library grants…

Application of an LC–MS/MS method for the analysis of amlodipine, valsartan and hydrochlorothiazide in polypill for a bioequivalence study

Directory of Open Access Journals (Sweden)

Jaivik V. Shah

2017-10-01

Full Text Available A sensitive and selective method has been proposed for the simultaneous determination of amlodipine (AML, valsartan (VAL and hydrochlorothiazide (HCTZ in human plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analytes and their deuterated analogs were quantitatively extracted from 100 µL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18e (100 mm × 4.6 mm analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively, under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/mL for AML, 5.00–10,000 ng/mL for VAL and 0.20–200 ng/mL for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision (% CV across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation (test and reference in 18 healthy Indian males under fasting. The mean log-transformed ratios of Cmax, AUC0–120h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

A manual of nuclear medicine procedures

International Nuclear Information System (INIS)

Das, B.K.; Noreen Norfaraheen Lee Abdullah

2012-01-01

Nuclear medicine is a fast growing specialty. The procedures provide quantitative parameters of organ functions required for modern practice of medicine. With the development of new machines and increased application of computer software, the procedures are under continuous change. Some procedures have become outdated or redundant while new methods have been introduced to enhance the quality of information obtained from a particular application. Although there are a few books published abroad to inform doctors and technical staff about the procedures, a comprehensive source to give quick information about how different test are performed, particularly the new developments and the expected outcome both in normal and abnormal cases has been a long felt need. The physician ordering a Nuclear Medicine test also needs to know what patient preparations are required for optimal results, how to satisfy the queries of the patient particularly in respect of radiation exposure which sometimes can be a major concern of the patient. This manual has been prepared not only to describe technical details of various procedures that are currently practiced in Nuclear Medicine, but also to provide quick information for the doctors and health care personnel on how to inform the patients about the investigation for which they are being referred and how to interpret the results. Since there is no such comprehensive book published yet in Asia including South-East Asia, it is likely to be in great demand in the region. All students of Master Degree, M.D., DRM, DMRIT, M.Sc. (Nuclear Medicine) and technologists already working in various diagnostic centers will likely buy this book. General practitioners and specialists who refer patients for different radioisotope investigations may find this book useful for quick reference. (author)

MITS Data Acquisition Subsystem Acceptance Test procedure

International Nuclear Information System (INIS)

Allison, R.

1980-01-01

This is an acceptance procedure for the Data Acquisition Subsystem of the Machine Interface Test System (MITS). Prerequisites, requirements, and detailed step-by-step instruction are presented for inspecting and performance testing the subsystem

Radiological Work Planning and Procedures

CERN Document Server

Kurtz, J E

2000-01-01

Each facility is tasked with maintaining personnel radiation exposure as low as reasonably achievable (ALARA). A continued effort is required to meet this goal by developing and implementing improvements to technical work documents (TWDs) and work performance. A review of selected TWDs from most facilities shows there is a need to incorporate more radiological control requirements into the TWD. The Radioactive Work Permit (RWP) provides a mechanism to place some of the requirements but does not provide all the information needed by the worker as he/she is accomplishing the steps of the TWD. Requiring the engineers, planners and procedure writers to put the radiological control requirements in the work steps would be very easy if all personnel had a strong background in radiological work planning and radiological controls. Unfortunately, many of these personnel do not have the background necessary to include these requirements without assistance by the Radiological Control organization at each facility. In add...

Δt tuneup procedure for the LAMPF 805-MHz linac

International Nuclear Information System (INIS)

Crandall, K.R.

1976-05-01

An important part of tuning the LAMPF accelerator is the adjustment of the phases and amplitudes in the 805-MHz linac. The technique used is called the Δt procedure because of the time-of-flight measurements that are required. The theory behind the Δt procedure, a brief description of the hardware, and a description of the many computer programs that have been written to implement the procedure are presented

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

Science.gov (United States)

Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

2018-01-01

A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

RTOD-photo operations and procedures manual

Energy Technology Data Exchange (ETDEWEB)

1966-03-15

This document presents a survey of the EG&G NRDS photographic operation in four major sections and includes the work scope, procedures, some technical backgrounding and operational information. Two sections, Instrumentation and Photo Systems, include the areas of direct responsibilities while a section on Film Handling and Coordination and a section covering special information, pertinent to the project, are included to adequately complete this survey. The photographic group is housed in two trailers within the control point area at NRDS and from these trailers provides photographic support at a number of locations. Four camera bunkers, three camera towers, a kinescope system, a microfilm system and remote camera controls comprise the facilities that the group maintains and operates outside these trailers. The work load includes major items such as: motion picture coverage of the nuclear rocket engine tests, data record microfilming, kinescope recording, and documentary coverage of the company related operational responsibilities. In addition, a number of minor photographic services are extended, when required. The nature of the work, because of its importance within the research and development efforts at NRDS, requires optimum quality and efficiency throughout. The many procedures outlined here have been designed to satisfy these requirements.

46 CFR 2.75-70 - Welding procedure and performance qualifications.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Welding procedure and performance qualifications. 2.75... for Construction Personnel § 2.75-70 Welding procedure and performance qualifications. (a) Welding... requirements for the welding of pressure piping, boilers, pressure vessels, and nonpressure vessel type tanks...

42 CFR 433.320 - Procedures for refunds to CMS.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for refunds to CMS. 433.320 Section 433... Overpayments to Providers § 433.320 Procedures for refunds to CMS. (a) Basic requirements. (1) The agency must refund the Federal share of overpayments that are subject to recovery to CMS through a credit on its...

17 CFR 270.30a-3 - Controls and procedures.

Science.gov (United States)

2010-04-01

... and procedures, within the 90-day period prior to the filing date of each report on Form N-CSR (§§ 249... to be disclosed by the investment company on Form N-CSR (§§ 249.331 and 274.128 of this chapter) and... include, without limitation, controls and procedures designed to ensure that information required to be...

Efficient Reanalysis Procedures in Structural Topology Optimization

DEFF Research Database (Denmark)

Amir, Oded

This thesis examines efficient solution procedures for the structural analysis problem within topology optimization. The research is motivated by the observation that when the nested approach to structural optimization is applied, most of the computational effort is invested in repeated solutions...... on approximate reanalysis. For cases where memory limitations require the utilization of iterative equation solvers, we suggest efficient procedures based on alternative termination criteria for such solvers. These approaches are tested on two- and three-dimensional topology optimization problems including...

Procedure for reducing hydrogen ion concentration in acidic anion eluate

International Nuclear Information System (INIS)

Parobek, P.; Baloun, S.; Plevac, S.

1992-01-01

A procedure is suggested for reducing the concentration of hydrogen ions in the acidic anionic eluate formed during the separation of uranium. The procedure involves anex elution, precipitation, filtration, precipitate rinsing, and anex rinsing. The procedure is included in the uranium elution process and requires at least one ion exchanger column and at least one tank in the continuous or discontinuous mode. Sparing the neutralizing agent by reducing the hydrogen ion concentration in the acidic anionic eluate is a major asset of this procedure. (Z.S.). 1 fig

Establishment of in vitro-in vivo equivalence of highly variable drugs - a generic product development perspective.

Science.gov (United States)

Pathak, Shriram M; Aggarwal, Deepika; Venkateswarlu, V

2014-06-01

In vivo equivalence of highly variable drugs (HVD) has always been a subject of great concern, in terms of both safety and efficacy, for regulatory agencies. Successful demonstration of their bioequivalence thus presents the most crucial component of a generic application, significantly contributing toward the cost and time of development. For poorly soluble drugs, such as telmisartan, dissolution represents the rate-limiting step in the gastric region and in many cases may not be complete, thereby contributing to low and highly variable bioavailability. Consequently, simulation of gastrointestinal conditions is essential to adequately predict the in vivo behavior of drug formulations. In this study, we evaluated usefulness of physiologically relevant dissolution method over commonly used acidic media to forecast comparable in vivo performance of telmisartan formulation to that of reference samples. In the present study, telmisartan was classified as a HVD and a partial replicate design with repeating the reference product and scaling the bioequivalence for the reference variability has been presented. The design has effectively decreased sample size, without increasing patient risk. Results from this project suggest that scaled average bioequivalence (SABE) provides a good approach for evaluating the bioequivalence of HVD, meeting the need for international guidelines for bioequivalence.

4D Dynamic Required Navigation Performance Final Report

Science.gov (United States)

Finkelsztein, Daniel M.; Sturdy, James L.; Alaverdi, Omeed; Hochwarth, Joachim K.

2011-01-01

New advanced four dimensional trajectory (4DT) procedures under consideration for the Next Generation Air Transportation System (NextGen) require an aircraft to precisely navigate relative to a moving reference such as another aircraft. Examples are Self-Separation for enroute operations and Interval Management for in-trail and merging operations. The current construct of Required Navigation Performance (RNP), defined for fixed-reference-frame navigation, is not sufficiently specified to be applicable to defining performance levels of such air-to-air procedures. An extension of RNP to air-to-air navigation would enable these advanced procedures to be implemented with a specified level of performance. The objective of this research effort was to propose new 4D Dynamic RNP constructs that account for the dynamic spatial and temporal nature of Interval Management and Self-Separation, develop mathematical models of the Dynamic RNP constructs, "Required Self-Separation Performance" and "Required Interval Management Performance," and to analyze the performance characteristics of these air-to-air procedures using the newly developed models. This final report summarizes the activities led by Raytheon, in collaboration with GE Aviation and SAIC, and presents the results from this research effort to expand the RNP concept to a dynamic 4D frame of reference.

5 CFR 5502.105 - Agency procedures.

Science.gov (United States)

2010-01-01

....105 Administrative Personnel DEPARTMENT OF HEALTH AND HUMAN SERVICES SUPPLEMENTAL FINANCIAL DISCLOSURE REQUIREMENTS FOR EMPLOYEES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES § 5502.105 Agency procedures. (a) The designated agency ethics official or, with the concurrence of the designated agency ethics official, each of...

78 FR 21517 - Practices and Procedures

Science.gov (United States)

2013-04-11

... electronic format, including word processing applications, HTML or PDF. Commenters are asked to use a text format and not an image format for attachments. The email should contain a subject line indicating that... Administrative Procedure Act (APA). However, an exemption from notice and comment rulemaking requirements exists...

48 CFR 849.111-70 - Required review.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Required review. 849.111... MANAGEMENT TERMINATION OF CONTRACTS General Principles 849.111-70 Required review. (a) FAR 49.111 requires each agency to establish procedures, when necessary, for the administrative review of proposed...

Evaluation of Revised Computer-Based Procedure System Prototype

Energy Technology Data Exchange (ETDEWEB)

Katya Le Blanc; Johanna Oxstrand; Cheradan Fikstad

2013-01-01

The nuclear power industry is very procedure driven, i.e. almost all activities that take place at a nuclear power plant are conducted by following procedures. The paper-based procedures (PBPs) currently used by the industry do a good job at keeping the industry safe. However, these procedures are most often paired with methods and tools put in place to anticipate, prevent, and catch errors related to hands-on work. These tools are commonly called human performance tools. The drawback with the current implementation of these tools is that the task of performing one procedure becomes time and labor intensive. For example, concurrent and independent verification of procedure steps are required at times, which essentially means that at least two people have to be actively involved in the task. Even though the current use of PBPs and human performance tools are keeping the industry safe, there is room for improvement. The industry could potentially increase their efficiency and safety by replacing their existing PBPs with CBPs. If implemented correctly, the CBP system could reduce the time and focus spent on using the human performance tools. Some of the tools can be completely incorporated in the CBP system in a manner that the performer does not think about the fact that these tools are being used. Examples of these tools are procedure use and adherence, placekeeping, and peer checks. Other tools can be partly integrated in a fashion that reduce the time and labor they require, such as concurrent and independent verification. The incorporation of advanced technology, such as CBP systems, may help to manage the effects of aging systems, structures, and components. The introduction of advanced technology may also make the existing LWR fleet more attractive to the future workforce, which will be of importance when the future workforce will chose between existing fleet and the newly built nuclear power plants.

9 CFR 442.2 - Definitions and procedures for determining net weight compliance.

Science.gov (United States)

2010-01-01

... POULTRY PRODUCTS INSPECTION ACT QUANTITY OF CONTENTS LABELING AND PROCEDURES AND REQUIREMENTS FOR ACCURATE... Dressing 3.7Pressed and Blown Glass Tumblers and Stemware 3.8Volumetric Test Procedures for Paint, Varnish...

Outcomes of Reintervention on the Autograft After Ross Procedure.

Science.gov (United States)

Kumar, S Ram; Bansal, Neeraj; Wells, Winfield J; Starnes, Vaughn A

2016-11-01

After a Ross procedure, a small subset of patients requires reintervention for autograft dilatation or valve insufficiency. We sought to determine the indications, nature, and outcomes of autograft reinterventions in the left ventricular outflow tract after a Ross procedure. We retrospectively reviewed the charts of 316 consecutive patients, age 4 days to 70 years, who underwent a Ross procedure at our institution. Of these, 47 patients (15%) required autograft reintervention during a median follow-up of 8.2 years. Forty-seven patients, median age 26 years (interquartile range [IQR], 14.4 to 44.8 years), 32 (68%) men, required autograft reintervention a median 5.5 years (IQR, 1.8 to 9.4 years) after a Ross procedure. In 47% (22 of 47 patients), the autograft valve could be salvaged (15 valve-sparing aortic replacements, 7 valve repairs). The remaining 53% underwent replacement of the root (10 mechanical, 5 homograft) or valve alone (7 mechanical, 3 bioprosthetic). Twenty patients presented without autograft root dilatation 1 year (IQR, 0.5 to 2.9 years) after Ross. Fifteen of them (75%) required valve replacement. The 27 patients who demonstrated root dilatation presented 6.9 years (IQR, 4.5 to 9.7 years; p Ross, and 17 (63%) of these valves could be spared (p = 0.01). There was no surgical mortality and 5 (11%) major morbidity events. Patients were followed up for 4.9 years (IQR, 2.1 to 7 years) after left ventricular outflow tract reintervention. For patients whose autograft valve could be spared, 3-, 5-, and 8-year freedom from valve replacement was 92%, 86%, and 86%, respectively. At last follow-up, only 1 patient had greater than mild aortic insufficiency, and all but 1 had normal ejection fraction. Autograft reintervention after a Ross appears to follow a bimodal distribution. Patients with primary autograft leaflet problems tend to present early without root dilatation and frequently require valve replacement. The autograft valve can be salvaged in the

36 CFR 251.54 - Proposal and application requirements and procedures.

Science.gov (United States)

2010-07-01

..., DEPARTMENT OF AGRICULTURE LAND USES Special Uses § 251.54 Proposal and application requirements and... activity does not materially impact the characteristics or functions of the environmentally sensitive...-disposal facilities; (3) The availability of sufficient potable drinking water; (4) The risk of disease...

A simple and sensitive HPLC method for analysis of imipramine in human plasma with UV detection and liquid-liquid extraction: Application in bioequivalence studies.

