The bioequivalence of highly variable drugs and drug products

2005 ◽  
Vol 43 (10) ◽  
pp. 485-498 ◽  
Author(s):  
K.K. Midha ◽  
M.J. Rawson ◽  
J.W. Hubbard
Keyword(s):  
Highly Variable Drugs ◽  
Drug Products

Individual and Average Bioequivalence of Highly Variable Drugs and Drug Products

1997 ◽  
Vol 86 (11) ◽  
pp. 1193-1197 ◽  
Author(s):  
Kamal K. Midha ◽  
Maureen J. Rawson ◽  
John W. Hubbard
Keyword(s):  
Highly Variable Drugs ◽  
Average Bioequivalence ◽  
Drug Products

scholarly journals Pharmacogenetic perspectives in improving pharmacokinetic profiles for efficient bioequivalence trials with highly variable drugs: a review

2020 ◽  
pp. IPK02
Author(s):  
Pai-Jung Huang ◽  
Yunsheng Hsieh ◽  
Yan-Wen Huang ◽  
Li Ding ◽  
Chong Liu ◽  
...  
Keyword(s):  
Generic Drugs ◽  
Pharmacokinetic Studies ◽  
Metabolizing Enzymes ◽  
Highly Variable Drugs ◽  
Drug Products ◽  
Branded Drug ◽  
Coefficient Of Variability ◽  
Acceptance Limits ◽  
Study Designs ◽  
Screening Approaches

Conducting bioequivalence trials under traditional crossover study designs without exposing a large number of healthy volunteers to demonstrate two highly variable (%coefficient of variability greater than 30) test/reference (branded) drug products in different formulations to meet the standard 90% confidence interval criteria of relevant pharmacokinetic metrics between 0.80 and 1.25 and to maintain the consumer risk smaller than 5% has been a challenging task. Genetic polymorphisms encoding key drug-metabolizing enzymes can significantly influence absorption, distribution, metabolism and elimination of many highly variable generic drugs after administration. This article briefly reviews the case studies and examples of utilizing pharmacogenetic screening approaches in the recent literature to alleviate the resources and ethical burden of recruiting larger numbers of subjects in bioequivalence trials needed to perform pharmacokinetic studies for formulations of highly variable drug products without widening the bioequivalence acceptance limits.

scholarly journals Regulatory and Study Conditions for the Determination of Bioequivalence of Highly Variable Drugs

2009 ◽  
Vol 12 (1) ◽  
pp. 138 ◽  
Author(s):  
Laszlo Endrenyi ◽  
Laszlo Tothfalusi
Keyword(s):  
Point Estimate ◽  
Highly Variable Drugs ◽  
Geometric Means ◽  
Drug Products ◽  
Consumer Risk ◽  
Alternative Settings ◽  
Power Curves ◽  
Undesirable Outcome ◽  
Regulatory Criterion

Purpose. The FDA Working Group on Highly Variable (HV) Drugs recently presented interim procedures and conditions for determining the bioequivalence (BE) of HV drug products. They included analysis by the method of scaled average BE (SABE), a switching coefficient of variation of CVS = 30% and a regulatory standardized variation of CV0 = 25% for applying SABE, and the use of a secondary regulatory criterion restricting to 0.80-1.25 the point estimate for the ratio of estimated geometric means (GMR) of the two formulations. These conditions are scrutinized in the present communication. Methods. 3-period BE studies were simulated with various statistical and regulatory assumptions. Power curves, obtained by gradually increasing the true GMR, compared performances of the methods of SABE, a constrained point estimate of GMR (PE/GMR), and the composite of these two approaches. The consumer risk of each procedure was evaluated. Results. With CV0 = 30% and PE/GMR = 0.80-1.25, the composite criterion of BE relied on the confidence limits of SABE. In contrast, with CV0 = 25% and/or PE/GMR = 0.87-1.15, the composite criterion approached almost completely the features of the GMR point estimate, especially at high within-subject variation. The consumer risk was near 5% with CV0 = 30% but much higher when CV0 = 25%. Conclusions. The condition of CVS = CV0 = 30% and PE/GMR = 0.80-1.25 is recommended as a composite regulatory criterion. With alternative settings of the conditions, such as the recommended CV0 = 25% and/or PE/GMR = 0.87-1.15, the composite criterion would reflect almost entirely the GMR point estimate. This would be an undesirable outcome.

