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 They argue that the current framework is outdated and overly prescriptive, and they recommend transitioning to a science- and risk-based approach that aligns with modern ICH quality frameworks to reduce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.

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supports the proposed action to revise and improve the SUPAC guidances, arguing that the current documents are outdated and inconsistent.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.

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.

Muhammad Ahmed Qamar, a Regulatory Affairs Scientist, supports updating the SUPAC-IR guidance to align with modern ICH guidelines, global regulatory standards, and current manufacturing technologies. He argues for a targeted update that maintains the existing risk-based framework while adding clarity through decision tables, worked examples, and technology-neutral terminology to reduce industry confusion and duplication.

The Consumer Healthcare Products Association (CHPA) supports the FDA's efforts to update the SUPAC guidances and suggests specific improvements to enhance clarity and consistency. They advocate for a more structured, risk-based framework that aligns with international standards, incorporates modern quality system tools, and addresses current gaps such as oral liquid dosage forms.

Amneal Pharmaceuticals LLC supports the FDA's information solicitation regarding SUPAC guidances and recommends updating them to reflect modern manufacturing technologies and risk-based principles. The company argues for consolidating the guidances, harmonizing terminology with other FDA regulations, and incorporating more flexible, science-driven approaches for various dosage forms and complex generics.

Zhejiang Hisun Pharmaceutical Co., Ltd. provides detailed technical feedback and specific questions regarding the proposed scale-up and postapproval change guidances. They advocate for clearer definitions of "same" equipment/SOPs, more nuanced classifications for site and batch size changes, and the inclusion of specific excipient categories and injection products in the guidance.

The International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) supports the FDA's initiative to modernize the SUPAC guidances. They argue that the updates should align with modern regulatory science, such as Quality by Design (QbD) and ICH Q12, while moving away from rigid numerical thresholds toward science-based, risk-based control strategies.

The Association for Accessible Medicines (AAM) supports the FDA's risk-based approach to CMC changes but argues that the current SUPAC guidances are a confusing patchwork that needs consolidation into a single, structured framework. They recommend harmonizing these guidances with international standards (like ICH Q12), updating outdated numerical limits to allow for more flexibility, and expanding coverage to include complex products and modern manufacturing technologies.