GFI How-to-Prepare-a-PreRFD - February 2018

How to Prepare a Pre-Request for
Designation (Pre-RFD)
____________________________________________________

Guidance for Industry

Submit electronic comments to https://www.regulations.gov. Submit written comments to the
Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. You should identify all comments with the docket number listed in the
notice of availability that publishes in the Federal Register.
Additional copies of this guidance are available from the Office of Combination Products website at
https://www.fda.gov/CombinationProducts/default.htm.
For questions on the content of this guidance, contact the Office of Combination Products at
[email protected]

An agency may not conduct or sponsor, and a person is not required to respond to,
a collection of information unless it displays a currently valid OMB control
number. The OMB control number for this information collection is 0910-0845
(expires October 31, 2020).
See additional PRA statement in Section VI of the guidance.

U.S. Department of Health and Human Services
Food and Drug Administration
Office of Combination Products in the Office of the Commissioner
February 2018

Contains Nonbinding Recommendations

TABLE OF CONTENTS
I.

PURPOSE................................................................................................................................ 3

II. BACKGROUND ..................................................................................................................... 3
III.
GENERAL INFORMATION REGARDING THE PRE-RFD PROCESS FOR NONCOMBINATION AND COMBINATION PRODUCTS ............................................................... 4
A. What is a Pre-RFD? ............................................................................................................. 4
B. When should I submit a Pre-RFD? ...................................................................................... 6
C. May I request a meeting with OCP to explain my product? ................................................ 6
D. How do I submit a Pre-RFD for my product?...................................................................... 7
E. How promptly will FDA review my Pre-RFD? ................................................................... 7
F.

May I withdraw my Pre-RFD after submission? ................................................................. 8

G. What if I disagree with OCP’s preliminary assessment? ..................................................... 8
H. How can I contact OCP? ...................................................................................................... 8
I.

Where can I find more information? .................................................................................... 8

IV.

WHAT INFORMATION SHOULD I INCLUDE IN A PRE-RFD? .................................. 9

A. What is the basic information that I should include in my Pre-RFD? ................................. 9
B. What if I have additional information about my product that I would like to share with
FDA in my Pre-RFD? ............................................................................................................... 10
C. What format should I follow for my Pre-RFD? ................................................................. 10
D. Does FDA accept electronic submissions for Pre-RFDs? ................................................. 10
E. How should my Pre-RFD be addressed if I submit it via standard mail? .......................... 10
F.

Is there a page limit for Pre-RFDs? ................................................................................... 11

V. CONCLUSION ..................................................................................................................... 11
VI.

Paperwork Reduction Act of 1995 ..................................................................................... 11

VII.

Appendix:........................................................................................................................... 13

A. Pre-RFD Screening Checklist: ........................................................................................... 13
B. Pre-RFD Process Flow ....................................................................................................... 15

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Contains Nonbinding Recommendations

How to Prepare a Pre-Request for Designation (Pre-RFD)
Guidance for Industry
This guidance represents the current thinking of the Food and Drug Administration (FDA or
Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
or the public. You can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations. To discuss an alternative approach, contact the FDA office
responsible for this guidance as listed on the title page.

I.

PURPOSE

This guidance is intended to assist sponsors in obtaining a preliminary assessment from the U.S.
Food and Drug Administration (FDA or Agency) through the Pre-Request for Designation (PreRFD) process. Specifically, this guidance explains the Pre-RFD process at the Office of
Combination Products (OCP) and helps a sponsor understand the type of information to provide
in a Pre-RFD.
The Pre-RFD process is available to provide informal, non-binding feedback regarding the
regulatory identity or classification of a human medical product as a drug, device, biological
product, or combination product. In addition, this informal process provides information about a
non-combination or combination product’s assignment to the appropriate Agency Center (Center
for Drug Evaluation and Research (CDER), Center for Devices and Radiological Health
(CDRH), or Center for Biologics Evaluation and Research (CBER)) for premarket review and
regulation.
Additional information on topics outside the scope of this guidance may be found on our website
(at http://www.fda.gov/CombinationProducts/default.htm.) These topics include the definitions
of a non-combination and combination product, as well as information about the formal Request
for Designation (RFD) process.

II.

