International Combination Products
31
Introduction
Chapter 4 will provide an overview of how the
United States Food and Drug Administration
(FDA) assigns jurisdiction of combination
products. This chapter will also discuss how to
request a designation for a potential combination
product. Lastly, this chapter will briefly introduce
a few of the different pathways for combination
products to be marketed. Regulatory profession-
als need to understand how to determine the
jurisdiction of a combination product in order
to understand the potential regulatory pathways
that are available to bring the product to market.
Introduction
How do you know which FDA center will have
primary jurisdiction for your combination prod-
uct? How can you determine which constituent
part of your combination product is the driver for
the product? There are several avenues available
to make the determination.
To ascertain which FDA center has the
primary responsibility for review of a premarket
application for a combination product, a regula-
tory professional must first determine the mode
of action including the primary mode of action
(PMOA). Why is this important? It is important
because FDA is required to assign a combination
product to a lead center based on its PMOA.
As published in the 25 August 2005 edition of
the Federal Register,1 FDA promulgated a final
PMOA Rule to describe the principles of how
combination products are assigned to an agency
center. The regulation defined mode of action
(MOA) and PMOA and provided an algorithm
for how FDA would assign combination prod-
ucts for which the PMOA cannot be determined
with “reasonable certainty.” The rule became
effective 23 November 2005.2
Constituent Parts
FDA defined MOA as the means by which
a product achieves an intended therapeutic
effect or action. For purposes of this definition,
“therapeutic” action or effect includes any effect
or action of the combination product intended
to diagnose, cure, mitigate, treat, or prevent
disease or affect the structure or any function
of the body. Because combination products are
comprised of more than one type of regulated
article (biological product, device, or drug), they
typically will have more than one identifiable
MOA. Specifically, each regulated article of the
combination product, referred to as “constituent
part” per 21CFR3(k)(1–3) and 21CFR4.2,3,4 will
contribute either a biological product, device, or
drug MOA. The definitions of biological product,
device, and drug MOAs are closely related to
the following statutory definitions of a biolog-
ical product, device, and drug respectively. See
Chapter 1 What are combination products?
• A constituent part has a biological product
MOA if it acts by means of a virus, thera-
peutic serum, toxin, antitoxin, vaccine, blood,
blood component or derivative, allergenic
4 Jurisdiction and Regulatory Pathway
31
Introduction
Chapter 4 will provide an overview of how the
United States Food and Drug Administration
(FDA) assigns jurisdiction of combination
products. This chapter will also discuss how to
request a designation for a potential combination
product. Lastly, this chapter will briefly introduce
a few of the different pathways for combination
products to be marketed. Regulatory profession-
als need to understand how to determine the
jurisdiction of a combination product in order
to understand the potential regulatory pathways
that are available to bring the product to market.
Introduction
How do you know which FDA center will have
primary jurisdiction for your combination prod-
uct? How can you determine which constituent
part of your combination product is the driver for
the product? There are several avenues available
to make the determination.
To ascertain which FDA center has the
primary responsibility for review of a premarket
application for a combination product, a regula-
tory professional must first determine the mode
of action including the primary mode of action
(PMOA). Why is this important? It is important
because FDA is required to assign a combination
product to a lead center based on its PMOA.
As published in the 25 August 2005 edition of
the Federal Register,1 FDA promulgated a final
PMOA Rule to describe the principles of how
combination products are assigned to an agency
center. The regulation defined mode of action
(MOA) and PMOA and provided an algorithm
for how FDA would assign combination prod-
ucts for which the PMOA cannot be determined
with “reasonable certainty.” The rule became
effective 23 November 2005.2
Constituent Parts
FDA defined MOA as the means by which
a product achieves an intended therapeutic
effect or action. For purposes of this definition,
“therapeutic” action or effect includes any effect
or action of the combination product intended
to diagnose, cure, mitigate, treat, or prevent
disease or affect the structure or any function
of the body. Because combination products are
comprised of more than one type of regulated
article (biological product, device, or drug), they
typically will have more than one identifiable
MOA. Specifically, each regulated article of the
combination product, referred to as “constituent
part” per 21CFR3(k)(1–3) and 21CFR4.2,3,4 will
contribute either a biological product, device, or
drug MOA. The definitions of biological product,
device, and drug MOAs are closely related to
the following statutory definitions of a biolog-
ical product, device, and drug respectively. See
Chapter 1 What are combination products?
• A constituent part has a biological product
MOA if it acts by means of a virus, thera-
peutic serum, toxin, antitoxin, vaccine, blood,
blood component or derivative, allergenic
4 Jurisdiction and Regulatory Pathway