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 They argue that the current framework is outdated and overly prescriptive, and they recommend transitioning to a science- and risk-based approach that aligns with modern ICH quality frameworks to reduce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supports the proposed action to revise and improve the SUPAC guidances, arguing that the current documents are outdated and inconsistent.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.

The commenter provides specific technical feedback and detailed definitions regarding pharmaceutical manufacturing processes, including particle size reduction, blending, granulation, and coating. They specifically request clarifications on the distinction between vibrating and tumbling mills, thermal degradation in hot melt granulation, and residence time calibration in melt extrusion.

The commenter argues that the current SUPAC guidance for Manufacturing Equipment Addendum lacks specific scale-up principles and strategies for larger equipment. They provide a detailed technical framework for scale-up strategies across various pharmaceutical processes (e.g., milling, blending, granulation, drying) to be included in the new guidance.

The American Association of Pharmaceutical Scientists (AAPS) supports the proposed guidance but requests specific updates to include continuous manufacturing technologies, nanomills, acoustic mixing, and amorphous solid dispersions. They also advocate for expanding excipient categories to include lipid-based drug delivery systems and clarifying risk assessments for manufacturing transfers between different organizations (e.g., CDMOs).

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 argues that the current SUPAC guidance for Manufacturing Equipment Addendum lacks essential scale-up principles and strategies for commercial production. They provide specific technical details and "scale-up factors" for various pharmaceutical processes (such as milling, blending, and granulation) and urge the FDA to include these in the new guidance to prevent industry mistakes.