Converging Generic Drug Product Development: Bioequivalence Design and Reference Product Selection

Area of Science:

• Pharmaceutical Sciences
• Regulatory Affairs
• Drug Development

Background:

• Regulatory agencies worldwide have differing criteria for selecting reference products in bioequivalence (BE) studies.
• These variations necessitate repetitive BE studies for the same generic product in different global markets, increasing costs and ethical concerns.

Purpose of the Study:

• To analyze current regulatory policies on reference product selection for pharmaceutical equivalence (PE) and BE studies.
• To discuss the cost implications of disparate regulatory practices.
• To explore opportunities for harmonizing reference product selection criteria to reduce repetitive BE studies.

Main Methods:

• Review of regulatory guidance documents from major global jurisdictions.
• Comparative analysis of criteria for generic product definition, BE study design, and reference product selection.
• Presentation of a case study illustrating potential harmonization and its economic benefits.

Main Results:

• Significant differences exist in reference product selection criteria across major regulatory authorities.
• Repetitive BE studies lead to substantial financial burdens and increased drug exposure for study participants.
• Harmonization presents a viable strategy for streamlining BE study requirements.

Conclusions:

• Harmonizing reference product selection criteria can lead to a single BE study accepted by multiple regulatory agencies.
• This harmonization promises substantial reductions in operational costs for generic drug development.
• Minimizing repetitive studies also decreases the exposure of healthy individuals to investigational drugs.