SUPAC.pptx
- 1. SUPAC GUIDELINES Dr. Vinod M. Thakare NAGPUR COLLEGE OF PHARMACY WANADONGARI, HINGNA ROAD, NAGPUR
- 2. Contents Introduction History of SUPAC Purpose of SUPAC Guidelines SUPAC documents Needs for SUPAC Level of changes Limitations References
- 3. SUPAC Guidelines SUPAC stands for scale up and post approval changes Defination:- The scale up process and changes made after the approval in composition, manufacturing process, manufacturing equipment and change of site is collectively called as SUPAC. It is the guideline that comes under Chemistry Manufacturing and controls section of USFDA. During a stage of F&D , initially, development process is carried out in small batch sizes are generally in the multiples of 10X i.e (small scale or lab scale)
- 4. Then this batches are increased to multiples of 100X i.e (medium scale or pilot scale). While in production scale or large scale, manufacturing is carried out in large numbers usually multiples of 1000X depending upon the requirement. This increase in batch size is termed as scale up. Sometimes, batch sizes need to be reduced depending upon the market requirements. This is termed as (Scaled down). During such a changes the quantities of active ingredients, excipients, & formulation parameters differ from lab scale to manufacturing scale.
- 5. • Hence while making such a changes from lab scale to pilot scale ar to plant scale, submission of all this data including excipients, their purpose and quantities to FDA is necessary for getting the marketing approval.
- 6. History of SUPAC FDA regulations 1962-1974 1974-1985 1985-1999 These three sets of regulations defined and handled PAC’s in different ways The SUPAC task force, established by the centre for Drug evaluation and research Chemistry manufacturing and control coordinating committee.
- 7. Purpose of the guidance This guidance provides recommendations to sponsors of new drug applications(NDA’s), abbreviated new drug applications (ANDA’s) who intend during the post approval to change (during the post approval period) 1.The components or the composition 2. The site of manufacture 3. The scale up/scale down of manufacture 4.The manufacturing(process or equipment)
- 8. Need for SUPAC Guideline To expedite the processes of post approval changes of drug products FDA can assure their safety and effectiveness. Lower the regulatory burden for industry
- 9. SUPAC documents List of document issued by FDA for help applicant with post approval changes. Documents are divided into IR (immediate release), MR (modified release), SS (non-sterile semisolid dosage form like creams, ointments and etc) Various types of changes are required 1) Components and compositions of drug product 2) Manufacturing process and equipment 3) Batch size 4) Manufacturing site change
- 10. SUPAC Guideline defines • Level of changes minor changes moderate changes major changes • Filling annual report changes being affected prior approval supplement supplement • Tests application/compendial tests in-vitro dissolution/ release in-vivo studies
- 11. Level of changes Level 1 ( minor):- Likelihood of impact on formulation quality and performance: 1) Those changes that are unlikely to have any detectable impact on formulation quality and performance 2) Example- Changes in the color, flavors.
- 12. Level-2 (moderate) 1) Changes are those that could have significant impact on the formulation quality and performance. 2) Example –Changes in the technical grade of excipient (Avicel pH102 vs Avicel pH200) changes expressed as percent (w/w of total formulation) . Level-3(major) 1) Changes are those that are likely to have significant impact on formulation quality and performance. 2) 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.
- 13. (A)Component and composition changes 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 .
- 14. Level 1 changes Ex – • Deletion or partial deletion of an ingredient which affect the colour and flavor of product. • Change in ingredient of the printing ink to another approved ingredient. • Changes in excipients. • Total additive effect of all excipient changes should not be more than 5%. Test documentation • Chemistry documentation Application/compendial release requirements stability testing Stability testing:-one batch on long term stability data reported in annual report.
- 15. Dissolution Documentation None beyond the compendial requirements In vivo bioequivalence documentation None Filling documentation Annual report
- 16. Level 2 changes Test and filling documentation vary depending upon three factors 1. Therapeutic range: narrow or non- narrow 2. Solubility: determined in PH range (1-8) and temp(37+0.50c) 3. Permeability: low or high Test Documentation • Chemistry documentation Stability testing : 1 batch with 3 month accelerated stability data in supplement and 1 batch on long term stability.
