International Combination Products
35
The regulatory professional should ensure the
MOA and PMOA sections contain this infor-
mation. The sponsor or applicant should attempt
to use the assignment algorithm to determine if
another similar product is on the market when
providing the rationale for the PMOA and juris-
dictional center recommendation.
If OCP cannot determine the PMOA based
on the data provided in the RFD, OCP will
assign the combination product based on the
assignment algorithm found in 21CFR3.4(b),
discussed earlier in this chapter.
Assignment Algorithm
The assignment algorithm used by FDA has two
steps. The first step is to check for other combi-
nation products that present similar questions of
safety and effectiveness as a whole, compared to
the unclassified combination product. The second
step occurs if there are no combination products
with similar questions of safety and effectiveness.
In this case, OCP will assign the combination
product to the center with the most expertise
related to the most significant safety and effec-
tiveness questions presented by the combination
product. Some factors FDA weighs when evalu-
ating a product for classification or assignment to
a center are:
• Does the device constituent part incorporate
a novel or complex design or have the poten-
tial for clinically significant failure modes?
• Does the drug have a narrow therapeutic
index?
• Is the biological constituent part fragile?
• Which constituent part poses the greatest
risks?
• Is the drug constituent part a new molecular
entity or new formulation?17
How to Write a Request for Designation (RFD):
Guidance for Industry contains an RFD screening
checklist in the appendix that the regulatory pro-
fessional can use to ensure the RFD contains the
relevant required information. It should be noted
that an RFD is submitted electronically via email
to combination@fda.gov as a PDF, with two
copies sent via mail to the OCP physical address
with “Request for Designation” clearly visible on
the outside of the package or envelope. In other
words, the RFD is not an eCTD submission.
FDA generally reviews an RFD for com-
pleteness within five working days of receipt. An
incomplete RFD is “not filed,” and the appli-
cant is notified of the information needed for
OCP to undertake a substantive review. If an
RFD is filed, the sponsor or applicant is sent an
acknowledgement letter with the filing date and
the date by which OCP will respond. Within 60
days after the RFD is filed, OCP issues a letter
specifying the agency component with primary
jurisdiction for the product’s premarket review
and regulation. The designation letter also usually
identifies any consulting agency components and
sometimes describes the regulations (e.g., FD&C
Act device or drug provisions) to which the prod-
uct will be subject. Under 21CFR3.8(b), if FDA
does not provide an answer within 60 days of the
RFD filing date, the sponsor’s recommendation
for classification or assignment is granted.18
Request for Reconsideration
If the sponsor or applicant disagrees with the
designation, it may request that an OCP product
jurisdiction officer reconsider the decision.
The Request for Reconsideration (RFR) must
be submitted within 15 days of receiving the
designation letter. The RFR cannot include new
information and must not exceed five pages. The
OCP product jurisdiction officer will consider
an RFR over five pages as a new RFD, subject
to all the requirements of an RFD. The product
jurisdiction officer at OCP, in turn, will review
the RFR and respond in writing within 15 days
of receipt.
Pre-Request for Designation
OCP was approached by sponsors and applicants
searching for more flexibility in interacting with
OCP and the three medical product centers
when obtaining feedback prior to submitting
a marketing application to FDA. These infor-
mal methods for obtaining feedback became
customary to sponsors and applicants, and for
some, more preferable than the RFD process.
35
The regulatory professional should ensure the
MOA and PMOA sections contain this infor-
mation. The sponsor or applicant should attempt
to use the assignment algorithm to determine if
another similar product is on the market when
providing the rationale for the PMOA and juris-
dictional center recommendation.
If OCP cannot determine the PMOA based
on the data provided in the RFD, OCP will
assign the combination product based on the
assignment algorithm found in 21CFR3.4(b),
discussed earlier in this chapter.
Assignment Algorithm
The assignment algorithm used by FDA has two
steps. The first step is to check for other combi-
nation products that present similar questions of
safety and effectiveness as a whole, compared to
the unclassified combination product. The second
step occurs if there are no combination products
with similar questions of safety and effectiveness.
In this case, OCP will assign the combination
product to the center with the most expertise
related to the most significant safety and effec-
tiveness questions presented by the combination
product. Some factors FDA weighs when evalu-
ating a product for classification or assignment to
a center are:
• Does the device constituent part incorporate
a novel or complex design or have the poten-
tial for clinically significant failure modes?
• Does the drug have a narrow therapeutic
index?
• Is the biological constituent part fragile?
• Which constituent part poses the greatest
risks?
• Is the drug constituent part a new molecular
entity or new formulation?17
How to Write a Request for Designation (RFD):
Guidance for Industry contains an RFD screening
checklist in the appendix that the regulatory pro-
fessional can use to ensure the RFD contains the
relevant required information. It should be noted
that an RFD is submitted electronically via email
to combination@fda.gov as a PDF, with two
copies sent via mail to the OCP physical address
with “Request for Designation” clearly visible on
the outside of the package or envelope. In other
words, the RFD is not an eCTD submission.
FDA generally reviews an RFD for com-
pleteness within five working days of receipt. An
incomplete RFD is “not filed,” and the appli-
cant is notified of the information needed for
OCP to undertake a substantive review. If an
RFD is filed, the sponsor or applicant is sent an
acknowledgement letter with the filing date and
the date by which OCP will respond. Within 60
days after the RFD is filed, OCP issues a letter
specifying the agency component with primary
jurisdiction for the product’s premarket review
and regulation. The designation letter also usually
identifies any consulting agency components and
sometimes describes the regulations (e.g., FD&C
Act device or drug provisions) to which the prod-
uct will be subject. Under 21CFR3.8(b), if FDA
does not provide an answer within 60 days of the
RFD filing date, the sponsor’s recommendation
for classification or assignment is granted.18
Request for Reconsideration
If the sponsor or applicant disagrees with the
designation, it may request that an OCP product
jurisdiction officer reconsider the decision.
The Request for Reconsideration (RFR) must
be submitted within 15 days of receiving the
designation letter. The RFR cannot include new
information and must not exceed five pages. The
OCP product jurisdiction officer will consider
an RFR over five pages as a new RFD, subject
to all the requirements of an RFD. The product
jurisdiction officer at OCP, in turn, will review
the RFR and respond in writing within 15 days
of receipt.
Pre-Request for Designation
OCP was approached by sponsors and applicants
searching for more flexibility in interacting with
OCP and the three medical product centers
when obtaining feedback prior to submitting
a marketing application to FDA. These infor-
mal methods for obtaining feedback became
customary to sponsors and applicants, and for
some, more preferable than the RFD process.