1. Adverse Event Reporting for Combination Products Bradley Merrill Thompson Leighton Hansel Colleen Hittle

2. FDA’s concept paper General principles –For most combination products, appropriate AE reporting may be achieved by following the regulatory provisions associated with the type of marketing application used for approval. –But this does leave gaps. For example, following the MDR for a drug/device combination would leave out some important drug type information.

3. Differences in AE reporting schemes Device malfunction reporting Five day MDR reporting Drug and biological product “alert” reporting Blood related deaths

4. FDA’s conceptual alternatives Combination products approved under one marketing application. –For these, FDA could simply require that the manufacturer follow the rules associated with the marketing application. Combination products approved under separate marketing applications. –If both applications filed by the same manufacturer, where the most likely part associated with the incident can be identified, the manufacturer would follow the rules associated with that part. –If not, the manufacturer would follow the rules associated with the lead review Center. –If the two applications are filed by separate manufacturers, each manufacturer would file according to the marketing application used for the part they made. –FDA is unsure of what to do when a manufacturer believes that the other manufacturer has the responsibility.

5. CPC Comments Let’s remember that combination products come in three flavors: –Cross labeled –Kits –Single entity CPC in its comment letter put together a table showing how interim and unified safety reporting systems could be accomplished.

6. Conceptual alternatives Option123456 Basic rule File based on the sub- mission or center type Always file two FDA should use discretion to decide at the time of approval The manufact- urer should have the discretion to decide which best applies Always file 1½, that is a primary sub- mission and a supple- mental sub- mission FDA should develop a single unified reporting process for combin- ation products

7. Questions or comments?