[Federal Register Volume 84, Number 247 (Thursday, December 26, 2019)]
[Notices]
[Pages 70976-70979]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-27799]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-4739]


Requesting Food and Drug Administration Feedback on Combination 
Products; Draft Guidance for Industry and Food and Drug Administration 
Staff; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Requesting 
FDA Feedback on Combination Products.'' The purpose of this guidance is 
to discuss ways in which combination product sponsors can obtain 
feedback from FDA on scientific and regulatory questions and to 
describe best practices for FDA and sponsors when interacting on these 
topics. These interactions can occur through application-based 
mechanisms, such as the pre-submission process used in the Center for 
Devices and Radiological Health (CDRH) and the Center for Biologics and 
Research (CBER) and the formal meetings used in the Center for Drug 
Evaluation and Research (CDER) and CBER, or through Combination Product 
Agreement Meetings (CPAMs), as appropriate.

DATES: Submit either electronic or written comments on the draft 
guidance by February 24, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that

[[Page 70977]]

identifies you in the body of your comments, that information will be 
posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2019-D-4739 for ``Requesting FDA Feedback on Combination 
Products.'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at https://www.regulations.gov or at the Dockets Management Staff 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to 
the Office of Combination Products, Food and Drug Administration, Bldg. 
32, Rm. 5129, 10903 New Hampshire Ave., Silver Spring, MD 20993. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Melissa Burns, Office of Combination 
Products, Food and Drug Administration, 301-796-5616, 
melissa.burns@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
and FDA staff entitled ``Requesting FDA Feedback on Combination 
Products.'' The purpose of this guidance is to discuss ways in which 
combination product sponsors can obtain feedback from the Agency on 
scientific and regulatory questions. These interactions can occur 
through application-based mechanisms, such as the pre-submission 
process used in CDRH and CBER and the formal meetings used in CDER and 
CBER, or through CPAMs, as appropriate.
    We are publishing this guidance consistent with the Agency's 
ongoing commitment to enhancing clarity and transparency regarding 
regulatory considerations for combination products, and in accordance 
with the mandate under section 503(g)(8)(C)(vi) of the Federal Food, 
Drug, and Cosmetics Act (FD&C Act) (21 U.S.C. 353(g)(8)(C)(vi)), which 
was added by section 3038 of the 21st Century Cures Act (Pub. L. 114-
255) (Cures Act). Section 503(g)(8)(C)(vi) requires FDA to issue a 
final guidance addressing: (1) The structured process for managing pre-
submission interactions with sponsors developing combination products; 
(2) best practices to ensure FDA feedback in such pre-submission 
interactions represents the Agency's best advice based on the 
information provided during these pre-submission interactions; and (3) 
how CPAMs relate to other FDA meeting types, what information should be 
submitted prior to a CPAM, and the form and content of agreements 
reached through a CPAM.
    FDA is in the process of operationalizing the procedures related to 
submission and receipt of a CPAM request. Therefore, if a sponsor 
wishes to submit a CPAM request to FDA at this time, the sponsor should 
first contact the Product Jurisdiction Office for the lead Center 
(CBERProductJurisdiction@fda.hhs.gov, 
CDERProductJurisdiction@fda.hhs.gov, or 
CDRHProductJurisdiction@fda.hhs.gov) and the Office of Combination 
Products (combination@fda.hhs.gov) prior to submitting a CPAM request 
to help ensure that the CPAM request is efficiently received and 
processed by FDA.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Requesting 
FDA Feedback on Combination Products.'' 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.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-
3521), Federal Agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ''Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance

[[Page 70978]]

