International Combination Products
37
material was processed and a characteriza-
tion of the identity of the final product.
• An explanation of how the product works.
And, though optional, additional informa-
tion describing details (i.e., study conditions/
methods, identification of controls, results,
and conclusions) of relevant testing that
supports how the product works may be
included. Please be aware that comparisons
to other products or biocompatibility testing
results are typically not helpful in under-
standing how the product works.
• An explanation of how the product will be
marketed. For instance, will the product
have separately marketed constituent parts
that are to be labeled for use together, or
will it have components that either will be
physically or chemically combined to make a
single entity, or will be co-packaged?
• A listing of all components/ingredients,
including the amount and reasoning for
including each component/ingredient, in the
product. If the product contains a solution/
liquid/gel/powder, please provide a listing
of all ingredients (active and inactive), their
amount/concentration, and the reason for
including the ingredient in the product.
• Proposed use/intended use/indications for
use statement.
• Instructions for use/conditions of use.
• All known methods of action and the mech-
anism(s) by which each is achieved.
• For products that might be combination
products, any information that might sup-
port the relative contribution of different
components to the overall intended thera-
peutic/diagnostic effects of the combination
product. Though optional, a detailed descrip-
tion of any supporting tests/studies if such
information is available may be provided for
FDA to consider.
• A list of claims the sponsors intends to make
or has made regarding the product.20
Additional information may be provided if
it will aid OCP in determining classification
or PMOA for assigning jurisdiction. As with
the RFD, specific attention should be given to
providing clear and concise information on the
indications or intended use(s) all of the MOAs
for the product a comprehensive description of
the product, including detailed information on
the composition claims that have been made
or plan on being made about the product and,
of course, any information or data that would
elucidate the PMOA. The Pre-RFD guidance
contains a screening checklist to assist the regu-
latory professional in providing all pertinent data
or information to OCP. As with the RFD, the
Pre-RFD is submitted to OCP via email in PDF
or Microsoft Word format. No paper copies are
required to be submitted.
OCP follows the same process and timing
as with the RFD in reviewing the Pre-RFD for
adequacy and providing an acknowledgement
letter within five days of receipt. OCP will strive
to provide feedback within 60 calendar days after
receipt of the Pre-RFD information. However,
the review could take longer than 60 calendar
days if the Pre-RFD contains a large amount of
data or if the quality or adequacy of the infor-
mation submitted slows down the review time.21
Therefore, even though no page limit is provided,
it is best to minimize the size of the Pre-RFD in
order to receive a preliminary response within 60
calendar days.
Unlike the RFD, there is no request for
reconsideration process for the Pre-RFD. If the
sponsor or applicant does not agree with the
preliminary assessment by OCP, the sponsor
or applicant should contact OCP to discuss
the assessment findings. If new or additional
information is available, the sponsor or applicant
should discuss this with OCP prior to submitting
another Pre-RFD. Providing new information
or data will result in a new Pre-RFD, and a new
assessment will be started. Alternatively, the
sponsor or applicant can submit an RFD and
receive a binding determination.22
Pre-RFD Meetings
Meetings for a Pre-RFD are not necessary, but
OCP is willing to meet if the sponsor or appli-
cant believes it will help OCP better understand
how the product works. A meeting can be
requested either before or after the submis-
sion of the Pre-RFD to OCP. If the meeting
37
material was processed and a characteriza-
tion of the identity of the final product.
• An explanation of how the product works.
And, though optional, additional informa-
tion describing details (i.e., study conditions/
methods, identification of controls, results,
and conclusions) of relevant testing that
supports how the product works may be
included. Please be aware that comparisons
to other products or biocompatibility testing
results are typically not helpful in under-
standing how the product works.
• An explanation of how the product will be
marketed. For instance, will the product
have separately marketed constituent parts
that are to be labeled for use together, or
will it have components that either will be
physically or chemically combined to make a
single entity, or will be co-packaged?
• A listing of all components/ingredients,
including the amount and reasoning for
including each component/ingredient, in the
product. If the product contains a solution/
liquid/gel/powder, please provide a listing
of all ingredients (active and inactive), their
amount/concentration, and the reason for
including the ingredient in the product.
• Proposed use/intended use/indications for
use statement.
• Instructions for use/conditions of use.
• All known methods of action and the mech-
anism(s) by which each is achieved.
• For products that might be combination
products, any information that might sup-
port the relative contribution of different
components to the overall intended thera-
peutic/diagnostic effects of the combination
product. Though optional, a detailed descrip-
tion of any supporting tests/studies if such
information is available may be provided for
FDA to consider.
• A list of claims the sponsors intends to make
or has made regarding the product.20
Additional information may be provided if
it will aid OCP in determining classification
or PMOA for assigning jurisdiction. As with
the RFD, specific attention should be given to
providing clear and concise information on the
indications or intended use(s) all of the MOAs
for the product a comprehensive description of
the product, including detailed information on
the composition claims that have been made
or plan on being made about the product and,
of course, any information or data that would
elucidate the PMOA. The Pre-RFD guidance
contains a screening checklist to assist the regu-
latory professional in providing all pertinent data
or information to OCP. As with the RFD, the
Pre-RFD is submitted to OCP via email in PDF
or Microsoft Word format. No paper copies are
required to be submitted.
OCP follows the same process and timing
as with the RFD in reviewing the Pre-RFD for
adequacy and providing an acknowledgement
letter within five days of receipt. OCP will strive
to provide feedback within 60 calendar days after
receipt of the Pre-RFD information. However,
the review could take longer than 60 calendar
days if the Pre-RFD contains a large amount of
data or if the quality or adequacy of the infor-
mation submitted slows down the review time.21
Therefore, even though no page limit is provided,
it is best to minimize the size of the Pre-RFD in
order to receive a preliminary response within 60
calendar days.
Unlike the RFD, there is no request for
reconsideration process for the Pre-RFD. If the
sponsor or applicant does not agree with the
preliminary assessment by OCP, the sponsor
or applicant should contact OCP to discuss
the assessment findings. If new or additional
information is available, the sponsor or applicant
should discuss this with OCP prior to submitting
another Pre-RFD. Providing new information
or data will result in a new Pre-RFD, and a new
assessment will be started. Alternatively, the
sponsor or applicant can submit an RFD and
receive a binding determination.22
Pre-RFD Meetings
Meetings for a Pre-RFD are not necessary, but
OCP is willing to meet if the sponsor or appli-
cant believes it will help OCP better understand
how the product works. A meeting can be
requested either before or after the submis-
sion of the Pre-RFD to OCP. If the meeting