Adverse Event Reporting for Combination

Products

Bradley Merrill ThompsonLeighton Hansel

Colleen Hittle

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.

Differences in AE reporting schemes

• Device malfunction reporting• Five day MDR reporting• Drug and biological product

“alert” reporting• Blood related deaths

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.

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.

Conceptual alternatives

Option 1 2 3 4 5 6

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

Questions or comments?Questions or comments?