Chapter 4: Jurisdiction and Regulatory Pathway
34
premarket approval, or has received an inves-
tigational exemption
o Identity of the sponsors and the status of any
discussions or agreements between sponsors
regarding the product’s use as a component
of a new combination product
o Chemical, physical, or biological
composition
o Status and brief reports of developmental
work results, including animal testing
o Manufacturing process description, includ-
ing all component sources
o Proposed use or indications
o Description of all known modes of action,
sponsor’s identification of the PMOA, and
the basis for that determination
o Schedule and duration of use
o Drug or biologic dose and route of
administration
o Description of related products, includ-
ing the regulatory status of those related
products
o Any other relevant information
• Sponsor’s recommendation on which agency
component should have primary jurisdiction,
with accompanying statement of reasons
If any aspects of the requirements are not known,
they should be stated in the RFD in the appli-
cable section. As an example, proprietary name
requests can only be submitted under an IND
or a marketing application and are not approved
until the marketing application is approved. An
RFD would be submitted prior to an IND or
marketing application. Therefore, the proprietary
name would not be known at the time of an
RFD application.
The following discussion will focus on best
practices for the major sections of the RFD,
keeping in mind that the regulation dictates 15
pages maximum. The description of the product
should contain detailed diagrams, with an expla-
nation of how the sponsor or applicant intends to
market the combination product. For chemical,
biological, or physical composition, the sponsor
or applicant should identify all the components
or ingredients, the purpose of each, and their
concentration or amount. Tabular format is
preferrable and will save space. If preclinical or
clinical studies have been conducted, they should
be summarized succinctly in the status and brief
reports of developmental work section. Emphasis
should be placed on studies that support the
PMOA of the product. Manufacturing informa-
tion can be provided in a process flowchart with
a brief description. The proposed use or indica-
tions is a critical section, and the information
should be stated as concisely and clearly as pos-
sible. The information in this section should be
relevant to both the classification and the assign-
ment of the product, especially if the RFD covers
both topics. It is critically important for OCP
to understand the MOAs and the PMOA. The
RFD should contain a clear and concise descrip-
tion of all the known MOAs along with the
determination of the PMOA. For each MOA,
one should include a description, how the MOA
is achieved, and which component or ingredient
is responsible for each MOA. The manufacturer
should explain which MOA contributes either
a drug, biological, or device MOA and provide
the basis for this conclusion. Published literature
may be cited however, the cited reference should
not be provided in the RFD. Additionally, the
section of the RFD containing information on
the development of work or testing completed to
support the chosen MOAs should be referenced.
A rationale also must be provided to explain and
defend the choice of the PMOA. OCP looks at
the following in determining the PMOA from
the RFD:
• Proposed use(s) or indication(s)
• How the combination product achieves its
overall intended therapeutic effect(s)
• Relative contribution of each constituent
part of the proposed use(s) or indication(s),
and to the overall intended therapeutic
effect(s)
• Duration of the contribution of each
constituent part toward the intended thera-
peutic effect(s)
• Data or information provided or cited sci-
entific literature that describes and supports
the MOA expected to make the greatest
contribution to the overall intended thera-
peutic effect16
34
premarket approval, or has received an inves-
tigational exemption
o Identity of the sponsors and the status of any
discussions or agreements between sponsors
regarding the product’s use as a component
of a new combination product
o Chemical, physical, or biological
composition
o Status and brief reports of developmental
work results, including animal testing
o Manufacturing process description, includ-
ing all component sources
o Proposed use or indications
o Description of all known modes of action,
sponsor’s identification of the PMOA, and
the basis for that determination
o Schedule and duration of use
o Drug or biologic dose and route of
administration
o Description of related products, includ-
ing the regulatory status of those related
products
o Any other relevant information
• Sponsor’s recommendation on which agency
component should have primary jurisdiction,
with accompanying statement of reasons
If any aspects of the requirements are not known,
they should be stated in the RFD in the appli-
cable section. As an example, proprietary name
requests can only be submitted under an IND
or a marketing application and are not approved
until the marketing application is approved. An
RFD would be submitted prior to an IND or
marketing application. Therefore, the proprietary
name would not be known at the time of an
RFD application.
The following discussion will focus on best
practices for the major sections of the RFD,
keeping in mind that the regulation dictates 15
pages maximum. The description of the product
should contain detailed diagrams, with an expla-
nation of how the sponsor or applicant intends to
market the combination product. For chemical,
biological, or physical composition, the sponsor
or applicant should identify all the components
or ingredients, the purpose of each, and their
concentration or amount. Tabular format is
preferrable and will save space. If preclinical or
clinical studies have been conducted, they should
be summarized succinctly in the status and brief
reports of developmental work section. Emphasis
should be placed on studies that support the
PMOA of the product. Manufacturing informa-
tion can be provided in a process flowchart with
a brief description. The proposed use or indica-
tions is a critical section, and the information
should be stated as concisely and clearly as pos-
sible. The information in this section should be
relevant to both the classification and the assign-
ment of the product, especially if the RFD covers
both topics. It is critically important for OCP
to understand the MOAs and the PMOA. The
RFD should contain a clear and concise descrip-
tion of all the known MOAs along with the
determination of the PMOA. For each MOA,
one should include a description, how the MOA
is achieved, and which component or ingredient
is responsible for each MOA. The manufacturer
should explain which MOA contributes either
a drug, biological, or device MOA and provide
the basis for this conclusion. Published literature
may be cited however, the cited reference should
not be provided in the RFD. Additionally, the
section of the RFD containing information on
the development of work or testing completed to
support the chosen MOAs should be referenced.
A rationale also must be provided to explain and
defend the choice of the PMOA. OCP looks at
the following in determining the PMOA from
the RFD:
• Proposed use(s) or indication(s)
• How the combination product achieves its
overall intended therapeutic effect(s)
• Relative contribution of each constituent
part of the proposed use(s) or indication(s),
and to the overall intended therapeutic
effect(s)
• Duration of the contribution of each
constituent part toward the intended thera-
peutic effect(s)
• Data or information provided or cited sci-
entific literature that describes and supports
the MOA expected to make the greatest
contribution to the overall intended thera-
peutic effect16