Science.gov (United States)

Rezazadeh, Mahboubeh; Emami, Jaber

2016-01-01

High-performance liquid chromatography (HPLC) methods employing ultraviolet (UV) detector are not sufficiently sensitive to measure the low plasma concentrations following single oral dose of imipramine. Therefore, in the present study a simple, rapid and yet sensitive HPLC method with UV detection was developed and validated for quantitation of imipramine in human plasma samples. An efficient liquid-liquid extraction (LLE) of imipramine from plasma with the mixture of hexane/isoamyl alcohol (98:2) and back extraction of the drug in acidic medium concomitant with evaporation of organic phase allowed the use of UV detector to conveniently measure plasma levels of this compound as low level as 3 ng/ml. Separation was achieved on a μ-Bondapak C18 HPLC column using sodium hydrogen phosphate solution (0.01 M)/acetonitrile (60/40 v/v) at pH 3.5 ± 0.1 at 1.5 ml/min. Trimipramine was used as the internal standard for analysis of plasma samples. The retention times for imipramine and trimipramine were 4.3 and 5.2 min, respectively. Calibration curve was linear in the range of 3-40 ng/ml using human plasma with the average extraction recovery of 85 ± 5%. Imipramine was found to be stable in plasma samples with no evidence of degradation during three freeze-thaw cycles and three months storage at -70°C. The current validated method was finally applied in bioequivalence studies of two different imipramine products according to a standard two-way crossover design with a two weeks washout period.

Piezometer installation and monitoring procedure: Revision 1

International Nuclear Information System (INIS)

1987-04-01

The Deaf Smith County (Texas) site has been selected by the US Department of Energy as one of three candidate sites for characterization to determine its suitability as a geologic repository for high-level nuclear waste. The installation and monitoring of piezometers has been identified as one of the tasks required during the development of an underground Exploratory Shaft Facility to satisfy specific information needs through a program of in situ testing, instrumentation and monitoring. The scope of piezometer installation and monitoring encompasses the installation of fluid pressure measuring equipment and the subsequent collection, presentation and interpretation of piezometric data from strata surrounding the Exploratory Shaft Facility (ESF) prior to, during and following construction of the ESF, and as part of geohydrologic testing within the ESF. This procedure describes the required instrumentation, equipment, and sequence of activities for piezometer installation in the ESF. The procedure also includes details on the data recording and presentation requirements, personnel responsibilities, test management and quality assurance. 16 refs., 12 figs., 2 tabs

42 CFR 3.106 - Security requirements.

Science.gov (United States)

2010-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT PSO Requirements and Agency Procedures § 3.106 Security requirements. (a) Application. A PSO must secure patient safety work product in conformance with the security... the confidentiality and security of patient safety work product. (2) Distinguishing patient safety...

Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

Science.gov (United States)

Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

2015-12-07

In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

Procedures monitoring and MAAP analysis

International Nuclear Information System (INIS)

May, R.S.

1991-01-01

Numerous studies of severe accidents in light water reactors have shown that operator response can play a crucial role in the predicted outcomes of dominant accident scenarios. MAAP provides the capability to specify certain operator actions as input data. However, making reasonable assumptions about the nature and timing of operator response requires substantial knowledge about plant practices and procedures and what they imply for the event being analyzed. The appearance of knowledge based software technology in the mid-1980s provided a natural format for representing and maintaining procedures as IF-THEN rules. The boiling water reactor (BWR) Emergency Operating Procedures Tracking System (EOPTS) was composed of a rule base of procedures and a dedicated inference engine (problem-solver). Based on the general approach and experience of EOPTS, the authors have developed a prototype procedures monitoring system that reads MAAP transient output files and evaluate the EOP messages and instructions that would be implied during each transient time interval. The prototype system was built using the NEXPERT OBJECT expert system development system, running on a 386-class personal computer with 4 MB of memory. The limited scope prototype includes a reduced set of BWR6 EOPs procedures evaluation on a coarse time interval, a simple text-based user interface, and a summary-report generator. The prototype, which is limited to batch-mode analysis of MAAP output, is intended to demonstrate the concept and aid in the design of a production system, which will involve a direct link to MAAP and interactive capabilities

Human factors research plan for instrument procedures : FY12 version 1.1

Science.gov (United States)

2012-06-19

This research will support the development of instrument procedures for performance-based navigation (PBN) operations. These procedures include, but are not limited to, area navigation (RNAV) and required navigation performance (RNP) operations. The ...

The free fractions of circulating docosahexaenoic acid and eicosapentenoic acid as optimal end-point of measure in bioavailability studies on n-3 fatty acids.

Science.gov (United States)

Scarsi, Claudia; Levesque, Ann; Lisi, Lucia; Navarra, Pierluigi

2015-05-01

The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

36 CFR 223.195 - Procedures for identifying and marking unprocessed timber.

Science.gov (United States)

2010-07-01

... procedures required herein. (f) Waiver of branding requirements. Regional Foresters may waive the branding... individual timber sale basis, all or a portion of the branding requirements pursuant to paragraph (c)(2) of...) Regions 5 and 6. On an individual timber sale basis, the branding requirement pursuant to paragraph (c)(2...

Competence and lastingness in specialized clinical laboratories: technical report about requirements concerning quality of users competence and used processes in immunochemical diagnostic procedures using isotopic and non-isotopic tracer technologies

International Nuclear Information System (INIS)

Wiegel, B.

2005-01-01

From the citizens view this technical report about immunochemical diagnostic procedures using radioactive and nonradioactive tracer technologies describes the requirements in special laboratory diagnostics concerning competency and process control. Governmental or administrational obligations of inspecting both skill and sites to guarantee patients security are pointed out. (orig.)

Informed consent: not just for procedures anymore.

Science.gov (United States)

Feld, Andrew D

2004-06-01

The ethical and legal requirement to obtain informed consent prior to performing a procedure or administering a treatment derives from the concept of personal (patient) autonomy. The competent patient, after receiving appropriate disclosure of the material risks of the procedure or treatment, understanding those risks, the benefits, and the alternative approaches, makes a voluntary and uncoerced informed decision to proceed. This article will present a general overview of the modern concept of informed consent as a process (mutual communication) rather than an event (document signing). The historical evolution of this concept and the legal rulings that have shaped the requirements of informed consent will be cited. The benefits of informed decision making as a communication and risk management tool are presented. This review is intended as general information, and not as legal advice, which should be sought from a health-care attorney.

Biomonitoring test procedures and biological criteria

Energy Technology Data Exchange (ETDEWEB)

Kszos, L.A. [Oak Ridge National Lab., TN (United States); Lipschultz, M.J. [City of Las Vegas, NV (United States); Foster, W.E. [Saint Mary`s Coll., Winona, MN (United States)

1997-10-01

The Water Environment Federation recently issued a special publication, Biomonitoring in the Water Environment. In this paper, the authors highlight the contents of the chapter 3, Biomonitoring Test Procedures, identify current trends in test procedures and introduce the concept of biological criteria (biocriteria). The book chapter (and this paper) focuses on freshwater and marine chronic and acute toxicity tests used in the National Pollutant Discharge Elimination System (NPDES) permits program to identify effluents and receiving waters containing toxic materials in acutely or chronically toxic concentrations. The two major categories of toxicity tests include acute tests and chronic tests. The USEPA chronic tests required in NPDEs permits have been shortened to 7 days by focusing on the most sensitive life-cycle stages; these tests are often referred to as short-term chronic tests. The type of test(s) required depend on NPDES permit requirements, objectives of the test, available resources, requirements of the test organisms, and effluent characteristics such as variability in flow or toxicity. The permit writer will determine the requirements for toxicity test(s) by considering such factors as dilution, effluent variability, and exposure variability. Whether the required test is acute or chronic, the objective of the test is to estimate the safe or no effect concentration which is defined as the concentration which will permit normal propagation of fish and other aquatic life in the receiving waters. In this paper, the authors review the types of toxicity tests, the commonly used test organisms, and the uses of toxicity test data. In addition, they briefly describe research on new methods and the use of biological criteria.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

Science.gov (United States)

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

Complications with Outpatient Angiography and Interventional Procedures

International Nuclear Information System (INIS)

Young, Noel; Chi, Ka-Kit; Ajaka, Joe; McKay, Lesa; O'Neill, Diane; Wong, Kai Ping

2002-01-01

Purpose: To prospectively identify the complications, and rates of complication, in outpatient angiography and interventional procedures. Methods: There were 1050 consecutive patients, 646 men and 404 women, aged 17-89 years, with a total of 1239 procedures studied in a 2-year period, 1997 to 1999. Results: There were 560 cases of aorto-femoral angiography,resulting in 124 complications (22%), with pain or hematoma in 110.There were 206 cases of neck and cerebral angiography, resulting in 51 complications (25%), with pain and hematoma in 34, transient ischemic attack in 2 and cerebrovascular accident in 1. There were 197 interfentional procedures, with 177 being balloon dilatations, resulting in 68 complications (35%), with 2 having hematomas and 1 having hematoma/abscess requiring active treatment. There were 276 cases having various 'other' procedures (e.g., renal angiography),resulting in 65 complications (24%), with pain and hematoma in 61. No procedure-related death occurred. Eighteen cases (1.5%) had significant complications, with contrast allergy in eight. Conclusion: Outpatient angiography and intervention are relatively safe, with low significant complication rates

47 CFR 97.509 - Administering VE requirements.

Science.gov (United States)

2010-10-01

..., grandchildren, stepchildren, parents, grandparents, stepparents, brothers, sisters, stepbrothers, stepsisters... accommodate an examinee whose physical disabilities require a special examination procedure. The administering VEs may require a physician's certification indicating the nature of the disability before determining...

Methods for testing the logical structure of plant procedure documents

International Nuclear Information System (INIS)

Horne, C.P.; Colley, R.; Fahley, J.M.

1990-01-01

This paper describes an ongoing EPRI project to investigate computer based methods to improve the development, maintenance, and verification of plant operating procedures. This project began as an evaluation of the applicability of structured software analysis methods to operating procedures. It was found that these methods offer benefits, if procedures are transformed to a structured representation to make them amenable to computer analysis. The next task was to investigate methods to transform procedures into a structured representation. The use of natural language techniques to read and compile the procedure documents appears to be viable for this purpose and supports conformity to guidelines. The final task was to consider possibilities of automated verification methods for procedures. Methods to help verify procedures were defined and information requirements specified. These methods take the structured representation of procedures as input. The software system being constructed in this project is called PASS, standing for Procedures Analysis Software System

12 CFR 370.9 - Recordkeeping requirements.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Recordkeeping requirements. 370.9 Section 370.9 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY TEMPORARY LIQUIDITY GUARANTEE PROGRAM § 370.9 Recordkeeping requirements. The FDIC will establish procedures...

14 CFR 121.433 - Training required.

Science.gov (United States)

2010-01-01

... procedures set forth in a certificate holder's approved low-altitude windshear flight training program when... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Training required. 121.433 Section 121.433..., FLAG, AND SUPPLEMENTAL OPERATIONS Crewmember Qualifications § 121.433 Training required. (a) Initial...

The Precautionary Principle and statistical approaches to uncertainty

DEFF Research Database (Denmark)

Keiding, Niels; Budtz-Jørgensen, Esben

2004-01-01

is unhelpful, because lack of significance can be due either to uninformative data or to genuine lack of effect (the Type II error problem). Its inversion, bioequivalence testing, might sometimes be a model for the Precautionary Principle in its ability to "prove the null hypothesis". Current procedures...... for setting safe exposure levels are essentially derived from these classical statistical ideas, and we outline how uncertainties in the exposure and response measurements affect the no observed adverse effect level, the Benchmark approach and the "Hockey Stick" model. A particular problem concerns model...

5 CFR 3301.102 - Procedure for accomplishing disqualification.

Science.gov (United States)

2010-01-01

... ETHICAL CONDUCT FOR EMPLOYEES OF THE DEPARTMENT OF ENERGY § 3301.102 Procedure for accomplishing...) Disqualification from matter effecting prospective employers. A DOE employee who is required, in accordance with 5...

A Procedural Skills OSCE: Assessing Technical and Non-Technical Skills of Internal Medicine Residents

Science.gov (United States)

Pugh, Debra; Hamstra, Stanley J.; Wood, Timothy J.; Humphrey-Murto, Susan; Touchie, Claire; Yudkowsky, Rachel; Bordage, Georges

2015-01-01

Internists are required to perform a number of procedures that require mastery of technical and non-technical skills, however, formal assessment of these skills is often lacking. The purpose of this study was to develop, implement, and gather validity evidence for a procedural skills objective structured clinical examination (PS-OSCE) for internal…

48 CFR 32.006-4 - Procedures.

Science.gov (United States)

2010-10-01

... REQUIREMENTS CONTRACT FINANCING 32.006-4 Procedures. (a) In any case in which an agency's remedy coordination...) of this subsection. (e) Before making a decision to reduce or suspend further payments, the agency... determination and decision. (g) The agency shall retain in its files the written justification for each— (1...

Radiological Work Planning and Procedures

International Nuclear Information System (INIS)

KURTZ, J.E.

2000-01-01

Each facility is tasked with maintaining personnel radiation exposure as low as reasonably achievable (ALARA). A continued effort is required to meet this goal by developing and implementing improvements to technical work documents (TWDs) and work performance. A review of selected TWDs from most facilities shows there is a need to incorporate more radiological control requirements into the TWD. The Radioactive Work Permit (RWP) provides a mechanism to place some of the requirements but does not provide all the information needed by the worker as he/she is accomplishing the steps of the TWD. Requiring the engineers, planners and procedure writers to put the radiological control requirements in the work steps would be very easy if all personnel had a strong background in radiological work planning and radiological controls. Unfortunately, many of these personnel do not have the background necessary to include these requirements without assistance by the Radiological Control organization at each facility. In addition, there seems to be confusion as to what should be and what should not be included in the TWD

47 CFR 80.310 - Watch required by voluntary vessels.

Science.gov (United States)

2010-10-01

... Section 80.310 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Ship Station Safety...] Distress, Alarm, Urgency and Safety Procedures ...

24 CFR 511.11 - Project requirements.

Science.gov (United States)

2010-04-01

... low income occupancy or rent projections, or restrictions on return on investment or other similar policies that prevent an owner, whether for-profit or non-profit, from maximizing return or setting rent... requirements and with the affirmative marketing requirements and procedures adopted under § 511.13, for the...

The necessity to rationalize library procedures and activities

OpenAIRE

Matjaž Žaucer

2007-01-01

The necessity of the rationalization of work and procedures in libraries due to the altered requirements and needs of users and due to the expected aggravated demands of the environment are displayed in the article. The causes for the changes in the librarianship and the causes for the changes in the environment are stated. The article analyzes the searching procedure in the Slovenian union bibliographic and catalogue database using the UDC. Upon a practical experiment it was established that...

45 CFR 1634.12 - Emergency procedures and waivers.

Science.gov (United States)

2010-10-01

... COMPETITIVE BIDDING FOR GRANTS AND CONTRACTS § 1634.12 Emergency procedures and waivers. The President of the... requirements imposed by law on the awards of grants and contracts for a particular fiscal year. ...

A procedure for effective Dancoff factor calculation

International Nuclear Information System (INIS)

Milosevic, M.

