The document discusses the Scale-Up and Post Approval Changes (SUPAC) guidelines issued by the FDA for generic drug products, detailing changes in components, manufacturing processes, and batch sizes. It outlines three main categories of SUPAC changes for immediate-release, modified-release, and non-sterile semisolid dosage forms, emphasizing the need for validation and compliance with current good manufacturing practices. Additionally, it highlights the importance of dissolution profile comparisons and notes limitations such as outdated guidelines and the need for supplementary references.

1. Scale - Up and Post Approval ChangesSUPACPresented By:- Sonia P. Nagvenkar1

2. IndexDefinitionScientific RationalSUPAC Guidelines – SUPAC IR, SUPAC – MR, SUPAC –SSLevels of ChangeComponents and compositionManufacturing Site ChangesBatch size change (Scale up)Manufacturing change : Process & EquipmentLimitations of SUPAC2

3. Bioequivalent to the FDA reference listed drug (RLD)productGeneric Drug ProductLarger Batch size ANDA or AADA approved by FDASCALE UP3

4. What is SUPACIn the process of developing a new drug product, the batch sizes used in the earliest human studies are small. The size of the batches is gradually increased (Scale - up). The scale-up process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as Scale-Up and Post approval Changes, or SUPAC. 4

5. Scientific Rationale5to expedite the processes of post approval changes of drug products FDA can assure their safety and effectiveness. lower the regulatory burden for industry.

6. 6The FDA has issued various guidances for SUPAC changes designated as A. SUPAC-IR (for immediate-release solid oral dosage forms), B. SUPAC-MR (for modified-release solid oral dosage forms), and C. SUPAC-SS (for non-sterile semisolid dosage forms including creams, ointments, gels, and lotions).

7. SUPAC GUIDELINES - DEFINEMinor change

8. Moderate change

9. Major change

10. Application / Compendial Tests

11. In Vitro Dissolution / Release

12. In Vivo

13. Annual Report

14. Changes Being Effected Supplement

15. Prior Approval SupplementLevel of ChangesTestsFiling7

16. Likelihood of impact on formulation quality and performanceLevel 1: unlikely to have detectable impactLevel 2: could have significant impactLevel 3: likely to have significant impact Levels of change8

17. These guidelines provide recommendations for post approval changes in (1) the components or composition, (2) the site of manufacture,(3) the scale-up of manufacture, and (4) the manufacturing (process and equipment) 9

18. Components & Composition10This section focuses on changes in excipients in the drug productSUPAC-MR: Excipient critical or non critical to the drug release. - Changes in non release controlling excipients - Changes in release controlling excipientsSUPAC-SS: Changes in preservative

19. SUPAC - IR11

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22. SUPAC – MR Non Release Controlling Excipients14

23. SUPAC – MR Release Controlling Excipients15

24. SUPAC – SS Components and Composition16

25. SUPAC – SS Components and Composition - Preservative17

26. Manufacturing Site Changeschanges in location of the site of manufacture, packaging operations and/or analytical testing laboratorydo not include any scale-up changes, changes in manufacturing (including process and/or equipment), or changes in components or composition. current Good Manufacturing Practice (CGMP) inspection.18

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30. Batch Size Change (Scale Up)changes in the size of a batch from the pivotal/pilot scale biobatch material to larger production batchescompliance with CGMP'sNo change in SOP, formulation and manufacturing procedures or equipments usedAll scale-up changes should be properly validatedthe minimum batch size for the pivotal clinical trial batch or biobatch be at least 100000 dosage units /100 kg or 10%of a production batch, whichever is larger.22

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32. Manufacturing Changes24Changes affecting: - Equipments - Manufacturing processAppropriate validation studies are conducted