Supac
- 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
- 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
- 33. Manufacturing Changes - Equipments25
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- 37. Dissolution Profile Comparison Using Similarity Factor, f2FDA has placed more emphasis on a dissolution profile comparison in the area of post-approval changes Among several methods investigated for dissolution profile comparison, f2 is the simplest. f2 = 50 + log {[1+ (1/n) ∑t=1 * n (Rt-Tt)2]-0.5 *100} (where Rt and Tt are the cumulative percentage dissolved at each of the selected n time points of the reference and test product respectively. When the two profiles are identical, f2=100. FDA has set a public standard of f2 value between 50-100 to indicate similarity between two dissolution profiles.29
- 38. SUPAC limitations SUPAC: ► has not been updated (1995/97 for main guides) ► does not discuss multiple changes ► does not cover modified equipment ► must be used in conjunction with other references, e.g. excipient handbook30
- 39. Thank You31
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