1. March 28, 2006 Combination Products: Preparing for the Journey March 28, 2006 Pamela J. Weagraff Principal Consultant

2. March 28, 2006 Combination Products – Preparing for the Journey  Consider and understand the law, know the regulations, make use of available resources - why is obvious to understand how your product will be regulated but what about...  When: in earliest phase of product development as part of establishing Regulatory strategy  Where and Who: Office of Combination Products - Mark Kramer, Director, and staff, of Center Jurisdictional Offices  What and How: Office of Combination Product’s web site, http://www.fda.gov/oc/combinationhttp://www.fda.gov/oc/combination

3. March 28, 2006 Preparing for the Journey – When?  First Phase of Product Development - Regulatory Strategy: assignment to a center with primary jurisdiction, or a lead center, is based on a determination of the “primary mode of action” (PMOA) of the combination product; develop...  A brief description of the product and its major components, intended use of the product, (clinical/therapeutic claims, including patient population)  An explanation of the product’s modes of action (how the product works); which mode of action is primary and attributable to device, drug or biologic  Consider need for formal or informal request for designation

4. March 28, 2006 Preparing for the Journey – When?  Informal or Formal Request for Designation (RFD): consider...  Known FDA experience with similar products, established precedents – suggests informal RFD  Mitigation of business risk or lack of similar products – suggests formal RFD

5. March 28, 2006 Preparing for the Journey – Where and Who?  Establish a relationship with the Office of Combination Products Staff:  Assignment of combination products – to Product Assignment Officer or Director  Regulatory identity of a product as a drug, device, biological product, tissue (HCT/P) or combination product – to Product Classification Officer or Director  Premarketing or post-marketing issues, including requests for facilitation or guidance – to either the Associate Director or the Senior Scientific Advisor  General policy or regulatory issues – to Director or Associate Director

6. March 28, 2006  Establish a relationship: if you are reasonably certain of designation, questions can be directed to Center jurisdictional offices  CBER: Sheryl Lard-Whiteford, Ph.D., 301-827-0379  CDRH: Eugene Berk, 240-276-0104  CDER: Warren Rumble, 301-443-5581 Preparing for the Journey – Where and Who?

7. March 28, 2006  Apply the OC Resources – Informal RFD  Contact either OCP or Center Jurisdictional Office  Present information developed as part of Regulatory Strategy:  Brief description of the product / major components, intended use, (clinical/therapeutic claims, including patient population)  Explanation of modes of action (MOA) (how the product works); which MOA is primary and attributable to device, drug or biologic  Request feedback on center assignment Preparing for the Journey – What and How?

8. March 28, 2006  Apply the OC Resources – Formal RFD  Determine proceeding directly to RFD or submitting Pre- RFD  Contact OCP Director  Discuss plan for Pre-RFD and RFD or proceeding directly to RFD, provide Regulatory Strategy information  Request feedback on plan  Develop Pre-RFD or RFD according to OCP Guidance: “How to Write a Request for Designation”, August 2005, contact Leigh Hayes, OCP, 301-427-1934 Preparing for the Journey – What and How?

9. March 28, 2006  Pre-RFD or RFD:  Follow the guidance document; contact Leigh Hayes, OCP, 301-427-1934, with any questions  Logistics:  Electronic submissions accepted  OCP review for completeness = 5 days  If complete per regulation / guidance, distributed to qualified individuals in Centers for review  OCP RFD review = 60 days Preparing for the Journey – What and How?

10. > quintiles.com/quintilesconsulting 10 We’re off and assigned... Now what?

11. March 28, 2006  What good manufacturing practice regulations apply to combination products?  How are adverse events reported for combination products?  How will user fees for our combination product be applied?  What kind of safety and effectiveness information will be needed to support approval of our combination product?  How can master files can be used in the submission of information relevant to our combination product? Ask Questions, All of Them!

12. March 28, 2006  Include OCP staff in meetings with designated Center personnel for Pre-IND or Pre-IDE meetings, cc on submission cover letter  Keep OCP staff apprised of project status and request assistance in event of disputes, informal or formal  Become VERY familiar with the OCP web site Work the Relationship with OCP

13. > quintiles.com/quintilesconsulting 13 “Chance favors the prepared mind.” -- Louis Pasteur Thank you! Pamela J. Weagraff, MBA, RAC Principal Consultant, Medical Device Development Quintiles Consulting Tel: 508-528-1745 E-Mail: pamela.weagraff@quintiles.com