Comment from Bhasker Sambar

Technical Comments on FDA-2026-N-0809 Recommendations on Scale-Up and Post approval Changes (SUPAC), Guidance for Industry Date: July 10, 2026 Prepared by: Bhasker Sambar, Sr. Manager, External R&D and Technical Services Dear FDA Review Team, I am submitting the following technical comments in response to Docket No. FDA‑2026‑N‑0809, Recommendations on Scale-Up and Postapproval Changes Guidances for Industry; Request for Comments. My comments reflect 15 years of practical experience in complex pharmaceutical development, tech transfer, and CMC operations, and are not associated with my current or previous companies. Please feel free to contact me if any clarification is needed. Sincerely, Bhasker Sambar Email: bashu1986@gmail.com Sr. Manager, External R&D 1. Consolidate SUPAC into a Common Core Framework FDA should consider reorganizing the SUPAC guidance series into a single core document supported by appendices for each dosage form. The core guidance would include shared definitions, change‑level principles, documentation expectations, and general decision logic for classifying changes. Appendices could then address expectations for: Immediate‑release solid oral dosage forms Modified‑release solid oral dosage forms Nonsterile semisolid dosage forms Manufacturing equipment Long‑acting injectables This structure would reduce duplication and make SUPAC easier to use for applicants managing multiple dosage forms or change types. 2. Add a SUPAC–ICH Q12 Crosswalk FDA should clarify how SUPAC change levels interact with ICH Q12 tools such as established conditions, PACMPs, and lifecycle management documents. Specific scenarios needing clarification include: When a change falls within an approved established‑condition range When a change is already covered by an approved PACMP When a change affects parameters not identified as established conditions When a change affects established conditions requiring supplements or prior approval How lifecycle commitments and monitoring plans should be considered alongside SUPAC recommendations A crosswalk would reduce uncertainty and support consistent application of SUPAC within modern lifecycle management. 3. Modernize Dissolution, IVRT, IVPT, and Q3 Expectations FDA should update SUPAC recommendations for in vitro performance testing and product characterization. For immediate‑release and modified‑release solid oral dosage forms, FDA could clarify: When single‑medium or multimedia dissolution is expected When multipoint profile comparison is needed When alternatives to f₂ similarity are acceptable (e.g., rapid dissolution, high variability, non‑discriminatory methods) For nonsterile semisolid dosage forms, SUPAC‑SS should align with modern Q3 expectations, including: Rheology and viscosity pH Globule or particle‑size distribution Polymorphic form and phase behavior Assay and impurities Preservative effectiveness (where applicable) IVRT and IVPT expectations A dedicated appendix titled Recommended In Vitro Performance and Characterization Data Package by Dosage Form and Change Level would make expectations clearer without altering the SUPAC risk‑based approach. 4. Update Equipment‑Change Evaluation Based on Operating Principle FDA should revise the SUPAC Manufacturing Equipment Addendum to focus on operating principle, process impact, and potential effects on CQAs rather than equipment names or vendors. Examples of evaluation factors include: Operating principle (e.g., diffusion blending vs. high‑shear mixing) Product‑contact materials Energy or shear input Heat and mass transfer characteristics Residence time or hold time Control strategy, including PAT and automated controls This approach would help applicants justify low‑risk equipment changes more clearly. 5. Add a Scale‑Up Equivalence Checklist FDA should consider adding a checklist to help applicants document scientific comparability between approved and scaled processes. Key factors by unit operation include: Blending: fill ratio, geometry, mixing time, rotation speed, lubrication time Wet granulation: binder addition rate, impeller/chopper speed, torque or power profile Drying: bed depth, inlet/exhaust conditions, airflow, product temperature Compression: compression force, dwell time, turret speed, tablet attributes Coating: spray rate, atomization air, temperature profile, coating uniformity Semisolid manufacturing: mixing shear, homogenization, temperature profile, cooling rate Continuous manufacturing: residence‑time distribution, diversion strategy, startup/shutdown controls A checklist would promote consistent documentation and support modern process understanding.