BACKGROUND

Since its establishment on December 24, 2002, OCP has served as a resource for sponsors at
various stages of development of their product. Sponsors often seek OCP feedback on whether
their medical product will be regulated as a drug, a device, a biologic, or a combination product,
and which FDA medical product Center (CDER, CBER, or CDRH) will regulate it, if it is a noncombination product, or will have the primary jurisdiction for the premarket review and
regulation of the product, if it is a combination product.
There are two ways that a sponsor can receive such a feedback from OCP. One option is to
submit an RFD to receive a formal, binding determination for the sponsor’s product with respect
to classification and/or center assignment that may be changed under conditions specified in
section 563 of the Federal Food, Drug, and Cosmetic Act (FD&C) Act and 21 CFR 3.9 in the
regulations. The RFD process is codified in 21 CFR Part 3, and OCP has issued a guidance
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Contains Nonbinding Recommendations

about this process (see “How to Write a Request for Designation” at
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126053.htm). A second more
flexible option is for a sponsor to submit an inquiry to OCP to receive a preliminary
jurisdictional assessment, which is not binding.
Many sponsors seek to utilize more flexible approachable ways to interact with OCP and the
medical product Centers to obtain feedback from the Agency before submitting a marketing
application to the Agency. Over time, these informal methods of obtaining feedback have
become increasingly customary with sponsors, and for some, even preferable to the formal RFD
process. Accordingly, FDA is enhancing the transparency and consistency of the process, which
will now be called the “Pre-Request for Designation (Pre-RFD) Program,” available through
OCP. This guidance describes this structured process with clear recommendations for sponsors
wishing to submit Pre-RFDs. It also provides the process for review of Pre-RFDs by FDA staff,
the general timeframes for sponsors to receive feedback from OCP, and the process for
scheduling teleconferences and meetings in relation to a Pre-RFD.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word “should” in Agency guidance documents means that something is
suggested or recommended, but not required.

III.

GENERAL INFORMATION REGARDING THE PRE-RFD
PROCESS FOR NON-COMBINATION AND COMBINATION
1
PRODUCTS

A. What is a Pre-RFD?
A Pre-RFD is a clear and concise written submission that a sponsor may make to OCP to request
FDA’s preliminary, nonbinding assessment of (1) the regulatory identity or classification of a
product as a drug, device, biological product, or combination product, and/or (2) whether CBER,
CDER, or CDRH will regulate the product if it is a non-combination product, or which of those
Agency Centers will have primary jurisdiction for the premarket review and regulation, if it is a
combination product.
OCP will provide a written preliminary classification and/or jurisdictional assessment of the
product based on the information provided in a specific Pre-RFD. Our goal is to provide you
with our feedback within 60 calendar days of receipt of the basic information that you should
provide, and we will communicate with you during our review as needed. You can also contact
us at any time during the review to ask questions or get clarification. Moreover, if it appears that
1

For the purposes of this guidance document, parties who submit a Pre-RFD to the Agency are referred to as
“sponsors,” “you” or “your”; the terms “we,” “us,” and “our” refer to FDA staff from the Office of Combination
Products.

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we will not be able to complete our review within 60 calendar days after receipt of the
information, we will communicate the need for more review time to you in a timely manner.
Please note that if you change your product significantly after submitting the Pre-RFD to us,
such as changing its indication or ingredients, OCP’s feedback may no longer be applicable.
Accordingly, we recommend that you contact OCP if you make such a change. Additionally, if
you have classification or assignment questions regarding multiple related products or product
families that have different configurations, ingredients, and/or proposed uses or indications, we
recommend submitting a separate Pre-RFD for each product.
Though our Pre-RFD feedback is not binding on the Agency or sponsor, it is OCP’s intent to
provide the best advice possible based on the information provided in the Pre-RFD. OCP’s
review and written feedback will be made after an in-depth review, and it will contain a thorough
and detailed rationale for our assessment. Moreover, our review will include involvement from
the relevant Agency Centers, as well as the Office of Chief Counsel when necessary.
The following table highlights some of the key similarities and differences between the RFD and
Pre-RFD processes. 2 Regarding similarities, in both processes certain basic information is
needed for FDA to provide an assessment of the classification and assignment of a product. The
basic information includes, for example, a description of the product, proposed use or
indications, and a description of how the product achieves its intended therapeutic/diagnostic
effects. In addition, a sponsor has the option to include additional information in a Pre-RFD that
would be required for an RFD.
Differences between the RFD and Pre-RFD process include length of submission and depth of
regulatory analysis that a sponsor must provide. For example, RFDs cannot exceed 15 pages, but
no such length requirement exists for Pre-RFD submissions.3 Moreover, for an RFD, a sponsor
must provide an analysis of a product’s classification, a primary mode of action (PMOA)
analysis (if the RFD concerns combination product assignment), and a recommendation
regarding Agency Center assignment. Such information is optional in the Pre-RFD process
(additional details are provided in Section IV.A. and in Appendix A). We note that FDA would
conduct the same type of PMOA analysis in a Pre-RFD as in a RFD regardless of whether a
sponsor chooses to make a recommendation regarding the PMOA of its combination product in a
Pre-RFD.

