FDA Signals Potential Updates to SUPAC Guidances—Comments Due June 1, 2026

The FDA has issued a notice announcing the opening of a public docket to solicit information and comments on its longstanding Scale-Up and Postapproval Changes (SUPAC) guidances for specific dosage forms. The request signals the Agency’s interest in reassessing these documents in light of evolving science and regulatory practice.

Background on the SUPAC Guidances

The SUPAC guidances were developed by FDA in the 1990s. They introduced a risk-based approach for evaluating chemistry, manufacturing, and controls (CMC) changes that could affect a drug product’s identity, strength, quality, purity, or potency as these relate to safety and effectiveness. Their core intent was to reduce the regulatory burden associated with certain CMC changes to approved applications where those changes were not likely to adversely affect product quality and therefore product safety and efficacy.

The SUPAC guidances describe recommended testing and documentation for:

• Component and composition changes
• Manufacturing process and equipment changes
• Manufacturing scale changes
• Manufacturing site changes

Based on the SUPAC guidances, applicants are required to assess the effects of CMC changes and categorize them (e.g., major, moderate, or minor), with corresponding reporting requirements prior to distribution.

Which Guidances Are Under Review?

FDA is seeking comment on the continued utility of, and potential revisions to, the following guidances:

• SUPAC-IR – Immediate Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation
• SUPAC-IR Q&A – SUPAC-IR Questions and Answers about SUPAC-IR Guidance
• SUPAC-SS – Nonsterile Semisolid Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation
• SUPAC-MR – Modified Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation
• SUPAC-MEA – SUPAC: Manufacturing Equipment Addendum

What Information Is FDA Requesting?

FDA is seeking public input on:

1. Continued Utility
   • Which recommendations remain helpful and meaningful?
   • Are SUPAC risk principles being used beyond supporting CMC changes?
2. Challenges in Interpretation or Application
   • Are any sections no longer relevant or meaningful?
   • Are applicants able to effectively determine the type and level of change (major, moderate, minor) based on the guidances?
   • Are there areas of overlap or inconsistency within SUPAC guidances or between SUPAC and other FDA CMC guidances?
3. Clarity and Organization
   • Should FDA reorganize or consolidate the guidances?
   • Should certain recommendations from other FDA guidances be incorporated?
   • How can SUPAC be better aligned with current risk assessment and postapproval lifecycle management principles and tools?
4. New Topics
   • Are there additional topics that should be addressed?

FDA encourages commenters to provide specific rationale and supporting data where available.

Why Is FDA Conducting This Request for Comments?

Although FDA affirms that the core principle of a risk-based approach to CMC changes remains relevant, it acknowledges that:

• The SUPAC guidances were finalized nearly three decades ago (with one later update).
• The science of pharmaceutical manufacturing and risk assessment tools has evolved.
• Subsequent guidances may supersede or potentially conflict with aspects of SUPAC.

FDA is therefore considering whether updates are warranted to ensure the guidances reflect current expectations, contemporary scientific and technical considerations, and the Agency’s current thinking on risk-based approaches to CMC changes.

How to Submit Comments

Interested stakeholders may submit comments via the “Submit a Public Comment” button in the Federal Register docket for the ‘Recommendations on Scale-Up and Postapproval Changes Guidances for Industry; Request for Comments’ notice.

Deadline for Comments

To ensure consideration before FDA begins work on potential revisions, comments must be submitted by June 1, 2026.

Key Takeaways

FDA’s notice presents an opportunity to influence the future direction of FDA’s risk-based framework for CMC changes for specific dosage forms. FDA is seeking input on the practical utility, clarity, and alignment of SUPAC guidances in light of evolving science and regulatory practice.

Stakeholders who rely on SUPAC guidances for reducing the number of CMC changes that require approval of a supplemental application should consider whether the guidances continue to serve their intended purpose and where clarification, consolidation, or revision may be warranted—and submit comments by June 1, 2026.