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Scale - Up and Post Approval Changes SUPAC Presented By:- Sonia  P. Nagvenkar 1
Index Definition Scientific Rational SUPAC Guidelines – SUPAC IR, SUPAC – MR, SUPAC –SS Levels of Change Components and composition Manufacturing Site Changes Batch size change (Scale up) Manufacturing change : Process & Equipment Limitations of SUPAC 2
Bioequivalent to the FDA reference listed drug (RLD)product Generic Drug Product Larger Batch size  ANDA or AADA approved by FDA SCALE UP 3
What is SUPAC In 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
Scientific Rationale 5 to expedite the processes of post approval changes of drug products  FDA can assure their safety and effectiveness.  lower the regulatory burden for industry.
6 The 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).
SUPAC  GUIDELINES - DEFINE ,[object Object]
Moderate change
Major change
Application / Compendial Tests
In Vitro Dissolution / Release
In Vivo
Annual Report
Changes Being Effected Supplement
Prior Approval SupplementLevel of  Changes Tests Filing 7
	Likelihood of impact on formulation quality and performance Level  1: unlikely to have detectable impact Level  2: could have significant impact Level  3: likely to have significant impact  Levels  of change 8
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
Components & Composition 10 This section focuses on changes in excipients in the drug product SUPAC-MR: Excipient critical or non critical to the drug release.   - Changes in non release controlling excipients   - Changes in release controlling excipients SUPAC-SS: Changes in preservative
SUPAC - IR 11
12
13
SUPAC – MR   Non Release Controlling Excipients 14
SUPAC – MR   Release Controlling Excipients 15
SUPAC – SS    Components and Composition 16
SUPAC – SS    Components and Composition - Preservative 17
Manufacturing Site Changes changes in location of the site of manufacture, packaging operations  and/or analytical testing laboratory do 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
19
20
21
Batch Size Change (Scale Up) changes in the size of a batch from the pivotal/pilot scale biobatch material to larger production batches compliance with CGMP's No change in SOP, formulation and manufacturing procedures or equipments used All scale-up changes should be properly validated the 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
23
Manufacturing Changes 24 Changes affecting:     - Equipments     - Manufacturing process Appropriate validation studies are conducted

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Supac

  • 1. Scale - Up and Post Approval Changes SUPAC Presented By:- Sonia P. Nagvenkar 1
  • 2. Index Definition Scientific Rational SUPAC Guidelines – SUPAC IR, SUPAC – MR, SUPAC –SS Levels of Change Components and composition Manufacturing Site Changes Batch size change (Scale up) Manufacturing change : Process & Equipment Limitations of SUPAC 2
  • 3. Bioequivalent to the FDA reference listed drug (RLD)product Generic Drug Product Larger Batch size ANDA or AADA approved by FDA SCALE UP 3
  • 4. What is SUPAC In 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 Rationale 5 to expedite the processes of post approval changes of drug products FDA can assure their safety and effectiveness. lower the regulatory burden for industry.
  • 6. 6 The 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.
  • 15. Prior Approval SupplementLevel of Changes Tests Filing 7
  • 16. Likelihood of impact on formulation quality and performance Level  1: unlikely to have detectable impact Level  2: could have significant impact Level  3: likely to have significant impact  Levels  of change 8
  • 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 & Composition 10 This section focuses on changes in excipients in the drug product SUPAC-MR: Excipient critical or non critical to the drug release. - Changes in non release controlling excipients - Changes in release controlling excipients SUPAC-SS: Changes in preservative
  • 20. 12
  • 21. 13
  • 22. SUPAC – MR Non Release Controlling Excipients 14
  • 23. SUPAC – MR Release Controlling Excipients 15
  • 24. SUPAC – SS Components and Composition 16
  • 25. SUPAC – SS Components and Composition - Preservative 17
  • 26. Manufacturing Site Changes changes in location of the site of manufacture, packaging operations and/or analytical testing laboratory do 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
  • 27. 19
  • 28. 20
  • 29. 21
  • 30. Batch Size Change (Scale Up) changes in the size of a batch from the pivotal/pilot scale biobatch material to larger production batches compliance with CGMP's No change in SOP, formulation and manufacturing procedures or equipments used All scale-up changes should be properly validated the 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
  • 31. 23
  • 32. Manufacturing Changes 24 Changes affecting: - Equipments - Manufacturing process Appropriate validation studies are conducted
  • 33. Manufacturing Changes - Equipments 25
  • 35. 27
  • 36. 28
  • 37. Dissolution Profile Comparison Using Similarity Factor, f2 FDA 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  handbook 30
  • 40. 32