Biomedical Engineering Reference
In-Depth Information
Combination products as defined in further detail in the 21 Code of Federal
Regulations (CFR)
19
(Part 3) are composed of two or more different regulatory
entities, that is, drug-device, drug-biologic, device-biologic, or drug-device-bio-
logic products. Such products often involve cutting edge, novel technologies that
raise unique scientific, technical, policy and regulatory issues. Furthermore, the
FDA multi-center aspect of the premarket review and regulation of combination
products presents unique challenges in review management. The combination of
two distinct components that would normally be regulated under different regula-
tory authorities introduces additional factors to consider in the assignment of a lead
center and the formulation of appropriate regulatory requirements. FDA will
receive significantly more combination products for review as technological
advances continue to merge with therapeutic products and blur the historical lines
of separation between the FDA's medical product centers.
7.4.1
Definition of combination product
A combination product can be defined as:
(1)
a product comprising 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;
(2)
two or more separate products packaged together in a single package or as a
unit and comprising drug and device products, device and biological prod-
ucts, or biological and drug 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; or
(4)
any investigational drug, device, or biological product packaged separately
that according to its proposed labeling is for use only with another individu-
ally specified investigational drug, device, or biological product where both
are required to achieve the intended use, indication, or effect.
9
In accordance with the Federal Food, Drug, and Cosmetic Act section 503(g)(1),
7
the FDA is required to assign review responsibility for combination products
based on the product's 'primary mode of action'. The designation of an FDA
division does not preclude consultations with other FDA divisions and when such
consultation is used, the involvement of more than one FDA center in the
premarket review process presents unique challenges in review management. In
addition, where the FDA finds it is appropriate, they reserve the option to require
separate applications to be approved (by either the lead FDA center or a combina-
