Pharmacogenetic Approaches to Optimize Bioequivalence Studies in Generic Drug Development

Given the significant impacts of interindividual genetic variability on drug safety and pharmacokinetics, integrating pharmacogenetic (PGx) considerations into pharmacokinetic (PK) bioequivalence (BE) study design can improve subject safety and data robustness in generic drug development. While PGx...

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Bibliographic Details
Published in:Journal of clinical pharmacology Vol. 65; no. 11; pp. 1598 - 1608
Main Authors: Bae, Jihyun, Shon, Jihong, Kim, Myong‐Jin, Li, Karen
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01.11.2025
Subjects:
Bioequivalence
bioequivalence studies with pharmacokinetic endpoints
Cytochrome P450
Drug development
Drug Development - methods
Drugs, Generic - pharmacokinetics
Gene polymorphism
generic drug development
Generic drugs
Genetic variability
Humans
Information processing
Pharmacogenetics - methods
pharmacogenetics/pharmacogenomics
Pharmacokinetics
Pharmacovigilance
product‐specific guidances
regulatory/scientific affairs
Therapeutic Equivalency
United States
United States Food and Drug Administration
United States
generic drug development
bioequivalence studies with pharmacokinetic endpoints
product‐specific guidances
pharmacogenetics/pharmacogenomics
regulatory/scientific affairs
ISSN:0091-2700, 1552-4604, 1552-4604
Online Access:Get full text
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Summary:Given the significant impacts of interindividual genetic variability on drug safety and pharmacokinetics, integrating pharmacogenetic (PGx) considerations into pharmacokinetic (PK) bioequivalence (BE) study design can improve subject safety and data robustness in generic drug development. While PGx information has been often utilized in new drug development, its use in generic drug development has not been fully considered. To understand the current landscape of its utility in generic drug development, product‐specific guidances (PSGs) from the US Food and Drug Administration (FDA) containing PGx information were reviewed, along with study protocols submitted by generic drug applicants under abbreviated new drug applications (ANDAs) or controlled correspondences for the identified reference listed drugs (RLDs). Fifteen PSGs (15 RLDs) recommended PGx information as a consideration factor for subject population selection, particularly for drugs associated with inherited enzyme deficiencies or cytochrome P450 polymorphism. The PGx‐based considerations in these PSGs aimed to prevent serious adverse events (60%), optimize PK BE study design (7%), or address both factors (33%). Among the 15 RLDs, 5 had submitted ANDAs or correspondences with PK BE study protocols after their respective PSGs were published. Most of these submissions aligned with the PSG recommendations, incorporating PGx‐related exclusion criteria. These findings suggest that while the number of submissions is low, generic drug developers are increasingly integrating PGx considerations in PK BE studies, recognizing its potential to enhance safety and efficiency in generic drug development. Continuing efforts from both regulators and industry are critical to expand its application to other drug candidates.
Bibliography:Dr. Myong‐Jin Kim is a Fellow of the American College of Clinical Pharmacology (FCP)
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ISSN:0091-2700
1552-4604
1552-4604
DOI:10.1002/jcph.70058