
[Federal Register Volume 81, Number 116 (Thursday, June 16, 2016)]
[Notices]
[Pages 39269-39271]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-14190]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-0350]


Use of International Standard ISO 10993-1, `Biological evaluation 
of medical devices--Part 1: Evaluation and testing within a risk 
management process''; 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 the guidance entitled ``Use of International 
Standard ISO 10993-1, `Biological evaluation of medical devices--Part 
1: Evaluation and testing within a risk management process.' '' FDA has 
developed this guidance document to assist industry in preparing 
Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), 
Investigational Device Applications (IDEs), Premarket Notifications 
(510(k)s), and de novo requests for medical devices that come into 
direct contact or indirect contact with the human body in order to 
determine the potential for an unacceptable adverse biological response 
resulting from contact of the component materials of the device with 
the body.
    The purpose of this guidance is to provide further clarification 
and updated information on the use of International Standard ISO 10993-
1, ``Biological evaluation of medical devices--Part 1: Evaluation and 
testing within a risk management process'' to

[[Page 39270]]

support applications to FDA. This guidance supersedes Office of Device 
Evaluation (ODE) Blue Book Memorandum #G95-1 (1995), entitled ``Use of 
International Standard ISO-10993, `Biological Evaluation of Medical 
Devices--Part 1: Evaluation and Testing.' ''

DATES: Submit either electronic or written comments on this guidance at 
any time. General comments on Agency guidance documents are welcome at 
any time.

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-2013-D-0350 for ``Use of International Standard ISO 10993-1, 
`Biological evaluation of medical devices--Part 1: Evaluation and 
testing within a risk management process.' '' 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.
     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 guidance document entitled ``Use 
of International Standard ISO 10993-1, `Biological evaluation of 
medical devices--Part 1: Evaluation and testing within a risk 
management process' '' to the Office of the Center Director, Guidance 
and Policy Development, Center for Devices and Radiological Health, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 
5431, Silver Spring, MD 20993-0002. Send one self-addressed adhesive 
label to assist that office in processing your request.

FOR FURTHER INFORMATION CONTACT: Jennifer Goode, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1212, Silver Spring, MD 20993-0002, 301-796-6374.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA has developed this guidance document to assist industry in 
PMAs, HDEs, IDEs, 510(k)s, and de novo requests for medical devices 
that come into direct contact or indirect contact with the human body 
in order to determine the potential for an unacceptable adverse 
biological response resulting from contact of the component materials 
of the device with the body.
    The purpose of this guidance is to provide further clarification 
and updated information on the use of International Standard ISO 10993-
1, ``Biological evaluation of medical devices--Part 1: Evaluation and 
testing within a risk management process'' to support applications to 
FDA. This guidance supersedes ODE Blue Book Memorandum #G95-1 (1995), 
entitled ``Use of International Standard ISO-10993, `Biological 
Evaluation of Medical Devices--Part 1: Evaluation and Testing.' ''
    The scope of this document is limited to the biological evaluation 
of sterile and non-sterile medical devices that come into direct or 
indirect contact with the human body and covers the following topics: 
Use of risk assessments for biocompatibility evaluations for a proposed 
medical device; use of ISO 10993-1 and the FDA-modified matrix to 
determine the relevant biocompatibility endpoints for an evaluation; 
general biocompatibility testing considerations, including test article 
preparation; specific considerations for the following testing: 
Cytotoxicity, sensitization, hemocompatibility, pyrogenicity, 
implantation, genotoxicity, carcinogenicity, reproductive and 
developmental toxicity, and degradation assessments; chemical 
assessment recommendations; and considerations for labeling devices as 
``-free.''
    A draft of this guidance was made available in the Federal Register 
on

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April 23, 2013, and the comment period closed on July 22, 2013. The 
final guidance was revised in response to the comments to emphasize use 
of risk assessment and leveraging of prior information within a 
submission to potentially reduce the need for new biocompatibility 
testing.
    Commenters also requested additional details regarding 
biocompatibility testing of devices in contact with gas pathways and 
color additives used in medical devices. FDA has determined that these 
concepts would be appropriately addressed in separate guidance 
documents and have therefore been removed from this final guidance.

II. Significance of Guidance

    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 Use of International Standard ISO 10993-1, 
``Biological evaluation of medical devices--Part 1: Evaluation and 
testing within a risk management process.'' 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.

III. Electronic Access

    Persons interested in obtaining a copy of the guidance may do so by 
downloading an electronic copy from the Internet. A search capability 
for all Center for Devices and Radiological Health guidance documents 
is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance 
documents are also available at http://www.regulations.gov. Persons 
unable to download an electronic copy of ``Use of International 
Standard ISO 10993-1, `Biological evaluation of medical devices--Part 
1: Evaluation and testing within a risk management process' '' may send 
an email request to CDRH-Guidance@fda.hhs.gov to receive an electronic 
copy of the document. Please use the document number 1811 to identify 
the guidance you are requesting.

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 part 58 have been approved under 
OMB control number 0910-0119; the collections of information in 21 CFR 
parts 801 and 809 have been approved under OMB control number 0910-
0485; 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 812 have been approved under OMB control 
number 0910-0078; 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 814, subpart H, 
have been approved under OMB control number 0910-0332; the collections 
of information in 21 CFR part 820 have been approved under OMB control 
number 0910-0073; and 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 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.

    Dated: June 8, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-14190 Filed 6-15-16; 8:45 am]
 BILLING CODE 4164-01-P