2001-01-01

In this paper, a procedure for Dancoff factors calculation based on equivalence principle and its application in the SCALE-4.3 code system is described. This procedure is founded on principle of conservation of neutron absorption for resolved resonance range in a heterogeneous medium and an equivalent medium consisted of an infinite array of two-region pin cells, where the presence of other fuel rods is taken into account through a Dancoff factor. The neutron absorption in both media is obtained using a fine-group elastic slowing-down calculation. This procedure is implemented in a design oriented lattice physics code, which is applicable for any geometry where the method of collision probability is possible to apply to get a flux solution. Proposed procedure was benchmarked for recent exercise that represents a system with a fuel double heterogeneity, i.e., fuel in solid form (pellets) surrounded by fissile material in solution, and for a 5x5 irregular pressurised water reactor assembly, which requires different Dancoff factors. (author)

Training Requirements and Information Management System

Energy Technology Data Exchange (ETDEWEB)

Cillan, T.F.; Hodgson, M.A.

1992-05-01

This is the software user's guide for the Training Requirements and Information Management System. This guide defines and describes the software operating procedures as they apply to the end user of the software program. This guide is intended as a reference tool for the user who already has an indepth knowledge of the Training Requirements and Information Management System functions and data reporting requirement.

Administrative Procedure Act and mass procedures (illustrated by the nuclear licensing procedure)

International Nuclear Information System (INIS)

Naumann, R.

1977-01-01

The report deals with the administrative procedure law of 25.5.76 of the Fed. Government, esp. with its meaning for the administrative procedures for the permission for nuclear power plants, as fas ar so-called mass procedures are concerned. (UN) [de

Procedures for Calculating Residential Dehumidification Loads

Energy Technology Data Exchange (ETDEWEB)

Winkler, Jon [National Renewable Energy Lab. (NREL), Golden, CO (United States); Booten, Chuck [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-06-01

Residential building codes and voluntary labeling programs are continually increasing the energy efficiency requirements of residential buildings. Improving a building's thermal enclosure and installing energy-efficient appliances and lighting can result in significant reductions in sensible cooling loads leading to smaller air conditioners and shorter cooling seasons. However due to fresh air ventilation requirements and internal gains, latent cooling loads are not reduced by the same proportion. Thus, it's becoming more challenging for conventional cooling equipment to control indoor humidity at part-load cooling conditions and using conventional cooling equipment in a non-conventional building poses the potential risk of high indoor humidity. The objective of this project was to investigate the impact the chosen design condition has on the calculated part-load cooling moisture load, and compare calculated moisture loads and the required dehumidification capacity to whole-building simulations. Procedures for sizing whole-house supplemental dehumidification equipment have yet to be formalized; however minor modifications to current Air-Conditioner Contractors of America (ACCA) Manual J load calculation procedures are appropriate for calculating residential part-load cooling moisture loads. Though ASHRAE 1% DP design conditions are commonly used to determine the dehumidification requirements for commercial buildings, an appropriate DP design condition for residential buildings has not been investigated. Two methods for sizing supplemental dehumidification equipment were developed and tested. The first method closely followed Manual J cooling load calculations; whereas the second method made more conservative assumptions impacting both sensible and latent loads.

System requirements and design description for the document basis database interface (DocBasis)

International Nuclear Information System (INIS)

Lehman, W.J.

1997-01-01

This document describes system requirements and the design description for the Document Basis Database Interface (DocBasis). The DocBasis application is used to manage procedures used within the tank farms. The application maintains information in a small database to track the document basis for a procedure, as well as the current version/modification level and the basis for the procedure. The basis for each procedure is substantiated by Administrative, Technical, Procedural, and Regulatory requirements. The DocBasis user interface was developed by Science Applications International Corporation (SAIC)

75 FR 67165 - Proposed Collection; Comment Request for Revenue Procedure2007-XX (RP-155430-05)

Science.gov (United States)

2010-11-01

... Revenue Procedure 2007- XX (RP-155430-05) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice... soliciting comments concerning Revenue Procedure 2007-XX (RP-155430-05), Section 6707/6707A Accelerated... Procedure 2007-XX (RP-155430-05). Abstract: The collection of information this revenue procedure requires is...

12 CFR 404.4 - Request requirements.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

The application of workflow technology in the development of management procedures in NPPs

International Nuclear Information System (INIS)

Fang Zhaoxia; Huang Fang

2012-01-01

According to the national nuclear safety standards and guides, operating organizations of NPPs should document management programs against all safety related activities. One of the preconditions for the implementation of these programs is to setup a comprehensive instructions and procedures. The workflow technology which is a concept originally from computer technology can help in analysing work processes of different working areas in NPP, designing and developing management procedures hierarchy and requirements. The application of the workflow can not only comprehensively analyse the work process but also analyse the requirements for personnel which are related to the work process, therefore the procedures and programs developed could meet the requirements of national nuclear safety standards and guides. This paper also covers the application of workflow in other areas in NPPs. (authors)

15 CFR 296.12 - Reporting and auditing requirements.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Reporting and auditing requirements... INNOVATION PROGRAM General § 296.12 Reporting and auditing requirements. Each award by the Program shall contain procedures regarding technical, business, and financial reporting and auditing requirements to...

Modified Kidner procedure utilizing a Mitek bone anchor.

Science.gov (United States)

Dawson, D M; Julsrud, M E; Erdmann, B B; Jacobs, P M; Ringstrom, J B

1998-01-01

The recent development of small bone suture anchors has created several potential applications in reconstructive surgery of the foot. Mitek bone anchors are simple to insert, require less aggressive dissection and surgical time than reefing of the redundant posterior tibial tendon, and are a reliable method of tendon-to-bone fixation. Mitek bone anchors are an excellent technique for the treatment of redundant tibialis posterior tendon following a modified Kidner procedure. In modified Kidner procedures involving an excessively large os tibiale externum, Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone is an excellent means for secure plication of the posterior tibial tendon in cases involving intraoperative tendon laxity. A description of the Mitek Anchor System and technique of application in a modified Kinder procedure is presented. The purpose of this study was to describe patient satisfaction and long-term clinical outcomes of the modified Kinder procedure with and without the Mitek bone anchoring system. A retrospective study of the modified Kinder procedure was performed with 13 patients being evaluated, seven with Mitek anchoring and six without. The University of Maryland 100-point Painful Foot Center Scoring System was modified to be more specific to the modified Kinder procedure for assessment of subjective long-term results. Patient overall satisfaction was rated good to excellent by 85.6% of patients in the Mitek group and by 100% of patients in the non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative recovery to resumption of ambulation without assistive devices (average of 3 weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis posterior tendon, theoretically, increases medial arch support as evidenced by 14% of the Mitek group and 67% of the non-Mitek group requiring postoperative orthotics.

Percutaneous Cystgastrostomy as a Single-Step Procedure

International Nuclear Information System (INIS)

Curry, L.; Sookur, P.; Low, D.; Bhattacharya, S.; Fotheringham, T.

2009-01-01

The purpose of this study was to evaluate the success of percutaneous transgastric cystgastrostomy as a single-step procedure. We performed a retrospective analysis of single-step percutaneous transgastric cystgastrostomy carried out in 12 patients (8 male, 4 female; mean age 44 years; range 21-70 years), between 2002 and 2007, with large symptomatic pancreatic pseudocysts for whom up to 1-year follow-up data (mean 10 months) were available. All pseudocysts were drained by single-step percutaneous cystgastrostomy with the placement of either one or two stents. The procedure was completed successfully in all 12 patients. The pseudocysts showed complete resolution on further imaging in 7 of 12 patients with either enteric passage of the stent or stent removal by endoscopy. In 2 of 12 patients, the pseudocysts showed complete resolution on imaging, with the stents still noted in situ. In 2 of 12 patients, the pseudocysts became infected after 1 month and required surgical intervention. In 1 of 12 patients, the pseudocyst showed partial resolution on imaging, but subsequently reaccumulated and later required external drainage. In our experience, percutaneous cystgastrostomy as a single-step procedure has a high success rate and good short-term outcomes over 1-year follow-up and should be considered in the treatment of large symptomatic cysts.

THE CONSUMER PROTECTION ACT 68 OF 2008 AND PROCEDURAL FAIRNESS IN CONSUMER CONTRACTS

Directory of Open Access Journals (Sweden)

Philip N Stoop

2015-11-01

Full Text Available In general, the concept "contractual fairness" can be narrowed down, described and analysed with reference to the two interdependent types of fairness – substantive and procedural fairness. Measures aimed at procedural fairness in contracts address conduct during the bargaining process and generally aim at ensuring transparency. One could say that a contract is procedurally fair where its terms are transparent and do not mislead as to aspects of the goods, service, price and terms. Despite the noble aims of legislative measures aimed at procedural fairness there are certain limits to the efficacy of procedural measures and transparency. The special procedural measures which must be considered in terms of the Consumer Protection Act 68 of 2008 in order to decide if a contract is fair are analysed in this article, as are other measures contained in the Act, which may also increase procedural fairness, and are discussed so as to allow suppliers to predict whether their contracts will be procedurally fair or not in terms of the Act. The special procedural measures can be categorised under measures requiring disclosure and/or mandatory terms, and measures addressing bargaining position and choice. It is concluded that owing to the nature of all these factors and measures related to procedural fairness, it is clear that openness and transparency are required by the CPA.

States and state-preparing procedures in quantum mechanics

International Nuclear Information System (INIS)

Benioff, P.A.; Ekstein, Hans

D'Espagnat and others have shown that different preparation procedures that mix systems prepared in unequivalent states and objectively different, are nevertheless assigned the same state. This unpalatable result follows from the usual interpretative rules of quantum mechanics. It is shown here that this result is incompatible with the strengthened interpretative rules (requiring randomness of the measurement outcome sequence) recently proposed. Thus, the randomness requirement restores reasonableness

Bank Insolvency Procedures and Market Discipline in European Banking

OpenAIRE

Angkinand, Apanard; Wihlborg, Clas

2005-01-01

Market discipline in banking requires that explicit and implicit insurance schemes for financial sector firms are limited, and that the lack of insurance of important stakeholders is credible. This credibility cannot be achieved without transparent, predictable procedures for distress resolution for banks, including explicit rules for the liquidation of insolvent banks. We find that very few European countries have explicit procedures for dealing with problem banks. The propositions tested in...

Usability test of the ImPRO, computer-based procedure system

International Nuclear Information System (INIS)

Jung, Y.; Lee, J.

2006-01-01

ImPRO is a computer based procedure in both flowchart and success logic tree. It is evaluated on the basis of computer based procedure guidelines. It satisfies most requirements such as presentations and functionalities. Besides, SGTR has been performed with ImPRO to evaluate reading comprehension and situation awareness. ImPRO is a software engine which can interpret procedure script language, so that ImPRO is reliable by nature and verified with formal method. One bug, however, had hidden one year after release, but it was fixed. Finally backup paper procedures can be prepared on the same format as VDU in case of ImPRO failure. (authors)

The role the safety analysis report and other documents in the licensing procedure in the Federal Republic of Germany

International Nuclear Information System (INIS)

Albrecht, E.; Ballhaus, S.

1975-01-01

Legal requirements for the licensing procedure, requirements for and preparation of licensing documents, authorities and experts participating in the licensing procedure, course of the atomic licensing procedure e.g. application for construction and operation, public hearing, site and concept license, partial licenses. (HP) [de

Gadolinium Use in Spine Pain Management Procedures for Patients with Contrast Allergies: Results in 527 Procedures

International Nuclear Information System (INIS)

Safriel, Yair; Ang, Roberto; Ali, Muhammed

2008-01-01

Introduction. To review the safety and efficacy of gadolinium in spine pain management procedures in patients at high risk for a contrast reaction and who are not suitable candidates for the use of standard non-ionic contrast. Methods. We reviewed records over a 61-month period of all image-guided spinal pain management procedures where patients had allergies making them unsuitable candidates for standard non-ionic contrast and where gadolinium was used to confirm needle tip placement prior to injection of medication. Results. Three hundred and four outpatients underwent 527 procedures. A spinal needle was used in all but 41 procedures. Gadolinium was visualized using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. The gadolinium dose ranged from 0.2 to 10 ml per level. The highest dose received by one patient was 15.83 ml intradiscally during a three-level discogram. Three hundred and one patients were discharged without complication or known delayed complications. One patient had documented intrathecal injection but without sequelae and 2 patients who underwent cervical procedures experienced seizures requiring admission to the intensive care unit. Both the latter patients were discharged without any further complications. Conclusion. Based on our experience we recommend using gadolinium judiciously for needle tip confirmation. We feel more confident using gadolinium in the lumbar spine and in cervical nerve blocks. Gadolinium should probably not be used as an injectate volume expander. The indications for gadolinium use in cervical needle-guided spine procedures are less clear and use of a blunt-tipped needle should be considered

Nevada Applied Ecology Group procedures handbook for environmental transuranics

International Nuclear Information System (INIS)

White, M.G.; Dunaway, P.B.

1976-10-01

The activities of the Nevada Applied Ecology Group (NAEG) integrated research studies of environmental plutonium and other transuranics at the Nevada Test Site have required many standardized field and laboratory procedures. These include sampling techniques, collection and preparation, radiochemical and wet chemistry analysis, data bank storage and reporting, and statistical considerations for environmental samples of soil, vegetation, resuspended particles, animals, and other biological material. This document, printed in two volumes, includes most of the Nevada Applied Ecology Group standard procedures, with explanations as to the specific applications involved in the environmental studies. Where there is more than one document concerning a procedure, it has been included to indicate special studies or applications more complex than the routine standard sampling procedures utilized

Nevada Applied Ecology Group procedures handbook for environmental transuranics

International Nuclear Information System (INIS)

White, M.G.; Dunaway, P.B.

1976-10-01

The activities of the Nevada Applied Ecology Group (NAEG) integrated research studies of environmental plutonium and other transuranics at the Nevada Test Site have required many standardized field and laboratory procedures. These include sampling techniques, collection and preparation, radiochemical and wet chemistry analysis, data bank storage and reporting, and statistical considerations for environmental samples of soil, vegetation, resuspended particles, animals, and others. This document, printed in two volumes, includes most of the Nevada Applied Ecology Group standard procedures, with explanations as to the specific applications involved in the environmental studies. Where there is more than one document concerning a procedure, it has been included to indicate special studies or applications perhaps more complex than the routine standard sampling procedures utilized

15 CFR 911.8 - Technical requirements.

Science.gov (United States)

2010-01-01

... PROCEDURES CONCERNING USE OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.8 Technical requirements. (a) All platform operators of the NOAA DCS must use a data collection platform radio set whose technical... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Technical requirements. 911.8 Section...

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

Science.gov (United States)

Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

2009-03-01

Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

Issues involved in a knowledge-based approach to procedure synthesis

International Nuclear Information System (INIS)

Hajek, B.K.; Khartabil, L.F.; Miller, D.W.

