[Federal Register Volume 80, Number 203 (Wednesday, October 21, 2015)]
[Notices]
[Pages 63802-63804]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-26637]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-3454]


Manufacturing Site Change Supplements: Content and Submission; 
Draft Guidance for Industry and Food and Drug Administration Staff; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of the draft guidance entitled ``Manufacturing Site Change 
Supplements: Content and Submission''. This draft guidance describes 
the decision-making steps that FDA recommends to determine whether a 
premarket approval application (PMA) supplement should be submitted 
when a manufacturer intends to change the manufacturing site (including 
a change to the processing, packaging, or sterilization site) of its 
legally marketed PMA-approved device. This guidance also discusses the 
general factors FDA intends to consider to determine whether a 
preapproval inspection is necessary before approval of the PMA 
supplement. This draft guidance is not final nor is it in effect at 
this time.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment of this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by January 19, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2015-N-3454 for ``Manufacturing Site Change Supplements: Content 
and Submission.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at http://www.regulations.gov or at the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

[[Page 63803]]

     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    An electronic copy of the guidance document is available for 
download from the Internet. See the SUPPLEMENTARY INFORMATION section 
for information on electronic access to the guidance. Submit written 
requests for a single hard copy of the draft guidance document entitled 
``Manufacturing Site Change Supplements: Content and Submission'' to 
the Office of the Center Director, Guidance and Policy Development, 
Center for Devices and Radiological Health (CDRH), Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, Silver 
Spring, MD 20993-0002; or to the Office of Communication, Outreach, and 
Development, Center for Biologics Evaluation and Research (CBER), 10903 
New Hampshire Ave., Bldg. 71, Rm. 3103, Silver Spring, MD 20993-0002. 
Send one self-addressed adhesive label to assist that office in 
processing your request, or fax your request to 301-847-8149.

FOR FURTHER INFORMATION CONTACT: William MacFarland, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Silver Spring, MD 20993-0002, 301-796-5547; 
or Stephen Ripley, Center for Biologics Evaluation and Research, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993, 240-402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    Under section 515(d)(6) of the Federal Food, Drug, and Cosmetic Act 
(the FD&C Act) (21 U.S.C. 360e(d)(6)), a PMA supplement must be 
submitted for review and approval by FDA before making a change that 
affects the device's safety or effectiveness, unless such change is a 
modification in a manufacturing procedure or method of manufacture, 
which would be eligible for a 30-day notice. The PMA regulations 
provide general criteria in Sec.  814. 39 (21 CFR 814.39) for 
determining when PMA holders are required to submit a PMA supplement or 
are eligible to submit a 30-day notice. Pursuant to Sec.  814.39(a)(3), 
a PMA holder must submit a PMA supplement for review and approval by 
FDA concerning the ``use of a different facility or establishment to 
manufacture, process, or package the device'' that affects the safety 
or effectiveness of a device before implementing the change. With 
respect to establishment inspections, section 510(h) of the FD&C Act 
(21 U.S.C. 360(h)) requires every registered establishment to be 
subject to inspections pursuant to section 704 of the FD&C Act (21 
U.S.C. 374) and to be inspected at least once in the 2-year period 
after registration and at least once in every successive 2-year period 
thereafter.
    In March 1996, CDRH sent a letter to the medical device industry 
that announced a 1-year pilot program to improve the processing of PMA 
supplements for changes in manufacturing sites. The letter discussed 
the need to improve the speed and efficiency of CDRH review and 
approval of manufacturing site change supplements, and stated that CDRH 
did not require preapproval inspection for all site changes. CDRH later 
developed the draft guidance entitled ``Likelihood of Facilities 
Inspections When Modifying Devices Subject to Premarket Approval,'' 
which was issued on August 5, 1999. This guidance was never finalized.
    The PMA supplements described in the March 1996 letter and the 1999 
draft guidance were called ``site change supplements'' or, if no 
preapproval inspection was required, they were termed ``express 
supplements.'' FDA now identifies all such submissions as ``site change 
supplements'' with a designation of whether or not an inspection is 
needed before the change can be implemented. Based on feedback from 
industry and the Agency's experience over many years, FDA has made 
substantial revisions and updates to the 1999 draft guidance and is 
reissuing it for comment as this Level 1 draft guidance.
    This guidance document explains: (1) What constitutes a 
manufacturing site change and when a manufacturer should submit a PMA 
supplement for a site change; (2) what documentation a manufacturer 
should submit in the site change supplement; and (3) the general 
factors that FDA intends to consider when determining whether to 
conduct an establishment inspection prior to approval of a site change 
supplement. This guidance is intended to help industry decide when a 
change in manufacturing site should be submitted in a PMA site change 
supplement. The guidance is also intended to help industry predict when 
a preapproval inspection in connection with a PMA supplement for a 
manufacturing site change will likely be needed to evaluate the firm's 
implementation of Quality System regulation requirements, 21 CFR part 
820. As a result, this guidance should help manufacturers manage the 
timeframes associated with implementing the changes in the 
manufacturing site and any processes, methods, procedures, 
qualifications, and validations.
    Please note that this guidance only applies to a manufacturer of a 
device with an approved PMA, a product development protocol, or a 
humanitarian device exemption. This guidance does not address 
manufacturing site changes for devices cleared under premarket 
notification (510(k)) submissions.

II. 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 manufacturing 
site change supplements' content and submission. It does not establish 
any rights for any person and is not binding on FDA or the public. You 
can use an alternative

[[Page 63804]]

approach if it satisfies the requirements of the applicable statutes 
and regulations.

III. Electronic Access

    Persons interested in obtaining a copy of the draft guidance may do 
so by downloading an electronic copy from the Internet. A search 
capability for all CDRH guidance documents is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance documents are also available at 
http://www.regulations.gov or from CBER at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm. Persons unable to download an electronic copy of 
``Manufacturing Site Change Supplements: Content and Submission'' may 
send an email request to [email protected] to receive an 
electronic copy of the document. Please use the document number 1269 to 
identify the guidance you are requesting.

IV. Paperwork Reduction Act of 1995

    This draft 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 part 814, subparts B and E have 
been approved under OMB control number 0910-0231; the collections of 
information in 21 CFR part 814, subpart H have been approved under OMB 
control number 0910-0332; and the collections of information in 21 CFR 
part 820 have been approved under OMB control number 0910-0073.

    Dated: October 15, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-26637 Filed 10-20-15; 8:45 am]
BILLING CODE 4164-01-P