Recommendations on Scale-Up and Postapproval Changes Guidances for Industry; Request for Comments

Cytokinetics Inc. supports the FDA's request for comments on modernizing the SUPAC-IR and SUPAC-MR guidances. They argue that the current framework is outdated and overly prescriptive, and they recommend transitioning to a science- and risk-based approach that aligns with modern ICH quality frameworks to reduce regulatory burden while maintaining safety.

The commenter provides extensive technical feedback and specific recommendations for revising the SUPAC Guidance documents. They suggest aligning the guidance with ICH standards, harmonizing dissolution testing criteria, and streamlining redundant sections between different dosage form GUIs.

An anonymous commenter supports the proposed action to revise and improve the SUPAC guidances, arguing that the current documents are outdated and inconsistent. They recommend consolidating CMC change guidances, integrating ICH Q9 and Q12 standards, and expanding the scope to include continuous manufacturing and specific dosage form variations.

Lonza, a Contract Development and Manufacturing Organization (CDMO), supports the FDA's initiative to update the SUPAC guidances to align with modern science-based and risk-based approaches. They suggest incorporating specific guidance on co-processed excipients, modern manufacturing technologies, and packaging equipment to reduce regulatory uncertainty and improve lifecycle management.

Bhasker Sambar, a pharmaceutical development professional, supports the modernization of the SUPAC guidance series. He recommends consolidating the guidance into a common core framework with dosage-specific appendices, adding an ICH Q12 crosswalk, and updating expectations for in vitro testing, equipment evaluation, and scale-up equivalence.

Zydus Lifesciences Limited supports the SUPAC guidances as a critical framework but recommends updates to modernize them, reduce ambiguity, and align them with current scientific knowledge and ICH standards. They specifically advocate for consolidating overarching principles into a unified guidance, providing clearer risk-based decision frameworks, and developing new guidance for complex dosage forms.

The commenter recommends updating the relevant Guidances for Industry regarding Scale-Up and Postapproval Changes to align with the ICH Q12 framework. They also suggest updating the list of Narrow Therapeutic Range Drugs in Appendix A of the SUPAC-IR guidance.

Sumiya Mushtaq, a regulatory affairs professional and pharmacist, supports the proposed revisions to the SUPAC guidances but suggests specific improvements to enhance clarity and consistency. The commenter argues for more explicit documentation expectations, harmonization with the ICH Q12 framework, modernization of in vitro testing standards, and a consolidated structure to reduce submission deficiencies.

Viatris Inc. supports the FDA's efforts to update the SUPAC guidances, emphasizing the need to retain core risk-based principles while modernizing the framework. They argue for the removal of prescriptive elements, the inclusion of modern science-based tools (like QbD and PACMPs), and better harmonization with ICH guidelines to reduce regulatory burden and improve efficiency.

The Pathway for Patient Health Collaborative Community argues that the SUPAC guidance family should not be withdrawn without replacement or consolidation because it contains unique, product-specific quantitative frameworks and protocols not covered by ICH Q12 or the 2004 Changes guidance. They recommend specific consolidations and updates to preserve these "orphaned" contents while aligning with modern regulatory frameworks like ICH Q12 and ICH Q9.