As we all know, The definition of the Combination product is ” a product comprised of
any combination of a drug and a device; a device and a biological product; a biological product
and a drug; or a drug, a device, and a biological product. Under § 3.2(e), a combination product
includes:
1. A product comprised of two or more regulated components, i.e., drug/device,
biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or
otherwise combined or mixed and produced as a single entity (single-entity combination
products);

2. Two or more separate products packaged together in a single package or as a unit and
comprised of drug and device products, device and biological products, or biological and drug
products (co-packaged combination products);

3. A drug, device, or biological product packaged separately that according to its
investigational plan or proposed labeling is intended for use only with an approved individually
specified drug, device, or biological product where both are required to achieve the intended use,
indication, or effect and where upon approval of the proposed product the labeling of the
approved product would need to be changed, e.g., to reflect a change in intended use, dosage
form, strength, route of administration, or significant change in dose (a type of cross-labeled
combination product); or

4. Any investigational drug, device, or biological product packaged separately that
according to its proposed labeling is for use only with another individually specified
investigational drug, device, or biological product where both are required to achieve the
intended use, indication, or effect (another type of cross-labeled combination product). ”

The US FDA requires the manufacturer of a combination product to determine the Primary mode of action (PMOA) of the combination device so that it can be properly directed to the appropriate review center within the FDA.

One of the main issues manufacturers face is defining the PMOA. In many instances, the combination device does not have a single primary mode of action. This becomes even more difficult with implantable devices.

Do you have experiences with defining PMOA for a combination Device? if not, what do you think is the best way to identify the PMOA.