- 17. Dissolution documentation Case A – High permeability, High solubility Case B – low permeability, High Solubility Case C – High permeability, Low Solubility Drugs In vivo Bioequivalence documentation -None Filing documentation – prior approval supplement( Accelerated stability study) annual report(long term stability data)
- 18. Level 3 changes Test documentation • Chemistry Documentation – 1 batch with 3 months(SBOIA) or 3 batches with 3 months (SBOINA) (Significant body for information available) • Dissolution documentation – Case B • In vivo Bioequivalence – Full bioequivalence study. Filing documentation – prior approval supplement , annual report
- 19. (B)Manufacturing changes A. Equipment Level 1 • This consist of Change from non-automated to automated equipment or vice versa to move ingredients • Change to alternative equipment of same design and the operating principle of the same or different capacity Test and filing documentation • Chemistry documentation • Dissolution documentation
- 20. Level 2 Change in equipment to a different design Test and filing documentation as per level 3 of the site change except Case C dissolution instead of Case B.
- 21. B. Process changes Level 1 • This changes includes process changes like mixing times and operating speed within application/validation range • Test and filing document as per level 1 of site change Level 2 • This changes includes process changes like mixing times and operating speed outside the application/validation range • Test and filing documentation – as per the level 2 changes in site changes
- 22. Level 3 Change in the type of the process used in the manufacture of the product, such as a change in from the wet granulation to the direct compression of dry powder. Documentation – prior approval supplement , annual report
- 23. (C)Change in batch size Post approval changes in the size of a batch from the pivotal/pilot scale batch material to larger or smaller production . Scale down below 1,00,000 dosage units is not covered by this guideline. Scale up changes should be properly validated and if needed, inspected by appropriate agency personnel.
- 24. Level 1 Level Classification Test Documentation Filling Documentation I • Changes in the batch size up to and including factor of 10 times the size of the pilot / bio batch where • The equipment is of same design and principle • Both manufacturer. According to the CGMP compliance. • Same SOP’s followed • Chemistry documentation • Dissolution documentation • In-vivo bioequivalence documentation Annual report(changes being affected supplement; annual reprt (long term stability test data)
- 25. Level 2 Level Classification Test Documentation Filling Documentation II • Changes in the batch size beyond factor of 10 times the size of the pilot / biobatch where • The equipment is of same design and principle • Both manufacturer. According to the CGMP compliance. • Same SOP’s followed • Chemistry documentation • Dissolution documentation • In-vivo bioequivalence documentation Annual report(changes being affected supplement; annual reprt (long term stability test data)
- 26. (D)Site changes Site changes consists of changes in location of the site of manufacture for both company owned and contract manufacturing facilities Scale-up is addressed in section V of this guidance New manufacturing location should have a satisfactory current Good Manufacturing Practice (CGMP) inspection.
- 27. Level 1 Level Classification Test Documentation Filling Documentation I • Consists of site changes within single facility • No change in SOPs, equipment, environmental conditions(e.g temperature and humidity) and controls • Common personnel • No change in manufacturing batch record, except for administrative information and location of facility • Chemistry documentation • Dissolution documentation • In-vivo bioequivalence documentation • Annual report(changes being affected supplement; annual reprt (long term stability test data)
- 28. Level 2 Level Classification Test Documentation Filling Documentation II • Changes within a contiguous campus • Or between facilities in adjuscent city blocks where same SOPs, equipment, environmental conditions(e.g temperature and humidity) ,controls and personnels are used • No change in manufacturing batch record, except for administrative information and location of facility • Chemistry documentation • Dissolution documentation • In-vivo bioequivalence documentation • Annual report(changes being affected supplement; annual reprt (long term stability test data)
- 29. Level 3 Level Classification Test Documentation Filling Documentation III • Different campus • Different personnel 1) Chemistry documentation: • Location of new site • updated batch records • Application/ compendial release requirements 1) Dissolution documents: • Multipoint dissolution profile in application/ compendia medium at 15, 30, 45, 60 and 120 min USB buffer media at 4.5-7.5 for (extended release) • Three different media (e.g water, 0.1 N HCL, and USB buffer media at PH 4.5 and 6.8 for (delayed release) • Annual report(changes being affected supplement; annual reprt (long term stability test data)
- 30. SUPAC Guidelines Limitation 1. Has not been updated(1995/97) for main guide 2. Does not discuss multiple changes. 3. Does not cover modified equipment. 4. Must be used in conjunction with other references e.g excipient handbook.
- 31. Thank you