Combination Products: Preparing for the Journey March 28, 2006

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

2. 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/combination

3. 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. 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. 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. Preparing for the Journey – Where and Who? • 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

7. Preparing for the Journey – What and How? • 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

8. Preparing for the Journey – What and How? • 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

9. Preparing for the Journey – What and How? • 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

10. We’re off and assigned . . . Now what?

11. Ask Questions, All of Them! • 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?

12. Work the Relationship with OCP • 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

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