SUPAC GUIDELINES, History, levels of changes, changes in components, batch size

SUPAC GUIDELINES-HISTORY, LEVELS OF CHANGES, Changes in components or composition

1. SUPAC GUIDELINES Scale-Up and post approval changes Geethanjali College of Pharmacy, Hyd. Presented by: Gundlapally Yokshita J agati Saketh K Vaishnav Karamtod Devika Kavali Sri Lakshmi Kethavath Shashikala Under the guidance: P. NAGA CHANDRIKA, M.Pharm , ( Ph.D )

2. INTRODUCTION 1 SUPAC GUIDELINES -HISTORY 4 SUPAC GUIDELINES 5 ADVANTAGES AND DISADVANTAGES 16 REFERENCE 18

3. INTRODUCTION: SUPAC, which stands for scale-up and post approval changes, refers to guidelines that govern changes made during the post-approval phase of drug manufacturing. In pharmaceutical technology, the transfer of a pharmaceuticals product from small scale to the production scale is termed as scale-up with an increase in simultaneous production outputs. These guidelines apply when there are changes :  In composition or components,  In Manufacturing site,  In Scale-up or scale-down of batch size,  In Manufacturing procedures or equipment . It is important to make sure that the applied process is capable enough to manufacture an appropriate quality product and as well as to know that the product after scale-up doesn’t suffer any changes in the physical and chemical properties of the product. 3

4. SUPAC GUIDELINES-HISTORY :  Two workshops were held in 1991 and 1992 by the APPS , FDA and UPS . The purpose is to discuss the fundamentals of modifying the procedure or composition of drug products after they have been approved by the appropriate authorities.  In the end, these adjustments included adjustments to the formulation or composition of the product, alteration to the processes, modification to the size of the processes and adaptation to the site or campus where the operations were performed. The contents of the workshop were finally made public by the FDA in the form of a guidelines paper titled “scale-up post approval changes”.

5. SUPAC Guidelines- Define: Level of changes- Minor change, Moderate change, Major change. Tests - Application/ compendial tests, In vitro dissolution/ releases, In vivo. Filing - Annual report, Changes being effected supplement, Prior approval supplement. 5

6. LEVELS OF CHANGES: Level 1: Unlikely to have detectable impact. Level 2: Could have significant impact. Level 3: likely to have significant impact. 6

7. 1) Changes in components or composition: This section focuses on changes in excipients in the drug product. SUPAC-IR : Changes made for immediate – release solid oral dosage forms. SUPAC-MR: Changes made for modified – release solid oral dosage form. SUPAC-SS : Changes made for non-sterile semisolid dosage forms. SUPAC-IR: 7 LEVELS CLASSIFICATION EXCIPIENT RANGE TEST DOCUMENTATION FILING DOCUMENTATION LEVEL-1 Delition or partial delition of an ingredient. Changes in excipients, expressed as % (w/w) of total formulation, less than or equal to excipient %. Filler ±5 Disintegrant Starch ±3 Other ±1 Blinder ±0.5 Lubricant Ca or mg stearate± 0.25 Other ±1 Glidant Talc ±1 Other ±0.1 Filmcoat ±1 Stability application/ compendial requirement. -Annual report.

8. . LEVEL-2 -Change in technical grade of excipients. -Change in excipients expressed as (W/W)of total formulation greater than level-1 changes. Filter 1.0 Disintegrant Starch 6 Other 1 Binder 1 Lubricant Ca or mg stearate 0.5 Others 1 Glidant Talc 2 Other 0.2 Film coat 2 -stability application/ compendial requirement -dissolution data depends on solubility TR’s and permeability CASE-A : high permeability, high solubility drugs (single point dissolution) CASE-B : low permeability, high solubility(drugs multiple point) CASE-C : high permeability, low solubility(drugs multi point and multi media dissolution profile). -prior approval, -annual report. LEVEL-3 Higher than SUPAC-IR level 1 and 2 excipient ranges. -stability application, CASE B dissolution profile -biostudy or IVIVC. -prior approval supplement, annual report. 8

9. SUPAC – MR: 9 LEVELS CLASSIFICATION TEST DOCUMENTATION FILING LEVEL-1 Deletion of ingredients upto SUPAC –IR level -1 excipient ranges. -stability -application/ compendial requirements. -annual report LEVEL- 2 -changes in technical grade of excipients - upto SUPAC –IR level 2 excipient range. -stability -multipoint dissolution profile(15,30,45,60and 120 min) -USP buffer media at 4.5-7.5 three media ( eg : water,0.1Hcl) -USP buffer media at PH 4.5-6.8 for delayed release. -Prior approval supplement -annual report. LEVEL-3 Higher than SUPAC-IR level 1and 2 excipient range. -stability -biostudy of IVIVC -prior approval supplement -annual report.