2

Please note that the information listed in this Pre-RFD Guidance does not include all the necessary information
required for an RFD. If you wish to submit an RFD, you should consult 21 CFR 3.7 as well as the guidance about
what to include in an RFD (see “How to Write a Request for Designation” at
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126053.htm).
3

Although there is no page limit for Pre-RFDs, we encourage you to limit your Pre-RFD to a succinct summary of
information relevant for OCP to make its preliminary assessment (see Sections III.E and IV.F).

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Submission Type
Description of Product
Proposed Use or Indications
for Use
Description of the
manufacturing processes,
including the sources of all
components
Supportive Data/Studies
Description of how a product
achieves its intended
therapeutic/diagnostic effects
Analysis of Classification,
Primary Mode of Action
(PMOA), if it is a combination
product, and Jurisdictional
Assignment
Description of Related
Products
Sponsor Recommendation
Page limit

RFD
(Information Required)
Yes
Yes

Pre-RFD
(Information Recommended)
Yes
Yes

Yes

Yes
Yes

Optional (if available;
recommended if it is a human
cell, tissue, or cellular- or tissuebased product (HCT/P) or a
biological product)
Optional (if available)
Yes

Yes

Optional (if available)

Yes

Optional (if available)

Yes
Yes

Optional (if available)
No 4

B. When should I submit a Pre-RFD?
A Pre-RFD may be submitted at any point during medical product development.
A Pre-RFD is especially beneficial when the classification of a product or the Agency Center to
which it should be assigned is unclear or in dispute and your product is very early in its
development, or if you are contemplating whether to pursue a specific configuration or a specific
indication. Understanding how FDA regulates your product and the appropriate regulatory
pathway to market for your product will help lead to better decision-making for your company.
We note that a Pre-RFD is not necessary for every product. For example, some products have
clearly established classification and jurisdictional assignments. OCP has published a list of
various examples of these types of products on its website at [email protected].

C. May I request a meeting with OCP to explain my product?
We encourage you to contact OCP before submitting your Pre-RFD if you have any questions,
including if you are uncertain about the type of information to include.

4

See footnote 3.

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In most cases, the Agency will be able to make its preliminary assessment based on a wellwritten Pre-RFD. However, if you believe a meeting with OCP would be helpful in providing the
Agency with a better understanding of how the product works, you can request a meeting either
prior to or after submission of a Pre-RFD. If you request a meeting after submission of a PreRFD but prior to our feedback, please keep in mind that such a meeting will potentially extend
the timeframe of review of your product, so that we can adequately consider issues raised during
the meeting.
If you request a meeting, you should include an explanation of the issues you would like to
address and any supportive information. Please note that the timing to schedule meetings may
vary based on factors including the number of subject matter experts to be included from
interested Agency Centers, the availability of conference rooms, and the complexity of the issues
the product raises. When possible and appropriate, OCP encourages you to consider a
teleconference instead of an in-person meeting.
Generally speaking, FDA will need about four weeks to review information submitted as part of
the meeting request prior to the meeting. This timeframe will give OCP and the necessary
subject matter experts from the Agency Centers adequate time to review, comment, and possibly
follow-up on any issues prior to your meeting. Therefore, it is very important that you provide
complete background information at the time of your initial meeting request. If you wish to
supplement your background information package with any new or modified information after
this date, we may have to reschedule the meeting or delay our feedback on discussion topics
related to the new or updated information. While it is important to provide a complete
background package, submission of extraneous information can be counterproductive. In order
for us to provide the most efficient and beneficial advice to you, please keep your background
information targeted and focused on the issues in your Pre-RFD that you would like us to
consider.

D. How do I submit a Pre-RFD for my product?
Part III of this document addresses the recommended format and specific content of a Pre-RFD
in detail. You may submit a Pre-RFD, and include any relevant data pertaining to your product,
which should be clearly labeled as such, to [email protected] or to the address listed below
in Section IV.E.

