FDA seeks feedback on overhaul of its SUPAC guidelines

The US Food and Drug Administration (FDA) is seeking public feedback on whether its scale-up and post-approval changes (SUPAC) guidance documents for the pharmaceutical industry need to be updated and modernized.

The agency is interested in comments regarding whether the International Council on Harmonisation’s (ICH) guidelines on quality risk management under ICH Q9 and post-approval changes under ICH Q12 either supersede or conflict with recommendations in the SUPAC guidelines.

The notice concerns five guidance documents: immediate-release dosage forms (IR), modified-release (MR) dosage forms, and non-sterile semi-solid dosage forms. It also covers a manufacturing equipment addendum (SUPAC-MEA) as well as a question-and-answer guidance on the IR guidance.

FDA published the first SUPAC guidance on IR dosage forms in November 1995; the guidance set out the framework for assessing post-approval changes for the other dosage forms.

The risk-based approach for assessing post-approval manufacturing changes initially introduced in the SUPAC guidelines, was formally codified in Section 116 of the Food and Drug Administration Modernization Act (FDAMA) in November 1997. This section amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) by adding Section 506A, which outlines the procedures for making and reporting any chemistry, manufacturing and controls (CMC) changes to approved applications and abbreviated new drug applications (ANDAs).

In April 2004, FDA issued a final rule to implement section 506A of the FD&C Act. The rule requires applicants to evaluate how changes in CMC affect the identity, strength, quality, purity, and potency of a drug product, and the product's safety and effectiveness. Additionally, the final rule established classification categories to determine if CMC changes are major, moderate, or minor. Minor changes would only require the submission of an annual report, while major changes would necessitate the filing of a manufacturing supplement.

The notice requesting feedback said that “we have determined that the SUPAC guidances may benefit from additional public comment on the topics outlined in this notice to ensure that these guidances align with current expectations, risk assessment strategies, and contemporary scientific and technical considerations.”

FDA further notes that “the effectiveness of the SUPAC guidances may be impacted by subsequent guidances (e.g., ICH Q9(R1) and ICH Q12), where particular recommendations in those guidances either supersede or potentially conflict with certain recommendations in the SUPAC guidances.”

FDA is requesting public comment on several questions, including:

Are there sections of the SUPAC guidances that should be retained?
Are there any challenges with respect to interpreting or applying the recommendations in the SUPAC guidances?
Does FDA need to provide clarity on the recommendations in the SUPAC guidances?
Is there a need for new topics that should be added to the SUPAC guidances?

FDA is currently looking at alternative ways to modernize its approach to regulating post-approval changes. Under its PreCheck program, FDA gave the go-ahead for firms to build manufacturing facilities if they locate in the US. This program is unlike SUPAC which manages changes to a product after it is approved. (RELATED: This Week at FDA: PreCheck manufacturing program, new FDA chief counsel, and more, Regulatory Focus 8 August 2025)

SUPAC notice

FDA seeks feedback on overhaul of its SUPAC guidelines

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