10. SUPAC-SS LEVELS CLASSIFICATION TEST DOCUMENTATION FILING LEVEL -1 Quantity 10% or less change in approved amount of preservative. -application / compendial requirement. -preservative effectiveness test at low specified levels. -annual report. LEVEL-2 10%-20% change in approved amount of preservative. -application requirement. -preservative effectiveness. -changes being effected. -annual report. LEVEL-3 >20% change in approved amount of preservative. -application requirement. - excecuted batch records. -prior approval supplement. -annual report. 10

11. 2) MANUFACTURING SITE CHANGES: LEVELS CLASSIFICATION TEST DOCUMENTATION FILING LEVEL-1 -Site change within a single facility, -No change in SOP, -Common personnel. -Application/ compendial requirement. -Annual report. LEVEL-2 -Same continuous campus, -Common personnel, -No other changes. -Application/ compendial requirement -Notification of location of new site--Updated batch records -Annual report. -Changes being effected supplement. LEVEL-3 -Different campus, -Different personnel. -Application/ compendial requirement -Notification of location SUPAC –MR, IR -Annual report -Prior approval supplement. 11

12. 3) BATCH SIZE CHANGE(SCALE UP): LEVELS CLASSIFICATION TEST DOCUMENTATION FILING LEVELS-1 Change in batch size, upto and including a factor of 10 times the size of pilot/ biobatch .. -Updated batch records . -Application / compendial requirement stability. -Annual report. LEVELS-2 Change in batch beyond a factor of 10 times the size of the pilot or biobatch , no other changes -Updated batch records Application/ compendial requirement Stability SUPAC-IR (multipoint dissolution profile) SUPAC-MR : multipoint dissolution profile( eg : USP buffer) Three other media. -SUPAC-SS: invitro release test document. -Annual report. -Changes being affected supplement. 12

13. 4)MANUFACTURING CHANGES : Manufacturing changes may affected both equipment used in the manufacturing process and the process itself. - Appropriate validation studies are conducted. EQUIPMENT: LEVELS CLLASSIFICATION TEST DOCUMENTATION FILING LEVEL-1 -Alternate equipment of same design and principles automated equipment -Updated batch records -Application/ compendial requirements -stability -annual report LEVEL-2 Change to equipment of different design and principle -Updated batch records -application/ compendial requirement -stability. SUPAC-IR: multi-point dissolution profiles in multiple medias SUPAC-MR: multi-point dissolution profiles in multiple medias SUPAC-SS -annual report -changes being effected supplement 13

14. MANUFACTURING CHANGES- PROCESS: LEVELS CLASSIFICATION TEST DOCUENT FILING LEVEL-1 -Adjustment of equipment operating conditions(operating speeds, mixing times) -Updated batch records -application / compendial requirement. -stability -SUPAC-IR(multi-point dissolution profile) -Annual report -changes being effected supplement 14 LEVEL-2 Beyond approved application ranges -SUPAC-SS: change in the process of combining two phases -SUPAC-MR: multi- point dissolution profiles in multiple medias ( eg : USP buffer media at PH 4.5-7.5 for extended release) -three media( eg : water, 0.1Hcl 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 supplement

15. . LEVELS CLASSIFICATION TEST DOCUMENTATION FILING LEVEL-3 (SUPAC-IR SUPAC-MR) Changes in this type of process used( eg : wet granulation to direct compression) -Updated batch records -Application/ compendial requirements -Stability -Biostudy or IVIVC -SUPAC-IR: Multi –point dissolution profile -SUPAC-MR : Multi-point dissolution profile in multiple media( eg : USP buffer media at PH 4.5-7.5 for extended release) Three other media(water, 0.1N Hcl and USP buffer media at PH 4.5 and 6.8 for delayed release) -Prior approval supplement -annual report 15

16. ADVANTAGES: Easy scale-up running is observed in both production and quality assurance More capacious workspaces of the production division.. -Installation, maintenance, and repair of equipment becomes attainable with the assistance of expert from the engineering department. DISADVANTAGES: -It does not discuss multiple changes. - It does not cover modified equipment. It must be used in conjunction with other reference. - It has no been updated. 16

17. REFERENCE: 1) Lachman leon and schwartz . B joseph pharmaceuticals dosage form: tablet. Vol 3 edition-2 . 2) SUPAC Slideshare by Rohit 3)Savant D.A Pharma Pthway Industry and Applied pharmacy8th Edition. 4)Nash R.A Wachter A.H Pharmaceutical process validation; 3 rd Edition.

18. Thank you