International Combination Products
33
for designation (Pre-RFD). These procedures
generally are appropriate where the combination
product’s most important therapeutic action is
clear, or when FDA has experience in jurisdic-
tion decisions for similar combination products.
However, one disadvantage of the informal
approach is that the advice is not binding on
FDA and may be subject to change.
Formal designation of a combination
product is achieved by submitting an RFD or an
applicant’s letter of request, which is a written
submission to OCP requesting designation
of the center with primary jurisdiction for a
product. An RFD submission is not necessary for
every product but generally is indicated when a
combination product’s jurisdiction is unclear or
in dispute.10
The RFD process also may be used by a
sponsor or applicant to figure out the classifi-
cation of a product (i.e., drug, medical device,
biological, or combination product).11 At the end
of the RFD process, the sponsor or applicant
will receive a formal classification determina-
tion. However, as part of the RFD process, the
sponsor or applicant must recommend a classifi-
cation in order for the application to be reviewed.
Basically, if a sponsor or applicant is uncertain of
their product’s classification and jurisdiction, the
RFD process will provide a remedy for both.
FDA action on an RFD is a binding juris-
dictional determination with respect to center
assignment and is subject to change only under
conditions specified in 21CFR3.9 and FD&C Act
Section 563.12,13 However, while a designation is
binding for a particular product’s assignment, such
assignment pertains only to the product described
in the RFD. For example, if the product’s configu-
ration, composition, modes of action, intended use,
or any other key aspect changes after the designa-
tion letter is issued, it may be necessary to submit
a new RFD to determine the modified product’s
appropriate assignment.
Before submitting an RFD, the sponsor or
applicant should contact OCP if it is unsure of
the information required in the RFD, has any
questions regarding the RFD process, or would
like to provide OCP with details on how the
product works. OCP will provide general infor-
mation regarding the RFD process and respond
to questions about the process. Additionally,
a sponsor or applicant may request a meeting
with OCP. The meeting request can be mailed
or emailed (combination@fda.gov) to OCP. If
the meeting request is mailed, the cover letter
should prominently state “Meeting Request.”
OCP generally will not grant a meeting after a
sponsor or applicant has already submitted the
RFD. The meeting request should include an
explanation of any issues the sponsor or appli-
cant would like to discuss in the meeting. OCP
makes the final decision on whether a meet-
ing is granted. Currently, there is no statutory
timeframe for either acceptance or rejection of a
meeting request. The sponsor or applicant should
call OCP to establish, if possible, a timeframe for
responding to the meeting request.
According to 21CFR3.7(c), an RFD is
limited by regulation to 15 pages, including
attachments.14 FDA expects that a well-thought-
out and well-written RFD should not require
more than 15 pages. Additionally, FDA does
not expect to receive large attachments with
extensive data, since the RFD is likely to be sub-
mitted early on in the development process. Any
attachment should be supportive information for
the classification chosen or to bolster the choice
of FDA center with jurisdiction for review. An
RFD should be submitted prior to submitting
an investigational or marketing application. As
described in 21CFR3.7(c), the following infor-
mation is required in an RFD submission. FDA
has issued How to Write a Request for Designation:
Guidance for Industry,15 which further elaborates
on these requirements:
• Sponsor identity, including company name
and address, establishment registration num-
ber, company contact person, and telephone
number
• Product description, including:
o Classification, name of the product, and all
component products, if applicable
o Common, generic, or usual name of the
product and all component products
o Proprietary product name
o Identification of any product component
that has received premarket approval
already, is marketed as not being subject to
33
for designation (Pre-RFD). These procedures
generally are appropriate where the combination
product’s most important therapeutic action is
clear, or when FDA has experience in jurisdic-
tion decisions for similar combination products.
However, one disadvantage of the informal
approach is that the advice is not binding on
FDA and may be subject to change.
Formal designation of a combination
product is achieved by submitting an RFD or an
applicant’s letter of request, which is a written
submission to OCP requesting designation
of the center with primary jurisdiction for a
product. An RFD submission is not necessary for
every product but generally is indicated when a
combination product’s jurisdiction is unclear or
in dispute.10
The RFD process also may be used by a
sponsor or applicant to figure out the classifi-
cation of a product (i.e., drug, medical device,
biological, or combination product).11 At the end
of the RFD process, the sponsor or applicant
will receive a formal classification determina-
tion. However, as part of the RFD process, the
sponsor or applicant must recommend a classifi-
cation in order for the application to be reviewed.
Basically, if a sponsor or applicant is uncertain of
their product’s classification and jurisdiction, the
RFD process will provide a remedy for both.
FDA action on an RFD is a binding juris-
dictional determination with respect to center
assignment and is subject to change only under
conditions specified in 21CFR3.9 and FD&C Act
Section 563.12,13 However, while a designation is
binding for a particular product’s assignment, such
assignment pertains only to the product described
in the RFD. For example, if the product’s configu-
ration, composition, modes of action, intended use,
or any other key aspect changes after the designa-
tion letter is issued, it may be necessary to submit
a new RFD to determine the modified product’s
appropriate assignment.
Before submitting an RFD, the sponsor or
applicant should contact OCP if it is unsure of
the information required in the RFD, has any
questions regarding the RFD process, or would
like to provide OCP with details on how the
product works. OCP will provide general infor-
mation regarding the RFD process and respond
to questions about the process. Additionally,
a sponsor or applicant may request a meeting
with OCP. The meeting request can be mailed
or emailed (combination@fda.gov) to OCP. If
the meeting request is mailed, the cover letter
should prominently state “Meeting Request.”
OCP generally will not grant a meeting after a
sponsor or applicant has already submitted the
RFD. The meeting request should include an
explanation of any issues the sponsor or appli-
cant would like to discuss in the meeting. OCP
makes the final decision on whether a meet-
ing is granted. Currently, there is no statutory
timeframe for either acceptance or rejection of a
meeting request. The sponsor or applicant should
call OCP to establish, if possible, a timeframe for
responding to the meeting request.
According to 21CFR3.7(c), an RFD is
limited by regulation to 15 pages, including
attachments.14 FDA expects that a well-thought-
out and well-written RFD should not require
more than 15 pages. Additionally, FDA does
not expect to receive large attachments with
extensive data, since the RFD is likely to be sub-
mitted early on in the development process. Any
attachment should be supportive information for
the classification chosen or to bolster the choice
of FDA center with jurisdiction for review. An
RFD should be submitted prior to submitting
an investigational or marketing application. As
described in 21CFR3.7(c), the following infor-
mation is required in an RFD submission. FDA
has issued How to Write a Request for Designation:
Guidance for Industry,15 which further elaborates
on these requirements:
• Sponsor identity, including company name
and address, establishment registration num-
ber, company contact person, and telephone
number
• Product description, including:
o Classification, name of the product, and all
component products, if applicable
o Common, generic, or usual name of the
product and all component products
o Proprietary product name
o Identification of any product component
that has received premarket approval
already, is marketed as not being subject to