of FDA's functions, including whether the information will have 
practical utility; (2) the accuracy of FDA's estimate of the burden of 
the proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Combination Product Agreement Meetings Under FD&C Act 
Section 503(g)(2)(A)(i); Requesting FDA Feedback on Combination 
Products.
    Description of Respondents: Respondents to this collection of 
information are combination product sponsors that submit CPAM requests.
    Burden Estimate: This draft guidance includes recommendations 
regarding information that sponsors should include in CPAM requests. 
Specifically, the draft guidance states that for CPAM requests, 
sponsors should:\1\
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    \1\ The draft guidance also notes that combination products must 
be identified as such in CPAM requests under section 
503(g)(8)(C)(v)(I) of the FD&C Act.
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     Product Information.
    [cir] Include the product name, description of the overall 
combination product and constituent parts, indications for use 
statement, and, as applicable, route of administration and dosing 
information.
    [cir] Include, as relevant:
    [ssquf] For a drug- or biological product-led combination product 
that includes a device constituent part, a device description, design 
diagram or other image, and identify components that are part of the 
device.
    [ssquf] For a device-led combination product, provide the chemical 
name, established or proper name (if available), and structure, for the 
drug and/or biological product constituent part(s).
    [ssquf] For a device-led combination product, provide the route of 
administration and/or dosing information for the drug and/or biological 
product constituent part(s).
    [ssquf] For combination products that contain an active ingredient 
that is included in an approved drug product that the sponsor seeks to 
cross reference or rely upon in its submission, identify the 
application number of the approved product.
    [ssquf] For combination products that contain a device constituent 
part that is a cleared or approved device that the sponsor seeks to 
cross reference, identify the application or submission number for the 
previously cleared or approved device.
     Background. Describe the status of product development, 
summarize any previous interactions with FDA on the product, including 
applications, application-based mechanisms, other meetings, Request for 
Designations (RFDs) or pre-RFDs, and identify the proposed regulatory 
pathway if not already established.
     Meeting Request. Include the requested form of 
communication (i.e., face-to-face meeting, teleconference, or written 
response). Summarize why the specific communication format is 
appropriate. If proposing a face-to-face meeting or teleconference, 
provide three proposed meeting dates/times, dates and times when the 
sponsor is not available, and a proposed agenda.
     Agreement Proposals Generally. Identify the specific 
proposals for which the sponsor seeks FDA agreement. Proposals should 
be grouped by discipline (e.g., Pharmacology/Toxicology, Pharmaceutical 
Quality/Chemistry and Manufacturing Controls (CMC), Engineering, Human 
Factors) where possible. The proposals should be limited to those for 
which the sponsor is seeking agreement from FDA.
     Rationale and Data Supporting Proposals. Provide 
rationale(s) and data adequate to support FDA's review of the agreement 
proposals. Organize the rationale(s) and data by topic when 
appropriate.
     Attendees. Include a list of planned participants from the 
sponsor's organization, including names and titles. A list of names, 
titles and affiliations of consultants and interpreters should also be 
included. If this information changes, it should be updated no later 
than 5 business days prior to the meeting. If the sponsor wishes to 
request that a specific FDA staff member or expertise be included in 
the meeting, that information should be included in the CPAM request.
    FDA has not received any CPAM requests since the enactment of the 
Cures Act in December 2016. FDA estimates that less than one CPAM 
request will be received per year by each medical product center (CBER, 
CDER, and CDRH). To provide a conservative estimate of burden, FDA 
estimates that approximately one CPAM request will be submitted per 
year to each medical product center. FDA estimates that it will take 
sponsors approximately 25 hours to compile and draft the information 
that this draft guidance recommends should be included in a CPAM 
request.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of
           FDA center                Number of     responses per   Total annual      Hours per      Total hours
                                    respondents     respondent       responses       response
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CDER............................               1               1               1              25              25
CDRH............................               1               1               1              25              25
CBER............................               1               1               1              25              25
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
    Total.......................  ..............  ..............  ..............  ..............              75
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    This draft guidance also refers to previously approved collections 
of information found in FDA regulations. The collections of information 
pertaining to orphan drug provisions in 21 CFR part 316 are approved 
under OMB control number 0910-0167; the collections of information 
pertaining to investigational device exemption submission provisions in 
21 CFR part 812 are approved under OMB control number 0910-0078; the 
collections of information pertaining to investigational new drug 
submission provisions in 21 CFR part 312 are approved under OMB control 
number 0910-0014; and the collections of information pertaining to 
biologics licensing submission

[[Page 70979]]

provisions in 21 CFR part 601 are approved under OMB control number 
0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/combination-products/guidance-regulatory-information/combination-products-guidance-documents or https://www.regulations.gov.

    Dated: December 18, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-27799 Filed 12-23-19; 8:45 am]
 BILLING CODE 4164-01-P


