Document ID: FDA-2013-N-0012-0004
Agency: fda
Document Type: Notice
Title: Linking Marketplace Heparin Product Attributes and Manufacturing Processes to Bioactivity and Immunogenicity
Posted Date: 2013-06-19T04:00Z

[Federal Register Volume 78, Number 118 (Wednesday, June 19, 2013)]
[Notices]
[Pages 36786-36787]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-14579]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0012]

Linking Marketplace Heparin Product Attributes and Manufacturing 
Processes to Bioactivity and Immunogenicity

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of grant funds for the support of a sole source award to 
the University of North Carolina. The goal of the award is to identify 
what component(s) of the complex heparin mixtures have the propensity 
to cause heparin induced thrombocytopenia (HIT) to improve the safety 
of heparin drug products. The FDA seeks to identify the components of 
the heparin mixture that are associated with HIT so that actions may be 
taken to reduce these events and improve patient outcomes with this 
widely used drug.

DATES: Important dates are as follows:
    1. The application due date is July 15, 2013.
    2. The anticipated start date is August, 2013.
    3. The opening date is the date this announcement is published in 
the Federal Register.
    4. The expiration date is July 16, 2013.

ADDRESSES: Submit the paper application to: Gladys Melendez at the Food 
and Drug Administration, Grants Management (HFA-500), 5630 Fishers 
Lane, Rockville, MD 20857. For more information, see section III of the 
SUPPLEMENTARY INFORMATION section of this notice.

FOR FURTHER INFORMATION CONTACT: David Keire, Center for Drug 
Evaluation and Research, Food and Drug Administration, 1114 Market St., 
rm. 1002, St Louis, MO, 63130, 314-539-3850; or Gladys Melendez, Office 
of Acquisition Support and Grant Services, Food and Drug 
Administration, 5630 Fishers Lane, Rockville, MD 20857, 301-827-7175, 
email: Gladys.bohler@fda.hhs.gov.
    For more information on this funding opportunity announcement (FOA) 
and to obtain detailed requirements, please contact Gladys.bohler@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

    Request for Application: FDA RFA-13-007
    [Catalog of Federal Domestic Assistance: 93.103]

A. Background

    The goal of this Research Project is to identify which components 
of heparin drug mixtures have the propensity to cause heparin induced 
thrombocytopenia (HIT) in order to improve the safety profile of this 
widely used anticoagulant. Heparin is a heterogeneous mixture of 
polysaccharides of varying length, sulfation pattern, acylation and 
conformation that has been in clinical use since the 1930s. HIT is a 
drug-dependent immune disorder caused by antibodies to complexes formed 
between platelet factor 4 (PF4) and heparin which can occur in patients 
who undergo major trauma (e.g. broken bones and cardiovascular surgery) 
and receive heparin. The condition leads to formation of abnormal blood 
clots and concomitant complications associated with clots. PF4-heparin 
antibodies are observed in all patients with HIT. In addition, low 
molecular weight heparins or the synthetic pentasaccharide 
(fondaparinux) have also been shown to cause HIT antibody formation 
although these smaller chain length heparins are much less likely to 
lead to clinical HIT symptoms.
    The major limitation in the available reagents for studies aimed at 
identifying the components of heparin that lead to the pathogenesis of 
HIT is the lack of pure component heparin standards. Therefore, this 
collaboration brings together the following capabilities and 
laboratories: (1) Synthesis of heparin chains of the same length, 
sulfation pattern and conformation (Dr. Liu at the University of North 
Carolina and Dr. Linhardt at Rensselaer Polytechnical Institute), (2) 
synthesis and physicochemical characterization of heparin and heparin-
PF4 complexes (Keire FDA/DPA St Louis) and (3) a HIT-immunogenicity 
animal model (Dr. Arepally at Duke University). FDA believes that this 
combination of skills and expertise has the potential to make pure 
standards, fully characterize the standards, create and characterize 
PF4-heparin standard aggregates and assess their propensity to elicit 
an immune response in an animal model. This research is unique and not 
otherwise available. The ability to make pure heparin standards in gram 
quantities and fully characterize their properties is only available 
from the Liu and Linhardt laboratories. Furthermore, Dr. Arepally's 
mouse model of HIT immunogenicity is not available in any other 
laboratory. When completed the study will identify heparin components 
that enhance HIT propensity and which could potentially be minimized in 
heparin manufacturing, leading to safer heparin drugs with better 
patient outcomes.

B. Research Objectives

    The research objective is to identify the components of the heparin 
mixture that have the propensity to lead to HIT pathogenesis.

C. Eligibility Information

    This is a sole source RFA because the investigators identified in 
this document have unique skills and expertise necessary to perform the 
proposed work.

II. Award Information/Funds Available

A. Award Amount

    Only one award will be available to the University of North 
Carolina in the amount of $250,000 (Total Cost) in the first year.

B. Length of Support

    Depending on research progress and subject to the availability of 
funds additional funds may be awarded under this grant for up to a five 
year project period reflecting $250,000 Total Cost per year.

III. Paper Application, Registration, and Submission Information

    To submit a paper application in response to this FOA, applicants 
should first review the full announcement. Persons interested in 
applying for a grant may obtain an application at http://grants.nih.gov/grants/forms.htm.
    For all paper application submissions, the following steps are 
required:
     Step 1: Obtain a Dun and Bradstreet (DUNS) Number
     Step 2: Register With Central Contractor Registration

[[Page 36787]]

     Step 3: Register With Electronic Research Administration 
(eRA) Commons
    Steps 1 and 2, in detail, can be found at http://www07.grants.gov/applicants/organization_registration.jsp. Step 3, in detail, can be 
found at https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp. After you have followed these steps, 
submit paper applications to: Gladys Melendez; Grants Management, Food 
and Drug Administration, 5630 Fishers Lane, rm. 2032; HFA-500; 
Rockville, MD 20857.

    Dated: June 12, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-14579 Filed 6-18-13; 8:45 am]
BILLING CODE 4160-01-P