[Federal Register Volume 84, Number 25 (Wednesday, February 6, 2019)]
[Notices]
[Pages 2236-2237]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-01196]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-0078]


Principles of Premarket Pathways for Combination Products; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Principles 
of Premarket Pathways for Combination Products.'' This draft guidance 
presents FDA's current thinking on principles for premarket review of 
combination products, including how to determine which type of 
premarket submission is appropriate. FDA is publishing this draft 
guidance as part of its efforts to implement the 21st Century Cures Act 
(Cures Act) and in keeping with the Agency's long-standing commitment 
to transparency, efficiency, and regulatory consistency to facilitate 
development of safe and effective combination products.

DATES: Submit either electronic or written comments on the draft 
guidance by May 7, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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 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-0078 for ``Principles of Premarket Pathways 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)).

[[Page 2237]]

    Submit written requests for single copies of the draft guidance to 
the Office of Combination Products, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993-0002. 
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: John Barlow Weiner, Office of 
Combination Products, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993-0002, 301-796-8930.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Principles of Premarket Pathways for Combination Products.'' 
This draft guidance presents FDA's current thinking on principles for 
premarket review of combination products, including how to determine 
which type of premarket submission is appropriate. This draft guidance 
provides general, high-level information relevant to combination 
products.
    Section 3038 of the Cures Act (Pub. L. 114-255), enacted in 
December 2016, substantially amended section 503(g) of the Federal 
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 353(g)), the 
principal section of the FD&C Act expressly addressing combination 
products. General themes of these amendments include enhancing clarity, 
predictability, efficiency, and consistency of premarket regulatory 
expectations for combination products, including by ensuring that 
Agency components and staff coordinate appropriately on premarket 
review of these products, and that Agency thinking is aligned in 
conducting these reviews. This guidance is part of FDA's efforts to 
implement section 3038 of the Cures Act.
    The draft guidance describes premarket pathways available for 
combination products and related considerations as well as illustrative 
examples on how these principles can be applied.
    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 ``Principles 
of Premarket Pathways 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.

II. Other Issues for Consideration

    The FD&C Act (section 503(g)(1)(B)) provides that the Secretary of 
HHS shall conduct the premarket review of any combination product under 
a single application, whenever appropriate. FDA requests public comment 
on those circumstances when a single application may not be 
appropriate, and thus two applications--one to the lead center and one 
to the non-lead center--should be submitted. In those circumstances, 
are there steps FDA should take to avoid duplication of effort or 
duplicate data submission and to minimize unnecessary burden? As 
described in the draft guidance, FDA's current thinking is that a 
single application is generally appropriate for a combination product. 
However, the Agency anticipates that a single application may not be 
appropriate in limited cases; for example, when the characteristics of 
the non-lead constituent part give rise to safety and effectiveness or 
regulatory oversight issues that may be best addressed through separate 
applications. Such cases may include, for example, when a complex 
device-led co-packaged or cross-labeled combination product includes a 
constituent part that is a new molecular entity (NME) that potentially 
has, or is intended to have, systemic effects. In this case, the NME 
may need to be reviewed in a separate application. FDA requests public 
comment on this issue.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

IV. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations and guidance. 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 part 3 have been 
approved under OMB control number 0910-0523 and the collections of 
information in the guidance ``How to Prepare a Pre-Request for 
Designation (Pre-RFD)'' have been approved under OMB control number 
0910-0845. The collections of information for applications for FDA 
approval to market a new drug (certain provisions of 21 CFR part 314) 
have been approved under OMB control number 0910-0001; the collections 
of information in 21 CFR part 601 have been approved under 0910-0338; 
and the collections of information in section 351(k) of the Public 
Health Service Act (42 U.S.C. 262) have been approved under 0910-0719. 
The collections of information in 21 CFR part 807, subpart E, have been 
approved under OMB control number 0910-0120; the collections of 
information in 21 CFR part 814, subparts A through E, have been 
approved under OMB control number 0910-0231; the collections of 
information in 21 CFR part 860 have been approved under OMB control 
number 0910-0138; the collections of information in the guidance 
document ``Requests for Feedback on Medical Device Submissions: The 
Pre-Submission Program and Meetings with Food and Drug Administration 
Staff'' have been approved under OMB control number 0910-0756; and the 
collections of information in the guidance ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' have been 
approved under OMB control number 0910-0844.

    Dated: January 17, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-01196 Filed 2-5-19; 8:45 am]
 BILLING CODE 4164-01-P