1992-01-01

Many knowledge-based systems (KBSs) have been built to assist human operators in managing nuclear power plant operating functions, such as monitoring, fault diagnosis, alarm filtering, and procedure management. For procedure management, KBSs have been built to display and track existing written procedures or to dynamically follow procedure execution by monitoring plant data and action execution and suggesting recovery steps. More recent works build KBSs able to synthesize procedures. This paper addresses and examines the main issues related to the implementation of on-line procedure synthesis using KBSs. A KBS for procedure synthesis can provide a more robust and effective procedural plan during accidents. Currently existing procedures for abnormal plant conditions, written as precompiled step sets based on the event and symptom approaches, are inherently not robust because anticipation of all potential plant states and associated plant responses is not possible. Thus, their failure recovery capability is limited to the precompiled set. Procedure synthesis has the potential to overcome these two problems because it does not require such precompilation of large sets of plant states and associated recovery procedures. Other benefits obtained from a complete procedure synthesis system are providing (a) a methodology for off-line procedure verification and (b) a methodology for the eventual automation of plant operations

Emergency procedures

International Nuclear Information System (INIS)

Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

2004-01-01

The following subjects are discussed - Emergency Procedures: emergency equipment, emergency procedures; emergency procedure involving X-Ray equipment; emergency procedure involving radioactive sources

Biaxial testing for fabrics and foils optimizing devices and procedures

CERN Document Server

Beccarelli, Paolo

2015-01-01

This book offers a well-structured, critical review of current design practice for tensioned membrane structures, including a detailed analysis of the experimental data required and critical issues relating to the lack of a set of design codes and testing procedures. The technical requirements for biaxial testing equipment are analyzed in detail, and aspects that need to be considered when developing biaxial testing procedures are emphasized. The analysis is supported by the results of a round-robin exercise comparing biaxial testing machines that involved four of the main research laboratories in the field. The biaxial testing devices and procedures presently used in Europe are extensively discussed, and information is provided on the design and implementation of a biaxial testing rig for architectural fabrics at Politecnico di Milano, which represents a benchmark in the field. The significance of the most recent developments in biaxial testing is also explored.

CEL Working procedures for WRAP 2A formulation development test

International Nuclear Information System (INIS)

Duchsherer, M.J.

1994-01-01

The WRAP 2A facility will encapsulate retrieved, stored, and newly generated contact-handled mixed low level waste (MLLW) into 55-500 gal cementitous forms. Standardized test procedures will be required to facilitate this process. Cementitous specimens will be prepared from simulated drum wastes and will be tested in the Chemical Engineering Laboratory using the laboratory operating/working procedures encorporated into this document

Logistic Costs of Privileged Procedures in the Republic of Croatia

Directory of Open Access Journals (Sweden)

Čedomir Ivaković

2006-07-01

Full Text Available Logistic processes condition more and more the rationalizationof time required for manipulation of goods (loading,unloading, storage. The customs representation costs that arethe result of loss of time due to the customs procedures exclusivelyduring the working hours of the customs office affect alsothe total logistic costs, and may be significantly reduced by applyingthe privileged procedures in import and export.

A Generic Procedure for BRDF Normalization of Remotely Sensed Data

Energy Technology Data Exchange (ETDEWEB)

D. Yuan

2003-04-01

A generic procedure for Bidirectional Reflectance Distribution Function (BRDF) normalization for airborne multispectral images has been developed and implemented as an add-on module of ENVI at the U.S. Department of Energy's Remote Sensing Laboratory. The main advantage of this procedure is that it does not require multiple image acquisitions over the same area for establishing empirical BRDF functions.

The Payer and Patient Cost Burden of Open Breast Conserving Procedures Following Percutaneous Breast Biopsy.

Science.gov (United States)

Kimball, Chloe C; Nichols, Christine I; Vose, Joshua G

2018-01-01

Percutaneous core-needle biopsy (PCNB) is the standard of care to biopsy and diagnose suspicious breast lesions. Dependent on histology, many patients require additional open procedures for definitive diagnosis and excision. This study estimated the payer and patient out-of-pocket (OOP) costs, and complication risk, among those requiring at least 1 open procedure following PCNB. This retrospective study used the Truven Commercial database (2009-2014). Women who underwent PCNB, with continuous insurance, and no history of cancer, chemotherapy, radiation, or breast surgery in the prior year were included. Open procedures were defined as open biopsy or lumpectomy. Study follow-up ended at chemotherapy, radiation, mastectomy, or 90 days-whichever occurred first. In total, 143 771 patients (mean age 48) met selection criteria; 85.1% underwent isolated PCNB, 12.4% one open procedure, and 2.5% re-excision. Incidence of complications was significantly lower among those with PCNB alone (9.2%) vs 1 open procedure (15.6%) or re-excision (25.3%, P  open procedure vs PCNB alone (US $17 125 vs US $3935, P  open procedure vs PCNB alone (US $1527 vs US $669), and US $247 greater for re-excision vs 1 procedure. A meaningful proportion of patients underwent open procedure(s) following PCNB which was associated with increased complication risk and costs to both the payer and the patient. These results suggest a need for technologies to reduce the proportion of cases requiring open surgery and, in some cases, re-excision.

Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

Science.gov (United States)

Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

2014-04-11

Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

The plant operating procedure information modeling system for creation and maintenance of procedures

International Nuclear Information System (INIS)

Fanto, S.V.; Petras, D.S.; Reiner, R.T.; Frost, D.R.; Orendi, R.G.

1990-01-01

This paper reports that as a result of the accident at Three Mile Island, regulatory requirements were issued to upgrade Emergency Operating Procedures for nuclear power plants. The use of human-factored, function-oriented, EOPs were mandated to improve human reliability and to mitigate the consequences of a broad range of initiating events, subsequent failures and operator errors, without having to first diagnose the specific events. The Westinghouse Owners Group responded by developing the Emergency Response Guidelines in a human-factored, two-column format to aid in the transfer of the improved technical information to the operator during transients and accidents. The ERGs are a network of 43 interrelated guidelines which specify operator actions to be taken during plant emergencies to restore the plant to a safe and stable condition. Each utility then translates these guidelines into plant specific EOPs. The creation and maintenance of this large web of interconnecting ERGs/EOPs is an extremely complex task. This paper reports that in order to aid procedure documentation specialists with this time-consuming and tedious task, the Plant Operating Procedure Information Modeling system was developed to provide a controlled and consistent means to build and maintain the ERGs/EOPs and their supporting documentation

Medical interventional procedures--reducing the radiation risks

International Nuclear Information System (INIS)

Cousins, C.; Sharp, C.

2004-01-01

Over the last 40 years, the number of percutaneous interventional procedures using radiation has increased significantly, with many secondary care clinicians using fluoroscopically guided techniques. Many procedures can deliver high radiation doses to patients and staff, with the potential to cause immediate and delayed radiation effects. The challenge for interventionists is to maximize benefit, whilst minimizing radiation risk to patients and staff. Non-radiologist clinicians are often inadequately trained in radiation safety and radiobiology. However, clinical governance and legislation now requires a more rigorous approach to protecting patients and staff. Protection can be ensured, and risks can be controlled, by appropriate design, procurement and commissioning of equipment; quality assurance; and optimal operational technique, backed by audit. Interventionists need knowledge and skills to reduce the risks. Appropriate training should include awareness of the potential for radiation injury, equipment operational parameters, doses measurement and recording methods and dose reduction techniques. Clinical governance requires informed consent, appropriate patient counselling and follow-up

Medical interventional procedures--reducing the radiation risks

Energy Technology Data Exchange (ETDEWEB)

Cousins, C. E-mail: claire.cousins@addenbrookes.nhs.uk; Sharp, C

2004-06-01

Over the last 40 years, the number of percutaneous interventional procedures using radiation has increased significantly, with many secondary care clinicians using fluoroscopically guided techniques. Many procedures can deliver high radiation doses to patients and staff, with the potential to cause immediate and delayed radiation effects. The challenge for interventionists is to maximize benefit, whilst minimizing radiation risk to patients and staff. Non-radiologist clinicians are often inadequately trained in radiation safety and radiobiology. However, clinical governance and legislation now requires a more rigorous approach to protecting patients and staff. Protection can be ensured, and risks can be controlled, by appropriate design, procurement and commissioning of equipment; quality assurance; and optimal operational technique, backed by audit. Interventionists need knowledge and skills to reduce the risks. Appropriate training should include awareness of the potential for radiation injury, equipment operational parameters, doses measurement and recording methods and dose reduction techniques. Clinical governance requires informed consent, appropriate patient counselling and follow-up.

Subsea HIPPS design procedure

International Nuclear Information System (INIS)

Aaroe, R.; Lund, B.F.; Onshus, T.

1995-01-01

The paper is based on a feasibility study investigating the possibilities of using a HIPPS (High Integrity Pressure Protection System) to protect a subsea pipeline that is not rated for full wellhead shut-in pressure. The study was called the Subsea OPPS Feasibility Study, and was performed by SINTEF, Norway. Here, OPPS is an acronym for Overpressure Pipeline Protection System. A design procedure for a subsea HIPPS is described, based on the experience and knowledge gained through the ''Subsea OPPS Feasibility Study''. Before a subsea HIPPS can be applied, its technical feasibility, reliability and profitability must be demonstrated. The subsea HIPPS design procedure will help to organize and plan the design activities both with respect to development and verification of a subsea HIPPS. The paper also gives examples of how some of the discussed design steps were performed in the Subsea OPPS Feasibility Study. Finally, further work required to apply a subsea HIPPS is discussed

75 FR 54594 - Effectiveness of Licensing Procedures for Agricultural Commodities to Cuba

Science.gov (United States)

2010-09-08

...] Effectiveness of Licensing Procedures for Agricultural Commodities to Cuba AGENCY: Bureau of Industry and... Administration Regulations for the export of agricultural commodities to Cuba. BIS will include a description of...), to Cuba. Requirements and procedures associated with such authorization are set forth in section 740...

Can proceduralization support coping with the unexpected?

International Nuclear Information System (INIS)

Norros, Leena; Savioja, Paula; Liinasuo, Marja; Wahlstrom, Mikael

2014-01-01

Operations of safety critical industries unquestionably require a diversity of technical and organizational control measures to increase stability and predictability of the complex sociotechnical systems. Nevertheless, experiences from recent severe accidents and results of safety research have questioned the effectiveness of the prevailing safety management strategy that mainly relies on standardization and designed-in defenses. This paper discusses the identified need to balance between stability and flexibility in a concrete safety issue, i.e., proceduralization. The main research problem of our study is whether procedure guided practice can offer sufficient support for flexibility of operating activity. We shall frame our study with the help of a model that explains different aspects of procedures. We then elaborate how these different aspects were considered empirically in our 3-phase study. In the first study we interviewed 62 main control room operators and asked how they consider procedures to support balancing. In the second study we observed in detail 12 NPP operator crews' activity in a simulated loss-of-coolant accident. In a third study we inquired 5 procedure designers about their conceptions concerning procedure guidance in operator work. Drawing on either interview or behavioral data we analyzed the personnel's stance to the flexibility and stability balancing, and how the conceptions portray in the practices of procedure usage. Our results demonstrate that the operators are aware of the need for balancing flexibility and stability and consider successful balancing to represent 'good' professional action. In actual action many operators, however, tend towards more straightforward following of procedures. Designers also see the capability for balancing stability and flexibility as a key operator competence but describe actual acting simply as procedure-following. According to the documents of the nuclear community, procedure

Can proceduralization support coping with the unexpected?

Energy Technology Data Exchange (ETDEWEB)

Norros, Leena; Savioja, Paula; Liinasuo, Marja; Wahlstrom, Mikael [VTT Technical Research Centre of Finland, Vuorimiehentie (Finland)

2014-08-15

Operations of safety critical industries unquestionably require a diversity of technical and organizational control measures to increase stability and predictability of the complex sociotechnical systems. Nevertheless, experiences from recent severe accidents and results of safety research have questioned the effectiveness of the prevailing safety management strategy that mainly relies on standardization and designed-in defenses. This paper discusses the identified need to balance between stability and flexibility in a concrete safety issue, i.e., proceduralization. The main research problem of our study is whether procedure guided practice can offer sufficient support for flexibility of operating activity. We shall frame our study with the help of a model that explains different aspects of procedures. We then elaborate how these different aspects were considered empirically in our 3-phase study. In the first study we interviewed 62 main control room operators and asked how they consider procedures to support balancing. In the second study we observed in detail 12 NPP operator crews' activity in a simulated loss-of-coolant accident. In a third study we inquired 5 procedure designers about their conceptions concerning procedure guidance in operator work. Drawing on either interview or behavioral data we analyzed the personnel's stance to the flexibility and stability balancing, and how the conceptions portray in the practices of procedure usage. Our results demonstrate that the operators are aware of the need for balancing flexibility and stability and consider successful balancing to represent 'good' professional action. In actual action many operators, however, tend towards more straightforward following of procedures. Designers also see the capability for balancing stability and flexibility as a key operator competence but describe actual acting simply as procedure-following. According to the documents of the nuclear community, procedure

Determination of ergocalciferol in human plasma after Diels-Alder derivatization by LC–MS/MS and its application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Pritesh Contractor

2017-12-01

Full Text Available An accurate, sensitive and selective method is developed for determination of ergocalciferol (vitamin D2 in human plasma using LC–MS/MS. After liquid-liquid extraction with n-hexane, ergocalciferol was derivatized by reacting with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH C18 (100 mm×4.6 mm, 2.5 µm column using acetonitrile and 0.1% (v/v formic acid in water containing 0.14% methylamine within 6.0 min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring (MRM. Entire data processing was done using Watson LIMS™ software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity (0.10 ng/mL, superior extraction efficiency (≥83% and small sample volume (100 µL for processing. The method was linear in the concentration range of 0.10–100 ng/mL for ergocalciferol. The intra-batch and inter-batch accuracy and precision (% CV values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25 mg ergocalciferol capsules in 12 healthy subjects. Keywords: Ergocalciferol, Diels-Alder reaction, 4-phenyl-1,2,4-triazoline-3,5-dione, LC–MS/MS, Human plasma

Test Procedure - pumping system for caustic addition project

International Nuclear Information System (INIS)

Leshikar, G.A.

1994-01-01

This test procedure provides the requirements for sub-system testing and integrated operational testing of the submersible mixer pump and caustic addition equipment by WHC and Kaiser personnel at the Rotating Equipment Shop run-in pit (Bldg. 272E)

Procedures for analyzing the effectiveness of siren systems for alerting the public

International Nuclear Information System (INIS)

Keast, D.N.; Towers, D.A.; Anderson, G.S.; Kenoyer, J.L.; Desrosiers, A.E.

1982-09-01

NUREG-0654, Revision 1 (Criteria for Preparation and Evaluation of Radiological Emergency Response Plans and Preparedness in Support of Nuclear Power Plants), Appendix 3, discusses requirements of the licensees to implement a prompt notification system within the 10-mile emergency planning zone (EPZ) surrounding a nuclear facility. Sirens are being installed for use as part of or as the entire notification system by many licensees. This report describes a procedure for predicting siren system effectiveness under defined conditions within the EPZ's. The procedure requires a good topographical map and knowledge of the meteorology, demographics, and human activity patterns within the EPZ. The procedure is intended to be applied to systems of sirens and to obtain average results for a large number (30 or more) of listener locations

Pancreaticoduodenectomy: a rare procedure for the management of complex pancreaticoduodenal injuries.

