Document ID: FDA-2015-D-2167-0006
Agency: fda
Document Type: Notice
Title: Heparin-Containing Medical Devices and Combination Products:
Recommendations for Labeling and Safety Testing; Guidance for Industry
and Food and Drug Administration Staff; Availability
Posted Date: 2018-09-20T04:00Z

[Federal Register Volume 83, Number 183 (Thursday, September 20, 2018)]
[Notices]
[Pages 47623-47625]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-20472]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-2167]

Heparin-Containing Medical Devices and Combination Products: 
Recommendations for Labeling and Safety Testing; 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 a final guidance entitled ``Heparin-Containing 
Medical Devices and Combination Products: Recommendations for Labeling 
and Safety Testing.'' The United States Pharmacopeia (USP) drug 
substance monograph for Heparin Sodium, and drug product monographs for 
Heparin Lock Flush Solution and Heparin Sodium Injection, recently have 
undergone several revisions following serious and fatal events related 
to the use of heparin sodium products. Investigation of heparin product 
overdose errors identified the expression of drug strength in the 
labels as a major contributing factor in these errors. This guidance 
document addresses these safety concerns by clarifying new expectations 
for labeling with regard to the revised heparin USP monographs, as well 
as outlining safety testing recommendations.

DATES: The announcement of the guidance is published in the Federal 
Register on September 20, 2018.

ADDRESSES: You may submit either electronic or written comments on 
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

[[Page 47624]]

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-2015-D-2167 for ``Heparin-Containing Medical Devices and 
Combination Products: Recommendations for Labeling and Safety 
Testing.'' 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)).
    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 
``Heparin-Containing Medical Devices and Combination Products: 
Recommendations for Labeling and Safety Testing'' 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: Andrew Yeatts, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1643, Silver Spring, MD 20993-0002, 301-796-4539.

SUPPLEMENTARY INFORMATION: 

I. Background

    The USP \1\ heparin monographs have recently undergone several 
revisions following serious and fatal events related to the use of 
heparin sodium products. Investigation of heparin product overdose 
errors identified the expression of drug strength in the labels as a 
major contributing factor in these errors. This guidance document 
addresses these safety concerns by clarifying new expectations for 
labeling with regard to the revised heparin USP monographs, as well as 
outlining safety testing recommendations.
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    \1\ USP is a scientific nonprofit organization that develops 
standards for the identity, strength, quality, and purity of drugs 
and drug ingredients marketed in the United States. These standards 
are published in USP's official compendia, U.S. Pharmacopeia and 
National Formulary.
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    In addition, the outbreak of serious and often fatal events due to 
heparin contamination with over-sulfated chondroitin sulfate in 2008 
led the USP to include in its monograph additional testing of heparin 
source material to ensure its quality and purity. This guidance also 
outlines use of conformance to the monograph in premarket submissions, 
specifically testing and documentation requirements and/or 
recommendations contained in the current USP monographs and the 
guidance document ``Heparin for Drug and Medical Device Use: Monitoring 
Crude Heparin for Quality'' (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291390.pdf).\2\
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    \2\ The Agency updates guidances periodically. To make sure you 
have the most recent version of this guidance, check the FDA 
guidance page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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    FDA considered comments received on the draft guidance that 
appeared in the Federal Register of July 9, 2015 (80 FR 39440). FDA 
revised the guidance as appropriate in response to the comments.

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 ``Heparin-Containing Medical Devices and 
Combination Products: Recommendations for Labeling and Safety 
Testing.'' 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.

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 https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. This

[[Page 47625]]

guidance is also available at https://www.regulations.gov. Persons 
unable to download an electronic copy of ``Heparin-Containing Medical 
Devices and Combination Products: Recommendations for Labeling and 
Safety Testing'' may send an email request to [email protected] 
to receive an electronic copy of the document. Please use the document 
number 1817 to identify the guidance you are requesting.

IV. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information. 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 
the following FDA regulations and guidance have been approved by OMB as 
listed in the following table:

------------------------------------------------------------------------
 21 CFR part; guidance; or FDA                              OMB control
              form                        Topic                 No.
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211............................  Current good                  0910-0139
                                  manufacturing practice
                                  for finished
                                  pharmaceuticals.
807, subpart E.................  Premarket notification.       0910-0120
814, subparts A through E......  Premarket approval.....       0910-0231
814, subpart H.................  Humanitarian Device           0910-0332
                                  Exemption.
812............................  Investigational Device        0910-0078
                                  Exemption.
``De Novo Classification         De Novo classification        0910-0844
 Process (Evaluation of           process.
 Automatic Class III
 Designation)''.
801............................  Medical Device Labeling       0910-0485
                                  Regulations.
803............................  Medical Devices;              0910-0437
                                  Medical Device
                                  Reporting;
                                  Manufacturer
                                  reporting, importer
                                  reporting, user
                                  facility reporting,
                                  distributor reporting.
820............................  Quality System (QS)           0910-0073
                                  Regulation.
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    Dated: September 17, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-20472 Filed 9-19-18; 8:45 am]
 BILLING CODE 4164-01-P