US FDA Recommendations on Sameness Evaluation of Active Ingredient in ANDAs

US FDA Recommendations on Active Ingredients in ANDAs: Highlights

Through the guidance, the US FDA is helping applicants who are preparing an abbreviated new drug application (ANDA) by offering suggestions on how to demonstrate the similarity between the active ingredient in a proposed generic drug product and its Reference Listed Drug (RLD) as mandated in the Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the FDA’s regulations in 21 CFR 314.94(a)(5).

An ANDA depends on the agency’s earlier determination of safety and effectiveness for an RLD. Consequently, it may be approved without providing the same level of information needed for a new drug application (NDA) filed under the Section 505(b) of the FD&C Act. An ANDA must include details demonstrating that the active ingredient in the proposed generic drug product is identical to that of the RLD. Applicants should thoroughly assess the possible changes to or in the active ingredient during the drug product’s manufacturing process.

The FDA would deny approval of an ANDA if it would lack adequate information to establish that, among other factors, the active ingredient in the proposed generic drug is identical to RLD. Therefore, it is the responsibility of the ANDA applicant to supply enough information to prove that the proposed generic drug product is the “same as” the RLD concerning the active ingredient.

Tips for ANDA application

1. Whenever the chemical form of an active ingredient is purposefully altered throughout the drug product’s manufacturing process, the altered form needs to be checked for sameness.
2. To learn more about the chemical form of the active ingredient, consult the labeling sections of the RLD on dosage forms, strengths, description, and clinical pharmacology.
3. An active ingredient must satisfy either pharmacopeial or suitable internal standards, which are appropriately supported by orthogonal approaches.
4. Examine product-specific guidance (such as the need for pharmacodynamic data) to comprehend particular testing specifications needed to prove the sameness of an active ingredient.
5. Consult the FDA for additional guidance via pre-ANDA meetings or controlled correspondence.
6. To prove sameness, use different batches to characterize RLD and generic medication under comparable circumstances.
7. In case of mixtures, provide as many distinct components as possible and scientific justification to show how each component is identical to the reference.

APCER’s Regulatory Capabilities

Characterizing the drug substance and assessing its sameness in a generic application in comparison to the RLD during development would help the ANDA applicants to avoid queries (or refusal from the FDA to receive the application), which in turn would help the industry save time and resources. APCER’s team of Chemistry, Manufacturing and Controls (CMC) regulatory experts can provide suitable assessment during the early development phase of a drug product, so that appropriate data can be generated for a generic drug in comparison to its RLD. This would in turn streamline the development process and ensure compliance and the likelihood of successful market entry. Let APCER be your trusted ally in achieving your regulatory goals efficiently and effectively.