[Federal Register Volume 82, Number 221 (Friday, November 17, 2017)]
[Rules and Regulations]
[Pages 54290-54292]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-24838]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1271

[Docket No. FDA-2017-D-6146]


Regulatory Considerations for Human Cells, Tissues, and Cellular 
and Tissue-Based Products: Minimal Manipulation and Homologous Use; 
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 document entitled ``Regulatory Considerations for 
Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal 
Manipulation and Homologous Use; Guidance for Industry and Food and 
Drug Administration Staff.'' The guidance provides human cells, 
tissues, and cellular and tissue-based product (HCT/P) manufacturers, 
healthcare providers, and FDA staff, with FDA's current thinking on the 
regulatory criteria of minimal manipulation and homologous use. The 
guidance is intended to improve stakeholders' understanding of the 
definitions of minimal manipulation and homologous use and how the 
regulatory criteria apply to their HCT/Ps. It also informs 
manufacturers, healthcare providers, and other interested persons that 
the Agency generally intends to exercise enforcement discretion over 
the next 36 months under limited conditions, with respect to the 
investigational new drug (IND) application and premarket approval 
(biologics license application (BLA)) requirements, for certain HCT/Ps.

DATES: The announcement of the guidance is published in the Federal 
Register on November 17, 2017.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

[[Page 54291]]

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-2017-D-6146 for ``Regulatory Considerations for Human Cells, 
Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation 
and Homologous Use; Guidance for Industry and Food and Drug 
Administration Staff.'' 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 guidance to the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or 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 you may send an email request to the Office 
of Combination Products (OCP) at [email protected]. If you are 
submitting a written request, send one self-addressed adhesive label to 
assist that office in processing your request. The guidance may also be 
obtained by mail by calling CBER at 1-800-835-4709 or 240-402-8010. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.

FOR FURTHER INFORMATION CONTACT: Lori J. Churchyard, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911; or Angela Krueger, Office of Device Evaluation, Center 
for Devices and Radiological Health, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 66, Rm. 1676, Silver Spring, MD 20993-
0002, 301-796-6380; or Leigh Hayes, Office of Combination Products, 
Office of the Commissioner, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993-0002, 301-
796-8938.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a document entitled 
``Regulatory Considerations for Human Cells, Tissues, Cellular and 
Tissue-Based Products: Minimal Manipulation and Homologous Use; 
Guidance for Industry and Food and Drug Administration Staff.'' The 
guidance provides HCT/P manufacturers, healthcare providers, and FDA 
staff, with our current thinking on the criteria under part 1271 (21 
CFR part 1271), specifically the Sec.  1271.10(a)(1) (21 CFR 
1271.10(a)(1)) criterion of minimal manipulation and the Sec.  
1271.10(a)(2) criterion of homologous use. The interpretation of the 
minimal manipulation and homologous use criteria and definitions of 
related key terms have been of considerable interest to industry 
stakeholders since the criteria and definitions were first proposed.\1\ 
The guidance document is intended to improve stakeholders' 
understanding of the definitions of minimal manipulation in Sec.  
1271.3(f) and homologous use in Sec.  1271.3(c). It will also 
facilitate stakeholders' understanding of how the regulatory criteria 
in Sec.  1271.10(a)(1) and (2) apply to their HCT/Ps. The guidance 
document explains the regulatory scope of the regulations, as well as 
the Agency's compliance policy regarding certain regulatory 
requirements relating to HCT/Ps. In addition, the guidance document 
informs manufacturers, health care providers, and other interested 
persons that over the next 36 months, we intend to exercise enforcement 
discretion under limited

[[Page 54292]]

