Current Bioequivalence Study Designs in South Korea: A Comprehensive Analysis of Bioequivalence Study Reports Between 2013 and 2019

Abstract

Demonstration of bioequivalence (BE) is mandatory while developing generic drugs. The scientific concept of BE applies equally to different regulatory agencies. However, the application of the concept may differ for each agency, which can affect the design of BE studies. To evaluate the study practices in terms of the BE concept in South Korea, we retrospectively analyzed BE study reports available from Ministry of Food and Drug Safety between 2013 and 2019. Statistical estimation of the pharmacokinetic parameters, including peak concentration and area under the concentration–time curve to the last measurable concentration, as well as study design, number of subjects in a study, study duration, fasting status, and formulation of specific drugs were obtained. The drugs were classified per World Health Organization Anatomical Therapeutic Chemical Classification and Biopharmaceutics Classification System. Post-hoc intrasubject coefficient of variation and corresponding sample sizes were calculated from the 90% confidence intervals of pharmacokinetic parameters. A total of 143 generic drugs in 588 BE studies were analyzed. The largest number of studies were performed in the area of Cardiovascular system (172 studies), followed by Nervous system (143 studies) and Alimentary tract and metabolism (92 studies). Overall, BE studies in South Korea were conducted in accordance with the global guideline despite the differences in details. BE studies were focused on the several therapeutic areas and conducted in a similar manner. The number of subjects was generally larger than that estimated with 90% power.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects

“…Several design aspects of the accepted bioequivalence trials in our study share similarities with those submitted to other regulators [13,14,19]. This similarity can be attributed to the common adoption of a 2 × 2 crossover Fig.…”

“…The extracted CVws from the accepted trials (for both single APIs and fixed combinations) were assessed in relation to the trial sample size , trial design, and the different BCS classes (the recent Korean review found that highly variable drugs are mostly BCS Class II or IV [i.e. drugs with poor solubility]) [14]. Reasons for rejecting the submission of bioequivalence trials or for rejecting their results were explored in addition to the success rate of study centers per country.…”

“…pharmacokinetic parameter estimation, bioequivalence testing) [11][12][13]. A comprehensive design characterization was only provided by one study which covered bioequivalence trials that were assessed by the Ministry of Food and Drug Safety in South Korea [14]. However, the latter study excluded trials that did not demonstrate bioequivalence and those conducted for fixed-combination products.…”

Trends of clinical trials from 2017 to 2019 in Korea: an integrated analysis based on the Ministry of Food and Drug Safety (MFDS) and the Clinical Research Information Service (CRIS) registries

“…As more than half of the phase 1 trials were associated with fixed combination drugs or new formulations of marketed drugs in Korea [ 19 ], the trends of clinical trials could be influenced by several popular drug classes. Similarly, bioequivalence trials highly focused in several therapeutic areas were reported in another study [ 20 ].…”

Factors influencing drug switching and changes in low-density lipoprotein-cholesterol levels with atorvastatin: a real-world observational study

“…A generic drug is one whose active ingredients are equivalent to those of the original drug (also known as the reference or brand-name drug), has passed bioequivalence testing, and has been approved by regulatory authorities for interchangeable applications with the original drug [ 1 – 3 ]. Generics typically enter the market at a lower price than that of the original drugs; therefore, they provide numerous benefits such as reduced healthcare costs and enhanced patient access to medical care.…”