International Combination Products
39
The 2006 notice also explained that while
FDA does not plan to update the existing ICAs,
it believes transparency in jurisdictional decision
making should result in greater predictability and
reduce ambiguity on FDA perspectives. The agency
has implemented a number of mechanisms to
provide this transparency. For example, it has used
its website to disseminate information concerning
product jurisdiction. Some examples include:
• Jurisdictional determinations: Approximately
250 capsular descriptions of selected RFD
decisions have been posted on OCP’s
website.24
• Jurisdictional updates: Detailed statements
on updated classification and assignment
of specific product classes are available on
OCP’s website.25
The OCP website also includes RFD jurisdic-
tional determination letters26 for more than 65
approved or cleared products covered by an RFD,
redacted to remove trade secret and confidential
commercial information in accordance with the
Freedom of Information Act.27 The information
from these three sources can be used by sponsors
or applicants to compare their product to other
approved or cleared products to ascertain if any
are similar enough to leverage for classification or
jurisdiction, or if any of the information can be
supportive in a Pre-RFD or RFD submission.
Regulatory Pathway
The regulatory pathway for a combination prod-
uct is dependent on the classification and center
jurisdiction assigned based on the PMOA. Once
the PMOA has been identified as belonging to
the drug constituent part (CDER), biological
constituent part (CBER), or medical device con-
stituent part (CDRH), a sponsor or applicant can
begin figuring out the testing needed, identifying
any applicable product-specific guidance, and in
general, mapping out the regulatory strategy for
the product. Understanding the applicable regu-
latory pathway early in a combination product’s
development phase is essential for the sponsor to
establish a realistic regulatory strategy.
This chapter will not cover all possible reg-
ulatory pathways for combination products only
the major regulatory pathways are discussed. For
example, to obtain authorization to legally com-
mercialize regulated medical products in the US,
there are three types of applications for drugs,
one for biologics, and two for medical devices.
FD&C Act Section 50528 identifies the
following three different regulatory pathways for
drugs:
1. 505(b)(1)29 is for an NDA with full safety
and effectiveness data typically, an NDA is
submitted for new chemical or molecular
entities.
2. 505(b)(2)30 is for an NDA that requires full
safety and effectiveness data, but some of the
data can come from published literature or
by cross-referencing an approved, off-patent
NDA or ANDA. This is used for modifi-
cations of drugs (e.g., dosage form, route of
administration) that are off patent where an
ANDA is not appropriate, but duplicative
studies are not necessary.
3. 505(j)31 is for an ANDA for a drug that is
identical to an already marketed drug (inno-
vator drug). This means all characteristics of
the generic drug are the same as that of the
innovator drug. CMC data and a bioequiva-
lence studies are usually required to support
the ANDA.
PHS Act Section 351(h)32establishes the BLA for
biologic (or biological) and biosimilar products,
which are established per section 351(k) of the
PHS Act.33
Section 510(k) of the FD&C Act provides
for a premarket notification (510(k)) for medical
devices.34
This pathway is for medical devices that can
show substantial equivalence to a medical device
that is already on the market. Section 515 of the
FD&C Act established the PMA application
for Class III medical devices.35 The NDA, BLA,
510(k), and PMA are the main regulatory path-
ways that will be discussed in subsequent chapters.
Generally, for any of the regulatory path-
ways, the same types of questions need to be
asked to move towards the goal of a premarket
39
The 2006 notice also explained that while
FDA does not plan to update the existing ICAs,
it believes transparency in jurisdictional decision
making should result in greater predictability and
reduce ambiguity on FDA perspectives. The agency
has implemented a number of mechanisms to
provide this transparency. For example, it has used
its website to disseminate information concerning
product jurisdiction. Some examples include:
• Jurisdictional determinations: Approximately
250 capsular descriptions of selected RFD
decisions have been posted on OCP’s
website.24
• Jurisdictional updates: Detailed statements
on updated classification and assignment
of specific product classes are available on
OCP’s website.25
The OCP website also includes RFD jurisdic-
tional determination letters26 for more than 65
approved or cleared products covered by an RFD,
redacted to remove trade secret and confidential
commercial information in accordance with the
Freedom of Information Act.27 The information
from these three sources can be used by sponsors
or applicants to compare their product to other
approved or cleared products to ascertain if any
are similar enough to leverage for classification or
jurisdiction, or if any of the information can be
supportive in a Pre-RFD or RFD submission.
Regulatory Pathway
The regulatory pathway for a combination prod-
uct is dependent on the classification and center
jurisdiction assigned based on the PMOA. Once
the PMOA has been identified as belonging to
the drug constituent part (CDER), biological
constituent part (CBER), or medical device con-
stituent part (CDRH), a sponsor or applicant can
begin figuring out the testing needed, identifying
any applicable product-specific guidance, and in
general, mapping out the regulatory strategy for
the product. Understanding the applicable regu-
latory pathway early in a combination product’s
development phase is essential for the sponsor to
establish a realistic regulatory strategy.
This chapter will not cover all possible reg-
ulatory pathways for combination products only
the major regulatory pathways are discussed. For
example, to obtain authorization to legally com-
mercialize regulated medical products in the US,
there are three types of applications for drugs,
one for biologics, and two for medical devices.
FD&C Act Section 50528 identifies the
following three different regulatory pathways for
drugs:
1. 505(b)(1)29 is for an NDA with full safety
and effectiveness data typically, an NDA is
submitted for new chemical or molecular
entities.
2. 505(b)(2)30 is for an NDA that requires full
safety and effectiveness data, but some of the
data can come from published literature or
by cross-referencing an approved, off-patent
NDA or ANDA. This is used for modifi-
cations of drugs (e.g., dosage form, route of
administration) that are off patent where an
ANDA is not appropriate, but duplicative
studies are not necessary.
3. 505(j)31 is for an ANDA for a drug that is
identical to an already marketed drug (inno-
vator drug). This means all characteristics of
the generic drug are the same as that of the
innovator drug. CMC data and a bioequiva-
lence studies are usually required to support
the ANDA.
PHS Act Section 351(h)32establishes the BLA for
biologic (or biological) and biosimilar products,
which are established per section 351(k) of the
PHS Act.33
Section 510(k) of the FD&C Act provides
for a premarket notification (510(k)) for medical
devices.34
This pathway is for medical devices that can
show substantial equivalence to a medical device
that is already on the market. Section 515 of the
FD&C Act established the PMA application
for Class III medical devices.35 The NDA, BLA,
510(k), and PMA are the main regulatory path-
ways that will be discussed in subsequent chapters.
Generally, for any of the regulatory path-
ways, the same types of questions need to be
asked to move towards the goal of a premarket