E. How promptly will FDA review my Pre-RFD?
Within 5 business days of its receipt of a Pre-RFD, OCP aims to review the Pre-RFD submission
to ensure that it has adequate information for us to make our preliminary assessment. OCP will
then either send you an acknowledgement email that our assessment will proceed, or we will
detail the additional information needed before we can begin our assessment.
OCP’s goal is to provide feedback on a Pre-RFD within 60 calendar days after we receive
complete information to begin our review. However, please keep in mind that the speed of the
review depends on the quality and adequacy of the information submitted. Furthermore, if you
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choose to submit a large amount of data for FDA to consider, it may be necessary for us to take
longer than our goal of 60 calendar days to fully consider the information provided.

F. May I withdraw my Pre-RFD after submission?
Yes, you may withdraw your Pre-RFD by notifying OCP in writing, via email or correspondence
sent to the address below in section IV.E., any time after its submission and before FDA issues
its preliminary assessment.

G. What if I disagree with OCP’s preliminary assessment?
If you disagree with OCP’s preliminary assessment of your product, you may contact our office
to discuss our findings. After receiving our feedback, should you wish to present additional
information or new data that was not presented in the original Pre-RFD, we encourage you to
contact our office to discuss such additional information. We will be happy to provide you with
assistance before you submit a new Pre-RFD. Once you submit a new Pre-RFD to us, OCP will
consider this Pre-RFD a new submission and provide it with a new review and thorough
assessment.
Alternatively, you can submit an RFD for our consideration (see 21 CFR Part 3 and the guidance
document “How to Write an RFD” for additional information on the necessary information,
format, and page limit for an RFD). Once your RFD has been reviewed for completeness and
accepted for filing, we will review the RFD and provide, within 60 calendar days of filing, a
binding determination with respect to classification and/or center assignment that may be
changed under conditions specified in section 563 of the FD&C Act and 21 CFR 3.9 in the
regulations. If you disagree with the RFD decision, you may appeal that decision in accordance
with 21 CFR 10.75.

H. How can I contact OCP?
Contact information for OCP, including mailing address, e-mail address, phone number, and fax
number are listed below in Part IV.E.

I. Where can I find more information?
More information about product classification and assignment, as well as the regulation of
combination products, is available on the OCP website at
https://www.fda.gov/CombinationProducts/default.htm.

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IV. WHAT INFORMATION SHOULD I INCLUDE IN A PRE-RFD?
A. What is the basic information that I should include in my Pre-RFD?
1. Contact information including your name, company’s name, email address, and
telephone number.
2. A complete description of the product and, if applicable, the following
information.
a. The 510(k), Premarket Approval (PMA), New Drug Approval (NDA),
Abbreviated New Drug Approval (ANDA), Biologics License Application
(BLA), or any other FDA regulatory submission number associated with
the product.
b. Name of the product and all component products; and
c. A photo/diagram of the product
3. For products sourced from biologically-derived materials, describe how the
material was processed and a characterization of the identity of the final product.
4. An explanation of how the product works. And, though optional, you may
include additional information describing details (i.e., study conditions/methods,
identification of controls, results and conclusions) of relevant testing that supports
how the product works. Please be aware that comparisons to other products or
biocompatibility testing are typically not helpful in understanding how the
product works.
5. 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?
6. 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.
7. Proposed use/intended use/indications for use statement.
8. Instructions for use/conditions of use.
9. All known methods of action and the mechanism(s) by which each is achieved.

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10. For products that might be combination products, any information that you might
have, if any, to support the relative contribution of different components to the
overall intended therapeutic/diagnostic effects of the combination product.
Though optional, you may provide a detailed description of any supporting
tests/studies if such information is available and you would like FDA to consider
the information.
11. A list of claims that you intend to make or have made regarding the product.

B. What if I have additional information about my product that I would
like to share with FDA in my Pre-RFD?
In addition to the above requested information needed for FDA to conduct a Pre-RFD review,
you may also choose to provide additional information about a product. Information beyond that
which is listed in Section IV.A is optional. However, in the event that you have prepared other
information that you wish us to consider, we would be happy to do so. This information might
include, for example, a recommendation for lead Center, if your product is a combination
product, or any products that you believe may be similar to your product, or any other
information that you consider relevant for us to consider during our preliminary assessment. 5

C. What format should I follow for my Pre-RFD?
We recommend that you concisely provide the information identified in the screening checklist
in the Appendix and explained in detail in the above sections. It would be helpful if you include
for each section of the Pre-RFD a separate heading that corresponds to the headings listed in the
screening checklist followed by your response. We also recommend you use a standard typeface
(e.g., Times New Roman), which should be in an easily readable font size (e.g., 12).

