SUPAC(Scale Up and Post Approval changes for RA 1st sempptx

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1. Scale Up and Post Approval changes (SUPAC) 1 Prepared By : Charmi shah 2308212170009

2. CONTENTS 2

3. What is SUPAC? 3

4. P urpose of Guidelines This guidance provides recommendations to sponsors of new drug applications (NDA's), abbreviated new drug applications (ANDA's), and abbreviated antibiotic applications (AADA's) who intend, during the post approval period, to change: The components or composition The site of manufacture The scale-up/scale-down of manufacture The manufacturing (process and equipment) of an immediate release oral formulation. 4

5. A series of documents were issued by US FDA (CDER) to help applicants with post-approval changes. Currently finalized SUPAC guidance are as below : SUPAC-IR(immediate release) -Nov 1995. SUPAC-IR Ques and Answers- Feb 1997. SUPAC –MR(modified release)- Sep 1997. SUPAC SS(non sterile semisolid)- May 1997. (CDER- Centre for Drug Evaluation and Research) 5

6. SUPAC Guideline: Defines 6

7. LEVEL CHANGES Level 1 Those change that are unlikely to have any detectable impact on formulation quality and performance. E.g. Changes in the colour, flavours changes in the excipient express as the percentage (w/w)of total formulation, less than or equal to the following range. Level 2 Changes are those that could have significant impact on the formulation quality and performance. E.g. changes in the technical grade of excipient changes expressed as percent level 2 change. Level 3 Those that are likely to have significant impact on formulation quality and performance. E.g Any qualitative or quantitative excipient changes to a narrow therapeutic drug beyond the range for level 1 all other drug not meeting the dissolution criteria as per level 2. 7

8. Requirements for Post A pproval C hanges Components and composition of drug product Change in batch size Manufacturing equipment change Manufacturing site change 8

9. A)Components and Composition of Drug P roduct SUPAC-IR: Focus on changes in the amount of excipients in the drug product. 2. SUPAC-MR:  Excipient critical or non critical to the drug release.  9

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11. Component and Composition IR Level Classification Excipients range %w/w of total formulation Test Documentation Filling 1 Deletion/ partial deletion of ingredient (colour, flavour, etc) Filler ±5 Starch ±3 Stability application/ Annual compendial requirements report Annual repórt Changes in excipients less than or equal to. Lubricant Ca/Mg. stearate ± 0.25 2 Change in technical grade of excipients Filler±10 Stability application/ compendial requirements Depends on solubility, therapeutic range and permeability Case A,B,C Prior approval supplement Changes in excipients greater than level 1 Starch (±)6 Annual repórt 11

12. 12 Level classification Excipients range %w/w of total formulation Test Filling 3 Higher than level 1 and 2 excipient changes - Stability application/ compendial requirements Case B Biostudy / IVIVC Prior approval supplement Annual repórt

13. SUPAC MR: Component and composition 13 LEVEL CLASSIFICATION TEST DOCUMENTATION FILING 1 Deletion or partial deletion of an ingredient up to SUPAC-IR Level 1 . Stability Application/compendi al requirements. Annual report 2 Change in technical grade of excipients Stability Application/compendi al requirements. Prior approval supplement

14. LEVEL CLASSIFICATION TEST DOCUMENTATION FILING 3 Higher than SUPAC-IR Level 1 and Level 2 excipient Stability application/compendial requirements. Prior approval supplement 14

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16. Change in batch IR Level Classification Test Filling 1 Change in batch size up to 10 times more of pilot batch Update batch record/ Application/ compendial Requirements/stability Annual report 2 Change in batch size beyond 10 times more of pilot batch No other changes Application/compendial Requirements, stability Updated batch record Multipoint dissolution profile with three buffer until 80% drug released Annual report Changes being effected supplement 16

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18. 18 Equipment IR Level Classification Test Filling 1 Alternate equipment of same design and principles Automated Update batch record/ Application/compendial Requirements/stability Annual report 2 Change to equipment of different design and principles Application/compendial Requirements, stability Updated batch record Multipoint dissolution profile with three buffer until 80% drug released Annual report Changes being effected supplement

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20. Manufacturing site changes IR Level Classification Test Filling 1 Site change in single facility No change in SOP/equipment's/environmental conditions/common personnel Application/compendial requirements Annual report 2 Same continuous campus Common personnel No other changes Application/ compendial Requirements /Notification of location of new site/ Updated batch record/ Multipoint dissolution profile with three buffer until 80% drug released Annual report Changes being effected supplement 20

21. Level Classification Test Filling 3 Different campus Different personnel Application/ compendial Requirements Notification of location of new site Updated batch record Multipoint dissolution profile with three buffer until 80% drug released Prior approval supplement Annual report 21

22. Limitations of SUPAC:   SUPAC has not been updated (1995/97 for main guidelines) It does not discuss multiple of changes Does not cover modified equipment Must be used in conjunction with other references ex: excipient handbook 22

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