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Supac

  1. 1. BY SAYEDA SALMA 1ST M PHARM
  2. 2. What is supac ? In the process of developing the new product , the batch size used in earliest human studies are small. The sizes of the batch is gradually increased(scale up). The scale up 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 (supac).
  3. 3. SUPAC The FDA has issued various guidance for supac changes designated as: Supac-IR ( for immediate release solid oral dosage form). Supac-MR (for modified release solid oral dosage form). Supac-SS (for non sterile semisolid dosage form including creams, ointments, gels and lotions).
  4. 4. Supac guidelines-define Level of changes • Minor changes • Moderate changes • Major changes filing • Annual report • Changes being affected supplement • Prior approval supplement tests • Application/compendial tests • In-vitro dissolution/release • In-vivo
  5. 5. Level of changes Likelihood of impact on formulation quality and performance: • Level 1: Those changes that are unlikely to have any detectable impact on formulation quality and performance. • Example- Changes in the colour, flavours, Changes In the excipient expressed as percentage (w/w) of total formulation, less than or equal to the following range .
  6. 6. • Level2: Changes are those that could have significant impact on the formulation quality and performance. • Example -Changes in the technical grade of excipient (Avicel PH102 vs Avicel PH200) Changes expressed as percent (w/w of total formulation) .
  7. 7. • Level3:  Level 3 : changes are those that are likely to have significant impact on formulation quality and performance. Example -Any qualitative or quantitative excipient changes a narrow therapeutic drug beyond the range for level 1 and All other drug not meeting the dissolution criteria as level 2.
  8. 8. These guidelines provide recommdation for post approval changes in: • In component or compostion • The site of manufacture • The scale up of manufacture • The manufacturing(process and equipment)
  9. 9. Component and composition changes SUPAC-IR:  Focus on changes in the amount of 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.
  10. 10. SUPAC-IR ( components and composition)
  11. 11. SUPAC-IR • 1)Focus on the changes in amount of excipients in the drug product. • 2)Not focus on change in the amount of the drug substance .
  12. 12. LEVEL CLASSIFICATION EXCIPIENT RANGES (%w/w of total formulation) TEST DOCUMENTATION FILING DOCUMENTA TION 1) • Delition or partial delition of an ingredient (colour , flavor or change in ingredient of the ink). • -Changes in excipients, expressed as % (w/w) of total formulation, less than or equal to excipient.  Filler  ±5 Disintegrant  Starch  ±1 Binder  ±0.5 Lubricant  Calcium (Ca)or Magnesium  (Mg) Stearate ±0.25  stability  Application/Co mpendial requirements  Annual report
  13. 13. LEVEL CLASSIFICATION EXCIPIENT RANGES (%w/w of total formulation) TEST DOCUMENTATION FILING DOCUMEN TATION 2)  Change in technical grade of excipient.  Changes in excipients, expressed as % (w/w) of total formulation, greater than Level 1 changes.  Filler  ±10 Disintegrant  Starch  ±6 Other  ±1 Binder  ±1 Lubricant  Calcium (Ca) or  Magnesium (Mg)  Stearate ±0.5  Other ±2 Glidant Talc ±2 Other ±0.2  -stability application/co mpendial requirements.  Dissolution data depends on solubility, therapeutic range and permeability.  Case A(hp-hs)  Case B(lp-hs)  Case C(hp-ls) •Prior approval supplement •Annual report
  14. 14. LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 3)  Higher than SUPAC- IR.  Level 1 and Level 2 excipient ranges.  stability application/compend ial requirements.  Case B dissolution profile (Multi-point dissolution profile in the application /compendial medium at 15, 30, 45, 60, and 120 minutes or until an asymptote is reached for the proposed and currently accepted formulation).   Biostudy or IVIVC •Prior approval supplement. •Annual report.
  15. 15. SUPAC-MR (components and composition)
  16. 16. SUPAC-MR Components and composition of non-release controlling excipient and release controlling excipient.  Focuses on changes to non-release controlling excipients.  Changes in components or composition that have the effect of adding a new excipient or deleting an excipient are defined at level 3.
  17. 17. Non-release controlling excipient LEVEL CLASSIFICATION TEST DOCUMENTATION FILING 1)  Delition or partial delition of an ingredient –up to SUPAC-IR Level 1 excipient ranges.  stability- application/compen dial requirements.  Annual report
  18. 18. LEVEL 2 2)  change in technical grade of excipients  up to SUPAC-IR Level 2 excipient ranges  stability application/compen dial requirements.  Multi-point dissolution profiles (15,30,45,60 & 120 min) USP buffer media at pH 4.57.5 for extended release) Three different Media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed release) •Prior approval supplement. •Annual report
  19. 19. LEVEL 3 3)  Higher than SUPAC-IR Level 1 and Level 2 excipient ranges.  -stability application/compen dial requirements.  Biostudy or IVIVC  Prior approval supplement
  20. 20. SUPAC-MR (release controlling excipient) LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  ≤ 5% w/w change based on total release controlling excipient content.  No other changes  Stability  application/compendi al requirements  Annual report
  21. 21. LEVEL 2 2)  change in technical grade of excipients.  ≤ 10% w/w change based on total release controlling excipient content.  stability application/compendi al requirements.  Multi-point dissolution profiles (15,30,45,60 & 120 min) USP buffer pH 4.5-7.5 for extended release) Three different Media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for DR release)  Prior approval supplement  Annual report
  22. 22. SUPAC-SS (components and composition)
  23. 23. SUPAC-SS • for non sterile semisolid dosage form including creams , ointments , gels and lotions.