conditions with respect to the IND application or premarket approval 
(BLA) requirements, for certain HCT/Ps.
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    \1\ ``Establishment Registration and Listing for Manufacturers 
of Human Cellular and Tissue-Based Products'' 63 FR 26744 at 26748-
49 (May 14, 1998) https://www.gpo.gov/fdsys/pkg/FR-1998-05-14/pdf/98-12751.pdf.
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    In the Federal Register of December 23, 2014 (79 FR 77012), FDA 
announced the availability of the draft guidance entitled ``Minimal 
Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based 
Products; Draft Guidance for Industry and Food and Drug Administration 
Staff'' dated December 2014 (Minimal Manipulation Draft Guidance), and 
in the Federal Register of December 24, 2014 (79 FR 77414), FDA 
announced the availability of draft guidance entitled ``Human Cells, 
Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose 
Tissue: Regulatory Considerations; Draft Guidance for Industry'' dated 
December 2014 (Adipose Draft Guidance). Additionally, in the Federal 
Register of October 30, 2015 (80 FR 66850), FDA announced the 
availability of the draft guidance entitled ``Homologous Use of Human 
Cells, Tissues, and Cellular and Tissue-Based Products; Draft Guidance 
for Industry and FDA Staff'' dated October 2015 (Homologous Use Draft 
Guidance).
    Also in the Federal Register of October 30, 2015, FDA reopened the 
comment period on the Minimal Manipulation Draft Guidance (80 FR 
66844), Adipose Draft Guidance (80 FR 66849), and a third HCT/P-related 
guidance addressing the same surgical procedure exception in Sec.  
1271.15(b) (80 FR 66847) (Same Surgical Procedure Exception Draft 
Guidance). Comments on these three HCT/P-related guidances, as well as 
the Homologous Use Draft Guidance, were requested by April 29, 2016. 
Lastly, the Federal Register of October 30, 2015 (80 FR 66845), FDA 
announced a 1-day part 15 (21 CFR part 15) public hearing to obtain 
input on the four HCT/P-related guidances to be held on April 13, 2016.
    Due to considerable interest in the public hearing and to give 
stakeholders additional time to provide comments to the Agency, on 
February 29, 2016, FDA announced that the hearing was postponed. In the 
Federal Register of April 22, 2016 (81 FR 23661 and 81 FR 23664, 
respectively), FDA announced the rescheduled part 15 hearing date of 
September 12 and 13, 2016, and an extension of the comment period from 
April 29, 2016, until September 27, 2016, on the four HCT/P-related 
guidances. Also in the Federal Register of April 22, 2016 (81 FR 
23708), FDA announced a public workshop on the ``Scientific Evidence in 
Development of HCT/Ps Subject to Premarket Approval.''
    FDA received numerous comments on the Minimal Manipulation Draft 
Guidance, Homologous Use Draft Guidance, and the Adipose Draft Guidance 
in response to the request for comments, and those comments were 
considered in developing the final guidance in this notification.
    The guidance document announced in this notification finalizes the 
Minimal Manipulation Draft Guidance and the Homologous Use Draft 
Guidance. The guidance document also finalizes certain material related 
to adipose tissue that was included in the Adipose Draft Guidance. The 
material in this guidance document related to adipose tissue, together 
with the material related to adipose tissue included in the guidance 
finalizing the Same Surgical Procedure Exception Draft Guidance, the 
availability of which is announced elsewhere in this issue of the 
Federal Register, supersedes the Adipose Draft Guidance. Accordingly, 
FDA does not intend to finalize the Adipose Tissue Guidance, which is 
now withdrawn. Finally, this guidance supersedes the guidance entitled 
``Minimal Manipulation of Structural Tissue (Jurisdictional Update) 
Guidance for Industry and FDA Staff'' dated September 2006.
    FDA is also announcing via this Federal Register notification that, 
with the publication of this guidance document, it will cease posting 
the Tissue Reference Group (TRG) annual reports on FDA's Web site. The 
TRG was created as specified in the ``Proposed Approach to the 
Regulation of Cellular and Tissue-Based Products'' dated February 28, 
1997 (March 4, 1997; 62 FR 9721). The purpose of the TRG is to provide 
a single reference point for product specific questions received by FDA 
(either through the Centers, or from the Office of Combination 
Products) concerning jurisdiction and applicable regulation of HCT/Ps.
    In 1998, the TRG began publishing its recommendations in an annual 
report that was posted on FDA's Web site. Originally intended to assist 
industry in understanding the scientific rationale for the TRG 
recommendations, the recommendations are stated in general terms in 
order to protect proprietary information. As a result, FDA has received 
feedback from stakeholders that the annual reports do not provide 
helpful information. Therefore, we are announcing that although the TRG 
will continue to provide recommendations, the TRG annual reports will 
no longer be posted on FDA's Web site. We note that this final guidance 
is intended to help clarify the minimal manipulation and homologous use 
criteria in Sec.  1271.10(a)(1) and (2), and thus addresses many of the 
questions that had been posed to the TRG.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Regulatory Considerations for Human Cells, 
Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation 
and Homologous Use.'' 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. Paperwork Reduction Act of 1995

    The 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 part 1271 have been approved under OMB 
control number 0910-0543.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; or 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm; or https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/default.htm; or 
https://www.regulations.gov.

    Dated: November 13, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-24838 Filed 11-16-17; 8:45 am]
 BILLING CODE 4164-01-P