Science.gov (United States)

Asensio, Juan A; Petrone, Patrizio; Roldán, Gustavo; Kuncir, Eric; Demetriades, Demetrios

2003-12-01

Pancreaticoduodenectomy (Whipple's procedure) is a formidable procedure when undertaken for severe pancreaticoduodenal injury. The purposes of this study were to review our experience with this procedure for trauma; to classify injury grades for both pancreatic and duodenal injuries in patients undergoing pancreaticoduodenectomy according to the American Association for the Surgery of Trauma-Organ Injury Scale for pancreatic and duodenal injury; and to validate existing indications for performance of this procedure. We performed a retrospective 126-month study (May 1992 to December 2002) of all patients admitted with proven complex pancreaticoduodenal injuries requiring pancreaticoduodenectomy. Eighteen patients were included; mean age was 32 +/- 12 years (SD), mean Revised Trauma Score was 6.84 +/- 2.13 (SD), and mean Injury Severity Score was 27 +/- 8 (SD). There were 17 penetrating injuries (94%) and 1 blunt injury (6%). One of 18 patients had an emergency department thoracotomy and died (100% mortality); 5 of the remaining 17 patients required operating room thoracotomies, and only 1 survived (80% mortality). There was 1 AAST-OIS pancreas grade IV injury, and there were 17 pancreas grade V injuries and 18 AAST-OIS duodenum grade V injuries. Indications for pancreaticoduodenectomy were: massive uncontrollable retropancreatic hemorrhage, 13 patients (72%); massive unreconstructable injury to the head of the pancreas/main pancreatic duct and intrapancreatic portion/distal common bile duct, 18 patients (100%); and massive unreconstructable injury, 18 patients (100%). Mean estimated blood loss was 6,888 +/- 7,866 mL, and overall survival was 67% (12 of 18 patients). Complex pancreaticoduodenal injuries requiring pancreaticoduodenectomy (Whipple's procedure) are uncommon but highly lethal; virtually all are classified as AAST-OIS grade V for both pancreas and duodenum. Current indications for performance of pancreaticoduodenectomy are valid and should be strictly

HYPNOSIS FOR ACUTE PROCEDURAL PAIN: A Critical Review

Science.gov (United States)

Kendrick, Cassie; Sliwinski, Jim; Yu, Yimin; Johnson, Aimee; Fisher, William; Kekecs, Zoltán; Elkins, Gary

2015-01-01

Clinical evidence for the effectiveness of hypnosis in the treatment of acute, procedural pain was critically evaluated based on reports from randomized controlled clinical trials (RCTs). Results from the 29 RCTs meeting inclusion criteria suggest that hypnosis decreases pain compared to standard care and attention control groups and that it is at least as effective as comparable adjunct psychological or behavioral therapies. In addition, applying hypnosis in multiple sessions prior to the day of the procedure produced the highest percentage of significant results. Hypnosis was most effective in minor surgical procedures. However, interpretations are limited by considerable risk of bias. Further studies using minimally effective control conditions and systematic control of intervention dose and timing are required to strengthen conclusions. PMID:26599994

Hypnosis for Acute Procedural Pain: A Critical Review.

Science.gov (United States)

Kendrick, Cassie; Sliwinski, Jim; Yu, Yimin; Johnson, Aimee; Fisher, William; Kekecs, Zoltán; Elkins, Gary

2016-01-01

Clinical evidence for the effectiveness of hypnosis in the treatment of acute procedural pain was critically evaluated based on reports from randomized controlled clinical trials (RCTs). Results from the 29 RCTs meeting inclusion criteria suggest that hypnosis decreases pain compared to standard care and attention control groups and that it is at least as effective as comparable adjunct psychological or behavioral therapies. In addition, applying hypnosis in multiple sessions prior to the day of the procedure produced the highest percentage of significant results. Hypnosis was most effective in minor surgical procedures. However, interpretations are limited by considerable risk of bias. Further studies using minimally effective control conditions and systematic control of intervention dose and timing are required to strengthen conclusions.

Principles and procedures in forensic toxicology.

Science.gov (United States)

Wyman, John F

2012-09-01

The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

Design and drafting document control procedures for CPRF/ZTH experiment

International Nuclear Information System (INIS)

Pollat, L.L.; Kewish, R.W.

1989-01-01

This paper will present, in general, the control procedures for design approval, review, changes, and release of engineering documents. It will also discuss interface control for tasks so that possible design interference does not occur. A document control procedure to insure that design criteria are met and technical specifications translate into workable drawings was instituted to support the Confinement Physics Research Facility (CPRF/ZTH) construction program. Our goal, to eliminate any conflicts that might arise between various tasks as the final designs are developed, required tight control and up-to-date design information. Detailed procedure for reviews were instituted, since circumventing the process of design and drafting anywhere might have proven disastrous to the CPRF/ZTH program. Design is a process of translating technical requirements, according to established standards, into drawings that are usable for fabrication and assembly. Both the designer and engineer are responsible for adhering to standards that have been established by the Mechanical Engineering Section for the CPRF/ZTH program. 6 refs., 5 figs

77 FR 55183 - Effectiveness of Licensing Procedures for Agricultural Commodities to Cuba

Science.gov (United States)

2012-09-07

...] Effectiveness of Licensing Procedures for Agricultural Commodities to Cuba AGENCY: Bureau of Industry and... Administration Regulations for the export of agricultural commodities to Cuba. BIS will include a description of...), to Cuba. Requirements and procedures associated with such authorization are set forth in Sec. 740.18...

Could conscious sedation with midazolam for dental procedures be ...

African Journals Online (AJOL)

2012-04-25

Apr 25, 2012 ... they used CS. Minor oral surgical procedures and tooth extraction processes requiring no saline irrigation, however, ... The pre-diagnosis and related treatment plans .... accompanying tooth decay; orthodontic tooth extractions.

Development of a 3-dimensional flow analysis procedure for axial pump impellers

International Nuclear Information System (INIS)

Kim, Min Hwan; Kim, Jong In; Park, Jin Seok; Huh, Houng Huh; Chang, Moon Hee

1999-06-01

A fluid dynamic analysis procedure was developed using the three-dimensional solid model of an axial pump impeller which was theoretically designed using I-DEAS CAD/CAM/CAE software. The CFD software FLUENT was used in the flow field analysis. The steady-state flow regime in the MCP impeller and diffuser was simulated using the developed procedure. The results of calculation were analyzed to confirm whether the design requirements were properly implemented in the impeller model. The validity of the developed procedure was demonstrated by comparing the calculation results with the experimental data available. The pump performance at the design point could be effectively predicted using the developed procedure. The computed velocity distributions have shown a good agreement with the experimental data except for the regions near the wall. The computed head, however, was over-predicted than the experiment. The design period and cost required for the development of an axial pump impeller can be significantly reduced by applying the proposed methodology. (author). 7 refs., 2 tabs

Comprehensive renal scintillation procedures in spinal cord injury: comparison with excretory urography

International Nuclear Information System (INIS)

Lloyd, L.K.; Dubovsky, E.V.; Bueschen, A.J.; Witten, D.M.; Scott, J.W.; Kuhlemeier, K.; Stover, S.L.

1981-01-01

A 131 iodine orthoiodohippurate comprehensive renal scintillation procedure was performed and compared to results of excretory urography in 200 spinal cord injury patients. No severe urographic abnormalities were undetected by the comprehensive renal scintillation procedure. Only 1.4 per cent of renal units had greater than minimal pyelocaliectasis or ureterectasis in the presence of a normal radionuclide examination. A relatively large number of abnormalities were detected on the renal scintillation procedure when the excretory urogram was normal. Serial followup will be required to determine the significance of these findings but present data suggest that a comprehensive renal scintillation procedure and a plain film of the kidneys, ureters and bladder may be used for screening upper urinary tract abnormalities in lieu of an excretory urogram. This is particularly advantageous for the spinal cord injury population, since there have been no toxic or allergic reactions reported, no bowel preparation or dehydration is required and there is relatively low radiation exposure

29 CFR 15.26 - Claims procedures.

Science.gov (United States)

2010-07-01

... forth in § 15.21(d) will be accepted and considered a claim under the Act if it constitutes a demand for compensation from the Department. A demand is not required to be for a specific sum of money. (c) Notification... 29 Labor 1 2010-07-01 2010-07-01 true Claims procedures. 15.26 Section 15.26 Labor Office of the...

30 CFR 71.201 - Sampling; general requirements.

Science.gov (United States)

2010-07-01

... MINES Sampling Procedures § 71.201 Sampling; general requirements. (a) Each operator shall take... required by this part with a sampling device approved by the Secretary and the Secretary of Health and Human Services under part 74 (Coal Mine Dust Personal Sampler Units) of this title. (b) Sampling devices...

Middle-Ear Microsurgery Simulation to Improve New Robotic Procedures

Directory of Open Access Journals (Sweden)

Guillaume Kazmitcheff

2014-01-01

Full Text Available Otological microsurgery is delicate and requires high dexterity in bad ergonomic conditions. To assist surgeons in these indications, a teleoperated system, called RobOtol, is developed. This robot enhances gesture accuracy and handiness and allows exploration of new procedures for middle ear surgery. To plan new procedures that exploit the capacities given by the robot, a surgical simulator is developed. The simulation reproduces with high fidelity the behavior of the anatomical structures and can also be used as a training tool for an easier control of the robot for surgeons. In the paper, we introduce the middle ear surgical simulation and then we perform virtually two challenging procedures with the robot. We show how interactive simulation can assist in analyzing the benefits of robotics in the case of complex manipulations or ergonomics studies and allow the development of innovative surgical procedures. New robot-based microsurgical procedures are investigated. The improvement offered by RobOtol is also evaluated and discussed.

Concepts and procedures required for successful reduction of tensor magnetic gradiometer data obtained from an unexploded ordnance detection demonstration at Yuma Proving Grounds, Arizona

Science.gov (United States)

Bracken, Robert E.; Brown, Philip J.

2006-01-01

On March 12, 2003, data were gathered at Yuma Proving Grounds, in Arizona, using a Tensor Magnetic Gradiometer System (TMGS). This report shows how these data were processed and explains concepts required for successful TMGS data reduction. Important concepts discussed include extreme attitudinal sensitivity of vector measurements, low attitudinal sensitivity of gradient measurements, leakage of the common-mode field into gradient measurements, consequences of thermal drift, and effects of field curvature. Spatial-data collection procedures and a spin-calibration method are addressed. Discussions of data-reduction procedures include tracking of axial data by mathematically matching transfer functions among the axes, derivation and application of calibration coefficients, calculation of sensor-pair gradients, thermal-drift corrections, and gradient collocation. For presentation, the magnetic tensor at each data station is converted to a scalar quantity, the I2 tensor invariant, which is easily found by calculating the determinant of the tensor. At important processing junctures, the determinants for all stations in the mapped area are shown in shaded relief map-view. Final processed results are compared to a mathematical model to show the validity of the assumptions made during processing and the reasonableness of the ultimate answer obtained.

Information security policies and procedures a practitioner's reference

CERN Document Server

Peltier, Thomas R

2004-01-01

INFORMATION SECURITY POLICIES AND PROCEDURES Introduction Corporate Policies Organizationwide (Tier 1) Policies Organizationwide Policy Document Legal Requirements Duty of Loyalty Duty of Care Other Laws and Regulations Business Requirements Where to Begin? Summary Why Manage This Process as a Project? Introduction First Things First: Identify the Sponsor Defining the Scope of Work Time Management Cost Management Planning for Quality Managing Human Resources Creating a Communications Plan Summary Planning and Preparation Introduction Objectives of Policies, Stand

Residual stress effects in LMFBR fracture assessment procedures

International Nuclear Information System (INIS)

Hooton, D.G.

1984-01-01

Two post-yield fracture mechanics methods, which have been developed into fully detailed failure assessment procedures for ferritic structures, have been reviewed from the point of view of the manner in which as-welded residual stress effects are incorporated, and comparisons then made with finite element and theoretical models of centre-cracked plates containing residual/thermal stresses in the form of crack-driving force curves. Applying the procedures to austenitic structures, comparisons are made in terms of failure assessment curves and it is recommended that the preferred method for the prediction of critical crack sizes in LMFBR austenitic structures containing as-welded residual stresses is the CEGB-R6 procedure based on a flow stress defined at 3% strain in the parent plate. When the prediction of failure loads in such structures is required, it is suggested that the CEGB-R6 procedure be used with residual/thermal stresses factored to give a maximum total stress of flow stress magnitude

Human Uniqueness, Cognition by Description, and Procedural Memory

Directory of Open Access Journals (Sweden)

John Bolender

2008-06-01

Full Text Available Evidence will be reviewed suggesting a fairly direct link between the human ability to think about entities which one has never perceived — here called “cognition by description” — and procedural memory. Cognition by description is a uniquely hominid trait which makes religion, science, and history possible. It is hypothesized that cognition by description (in the manner of Bertrand Russell’s “knowledge by description” requires variable binding, which in turn utilizes quantifier raising. Quantifier raising plausibly depends upon the computational core of language, specifically the element of it which Noam Chomsky calls “internal Merge”. Internal Merge produces hierarchical structures by means of a memory of derivational steps, a process plausibly involving procedural memory. The hypothesis is testable, predicting that procedural memory deficits will be accompanied by impairments in cognition by description. We also discuss neural mechanisms plausibly underlying procedural memory and also, by our hypothesis, cognition by description.

Information processing requirements for on-board monitoring of automatic landing

Science.gov (United States)

Sorensen, J. A.; Karmarkar, J. S.

1977-01-01

A systematic procedure is presented for determining the information processing requirements for on-board monitoring of automatic landing systems. The monitoring system detects landing anomalies through use of appropriate statistical tests. The time-to-correct aircraft perturbations is determined from covariance analyses using a sequence of suitable aircraft/autoland/pilot models. The covariance results are used to establish landing safety and a fault recovery operating envelope via an event outcome tree. This procedure is demonstrated with examples using the NASA Terminal Configured Vehicle (B-737 aircraft). The procedure can also be used to define decision height, assess monitoring implementation requirements, and evaluate alternate autoland configurations.

European Utility Requirements: European nuclear energy

International Nuclear Information System (INIS)

Komsi, M.; Patrakka, E.

1997-01-01

The work procedure and the content of the European Utility Requirements (EUR) concerning the future LWRs is described in the article. European Utility Requirements, produced by utilities in a number of European countries, is a document specifying the details relating to engineered safety, operating performance, reliability and economics of the reactors to be built by manufacturers for the European market

Predicate Transformers for Recursive Procedures with Local Variables

NARCIS (Netherlands)

Hesselink, Wim H.

1999-01-01

The weakest precondition semantics of recursive procedures with local variables are developed for an imperative language with demonic and angelic operators for unbounded nondeterminate choice. This does not require stacking of local variables. The formalism serves as a foundation for a proof rule

Anaphylaxis and allergic reactions during surgery and medical procedures

Directory of Open Access Journals (Sweden)

Blas J Larrauri

2017-10-01

Full Text Available Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the responsible drugs include neuromuscular blocking agents, latex, or antibiotics. The frequency and etiology of systemic allergic reactions in other medical procedures are largely unknown. The identification of responsible drugs of anaphylaxis is a complex task, requiring testing of all medications and substances used during surgery. We describe our experience in a retrospective study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in endoscopic studies and one in a trans-vaginal ultrasound. The remaining two subjects, one in a trans-vaginal ultrasound and another during a dental procedure had a systemic allergic reaction. We studied all patients with all medications administered during the procedures, including latex and detergents and disinfectants. Three surgeries had to be suspended at induction of anesthesia, five were stopped incomplete and two were completed. Both patients that presented a reaction during endoscopy required intensive care unit admission and the rest were observed in a Hospital. The responsible drugs during surgery anaphylaxis were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho-phthalaldehyde (OPA was identified during endoscopic studies; latex was responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure. The aim of the present article is to review our experience studying allergic systemic reactions and anaphylaxis during general anesthesia and medical procedures, emphasizing the severity of these reactions and the need for causative drug identification.

