[Federal Register Volume 78, Number 122 (Tuesday, June 25, 2013)]
[Notices]
[Pages 38058-38059]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-15100]
[[Page 38058]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-D-0083]
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 guidance for industry entitled ``Heparin for Drug and
Medical Device Use: Monitoring Crude Heparin for Quality.'' This
guidance was initially published as a draft guidance on February 13,
2012. The draft was revised to clarify FDA's expectations and
recommendations and to include references to a recently-developed assay
for detecting ruminant contamination of crude heparin.
DATES: Submit either electronic or written comments on Agency guidances
at any time.
ADDRESSES: Submit written requests for single copies of this 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. See
the SUPPLEMENTARY INFORMATION section for electronic access to the
guidance document.
Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management, Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Frank W. Perrella, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4257, Silver Spring, MD 20993-0002, 301-
796-3265; or Dennis M. Bensley, Jr., Center for Veterinary Medicine,
Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855,
240-276-8268; or Scott McNamee, Center for Devices and Radiological
Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
66, Rm. 3416, Silver Spring, MD 20993-0002, 301-796-5523.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Heparin for Drug and Medical Device Use: Monitoring Crude
Heparin for Quality.'' This guidance provides recommendations that will
help active pharmaceutical ingredient (API) manufacturers,
pharmaceutical and medical device manufacturers of finished products,
and others, to prevent the use of crude heparin that might contain
oversulfated chondroitin sulfate (OSCS) or non-porcine material
(especially ruminant material) contaminants. This 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 crude heparin sourced from China. FDA is also
concerned about the potential for contamination of heparin with
ruminant materials. The control of the quality of crude heparin is
important to ensure the safety of drugs and devices and to protect
public health. FDA developed this 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 ruminant material (unless specifically approved as part
of drug or medical device application).
The guidance recommends that manufacturers test and confirm the
species origin of crude heparin in each lot of every 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.
FDA has posted a method entitled ``Heparin Multiplex Real-Time PCR
Assay (hMRTA),'' on the Internet at http://www.fda.gov/AnimalVeterinary/ScienceResearch/ToolsResources/ucm350289.htm. This
method will be updated occasionally and persons performing the assay
should visit the Web site regularly to ensure they are using the most
current version.
The guidance also recommends that manufacturers test for OSCS in
crude heparin in each lot of every 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. FDA has also
made an HPLC method for testing for the presence of OSCS in crude
heparin available on the Internet at http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM206230.pdf. Users of this method should also review the Web site
occasionally to ensure they are employing the most current version.
In addition to testing crude heparin for species of origin and the
presence of OSCS in crude heparin, manufacturers should reject for use
any crude heparin found to contain any amount of OSCS, or to be derived
from, in any amount, ruminant mucosa (unless approved in the drug or
device application). If imported into the United States, any such crude
heparin or heparin products in which it was used should be controlled,
and manufacturers should notify FDA of any such finding. The guidance
also recommends that manufacturers identify and audit crude heparin
suppliers and heparin API suppliers to ensure conformance to
appropriate quality standards. Manufacturers should employ the controls
described in the guidance for industry entitled ``Q7 Good Manufacturing
Practice Guidance for Active Pharmaceutical Ingredients'' and comply
with the quality system regulations (as applicable).
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
Agency's current thinking on Heparin for Drug and Medical Device Use:
Monitoring Crude Heparin for Quality. 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 either electronic comments regarding
this document to http://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES). It is only necessary to
send one set of 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, and will be posted to the docket at http://www.regulations.gov.
[[Page 38059]]
III. The 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). In the
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,
or to be derived from, in any amount, ruminant mucosa (unless approved
in the drug or device application) (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://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.
Dated: June 19, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-15100 Filed 6-24-13; 8:45 am]
BILLING CODE 4160-01-P