Comment from Mushtaq Sumiya

Re: Comments on possible revisions to the SUPAC guidances — a submission-quality and dossier-preparation perspective (Docket No. FDA-2026-N-0809) To the FDA Center for Drug Evaluation and Research, Office of Pharmaceutical Quality: Thank you for the opportunity to comment on possible revisions to the Agency's series of guidances for industry on scale-up and post-approval changes (SUPAC-IR, SUPAC-IR Questions and Answers, SUPAC-SS, SUPAC-MR, and the Manufacturing Equipment Addendum). I am a pharmacist (PharmD) and regulatory affairs professional with hands-on experience preparing ICH-harmonized Common Technical Document (CTD) submissions across international markets, and my research examines the determinants of submission quality in ANDA approval timelines. I offer the following input from a manufacturer / applicant-side, dossier-preparation perspective. 1.The risk-based reporting framework remains sound; the practical gap is applicant-side clarity on documentation expectations. The core SUPAC principle, tiering CMC change reporting by the likelihood that a change affects identity, strength, quality, purity, or potency, continues to serve its purpose well. In practice, however, a meaningful share of postapproval-change deficiencies traces not to the risk logic itself but to ambiguity about what testing and documentation are expected for a given change level. Revisions that make the expected data package for each change category more explicit, with clearer worked illustrations, would reduce avoidable back-and-forth at review and help applicants assemble a complete change submission the first time. 2.Align SUPAC documentation expectations with the ICH Q12 lifecycle framework. Since the SUPAC guidances were issued, ICH Q12 introduced Established Conditions and the Product Lifecycle Management document as structured tools for managing post approval CMC changes on a risk basis. Where SUPAC reporting categories and Q12 reporting-category concepts overlap, applicants would benefit from explicit guidance on how the two frameworks relate, so that a change is not classified one way under SUPAC and another way under a Q12-based established-conditions analysis. Harmonizing the vocabulary and decision logic would reduce inconsistency in how applicants document the same change. 3.Modernize the in vitro dissolution and in vitro release testing expectations. The dissolution (IR/MR) and in vitro release (semisolid) testing recommendations are central to SUPAC's in vitro documentation expectations, and analytical and modeling practice has advanced considerably since the guidances were issued. Revisions that address current dissolution method development and validation, the use of multimedia and biorelevant dissolution where appropriate, and the role of model-based approaches (including, where justified, physiologically based biopharmaceutics modeling) in supporting a postapproval change would help applicants build a defensible, contemporary bioequivalence rationale and reduce reliance on in vivo studies where in vitro evidence is sufficient. 4.Clarify the dividing line between SUPAC reporting and the need for in vivo bioequivalence. A recurring source of applicant uncertainty is when a level-2 or level-3 change can be supported by in vitro data alone versus when an in vivo bioequivalence study is expected. Revisions that sharpen this boundary, with criteria tied to change type, dosage form, and the strength of the available in vitro evidence, would let applicants make and document the right call before filing rather than discovering a gap at review. 5.Consolidate and cross-reference for usability. The SUPAC guidances are spread across multiple documents, and a separate Equipment Addendum, and applicants frequently must reconcile them with later, broader CMC postapproval-change guidance. A consolidated structure, or at minimum clear cross-references and a single decision framework spanning the dosage forms, would make the guidance easier to apply correctly and reduce the misclassification errors that drive avoidable deficiencies. These comments reflect a view that a meaningful portion of postapproval-change review burden is tractable at the point of submission preparation, by making documentation expectations explicit, modernizing the in vitro evidence framework, and harmonizing SUPAC with the current ICH lifecycle approach. I appreciate the Agency's openness to public input and would welcome the opportunity to contribute further. Respectfully submitted, Sumiya Mushtaq, PharmD, MBA, Regulatory Affairs Professional, drsumiyamushtaq28@gmail.com https://www.linkedin.com/in/sumiya-mushtaq