1. Comparability Protocols Nancy Sager Associate Director, QIS-Chemistry FDA/CDER/OPS

2. Overview What is a comparability protocol? Why has FDA issued a guidance on comparability protocols? What are the benefits of using comparability protocols? Why are we making the ACPS aware of this guidance? What are the principles of comparability protocols? (Stephen Moore)

3. Comparability Protocols A well-defined, detailed written plan for assessing the effect of specific postapproval chemistry, manufacturing, and controls (CMC) changes on the identity, strength, quality, purity, and potency of a specific drug product A plan for anticipated future CMC changes The protocol can be submitted in an original application or a prior approval supplement (postapproval)

4. Why Develop a Guidance Concept for comparability protocols first introduced for biotechnology products (1997) Industry requests to extend concept to all drugs and for additional guidance

5. Why Develop a Guidance Provide recommendations to applicants on developing a protocol to assess the effect of postapproval changes based on specific knowledge of a product and process (e.g., development data, manufacturing experience)

6. Why Develop a Guidance Consistent and complimentary to FDA initiatives on risk management –A well-planned protocol provides sufficient information for FDA to determine whether the potential for an adverse effect on the product can be adequately evaluated and can lower the risk for implementing the change without FDA’s prior approval –Augments the Scale-up and Postapproval Changes (SUPAC) and Changes to an Approved NDA or ANDA guidances

7. Why Develop a Guidance Consistent and complimentary to FDA initiatives on pharmaceutical cGMPs for the 21st century –Promote continual process and product improvement and innovation by facilitating CMC changes

8. Benefits FDA can designate, where appropriate, a reduced reporting category for future reporting of CMC changes covered by the approved protocol –Prior approval supplement –Changes-being-effected in 30 Days supplement (CBE- 30) –Changes-being-effected supplement (CBE-0) –Annual report

9. Benefits An FDA request for additional information to support a change is less likely when the change is covered under an approved protocol Could allow an applicant to implement CMC changes and place product in distribution sooner than without the use of a comparability protocol

10. Benefits Allows companies to “design their own SUPAC” based on their knowledge of and experience with a product Provides an opportunity for a reduced reporting category for CMC changes when the dosage form is not covered by a SUPAC type document

11. ACPS’s Role At this time, CDER has little experience with comparability protocols. The ACPS may be asked to provide advice on: Issues raised by public comments on the guidance Specific proposals for comparability protocols

12. Guidance Available at: http://www.fda.gov/cder/guidance/5427dft.pdf Draft guidance published: February 25, 2003 Comment period closes: June 25, 2003