Prescribability and switchability of highly variable drugs and drug products

1999 ◽  
Vol 62 (1-2) ◽  
pp. 33-40 ◽  
Author(s):  
K.K Midha ◽  
M.J Rawson ◽  
J.W Hubbard
Keyword(s):  
Highly Variable Drugs ◽  
Drug Products

Bioequivalence Approaches for Highly Variable Drugs and Drug Products

2007 ◽  
Vol 25 (1) ◽  
pp. 237-241 ◽  
Author(s):  
Sam H. Haidar ◽  
Barbara Davit ◽  
Mei-Ling Chen ◽  
Dale Conner ◽  
LaiMing Lee ◽  
...  
Keyword(s):  
Highly Variable Drugs ◽  
Drug Products

A Computerized Prescription Writing Program for Doctors

1985 ◽  
Vol 24 (02) ◽  
pp. 101-105
Author(s):  
C. S. Brown ◽  
S. I. Allen ◽  
D. C. Songco
Keyword(s):  
Medical Record ◽  
Drug Prescriptions ◽  
Computer Assisted ◽  
Writing Program ◽  
Typing Skill ◽  
Drug Products ◽  
Default Options ◽  
Almost All ◽  
Prescription Writing ◽  
Drug Dosages

SummaryA computer-assisted system designed to write drug prescriptions and patient instructions has been in operation in a dermatologist’s office for two years. Almost all prescriptions are generated by the machine. Drug dosages, directions, and labeling phrases are retrieved from a diagnosis-oriented formulary of 300 drug products. A prescription template with preselected default options is displayed on a terminal screen where selection is made with the use of the video pointer. Typing skill is not required, as a detailed prescription can be produced from the use of only five function keys. Prescriptions and sets of relevant instructions for the patient are computer-printed. Therapy summaries for the medical record also are automatically composed and printed.

Recycling of Drugs from Expired Drug Products

2016 ◽  
Author(s):  
RAJESH KOMARAGIRI
Keyword(s):  
Drug Products ◽  
Expired Drug

3D Printing in Pharmaceuticals: Regulatory Perspective

2019 ◽  
Vol 24 (42) ◽  
pp. 5081-5083 ◽  
Author(s):  
Mohd. A. Mirza ◽  
Zeenat Iqbal
Keyword(s):  
New Technologies ◽  
Pharmaceutical Product ◽  
Regulatory Agencies ◽  
Major Research ◽  
Data Bases ◽  
Drug Products ◽  
Regulatory Perspective ◽  
Regulatory Guidelines ◽  
Recent Developments ◽  
Technical Issues

Background: The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medical device and others, has recently forayed into the pharmaceutical industry.Commonly understood as an additive manufacturing technology, 3DP aims at delivering customized drug products and is the most acceptable form of“personalized medicine”. Methods: Data bases and search engines of regulatory agencies like USFDA and EMA have been searched thoroughly for relevant guidelines and approved products. Other portals like PubMed and Google Scholar were also ferreted for any relevant repository of publications are referred to wherever required. Results: So far only one pharmaceutical product has been approved in this category by USFDA and stringent regulatory agencies are working over the drafting of guidelines and technical issues. Major research of this category belongs to the academic domain. Conclusion: It is also implicit to such new technologies that there would be numerous challenges and doubts before these are accepted as safe and efficacious. The situation demands concerted and cautious efforts to bring in foolproof regulatory guidelines which would ultimately lead to the success of this revolutionary technology.

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