  24. 24. SUPAC-SS (Components and composition) LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  Delition or partial delition of an ingredient.  change in supplier or technical grade of any other excipient.  Up to 5 % change in approved amount of ingredient  Stability  application/ compendial requirements  Annual report
  25. 25. LEVEL 2 2)  Upto >5 % and ≤ 10 % change in approved amount of ingredient.  Change in particle size distribution of the drug substance, if the drug is in Suspension.  change in supplier or technical grade of any other excipient  stability application/compe ndial requirements  in vitro release test  Changes being effected supplement  Annual report
  26. 26. LEVEL 3 3)  change in approved amount of ingredient.  Change in crystalline form of ingredient  Stability  application/comp endial requirements  Prior approval supplement
  27. 27. SUPAC-SS (preservative) LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1) Quantitatively 10% or less change in the approved amount of preservative.  application/comp endial requirements  Preservative effectiveness test at lowest specified preservative level Annual report
  28. 28. LEVEL 2 2)  10% -20 % change in the approved amount of preservative  application/comp endial requirements.  Preservative effectiveness test at lowest specified preservative level  Changes being effected supplem ent  Annual report
  29. 29. LEVEL 3 3)  > 20% change in the approved amount of preservative (including deletion) or use of a different preservative.  application/compen dial requirements - executed batch records.  For new preservative, analytical method for identification and assay validation studies.  Preservative effectiveness test at lowest specified preservative.  Prior approval supplement  Annual report
  30. 30. Site changes It includes the changes in location of the site of manufacturing facilities for both company owner and contract manufacturer. It does not include scale up
  31. 31. LEVEL 1 LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  Site change within a single facility.  No change in SOP, environmental conditions or equipment's used.  Common personnel's  application/co mpendial requirements Annual report
  32. 32. Level 2 2)  Same continuous campus  Common personnel  No other changes  application/compendial requirements.  Notification of Location of new site  Updated batch records.  SUPAC – MR : Multi-point dissolution profiles (15,30,45,60 & 120 min) USP buffer media at pH 4.5-7.5 for extended release) Three different Media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed release)until 80% of Drug Released.  Annual report  Changes being Effected Supplement
  33. 33. LEVEL 3 3)  Different campus  Different personnel  application/compendial requirements  Notification of Location of new site  Updated batch record  SUPAC –IR : Multi-point dissolution profile in the application and compendial medium  SUPAC – MR : Multi-point dissolution profiles (15,30,45,60 & 120 min) USP buffer media at pH 4.5-7.5 for extended release) Three different Media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed release).  Annual report  Prior approval supplement
  34. 34. Change in batch size (scale up of manufacture) Post approval changes in the size of a batch from the pivotal/pilot scale biobatch material to larger or smaller production. Post Scale down below 1,00,000 dosage units is not covered by this guideline. Scale down Scale up changes should be properly validated and if needed, inspected by appropriate agency personnel. Scale up
  35. 35. Level 1 LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  Change in batch size, up to and including a factor of 10 times the size of the pilot/biobatch  Updated batch records application/compendial requirements stability Annual report
  36. 36. Level 2 2)  Changes in batch size beyond a factor of ten times the size of the pilot or biobatch  No other changes  -Updated batch records - application/compendial requirements  Stability  SUPAC –IR Multi-point dissolution profiles.  SUPAC – MR -Multi-point dissolution profiles in multiple medias (e.g., USP buffer media at pH 4.5-7.5 for extended release) three other media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed o Annual report o Changes being effected by suppleme nt
  37. 37. MANUFACTURING CHANGES (equipment) LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  Alternate equipment of same design and principles Automated equipment's  Updated batch records  application/compendial requirements stability Annual report
  38. 38. LEVEL 2 2)  Change to equipment of different design and principle  Updated batch records application/compendial requirements  Stability  SUPAC –IR Multi-point dissolution profiles in multiple medias  SUPAC – MR -Multi-point dissolution profiles in multiple medias  Annual report  Changes being Effected Suppleme nt
  39. 39. MANUFACTURING CHANGES (PROCESS)  LEVEL CLASSIFICATION TEST DOCUMENTATION FILING DOCUMENTATION 1)  Adjustment of equipment operating conditions (operating speeds, mixing times)  Within approved application ranges  Updated batch records  application/compendial requirements  Stability Annual report
  40. 40. LEVEL 2 2)  Adjustment of equipment operating conditions (operating speeds, mixing times)  Beyond approved application ranges  SUPAC – SS Change in the process of combining two phases  -Updated batch records - application/compendial requirements  Stability  SUPAC-IR Multi-point dissolution profile.  SUPAC-MR -Multi-point dissolution profiles in multiple medias (e.g., USP buffer media at pH 4.5-7.5 for extended release) three other media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed release).  SUPAC-SS In vitro release test Documentation.  Annual report  Changes being Effected Suppleme nt
  41. 41. LEVEL 3 3)  Changes in the type of process used (e.g. wet granulation to direct compressio n  Updated batch records - application/compendial requirements -Stability - Biostudy or IVIVC.  SUPAC-IR Multi-point dissolution profile.  SUPAC-MR Multi-point dissolution profiles in multiple medias (e.g., USP buffer media at pH 4.5-7.5 for extended release) three other media (e.g., Water, 0.1N HCl, and USP buffer media at Ph 4.5 And 6.8 for delayed release)  Prior approval supplement  Annual report
  42. 42. LIMITATIONS OF SUPAC • Supac has not been updated ( 1995/97 for main guidelines ) • Does not discuss multiple changes • Does not cover modified equipment • Must be used in conjunction with other references ex: excipient handbook.

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