Postoperative infections in craniofacial reconstructive procedures.

Science.gov (United States)

Fialkov, J A; Holy, C; Forrest, C R; Phillips, J H; Antonyshyn, O M

2001-07-01

The rate of, and possible risk factors for, postoperative craniofacial infection is unclear. To investigate this problem, we reviewed 349 cases of craniofacial skeletal procedures performed from 1996 to 1999 at our institution. Infection rate was determined and correlated with the use of implants, operative site, and cause of deformity. The inclusion criteria consisted of all procedures requiring autologous or prosthetic implantation in craniofacial skeletal sites, as well as all procedures involving bone or cartilage resection, osteotomies, debridement, reduction and/or fixation. Procedures that did not involve bone or cartilage surgery were excluded. The criteria for diagnosis of infection included clinical confirmation and one or more of 1) intravenous or oral antibiotic treatment outside of the prophylactic surgical regimen; 2) surgical intervention for drainage, irrigation, and or debridement; and 3) microbiological confirmation. Among the 280 surgical cases that fit the inclusion criteria and had complete records, there were 23 cases of postoperative infection (8.2%). The most common site for postoperative infection was the mandible (infection rate = 16.7%). Multiple logistic regression analysis revealed gunshot wound to be the most significant predictor of postoperative infection. Additionally, porous polyethylene implantation through a transoral route was correlated with a significant risk of postoperative infection.

Analysis of half diallel mating designs I: a practical analysis procedure for ANOVA approximation.

Science.gov (United States)

G.R. Johnson; J.N. King

1998-01-01

Procedures to analyze half-diallel mating designs using the SAS statistical package are presented. The procedure requires two runs of PROC and VARCOMP and results in estimates of additive and non-additive genetic variation. The procedures described can be modified to work on most statistical software packages which can compute variance component estimates. The...

Formal Verification of Real-Time System Requirements

Directory of Open Access Journals (Sweden)

Marcin Szpyrka

2000-01-01

Full Text Available The methodology of system requirements verification presented in this paper is a proposition of a practical procedure for reducing some negatives of the specification of requirements. The main problem that is considered is to create a complete description of the system requirements without any negatives. Verification of the initially defined requirements is based on the coloured Petri nets. Those nets are useful for testing some properties of system requirements such as completeness, consistency and optimality. An example ofthe litt controller is presented.

Enhancements to inventory control procedures used at Koeberg nuclear power station

International Nuclear Information System (INIS)

Barker, M.P.; Adams, A.R.

1991-01-01

In industry today, industrial engineers are forced to seek new and innovative ideas to reduce costs. This can often be accomplished by simplified or modernized operational procedures. With the advancement in computer technology, operational procedures can be enhanced. Despite the fact that Eskom's Koeberg nuclear power station is one of a kind in Africa, it, like most other industries requires a large stock holding capacity. There are currently 25 000 stock items in the Koeberg Stores Information System. Controlling all of these items is no minor task and management is continually trying to optimise the inventory control procedures. One of these procedures is described. 3 refs., 1 fig

Technical operations procedure for assembly and emplacement of the soil temperature test--test assembly

International Nuclear Information System (INIS)

Weber, A.P.

1978-01-01

A description is given of the plan for assembly, instrumentation, emplacement, and operational checkout of the soil temperature test assembly and dry well liner. The activities described cover all operations necessary to accomplish the receiving inspection, instrumentation and pre-construction handling of the dry well liner, plus all operations performed with the test article. Actual details of construction work are not covered by this procedure. Each part and/or section of this procedure is a separate function to be accomplished as required by the nature of the operation. The organization of the procedure is not intended to imply a special operational sequence or schedular requirement. Specific procedure operational sections include: receiving inspection; liner assembly operations; construction operations (by others); prepare shield plug; test article assembly and installation; and operational checkout

Radiation protection in medical research. Licensing requirement for the use of radiation and advice for the application procedure; Strahlenschutz in der medizinischen Forschung. Genehmigungsbeduerftigkeit von Strahlenanwendungen und Hinweise zum Antragsverfahren

Energy Technology Data Exchange (ETDEWEB)

Minkov, V.; Klammer, H.; Brix, G. [Bundesamt fuer Strahlenschutz, Abteilung fuer medizinischen und beruflichen Strahlenschutz, Neuherberg (Germany)

2017-07-15

In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. Questions and typical mistakes in the application process were identified and evaluated. The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants. (orig.) [German] Personen, bei denen Strahlenanwendungen zum Zweck der medizinischen Forschung durchgefuehrt

New procedures to evaluate visually lossless compression for display systems

Science.gov (United States)

Stolitzka, Dale F.; Schelkens, Peter; Bruylants, Tim

2017-09-01

Visually lossless image coding in isochronous display streaming or plesiochronous networks reduces link complexity and power consumption and increases available link bandwidth. A new set of codecs developed within the last four years promise a new level of coding quality, but require new techniques that are sufficiently sensitive to the small artifacts or color variations induced by this new breed of codecs. This paper begins with a summary of the new ISO/IEC 29170-2, a procedure for evaluation of lossless coding and reports the new work by JPEG to extend the procedure in two important ways, for HDR content and for evaluating the differences between still images, panning images and image sequences. ISO/IEC 29170-2 relies on processing test images through a well-defined process chain for subjective, forced-choice psychophysical experiments. The procedure sets an acceptable quality level equal to one just noticeable difference. Traditional image and video coding evaluation techniques, such as, those used for television evaluation have not proven sufficiently sensitive to the small artifacts that may be induced by this breed of codecs. In 2015, JPEG received new requirements to expand evaluation of visually lossless coding for high dynamic range images, slowly moving images, i.e., panning, and image sequences. These requirements are the basis for new amendments of the ISO/IEC 29170-2 procedures described in this paper. These amendments promise to be highly useful for the new content in television and cinema mezzanine networks. The amendments passed the final ballot in April 2017 and are on track to be published in 2018.

40 CFR 35.3135 - Specific capitalization grant agreement requirements.

Science.gov (United States)

2010-07-01

... received a capitalization grant and, if the deposit was expended, it was expended in accordance with title... after it receives the payment, the RA may withhold future quarterly grant payments, and require... procedures regarding the commitment or expenditure of revenues. (h) State accounting and auditing procedures...

Procedures for evaluating technical specifications (PETS)

International Nuclear Information System (INIS)

Samanta, P.K.; Boccio, J.L.; Vesely, W.E.

1987-01-01

In this paper, aspects of technical specifications relating to Generic Issues B-56 and B-61 are discussed from a risk-standpoint. These primarily deal with the risk issues associated with (1) adaptive diesel test requirements/surveillance test intervals, and (2) the effectiveness of cumulative outage time requirements for controlling downtime risk. Risk and reliability approaches are presented which (1) allow risk-acceptable test intervals to be determined for any diesel and (2) show the potential risk-control capability of prescribed allowed cumulative outage times. This work was conducted through NRC's Procedures for Evaluating Technical Specifications (PETS) Program. The overall objective of this program is to develop and demonstrate methodologies that utilize risk insights and reliability techniques for evaluating the scope, detailed requirements, and safety impact of plant technical specifications

Aspects of the licensing procedures for enrichment reduction in research reactors

International Nuclear Information System (INIS)

Krull, W.

1983-01-01

The enrichment reduction for research reactors requires a licensing procedure. For this purpose the qualification of the new fuel has to be demonstrated and changes in reactor safety have to be investigated like reactivity values, form-factors, Pu- and fission product inventory, safety margins and accidents. Calculations should be partly experimentally verified. The possible extent of the licensing procedure is discussed. (orig.) [de

Acceptance Test Procedure: SY101 air pallet system

International Nuclear Information System (INIS)

Koons, B.M.

1995-01-01

The purpose of this test procedure is to verify that the system(s) procured to load the SY-101 Mitigation Test Pump package fulfills its functional requirements. It will also help determine the man dose expected due to handling of the package during the actual event. The scope of this procedure focuses on the ability of the air pallets and container saddles to carry the container package from the new 100 foot concrete pad into 2403-WD where it will be stored awaiting final disposition. This test attempts to simulate the actual event of depositing the SY-101 hydrogen mitigation test pump into the 2403-WD building. However, at the time of testing road modifications required to drive the 100 ton trailer into CWC were not performed. Therefore a flatbed trailer will be use to transport the container to CWC. The time required to off load the container from the 100 ton trailer will be recorded for man dose evaluation on location. The cranes used for this test will also be different than the actual event. This is not considered to be an issue due to minimal effects on man dose

Methods and procedures of succession of generations

International Nuclear Information System (INIS)

Homann, A.; Bendzko, R.

2001-01-01

The presentation describes the methods and procedures of the succession of generations in the nuclear industry. The industrial development required specialised knowledge and creativity on a changing level. The relations ship between knowledge-transfer and transfer of the responsibility must be taken into account. The knowledge-transfer has to be planned as an investment. (authors)

CH2M Hill Hanford Group, Inc., Standards and Requirements Identification Document (SRID) Requirements Management System and Requirements Specification

International Nuclear Information System (INIS)

JOHNSON, A.L.

2000-01-01

The current Tank Farm Contractor (TFC) for the U. S. Department of Energy, Office of River Protection (ORP), River Protection Project (RPP), CH2M Hill Hanford Group, Inc. (CHG), will use a computer based requirements management system. The system will serve as a tool to assist in identifying, capturing, and maintaining the Standards/Requirements Identification Document (S/RID) requirements and links to implementing procedures and other documents. By managing requirements as one integrated set, CHG will be able to carry out its mission more efficiently and effectively. CHG has chosen the Dynamic Object Oriented Requirements System (DOORS(trademark)) as the preferred computer based requirements management system. Accordingly, the S/RID program will use DOORS(trademark). DOORS(trademark) will replace the Environmental Requirements Management Interface (ERMI) system as the tool for S/RID data management. The DOORS(trademark) S/RID test project currently resides on the DOORSTM test server. The S/RID project will be migrated to the DOORS(trademark) production server. After the migration the S/RID project will be considered a production project and will no longer reside on the test server

48 CFR 1344.302 - Requirements.

Science.gov (United States)

2010-10-01

... SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews § 1344.302 Requirements. The designee authorized to lower or raise the $25 million sales threshold for performing a review to determine if a contractor purchasing system review is needed is set forth in CAM 1301.70. ...

19 CFR 115.40 - Technical requirements for containers.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Technical requirements for containers. 115.40...; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Containers After Manufacture § 115.40 Technical requirements for...

40 CFR 86.206-11 - Equipment required; overview.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Equipment required; overview. 86.206-11 Section 86.206-11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... New Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.206-11 Equipment required...

40 CFR 86.206-94 - Equipment required; overview.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Equipment required; overview. 86.206-94 Section 86.206-94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... New Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.206-94 Equipment required...

Patient dose in interventional radiology: a multicentre study of the most frequent procedures in France

International Nuclear Information System (INIS)

Etard, Cecile; Bigand, Emeline; Salvat, Cecile; Vidal, Vincent; Beregi, Jean Paul; Hornbeck, Amaury; Greffier, Joel

2017-01-01

A national retrospective survey on patient doses was performed by the French Society of Medical physicists to assess reference levels (RLs) in interventional radiology as required by the European Directive 2013/59/Euratom. Fifteen interventional procedures in neuroradiology, vascular radiology and osteoarticular procedures were analysed. Kerma area product (KAP), fluoroscopy time (FT), reference air kerma and number of images were recorded for 10 to 30 patients per procedure. RLs were calculated as the 3rd quartiles of the distributions. Results on 4600 procedures from 36 departments confirmed the large variability in patient dose for the same procedure. RLs were proposed for the four dosimetric estimators and the 15 procedures. RLs in terms of KAP and FT were 90 Gm.cm 2 and 11 mins for cerebral angiography, 35 Gy.cm 2 and 16 mins for biliary drainage, 75 Gy.cm 2 and 6 mins for lower limbs arteriography and 70 Gy.cm 2 and 11 mins for vertebroplasty. For these four procedures, RLs were defined according to the complexity of the procedure. For all the procedures, the results were lower than most of those already published. This study reports RLs in interventional radiology based on a national survey. Continual evolution of practices and technologies requires regular updates of RLs. (orig.)

Patient dose in interventional radiology: a multicentre study of the most frequent procedures in France

Energy Technology Data Exchange (ETDEWEB)

Etard, Cecile [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France); French Society of Medical Physicists (SFPM), Paris (France); Bigand, Emeline [French Society of Medical Physicists (SFPM), Paris (France); La Timone University Hospital, Department of Radiology, Marseille Cedex (France); Salvat, Cecile [French Society of Medical Physicists (SFPM), Paris (France); Lariboisiere Hospital, Department of Medical Physics and Radiation Protection, Paris (France); Vidal, Vincent [La Timone University Hospital, Department of Radiology, Marseille Cedex (France); French Society of Radiology (SFR) - Interventional Radiology Federation (FRI), Paris (France); Beregi, Jean Paul [French Society of Radiology (SFR) - Interventional Radiology Federation (FRI), Paris (France); Nimes University Hospital, Medical Imaging Group Nimes, Department of Radiology, Nimes (France); Hornbeck, Amaury [French Society of Medical Physicists (SFPM), Paris (France); Trousseau University Hospital, Department of Pediatric Radiology, Paris (France); Greffier, Joel [French Society of Medical Physicists (SFPM), Paris (France); Nimes University Hospital, Medical Imaging Group Nimes, Department of Radiology, Nimes (France)

2017-10-15

A national retrospective survey on patient doses was performed by the French Society of Medical physicists to assess reference levels (RLs) in interventional radiology as required by the European Directive 2013/59/Euratom. Fifteen interventional procedures in neuroradiology, vascular radiology and osteoarticular procedures were analysed. Kerma area product (KAP), fluoroscopy time (FT), reference air kerma and number of images were recorded for 10 to 30 patients per procedure. RLs were calculated as the 3rd quartiles of the distributions. Results on 4600 procedures from 36 departments confirmed the large variability in patient dose for the same procedure. RLs were proposed for the four dosimetric estimators and the 15 procedures. RLs in terms of KAP and FT were 90 Gm.cm{sup 2} and 11 mins for cerebral angiography, 35 Gy.cm{sup 2} and 16 mins for biliary drainage, 75 Gy.cm{sup 2} and 6 mins for lower limbs arteriography and 70 Gy.cm{sup 2} and 11 mins for vertebroplasty. For these four procedures, RLs were defined according to the complexity of the procedure. For all the procedures, the results were lower than most of those already published. This study reports RLs in interventional radiology based on a national survey. Continual evolution of practices and technologies requires regular updates of RLs. (orig.)

26 CFR 301.6362-6 - Requirements relating to residence.

Science.gov (United States)

2010-04-01

... purposes other than its individual income tax (such as liability for State inheritance tax or jurisdiction...) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Seizure of Property for Collection of Taxes § 301.6362-6 Requirements relating to residence. (a) In general. A tax imposed by a State meets the...

14 CFR 61.87 - Solo requirements for student pilots.

Science.gov (United States)

2010-01-01

...; (5) Emergency procedures and equipment malfunctions; (6) Operation of hot air or gas source, ballast... balloon or an airship requiring more than one pilot flight crewmember. (b) Aeronautical knowledge. A... and procedures for pre-solo flight training in a balloon. A student pilot who is receiving training in...

