[Federal Register Volume 77, Number 29 (Monday, February 13, 2012)]
[Notices]
[Pages 7584-7585]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3229]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0083]


Draft Guidance for Industry on Heparin for Drug and Medical 
Device Use; Monitoring Crude Heparin for Quality; 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availability of a draft guidance for industry entitled ``Heparin for 
Drug and Medical Device Use: Monitoring Crude Heparin for Quality.'' 
This draft guidance is intended to alert manufacturers of active 
pharmaceutical ingredients (APIs), pharmaceutical and medical device 
manufacturers of finished products, and others to the potential risk of 
crude heparin contamination.

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 on this 
draft guidance before it begins work on the final version of the 
guidance, submit electronic or written comments on the draft guidance 
by April 13, 2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests.
    Submit electronic comments on the draft guidance to 
http:[sol][sol]www.regulations.gov. Submit written comments to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.

FOR FURTHER INFORMATION CONTACT: Frank W. Perrella, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 4337, Silver Spring, MD 20993-0002, 301-
796-3265; or Dennis M. Bensley, Jr., Center for Veterinary Medicine 
(HFV-140), Food and Drug Administration, 7519 Standish Pl., Rockville, 
MD 20855, 240-276-8268; or Jason Brookbank, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, rm. 3558, Silver Spring, MD 20993-0002, 301-796-5770.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Heparin for Drug and Medical Device Use: Monitoring Crude 
Heparin for Quality.'' This draft guidance provides recommendations 
that will help API manufacturers, pharmaceutical and medical device 
manufacturers of finished products, and others, to better control their 
use of crude heparin that might contain oversulfated chondroitin 
sulfate (OSCS) or non-porcine material (especially ruminant material) 
contaminants. This draft guidance on crude heparin recommends 
strategies to test for contamination and should be used in addition to 
the United States Pharmacopeia (USP) monograph testing required for 
other forms of heparin to detect the presence of OSCS.
    Following reports of serious adverse events (including deaths) 
among patients injected with heparin sodium in 2008, FDA identified the 
contaminant OSCS in heparin API manufactured in China. FDA is also 
concerned about the potential for contamination of heparin with the 
bovine spongiform encephalopathy (BSE) agent derived from ruminant 
materials. The control of the quality of crude heparin is critical to 
ensure the safety of drugs and devices and to protect public health. 
FDA developed this draft guidance to alert manufacturers to the risks 
of crude heparin contaminants and to recommend strategies to ensure 
that the heparin supply chain is not contaminated with OSCS or any non-
porcine origin material, especially ruminant material (unless 
specifically approved or cleared as part of drug or medical device 
application).
    The draft guidance recommends that manufacturers test and confirm 
the species origin of crude heparin in each shipment before use in the 
manufacture or preparation of a drug or medical device containing 
heparin. The test method should be qualified for use in testing crude 
heparin and for the identification of species origin. The method should 
be based on good scientific principles (e.g., sufficient accuracy and 
specificity) and possess a level of sensitivity commensurate with the 
current state of scientific knowledge and risk. Likewise, the draft 
guidance recommends that manufacturers test for OSCS in crude heparin 
in each shipment before use, using a qualified test method that is 
suitable for detecting low levels of OSCS concentrations and is based 
on good scientific principles. Manufacturers should reject for use and 
control or destroy crude heparin found to contain any amount of OSCS 
and notify FDA of any such finding. The draft guidance also recommends 
that manufacturers identify and audit crude heparin suppliers and 
heparin API suppliers to ensure conformance to current good 
manufacturing practice (CGMP), employ the controls described in the 
guidance for industry ``Q7 Good Manufacturing Practice Guidance for 
Active Pharmaceutical Ingredients,'' and comply with the quality system 
regulations (as applicable).
    This draft guidance is being issued consistent with FDA's good 
guidance

[[Page 7585]]

practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on this topic. 
It does not create or confer any rights for or on any person and does 
not operate to bind FDA or the public. An alternative approach may be 
used if such approach satisfies the requirements of the applicable 
statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

III. 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). In the 
draft guidance, FDA advises drug and medical device manufacturers who 
receive and use crude heparin to manufacture drugs and medical devices 
to notify the Agency of crude heparin found to contain any amount of 
OSCS (for human drugs 21 CFR 314.81(b)(1)(ii); for animal drugs 21 CFR 
514.80(b); for medical devices 21 CFR 803.50). The collections of 
information in 21 CFR 314.81(b)(1)(ii) have been approved under OMB 
control number 0910-0001; in 21 CFR 514.80(b) under OMB control number 
0910-0284; and in 21 CFR 803.50 under OMB control number 0910-0437.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http:[sol][sol]www.fda.gov/Drugs/
GuidanceComplianceRegulatoryInformation/Guidances/default.htm, 
http:[sol][sol]www.fda.gov/AnimalVeterinary/
GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm, 
http:[sol][sol]www.fda.gov/MedicalDvices/DeviceRegulationandGuidance/
GuidanceDocuments/default.htm, or http:[sol][sol]www.regulations.gov.

    Dated: February 8, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-3229 Filed 2-10-12; 8:45 am]
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