Population Bioequivalence

Current Regulatory Standpoint on Evaluating the Bioequivalence of Different Classes of Generic Drugs - Is the Evaluation in the Right Direction?

Current Drug Metabolism ◽

10.2174/1389200220666191007152542 ◽

2019 ◽

Vol 20 (10) ◽

pp. 835-844 ◽

Cited By ~ 1

Author(s):

Francis Micheal ◽

Mohanlal Sayana ◽

Balamurali Musuvathi Motial

Keyword(s):

Generic Drugs ◽

Bibliographic Databases ◽

Eligibility Criteria ◽

Individual Bioequivalence ◽

Population Bioequivalence ◽

Standard Tool ◽

Review Question ◽

Guidance Documents ◽

The Right

Background: The concept of evaluating bioequivalence has changed over a period of time. Currently, the Average Bioequivalence approach (ABE) is the gold standard tool for the evaluation of generics. Of late, many debates had arisen about employing ABE approach for the appraisal of all drug categories. This review aims to examine the limitations of ABE approach and the significances of Population Bioequivalence (PBE) and Individual Bioequivalence (IBE) approach, current regulatory thinking for assessing different categories of the drug, whether they are adequately assessed, and the evaluation is in the right direction. Methods: We carried out an organized search of bibliographic databases for peer-reviewed research literatures, regulatory recommendations, guidance documents using a focused review question and eligibility criteria. The standard tools were used to appraise the quality of retrieved documents and to make sure the authenticity of the data. Results: In total 73 references were used in the review, the majority of the references (guidance documents) were from the different regulatory agencies and product-specific guidance. There were 29 product-specific guidance from USFDA and EMA. The limitations of the ABE approach were discussed in detail along with the significances of Population Bioequivalence (PBE) approach and Individual Bioequivalence (IBE) approaches. Conclusion: It is apparent from the review that IBE approach is a precise method for evaluating the drugs as it answers drug interchangeability (prescribability and switchability). IBE approach is followed by PBE approach and ABE approach for the evaluation of different categories of drugs in terms of precision.

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Has the Time Come to Employ Population and Individual Bioequivalence for the Evaluation of Generics?

Current Drug Metabolism ◽

10.2174/1389200221666200401105119 ◽

2020 ◽

Vol 21 (2) ◽

pp. 112-125

Author(s):

Francis Micheal ◽

Mohanlal Sayana ◽

Rajendra Prasad ◽

Balamurali Musuvathi Motilal

Keyword(s):

Therapeutic Index ◽

Bioequivalence Study ◽

Open Label ◽

Statistical Parameters ◽

Population Mean ◽

Average Bioequivalence ◽

Individual Bioequivalence ◽

Population Bioequivalence ◽

Enteric Coated ◽

Bioequivalence Assessment

Background: Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses drug interchangeability as it considers only population mean for the evaluation especially when highly variable drug products and narrow therapeutic index drugs are dealt with. Hence, the alternative approaches like population bioequivalence and individual bioequivalence assessment approaches emerge as they consider inter/intra-subject variance and subject- by-formulation variance along with population mean. Objectives: The objective of the study was to apply different bioequivalence assessment approaches in a replicate bioequivalence study to evaluate the drug interchangeability. Methods: This was an open-label, single-dose, randomized, balanced, two-treatment, three-period, three-sequence, partial replicate crossover bioequivalence study of omeprazole enteric-coated tablet 20 mg conducted on 48 normal healthy subjects under fed conditions. The plasma concentration of omeprazole was analyzed by a validated bioanalytical method to determine the pharmacokinetic and statistical parameters to assess average bioequivalence, population bioequivalence, and individual bioequivalence. Results: In this study, test formulation was shown to be bio-inequivalent to the reference formulation by average bioequivalence, population bioequivalence, and individual bioequivalence approaches. Conclusion: The outcome of the evaluation clearly states that the bioequivalence outcome of all these approaches are the same. Obviously, it does not mean that these three approaches provide the same outcome though the consideration of variances varies. Certainly, population bioequivalence and individual bioequivalence approach will be more accurate for the assessment of drug interchangeability.

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