Comparability Protocols

1. Comparability Protocols Lore Fields MT(ASCP)SBB Consumer Safety Officer DBA/OBRR/CBER September 16, 2009

2. Agenda • Define Comparability Protocol (CP) • When can a CP be used? • CP Submissions • Content of CP submissions • Content of subsequent submissions • Summary

3. Comparability Protocol (CP) • What is a CP? Described in 601.12(e) An applicant may submit one or more protocols describing the specific tests and validation studies and acceptable limits to be achieved to demonstrate the lack of adverse effect for specified types of manufacturing changes on the identity, strength, quality, purity, or potency of the product as they may relate to the safety or effectiveness of the product. Any such protocols, or change to a protocol, shall be submitted as a supplement requiring approval from FDA prior to distribution of the product which, if approved, may justify a reduced reporting category for the particular change because the use of the protocol for that type of change reduces the potential risk of an adverse effect.

4. Comparability Protocol (CP) • What is a CP? (cont) • Submission option • Highly specific, well-defined plan for implementing a change in manufacturing • Demonstrate that change does not affect safety, identity, purity or potency

5. Comparability Protocol (CP) • What is a CP? (cont) • Specific for the change and for the applicant • FDA will approve CP if change does not adversely affect product • Approval of CP may allow a reduced reporting category for future implementation of the specific change in the CP • Expedite interstate distribution of products • Not appropriate for all changes

6. Comparability Protocol (CP) • When can a CP used? • Product manufactured using the change will meet approved product standards • Manufacturing process has been validated and all equipment has been qualified • Appropriate validated assays are available to detect effect of the change on the product • Implementation of single change in multiple locations operating under the same license using SOPs, forms, labels, etc. approved in CP

7. Comparability Protocol (CP) • When should a CP not be used? • Broad plan covering any conceivable change • Change has potential to adversely effect product • Pre-specified acceptance criteria are not available to determine effect on product • Change results in newly defined product that is not licensed • Use of new manufacturing facility needing pre-license inspection • Change in process, equipment or facility that may need pre-approval inspection

8. Comparability Protocol (CP) • CP Submissions • Submit as a PAS under 601.12(b) • May be combined with product manufacturing supplement • Once approved, CP must be implemented exactly as described in CP • If implementation deviates from CP, all future submissions for same change must be reported as PAS

9. Comparability Protocol (CP) • CP Submissions • Future supplements reporting implementation of same change described in CP may be reported in reduced category specified in approval letter (eg, PAS to CBE30) • Supplements reporting implementation of CP should include information committed to in approved CP • Submit a new CP or a change to an existing approved CP as a PAS

10. Routine SubmissionExample • Applicant wants to implement Platelet Pheresis collection at 4 centers using instrument X • Implements at center #1 • Develops SOPs; performs testing, validation, training, etc. • Submits supplement for center #1 as PAS • FDA approves implementation at center #1 • Center #1 distributes product interstate after approval • Submits implementation at centers #2 - #4 as PAS • Distribute product interstate after approval

11. Comparability Protocol (CP)Example • Applicant wants to implement Platelet Pheresis collection at 4 centers using instrument X • Implements at center #1 • Develops CP and SOPs; performs testing, validation, training, etc. • Submits CP and supplement for center #1 as PAS

12. Comparability Protocol (CP)Example • FDA approves CP and implementation at center #1 • Approval letter states future implementation of CP may be reported as CBE30 and expected content • Center #1 distributes product interstate after approval • Submits implementation for centers #2 - #4 using approved CP as CBE30 • Implementation must follow CP implementation plan • Distribute product interstate 30 days after FDA receives supplement

13. Comparability Protocol (CP) • Contents of CP Submission • FDA form 356h • Cover letter • SOPs • Records and Forms • Product Quality Control Logs • Labeling • May reference previously approved SOPs, forms and labeling (include reference number)

14. Comparability Protocol (CP) • Contents of CP Submission (cont) • Description of the change • Implementation plan, including description of training • Specific tests and validation protocols • Product acceptance criteria • Supportive data obtained from testing and validation • summary of validation and • 2 months QC

15. Comparability Protocol (CP) • Contents of CP Submission (cont) • QC testing procedures, including sampling plan • Description of actions if acceptable results not achieved • QA program oversight • Request a CBE-30 downgrade for subsequent facilities

16. Comparability Protocol (CP) Subsequent Submissions Content • Cover Letter • Summary of Validation • 2 Months QC

17. Summary • Comparability Protocol is a submission option • Specific change for manufacturing product • Requires full evaluation of potential impact of change on product • May allow future implementation of CP in a reduced reporting category – expedite interstate distribution

18. Summary • CP must be implemented exactly as approved • Report any changes in approved CP • CP not appropriate for all types of submissions