MFDS Releases Guideline on Assessing Identity of Active Ingredients in Generic Drugs (Guide-1452-01)

The document outlines the guidelines for assessing the identity of active ingredients in generic drugs, emphasizing the importance of understanding data requirements, evaluation methods, bioequivalence testing, batch variation, pharmacologic equivalence, and the overall regulatory framework to ensure compliance with safety and efficacy standards.

Note: The original document date is 31-Oct-2025, while it was publicly made available on 11-Nov-2025.

The document covers the following key points:

Purpose:
This guideline assists applicants and reviewers in understanding the data requirements for evaluating the identity of the active ingredient in a generic drug. It also highlights the role of pharmacologic equivalence and bioequivalence testing in establishing comparability with the reference drug.

Scope:
These guidelines pertain to generic drugs with identical active ingredients and administration routes as the reference drug, emphasizing clinical safety and efficacy. They also consider batch variation and its potential impact on pharmacologic equivalence. General recommendations apply to each active ingredient in fixed-combination drug products.

Data requirements:
Drugs used in the test include a reference drug compared to the test drug, aligned with the Standards for Pharmaceutical Equivalence Tests under Article 3-2. Evaluation items must consider main ingredient characteristics, physicochemical properties, batch variation, and factors affecting safety and effectiveness. Test methods are categorized based on source—methods from a process book cite the reference, while other methods are fully detailed. In addition, bioequivalence testing and scientifically justified evaluation methods form part of the supporting evidence to ensure similarity with the reference drug.

Evaluation of identity of main components:
Identity assessment compares the test drug's main ingredient to the reference drug, validating the reference's approval and usage. Pharmacologic equivalence is confirmed through appropriate evaluation methods considering chemical characteristics. Non-covalent derivatives (complexes, chelates, inclusion complexes) may be classified by chemical form. The main ingredient may exist as polymorphs or co-crystals; identity evaluation is typically based on chemical form, while also ensuring no significant batch variation that may impact quality, safety, or efficacy."