Quality procedure management for improved nuclear safety

International Nuclear Information System (INIS)

Forzano, P.; Castagna, P.

1995-01-01

Emergency Operating Procedures and Accident Management Procedures are the next step in the computerization of NPP control rooms. Different improvements are presently conceivable for this operator aid tool, and research activities are in development. Undergoing activities regard especially formal aspects of knowledge representation, Human-Machine interface and procedure life cycle management. These aspects have been investigated deeply by Ansaldo, and partially incorporated in the DIAM prototype. Nuclear Power Plant Procedures can be seen from essentially two viewpoints: the process and the information management. From the first point of view, it is important to supply the knowledge apt to solve problems connected with the control of the process, from the second one the focus of attention is on the knowledge representation, its structure, elicitation and maintenance, and formal quality assurance. These two aspects of procedure representation can be considered and solved separately. In particular, methodological, formal and management issues require long and tedious activities, that in most cases constitute a great barrier for procedures development and upgrade. To solve these problems, Ansaldo is developing DIAM, a wide integrated tool for procedure management to support in procedure writing, updating, usage, and documentation. One of the most challenging features of DIAM is AUTO-LAY, a CASE sub-tool that, in a complete automatical way, structures parts or complete flow diagram. This is the feature that is partial present in some other CASE products, that, anyway, do not allow complex graph handling and isomorphism between video and paper representation. AUTO-LAY has the unique prerogative to draw graphs of any complexity to section them in pages, and to automatically compose a document. This has been recognized in the literature as the most important a second-generation CASE improvement. (Author) 9 Figs., 5 Refs

[The LESS (Laparo-endoscopic Single-Site) procedure in urology. Technical and clinical aspects].

Science.gov (United States)

Neri, F; Cindolo, L; Gidaro, S; Schips, L

2010-01-01

Minimally invasive urology is rapidly advancing, and single-site laparoscopic surgery is being explored clinically. Such laparoscopic procedures are technically challenging and require an experienced laparoscopic surgeon due to the lack of port placement triangulation and instrument clashing. In the last years several surgeons all over the world have explored the feasibility and safety of LESS using several and different ports, approaches and devices. Hundreds of procedures have been described with overall favorable intraoperative and postoperative outcomes. Our experience consists of more than 30 procedures successfully completed for adrenal, kidney disease and varicocele. To date, LESS could be considered feasible and effective using currently available devices, however it is to be considered as an initial status technique requiring further confirmatory studies and advanced laparoscopic skills.

40 CFR 60.2095 - What site-specific documentation is required?

Science.gov (United States)

2010-07-01

.... (5) Procedures for operating the incinerator and associated air pollution control systems within the... incinerator operating limits. (7) Reporting and recordkeeping procedures. (8) The waste management plan... required? 60.2095 Section 60.2095 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...

Geologic mapping procedure: Final draft

International Nuclear Information System (INIS)

1987-09-01

Geologic mapping will provide a baseline record of the subsurface geology in the shafts and drifts of the Exploratory Shaft Facility (ESF). This information will be essential in confirming the specific repository horizon, selecting representative locations for the in situ tests, providing information for construction and decommissioning seal designs, documenting the excavation effects, and in providing information for performance assessment, which relates to the ultimate suitability of the site as a nuclear waste repository. Geologic mapping will be undertaken on the walls and roof, and locally on the floor within the completed At-Depth Facility (ADF) and on the walls of the two access shafts. Periodic mapping of the exposed face may be conducted during construction of the ADF. The mapping will be oriented toward the collection and presentation of geologic information in an engineering format and the portrayal of detailed stratigraphic information which may be useful in confirmation of drillhole data collected as part of the surface-based testing program. Geologic mapping can be considered as a predictive tool as well as a means of checking design assumptions. This document provides a description of the required procedures for geologic mapping for the ESF. Included in this procedure is information that qualified technical personnel can use to collect the required types of geologic descriptions, at the appropriate level of detail. 5 refs., 3 figs., 1 tab

3(omega) Power Balance Procedure on the NIF

International Nuclear Information System (INIS)

Glenzer, S; Jones, O; Speck, D R; Munro, D; Lerche, R; Salmon, T; Bliss, E; Gates, A; Boyd, B; Auerbach, J; Williams, W; Saroyan, A; Kalantar, D; MacGowan, B; Zacharias, R; Hayman, C; Sacks, R

2001-01-01

This document defines the detailed NIF full system shot procedure to obtain 8% power balance as specified by the SDR002 3.2.1.04. Because the 48 quads of the NIF will be set up over a period of five years, obtaining power balance will naturally be accomplished in two steps. First, as each quad is brought online, the four laser beams within each quad will be tuned by setting the PABTS splitter ratios so that each beam will give the same laser power on target during low energy square pulse shots. During the quad activation period all of the technical tools and procedures will be developed that are needed for attaining full laser power balance. After the initial settings of the 48 PABTS, if no other tuning is done the overall NIF power balance is expected to be about <15%. In the second step, an iteration procedure with approximately 18 full laser system shots will be needed to obtain 8% power balance by tuning out the remaining systematic differences among the quads to an acceptable small difference of 2% rms (at 3ω). This rms difference is smaller than the expected variation of the injection energy or the amplifier gain, and is also of the same order as the laser energy diagnostic accuracy. Therefore, 8% power balance will require a number of precision measurements that will need accurate calibrations combined with a laser performance model that accounts and corrects for variations of the injection energy and the amplifier gain. This document is intended to specify the procedure and the flow-down of requirements from the system design requirement of 8% power balance. It is further intended to help guide the laser shot planning, the laser controls, and the laser performance operations model groups. It should provide input relevant to power balance tuning for the development of an operations model that includes post-shot analysis (as described in NIF-0046491), shot planning (as described in this memo), and pre-shot analysis

Regulations and Procedures Manual

Energy Technology Data Exchange (ETDEWEB)

Young, Lydia J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2011-07-25

The purpose of the Regulations and Procedures Manual (RPM) is to provide LBNL personnel with a reference to University and Lawrence Berkeley National Laboratory (LBNL or Laboratory) policies and regulations by outlining normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory organizations. Much of the information in this manual has been condensed from detail provided in LBNL procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. RPM sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the LBNL organization responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which organization is responsible for a policy, please contact Requirements Manager Lydia Young or the RPM Editor.

42 CFR 35.15 - Consent to operative procedures.

Science.gov (United States)

2010-10-01

... emergencies when the patient is physically or mentally incapable of consenting and the delay required to... operative procedure shall be undertaken unless the patient or, in the case of a minor or incompetent, his... or refusal of consent shall be made a part of the clinical record. ...

Refinement procedure for the image alignment in high-resolution electron tomography

International Nuclear Information System (INIS)

Houben, L.; Bar Sadan, M.

2011-01-01

High-resolution electron tomography from a tilt series of transmission electron microscopy images requires an accurate image alignment procedure in order to maximise the resolution of the tomogram. This is the case in particular for ultra-high resolution where even very small misalignments between individual images can dramatically reduce the fidelity of the resultant reconstruction. A tomographic-reconstruction based and marker-free method is proposed, which uses an iterative optimisation of the tomogram resolution. The method utilises a search algorithm that maximises the contrast in tomogram sub-volumes. Unlike conventional cross-correlation analysis it provides the required correlation over a large tilt angle separation and guarantees a consistent alignment of images for the full range of object tilt angles. An assessment based on experimental reconstructions shows that the marker-free procedure is competitive to the reference of marker-based procedures at lower resolution and yields sub-pixel accuracy even for simulated high-resolution data. -- Highlights: → Alignment procedure for electron tomography based on iterative tomogram contrast optimisation. → Marker-free, independent of object, little user interaction. → Accuracy competitive with fiducial marker methods and suited for high-resolution tomography.

Standard Review Plan Maintenance Program implementing procedures document

International Nuclear Information System (INIS)

1996-11-01

The implementing Procedures Document (IPD) was developed by the Inspection Program Projects Branch, Office of Nuclear Reactor Regulation, with assistance from Pacific Northwest National Laboratory, for the Standard Review Plan Maintenance Program (SRP-MP). The SRP-MP was established to maintain the Standard Review Plan (SRP) on an on-going basis. The IPD provides guidance, including an overall approach and procedures, for SRP-MP tasks. The objective of the IPD is to ensure that modifications to SRP need to reflect current NRC requirements and guidance are identified and that a consistent methodology is used to develop and revise SRP sections

A procedure for solving the neutron diffusion equation on a parallel micro-processor; modifications to the nodal expansion codes RECNEC and HEXNEC to implement the procedure

International Nuclear Information System (INIS)

Putney, J.M.

1983-05-01

The characteristics of a simple parallel micro-processor (PMP) are reviewed and its software requirements discussed. One of the more immediate applications is the multi-spatial simulation of a nuclear reactor station. This is of particular interest because 3D reactor simulation might then be possible as part of operating procedure for PFR and CDFR. A major part of a multi-spatial reactor simulator is the solution of the neutron diffusion equation. A procedure is described for solving the equation on a PMP, which is applied to the nodal expansion method with modifications to the nodal expansion codes RECNEC and HEXNEC. Estimations of the micro-processor requirements for the simulation of both PFR and CDFR are given. (U.K.)

Radiation exposure of an anaesthesiologist in catheterisation and electrophysiological cardiac procedures

International Nuclear Information System (INIS)

Andreoli, Stefano; Moretti, Renzo; Lorini, Ferdinando Luca; Lagrotta, Mariavittoria

2016-01-01

Sometimes, cardiac catheterisation and electrophysiological procedures, diagnostic and interventional, require an anaesthesiological support. The anaesthesiologist receives radiation doses depending on various factors, such as type of procedure and exposure modality, anaesthesiological technique, individual protective devices and operator experience. The aim of this study was to investigate the dose per procedure, the exposure inhomogeneity and the effective dose, E, of a senior anaesthesiologist in the haemodynamic laboratory of Ospedali Riuniti, Bergamo. The dose monitoring was routinely performed with sets of several thermoluminescent dosemeters and an electronic personal dosemeter. The study covered 300 consecutive procedures over 1 y. The anaesthesiologist wore a protective apron, a thyroid collar and glasses (0.5 mm lead-equivalent). (authors)

Military Publications, Index of Test Operations Procedures

Science.gov (United States)

1981-10-01

serial number, aad design information for majur components. Prescribes vehicle, major component, and system descrip- tive elements required; such as...mount operating characteristics. Discusses preparation for test, instrumentation, and facil- ities. Describes procedures for force measurement, carriage...backlash and accuracy, turret friction, gun balance, manual handcrank force , manual response ratio, weapon and sighting system backlash, power controller

Standardization of specifications and inspection procedures for LEU plate-type research reactor fuels

International Nuclear Information System (INIS)

1988-06-01

With the transition to high density uranium LEU fuel, fabrication costs of research reactor fuel elements have a tendency to increase because of two reasons. First, the amount of the powder of the uranium compound required increases by more than a factor of five. Second, fabrication requirements are in many cases nearer the fabrication limits. Therefore, it is important that measures be undertaken to eliminate or reduce unnecessary requirements in the specification or inspection procedures of research reactor fuel elements utilizing LEU. An additional stimulus for standardizing specifications and inspection procedures at this time is provided by the fact that most LEU conversions will occur within a short time span, and that nearly all of them will require preparation of new specifications and inspection procedures. In this sense, the LEU conversions offer an opportunity for improving the rationality and efficiency of the fuel fabrication and inspection processes. This report focuses on the standardization of specifications and inspection processes of high uranium density LEU fuels for research reactors. However, in many cases the results can also be extended directly to other research reactor fuels. 15 refs, 1 fig., 3 tabs

14 CFR 11.38 - What public comment procedures does the FAA follow for Special Conditions?

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false What public comment procedures does the FAA... § 11.38 What public comment procedures does the FAA follow for Special Conditions? Even though the Administrative Procedure Act does not require notice and comment for rules of particular applicability, FAA does...

49 CFR 1511.9 - Accounting and auditing requirements.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Accounting and auditing requirements. 1511.9... SECURITY INFRASTRUCTURE FEE § 1511.9 Accounting and auditing requirements. (a) Each air carrier and foreign... fairness and reasonableness of the air carrier's and foreign air carrier's procedures used for accounting...

10 CFR 11.13 - Special requirements for transportation.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Special requirements for transportation. 11.13 Section 11.13 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR... Authorization § 11.13 Special requirements for transportation. (a) All individuals who, after 365 days following...

High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

Science.gov (United States)

Inoue, Satoki; Kawaguchi, Masahiko; Sakamoto, Takanori; Kitaguchi, Katsuyasu; Furuya, Hitoshi; Sakaki, Toshisuke

2002-07-01

group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group. Amrinone at an infusion rate of 15 or 5 microg x kg(-1) x min(-1) with a reloading at the beginning of rewarming accelerated the rewarming rate of core temperature during deliberate mild hypothermia. This suggests that high-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

Operating procedures and safety culture

International Nuclear Information System (INIS)

Carnino, A.

1993-01-01

The development of new technologies in recent years has led to a tremendous increase in the information to be mastered by operators in industrial processes. The information at operators disposal both in routine situations and accidental ones needs to be well prepared and organized to ensure reliability and safety. The man-machine interface should give operators all the necessary and clear indications on the process status and evolution so that the operators can operate the installation through adequate procedures. Procedures represent the real interface and mode of action of the operators on the machine, and they are of prime importance. Although they are by essence quite different, the routine, accident, and emergency procedures have in common one attribute: They all require a good safety culture both in their development and their implementation. From the definition given by the members of the International Nuclear Safety Advisory Group (INSAG), open-quotes Safety culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance,close quotes one can see that two aspects are embedded, a collective attitude that in fact is reflected in the managerial framework and an individual one that is linked to personnel behavior and work practices

A design procedure for the phase-controlled parallel-loaded resonant inverter

Science.gov (United States)

King, Roger J.

1989-01-01

High-frequency-link power conversion and distribution based on a resonant inverter (RI) has been recently proposed. The design of several topologies is reviewed, and a simple approximate design procedure is developed for the phase-controlled parallel-loaded RI. This design procedure seeks to ensure the benefits of resonant conversion and is verified by data from a laboratory 2.5 kVA, 20-kHz converter. A simple phasor analysis is introduced as a useful approximation for design purposes. The load is considered to be a linear impedance (or an ac current sink). The design procedure is verified using a 2.5-kVA 20-kHz RI. Also obtained are predictable worst-case ratings for each component of the resonant tank circuit and the inverter switches. For a given load VA requirement, below-resonance operation is found to result in a significantly lower tank VA requirement. Under transient conditions such as load short-circuit, a reversal of the expected commutation sequence is possible.

Refinement procedure for the image alignment in high-resolution electron tomography.