D. Does FDA accept electronic submissions for Pre-RFDs?
Yes. You may submit your Pre-RFD by e-mail to [email protected] in a common electronic
format, such as a Portable Document Format (PDF) or a Word Document. As explained in the
preceding section, only one electronic submission is necessary.

E. How should my Pre-RFD be addressed if I submit it via standard mail?
We encourage you to submit your Pre-RFD electronically to our inbox at [email protected].
However, if you choose to submit your Pre-RFD via standard mail, you should send it to the
following address:

5

We note that to the extent any information a sponsor provides in a Pre-RFD is trade secret or confidential
commercial information, such information is protected by the same confidentiality laws as those that protect such
information provided in an RFD.

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Office of Combination Products
Office of the Commissioner
Food and Drug Administration
WO32 Hub/Mail Room #5129
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
In order for the Pre-RFD to be sent to the correct location, the envelope should be clearly marked
as a “Pre-Request for Designation.” Only one Pre-RFD submission is necessary. In other words,
no copies of your original Pre-RFD submission are required.

F. Is there a page limit for Pre-RFDs?
No, there is no page limit for Pre-RFDs (nor is there a word limit for emailed Pre-RFD
submissions that are not in PDF or Word format). However, we encourage you to limit your PreRFD to a succinct summary of information relevant for OCP to make its preliminary assessment.

V.

CONCLUSION

This guidance provides our recommendations for the format and content of a Pre-RFD
submission. We recommend you pay particular attention to these sections of your Pre-RFD, as
applicable:
•
•
•
•

•

A complete description of the product, including its composition (what is your product?);
The intended use/indications for use of the product (why would your product be used?);
The methods of action of the product (how does your product work?);
If your product may be a combination product, information you may have, if any,
regarding the relative contribution of each of its components to the overall intended
therapeutic/diagnostic effects of the combination product; and
Any claims you have made or plan to make about your product.

OCP is always available as a resource to you. We strongly encourage you to contact OCP before
submitting your Pre-RFD if you have any questions, or if you are uncertain about the type of
information to include.

VI.

Paperwork Reduction Act of 1995

This guidance contains information collection provisions that are subject to review by the Office
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C.
3501-3520).
The time required to complete this information collection is estimated to average 13 hours per
response, including the time to review instructions, search existing data sources, gather the data
needed, and complete and review the information collection. Send comments regarding this
burden estimate to:

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Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
[email protected]
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB control number. The OMB control number
for this information collection is 0910-0845 (expires October 31, 2020).

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VII. Appendix:
A. Pre-RFD Screening Checklist:
1. Contact information including your name, company’s name, email address, and
telephone number.
2. A complete description of the product and, if applicable, the following
information.
a. The 510(k), PMA, NDA, ANDA, BLA, or any other FDA regulatory
submission number associated with the product.
b. Name of the product and all component products; and
c. A photo/diagram of the product
3. For products sourced from biologically-derived materials, describe how the
material was processed and a characterization of the identity of the final product.
4. An explanation of how the product works. Though optional, you may provide
additional information describing details (i.e., study conditions/methods,
identification of controls, results, and conclusions) of relevant testing that
supports how the product works. Please be aware that comparisons to other
products or biocompatibility testing are typically not helpful in understanding
how the product works.
5. An explanation of how the product will be marketed (e.g., kit configuration). For
instance, will the product have separately marketed constituent parts that are to be
labeled for use together, or will it have components that will be physically or
chemically combined to make a single entity or co-package?
6. A listing of all components/ingredients, including the amount and purpose 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 each ingredient
in the product.
7. Proposed use/intended use/indications for use statement.
8. Instructions for use/conditions of use.
9. All known methods of action and the mechanism(s) by which each is achieved.
10. For products that might be combination products, information that you might
have, if any, to support the relative contribution of different components to the
overall intended therapeutic/diagnostic effects of the combination product.
Though optional, you may provide detailed description of any relevant
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tests/studies if such information is available and you would like FDA to consider
the information.
11. A list of claims that you have made or plan to make regarding the product.

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B. Pre-RFD Process Flow

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