[Federal Register Volume 83, Number 55 (Wednesday, March 21, 2018)]
[Proposed Rules]
[Pages 12292-12294]
[FR Doc No: 2018-05687]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 4

[Docket No. FDA-2008-N-0424]

Postmarketing Safety Reporting for Combination Products; Draft
Guidance for Industry and Food and Drug Administration Staff;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification 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the availability of a draft guidance for industry and FDA staff
entitled ``Postmarketing Safety Reporting for Combination Products.''
This draft guidance addresses certain means by which applicants may
comply with the final rule on postmarketing safety reporting (PMSR)
requirements for combination products that FDA issued on December 20,
2016. Combination products are products composed of two or more
different types of medical products (drug, device, and/or biological
product). Although the PMSR regulations for drugs, devices, and
biological products share many similarities, each set of regulations
establishes distinct postmarketing reporting requirements, standards,
and timeframes. The final rule provides clarity on the PMSR
requirements for combination products to ensure consistent and complete
reporting while avoiding duplication. This draft guidance is not final
nor is it in effect at this time.

DATES: Submit either electronic or written comments on the draft
guidance by June 19, 2018 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final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 either electronic or written comments on any
Agency guidances 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 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-2008-N-0424 for ``Postmarket Safety Reporting for 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.gpo.gov/fdsys/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
two 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,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry
and FDA staff entitled ``Postmarket Safety Reporting for Combination
Products.'' This guidance addresses how to comply with the final rule
on postmarketing safety reporting (PMSR) requirements for combination
products that FDA issued on December 20, 2016 (81 FR 92603, hereafter
referred to as the ``combination product PMSR final rule'').
Combination products are products composed of two or more different
types of medical products (drug, device, and/or biological product).
Although the PMSR regulations for drugs, devices, and biological
products share many similarities, each set of regulations establishes
distinct reporting requirements, standards, and timeframes. The final
rule provides clarity on the PMSR requirements for combination products
to ensure consistent and complete reporting while avoiding duplication.
    Elsewhere in this issue of the Federal Register, FDA is also
publishing a compliance policy guidance for the combination product
PMSR final rule.
    The combination product PMSR final rule applies to combination
products that are subject to premarket review by FDA. The entities
subject to the final rule are ``Combination Product Applicants'' and
``Constituent Part Applicants.'' A Combination Product Applicant holds
the only application for a combination product or all the applications
for the separately marketed constituent parts of a combination product.
A Constituent Part Applicant holds an application for a constituent
part of a combination product the constituent parts of which are
marketed under separate applications held by different applicants.
Major provisions of the final rule are discussed in the guidance
including:
     Application Type-Based PMSR. These requirements apply to
both Combination Product Applicants and Constituent Part Applicants and
are based on the application type under which the combination product
or constituent part received marketing authorization.
     Constituent Part-Based PMSR. These requirements apply only
to Combination Product Applicants and are based on the types of
constituent parts included in the combination product. The rule
provides mechanisms for Combination Product Applicants to submit a
single report to satisfy multiple reporting requirements if all of the
information to be reported can be submitted in the same manner and the
report satisfies all applicable reporting requirements, including all
submission timelines.
     Information Sharing. These requirements apply only to
Constituent Part Applicants, mandating that these applicants share
certain adverse event information with one another relating to their
combination product.
     Submission Process for Combination Product PMSR
Information. These requirements specify how Combination Product and
Constituent Part Applicants must submit PMSR information to the Agency.
     Records Retention. These requirements specify what records
Combination Product and Constituent Part Applicants must maintain and
how long to maintain them.

II. Other Issues for Consideration

    The combination product PMSR final rule allows FDA to receive
complete, timely postmarketing safety information regarding combination
products, which is necessary to assure the continued safety and
effectiveness of such products, while minimizing unnecessary
duplication and burdens on Combination Product Applicants and
Constituent Part Applicants. In developing this guidance document to
accompany the final rule, FDA has clarified ways in which Combination
Product Applicants can streamline PMSR (see section V.A.3 of the
guidance). The guidance clarifies under what circumstances the criteria
for being able to submit a single report to FDA are met, i.e., that:
(1) The reports can be submitted in the same manner and (2) the
combined report satisfies all applicable reporting requirements,
including submission timelines (see section IV.C of the guidance). FDA
encourages comments on guidance content and mechanisms to improve
reporting efficiency while still ensuring complete and timely reporting
or topics where additional detailed discussion may be helpful in the
guidance. In particular, FDA requests feedback on the following issues
for consideration to assist the Agency in determining whether
additional streamlining of reports may be appropriate:
    1. There may be events that would be reportable for a Combination
Product Applicant as a malfunction and/or a Field Alert Report (FAR)
and/or a Biological Product Deviation Report (BPDR), e.g., a drug-
device combination product that failed to meet specifications may
trigger both a malfunction report and FAR. FDA requests feedback on
circumstances under which such reporting may be redundant or otherwise
unnecessary and, if so, alternative reporting approaches that will
assure timely and complete reporting of information to FDA. FDA
encourages the use of example scenarios to illustrate circumstances
under which submitting one or a subset of such reports may be
sufficient to ensure timely and complete reporting.
    2. Although outside the scope of the combination product PMSR final
rule, in response to comments to the combination product PMSR proposed
rule, FDA has addressed certain reporting considerations for entities
involved with the manufacture and distribution of combination products
but that are not ``applicants'' subject to this rule (see Appendix 3 of
the guidance). FDA requests feedback on what, if any, additional
guidance would be helpful to such entities.
    3. FDA is considering updating the Vaccine Adverse Event Reporting
System (VAERS) with data elements similar to those described in section
V.B.2 and Appendix 4 of the guidance for the FDA Adverse Events
Reporting System (FAERS) and the Electronic Medical Device Reporting
(eMDR) system. FDA is also evaluating what additional data elements to
include in VAERS with respect to combination products and welcomes
comments from combination product vaccine reporters on this topic.
    4. FDA also received comments to the combination product PMSR
proposed rule related to the safety reporting requirements for
investigational combination products. Although investigational
combination products are outside the scope of the combination product
PMSR final rule and this guidance, we will consider comments from
sponsors on the challenges and the need for additional transparency
related to safety reporting for investigational combination products.
FDA will consider these comments in determining the need for additional
policy and guidance on this topic.

III. Significance of Guidance

    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 ``Postmarket Safety Reporting for 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. This guidance
is not subject to Executive Order 12866.

IV. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of
information found in FDA regulations. These collections of information
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
collections of information in 21 CFR 314.80(c) and (e), as well as for
21 CFR 314.81(b) are approved under OMB control numbers 0910-0001,
0910-0230, and 0910-0291. The information collection provisions for 21
CFR 600.80 and 600.81 are approved under OMB control number 0910-0308.
Those for 21 CFR 606.170 are approved under OMB control number 0910-
0116. Those for 21 CFR 606.171 are approved under OMB control number
0910-0458. The information collection provisions for 21 CFR 803.50,
803.53, and 803.56 are approved under OMB control numbers 0910-0291 and
0910-0437. The information collection provisions for 21 CFR 806.10 and
806.20 are approved under OMB control number 0910-0359. The information
collection provisions for 21 CFR 4.102, 4.103, and 4.105 are approved
under OMB control number 0910-0834.

V. Electronic Access

    Persons with access to the internet may obtain the draft guidance
at either https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm109110.htm or https://www.regulations.gov.

    Dated: March 15, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-05687 Filed 3-20-18; 8:45 am]
BILLING CODE 4164-01-P