Science.gov (United States)

Houben, L; Bar Sadan, M

2011-01-01

High-resolution electron tomography from a tilt series of transmission electron microscopy images requires an accurate image alignment procedure in order to maximise the resolution of the tomogram. This is the case in particular for ultra-high resolution where even very small misalignments between individual images can dramatically reduce the fidelity of the resultant reconstruction. A tomographic-reconstruction based and marker-free method is proposed, which uses an iterative optimisation of the tomogram resolution. The method utilises a search algorithm that maximises the contrast in tomogram sub-volumes. Unlike conventional cross-correlation analysis it provides the required correlation over a large tilt angle separation and guarantees a consistent alignment of images for the full range of object tilt angles. An assessment based on experimental reconstructions shows that the marker-free procedure is competitive to the reference of marker-based procedures at lower resolution and yields sub-pixel accuracy even for simulated high-resolution data. Copyright © 2011 Elsevier B.V. All rights reserved.

Visual inspection requirements for high-reliability random-access memories

International Nuclear Information System (INIS)

Andrade, A.; McHenery, J.

1981-09-01

Visual inspection requirements are given for random-access memories for deep-space satellite electronics. The requirements, based primarily on Military Standard 883B, are illustrated in the order of their manufacturing operation to clarify and facilitate inspection procedures

Simplification and transformation of ASTM F1292 measurement procedure for fall accident injury criteria.

Science.gov (United States)

Kato, Maki; Shimodaira, Yoshie; Sato, Takeshi; Iida, Hiromi

2014-01-01

Protecting children from injuries caused by fall accidents from playground equipment is important. Therefore, measures toward minimizing the risk of fall accident injuries are required. The risk of injury can be evaluated using ASTM F1292. In this test, G-max and the HIC are used to estimate the risk of injury. However, the measurement procedure is too complicated for application to a large number of installed equipment. F1292 requires simplified by reducing the number of phases, even with a small risk of loss in accuracy. With this in mind, this study proposes a shortened measurement procedure and a transformation equation to estimate the risk as same as F1292. As the result of experiments, it was revealed that G-max and the HIC values for both procedures linearly increase with drop height. The differences in outcomes between the regression equations of the standardized procedure and those of the shortened procedure can be used as a correction value. They can be added to the value measured by the shortened procedure. This suggests that the combination of the shortened procedure and transformation equation would be equivalent to F1292, with the advantage of being more easily and efficiently applied to the evaluation of installed playground equipment.

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

Science.gov (United States)

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
.

Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

Science.gov (United States)

Agrawal, Shrutidevi; Singh, Inderjit; Kaur, Kanwal Jit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2004-05-19

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

Procedural Skills Education – Colonoscopy as a Model

Directory of Open Access Journals (Sweden)

Maitreyi Raman

2008-01-01

Full Text Available Traditionally, surgical and procedural apprenticeship has been an assumed activity of students, without a formal educational context. With increasing barriers to patient and operating room access such as shorter work week hours for residents, and operating room and endoscopy time at a premium, alternate strategies to maximizing procedural skill development are being considered. Recently, the traditional surgical apprenticeship model has been challenged, with greater emphasis on the need for surgical and procedural skills training to be more transparent and for alternatives to patient-based training to be considered. Colonoscopy performance is a complex psychomotor skill requiring practioners to integrate multiple sensory inputs, and involves higher cortical centres for optimal performance. Colonoscopy skills involve mastery in the cognitive, technical and process domains. In the present review, we propose a model for teaching colonoscopy to the novice trainee based on educational theory.

Towards Verification of Operational Procedures Using Auto-Generated Diagnostic Trees

Science.gov (United States)

Kurtoglu, Tolga; Lutz, Robyn; Patterson-Hine, Ann

2009-01-01

The design, development, and operation of complex space, lunar and planetary exploration systems require the development of general procedures that describe a detailed set of instructions capturing how mission tasks are performed. For both crewed and uncrewed NASA systems, mission safety and the accomplishment of the scientific mission objectives are highly dependent on the correctness of procedures. In this paper, we describe how to use the auto-generated diagnostic trees from existing diagnostic models to improve the verification of standard operating procedures. Specifically, we introduce a systematic method, namely the Diagnostic Tree for Verification (DTV), developed with the goal of leveraging the information contained within auto-generated diagnostic trees in order to check the correctness of procedures, to streamline the procedures in terms of reducing the number of steps or use of resources in them, and to propose alternative procedural steps adaptive to changing operational conditions. The application of the DTV method to a spacecraft electrical power system shows the feasibility of the approach and its range of capabilities

Procedures for field chemical analyses of water samples

International Nuclear Information System (INIS)

Korte, N.; Ealey, D.

1983-12-01

A successful water-quality monitoring program requires a clear understanding of appropriate measurement procedures in order to obtain reliable field data. It is imperative that the responsible personnel have a thorough knowledge of the limitations of the techniques being used. Unfortunately, there is a belief that field analyses are simple and straightforward. Yet, significant controversy as well as misuse of common measurement techniques abounds. This document describes procedures for field measurements of pH, carbonate and bicarbonate, specific conductance, dissolved oxygen, nitrate, Eh, and uranium. Each procedure section includes an extensive discussion regarding the limitations of the method as well as brief discussions of calibration procedures and available equipment. A key feature of these procedures is the consideration given to the ultimate use of the data. For example, if the data are to be used for geochemical modeling, more precautions are needed. In contrast, routine monitoring conducted merely to recognize gross changes can be accomplished with less effort. Finally, quality assurance documentation for each measurement is addressed in detail. Particular attention is given to recording sufficient information such that decisions concerning the quality of the data can be easily made. Application of the procedures and recommendations presented in this document should result in a uniform and credible water-quality monitoring program. 22 references, 4 figures, 3 tables

Retinal complications after aqueous shunt surgical procedures for glaucoma.

Science.gov (United States)

Law, S K; Kalenak, J W; Connor, T B; Pulido, J S; Han, D P; Mieler, W F

1996-12-01

To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

48 CFR 44.302 - Requirements.

Science.gov (United States)

2010-10-01

... during the next 12 months, perform a review to determine if a CPSR is needed. Sales include those... SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews 44.302 Requirements. (a) The ACO..., and the volume, complexity and dollar value of subcontracts. If a contractor's sales to the Government...

47 CFR 80.304 - Watch requirement during silence periods.

Science.gov (United States)

2010-10-01

....304 Section 80.304 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Safety Watch Requirements and Procedures Ship Station Safety Watches § 80.304 Watch requirement during silence periods. Each ship station operating on...

Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

Science.gov (United States)

Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

2013-11-01

The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 μl of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. Copyright © 2013 Elsevier B.V. All rights reserved.

An automated background estimation procedure for gamma ray spectra

International Nuclear Information System (INIS)

Tervo, R.J.; Kennett, T.J.; Prestwich, W.V.

1983-01-01

An objective and simple method has been developed to estimate the background continuum in Ge gamma ray spectra. Requiring no special procedures, the method is readily automated. Based upon the inherent statistical properties of the experimental data itself, nodes, which reflect background samples are located and used to produce an estimate of the continuum. A simple procedure to interpolate between nodes is reported and a range of rather typical experimental data is presented. All information necessary to implemented this technique is given including the relevant properties of various factors involved in its development. (orig.)

Automation of procedure writing for the RLWTF

International Nuclear Information System (INIS)

Farnham, M.; MacDonald, A.

1998-01-01

In August of 1997, the Radioactive Liquid Waste Treatment Facility (RLWTF) at Los Alamos National Laboratory (LANL) recognized the need to re-engineer document management business process. All nuclear facilities at LANL are required to ensure that both the latest approved revision of controlled documents and any changes to those documents are available to operating personnel at all times. The Nuclear Materials Technology (NMT) Division was also re-engineering its document management business processes and searching for a solution. Both groups contacted several internal and external organizations in search of potential software solutions in use that would meet requirements. This report describes the objectives and features required by the software package, the choice of Procedure Design as the software package, and its implementation

From document to database: modernizing requirements management

International Nuclear Information System (INIS)

Giajnorio, J.; Hamilton, S.

2007-01-01

The creation, communication, and management of design requirements are central to the successful completion of any large engineering project, both technically and commercially. Design requirements in the Canadian nuclear industry are typically numbered lists in multiple documents created using word processing software. As an alternative, GE Nuclear Products implemented a central requirements management database for a major project at Bruce Power. The database configured the off-the-shelf software product, Telelogic Doors, to GE's requirements structure. This paper describes the advantages realized by this scheme. Examples include traceability from customer requirements through to test procedures, concurrent engineering, and automated change history. (author)

Development of the material selection practice - a study exploring articulation of material requirements

DEFF Research Database (Denmark)

Lenau, Torben Anker; Hasling, Karen Marie

2014-01-01

indicates that students focus on technical requirements when using the matrix and justifying their selection of materials. This is surprising since the students attend an arts and crafts oriented design school and are encouraged and guided to consider non-technical requirements, as part of the course where...... the matrix is introduced. A possible reason for the undesired behavior could be that students are allowed very freely to define their own matrices, having only little guidance to which requirements to use. A more formal procedure for making the material matrices is therefore proposed. The procedure requires...

Misplaced Cervical Screws Requiring Reoperation.

Science.gov (United States)

Peterson, Jeremy C; Arnold, Paul M; Smith, Zachary A; Hsu, Wellington K; Fehlings, Michael G; Hart, Robert A; Hilibrand, Alan S; Nassr, Ahmad; Rahman, Ra'Kerry K; Tannoury, Chadi A; Tannoury, Tony; Mroz, Thomas E; Currier, Bradford L; De Giacomo, Anthony F; Fogelson, Jeremy L; Jobse, Bruce C; Massicotte, Eric M; Riew, K Daniel

2017-04-01

A multicenter, retrospective case series. In the past several years, screw fixation of the cervical spine has become commonplace. For the most part, this is a safe, low-risk procedure. While rare, screw backout or misplaced screws can lead to morbidity and increased costs. We report our experiences with this uncommon complication. A multicenter, retrospective case series was undertaken at 23 institutions in the United States. Patients were included who underwent cervical spine surgery from January 1, 2005, to December 31, 2011, and had misplacement of screws requiring reoperation. Institutional review board approval was obtained at all participating institutions, and detailed records were sent to a central data center. A total of 12 903 patients met the inclusion criteria and were analyzed. There were 11 instances of screw backout requiring reoperation, for an incidence of 0.085%. There were 7 posterior procedures. Importantly, there were no changes in the health-related quality-of-life metrics due to this complication. There were no new neurologic deficits; a patient most often presented with pain, and misplacement was diagnosed on plain X-ray or computed tomography scan. The most common location for screw backout was C6 (36%). This study represents the largest series to tabulate the incidence of misplacement of screws following cervical spine surgery, which led to revision procedures. The data suggest this is a rare event, despite the widespread use of cervical fixation. Patients suffering this complication can require revision, but do not usually suffer neurologic sequelae. These patients have increased cost of care. Meticulous technique and thorough knowledge of the relevant anatomy are the best means of preventing this complication.

AGREED-UPON PROCEDURES, PROCEDURES FOR AUDITING EUROPEAN GRANTS

Directory of Open Access Journals (Sweden)

Daniel Petru VARTEIU

2016-12-01

The audit of EU-funded projects is an audit based on agreed-upon procedures, which are established by the Managing Authority or the Intermediate Body. Agreed-upon procedures can be defined as engagements made in accordance with ISRS 4400, applicable to agreed-upon procedures, where the auditor undertakes to carry out the agreed-upon procedures and issue a report on factual findings. The report provided by the auditor does not express any assurance. It allows users to form their own opinions about the conformity of the expenses with the project budget as well as the eligibility of the expenses.

In Vitro Procedures with Radioisotopes in Medicine. Proceedings of the Symposium on In Vitro Procedures with Radioistopes in Clinical Medicine and Research

International Nuclear Information System (INIS)

1970-01-01

Radioactive tracer techniques are now being widely used in the study of substances of medical interest in vitro. The introduction of tracer techniques often leads to a considerable improvement in established medical laboratory procedures. Tracer techniques also form the basis of certain special procedures for the measurement of hormones, vitamins and other substances in specimens of blood, urine, body tissues, etc.; these techniques are of such elegance and simplicity that they may readily be carried out in the average medical radioisotope laboratory without the need for additional specialized equipment. In none of these procedures is radioactive material administered to the patient; indeed, they do not require his direct participation at all and may well be carried out in some central laboratory on specimens sent in from a wide area. They may thus freely be used in investigations on all classes of patient and are. particularly suitable for use in regions where local facilities are limited or where field studies are to be undertaken. Progress in these applications of tracer techniques was discussed in the Symposium on In Vitro Procedures with Radioisotopes in Clinical Medicine and Research, organized by the International Atomic Energy Agency in co-operation with the World Health Organization. The symposium was held in Vienna from 8 to 12 September 1969, and the full Proceedings appear in the present volume. A total of 191 participants nominated by 32 countries and 3 international organizations attended, and the 50 papers presented, which cover the applications of tracer, techniques in cytological studies, immunological studies, derivative, dilution and enzymatic analysis, saturation analysis, thyroid function studies and radioimmunoassay, indicate the great variety of in vitro procedures now in use. Invited review papers deal with the general aspects of the various main groups of applications. Many of the procedures discussed are still in the developmental stage

Clinical experience with the Bentall procedure: 28 years.

Science.gov (United States)

Joo, Hyun-Chel; Chang, Byung-Chul; Youn, Young-Nam; Yoo, Kyung-Jong; Lee, Sak

2012-09-01

We retrospectively analyzed 28 years of experience with the Bentall procedure in patients with aortic valve, aortic root, and ascending aortic disease. Between March 1982 and December 2010, a total of 218 patients underwent the Bentall procedure using a composite valved conduit. The "inclusion technique" was used in 30 patients (13.8%), the "open-button technique" in 181 patients (83.0%), and the Cabrol technique in 7 patients (3.2%). The early mortality rate was 5.5% (12/218). The mean follow-up duration was 108.0±81.0 months (range: 1-329 months). Seven patients required re-operation, and 1 patient required stent graft insertion at the descending thoracic aorta for progression of aortic arch or descending thoracic aortic dissection or aneurysm after the first operation, and 5 of them had Marfan syndrome. Kaplan-Meier estimated survival rates at 1, 5, 10, 20, and 25 years were 90.4%, 82.7%, 77.6%, 65.3%, and 60.3%, respectively. Freedom from reoperation rates at 1, 5, 10, 20, and 25 years were 99.0%, 98.3%, 95.5%, 90.8%, and 90.8%, respectively. In our experience, the Bentall procedure provided optimal survival with improved functional status. The disease of the aorta may progress, especially in patients with Marfan syndrome. Therefore, careful follow-up with regular computed tomography angiograms should be performed in these patients.

14 CFR 1261.603 - Procedures for salary offset.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Procedures for salary offset. 1261.603... salary offset. If NASA is both the paying and creditor agency, the following requirements must be met... of the debt through salary offset by deductions from the employee's current disposable pay, stating...

Development of transportation operations requirements

International Nuclear Information System (INIS)

Grady, S.T.; Best, R.E.; Danese, F.L.; Peterson, R.W.; Pope, R.B.

1990-01-01

Transport conditions at various utility sties vary dramatically in terms of characteristics at and near the site, requirements, administrative procedures, and other factors. Continuation of design efforts for the OCRWM transportation operations system requires that the operating requirements for the transportation system -- quantity of fuel per unit time per site -- be identified so that the effect the variations have on the system can be accommodated. The approach outlined in this paper provides for an identification of specific sites, evaluation of shipment capabilities at each site, and integration of the sites into multi-site shipping campaigns to scope the logistics management problem for the transportation operations system. 1 fig., 1 tab