
[Federal Register Volume 77, Number 117 (Monday, June 18, 2012)]
[Notices]
[Pages 36277-36279]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-14741]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0011]


Academic Development of a Training Program for Good Laboratory 
Practices in High Containment Environments (U24)

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 Funding Opportunity 
Announcement (FOA) entitled ``Academic Development of a Training 
Program for Good Laboratory Practices in High Containment Environments 
(U24).'' In this FOA, FDA announces its intention to accept and 
consider a single source application for an award to the University of 
Texas Medical Branch (UTMB) Galveston National Laboratory (GNL) for the 
development and implementation of a certified, academic training course 
for instruction in Good Laboratory Practices (GLP) in a Biosafety Level 
(BSL) 4 High Containment Environment. FDA seeks to support an effort to 
design a robust, collaborative, and educational program using problem-
based learning techniques designed to bring researchers and regulators 
together to educate each other on the challenges related to these 
issues and to identify solutions that are acceptable from both 
scientific and regulatory perspectives.

DATES: Important dates are as follows:
    1. The application due date is July 16, 2012.
    2. The anticipated start date is September 15, 2012.
    3. The opening date is June 18, 2012.
    4. The expiration date is July 17, 2012.

ADDRESSES: Submit the paper application to: Gladys Melendez Bohler, 
Office of Acquisitions and Grants Services (HFA-500), 5630 Fishers 
Lane, rm. 1078, Rockville, MD 20857, 301-827-7175, email: 
gladys.bohler@fda.hhs.gov. For more information, see section III of the 
SUPPLEMENTARY INFORMATION section of this notice.

FOR FURTHER INFORMATION CONTACT: CAPT. Estella Jones, Office of the 
Chief Scientist, Food and Drug Administration, Bldg. 32, rm. 4130, 
Silver Spring, MD 20993, 301-796-0742, Email: 
estella.jones@fda.hhs.gov.; or
Lisa Hensley, Office of Counterterrorism and Emerging Threats, Food and 
Drug Administration, Bldg. 32, rm. 4128, Silver Spring, MD 20993, 301-
796-8518, Email: lisa.hensley@fda.hhs.gov.; or
Gladys Melendez Bohler, Office of Acquisitions and Grants Services 
(HFA-500), 5630 Fishers Lane, rm. 1078, 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 refer to the full FOA 
located at http://www.fda.gov/EmergencyPreparedness/MedicalCountermeasures/default.htm.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

Request for Application: RFA-FD-12-024
Catalog of Federal Domestic Assistance: 93.103

A. Background

    FDA's Office of Counterterrorism and Emerging Threats (OCET) is a 
leader and active participant in the public health community and with 
the military defense community, helping to advance the development, 
evaluation, and approval of medical countermeasures to be used against 
threats involving chemical, biological, radiological, or nuclear (CBRN) 
agents. In 2010, FDA launched its Medical Countermeasures initiative 
(MCMi) in response to a report by the Secretary of the Department of 
Health and Human Services to assess the our nation's emergency 
readiness and in answer to a charge by President Obama to improve our 
nation's capacity to respond faster and more effectively to CBRN and 
emerging infectious disease threats--such as pandemic influenza. OCET 
was tasked with leading the implementation of the MCMi. OCET's 
activities are informed by the knowledge that protecting the civilian 
public and the warfighter against CBRN agents is a national security 
priority. A significant area of engagement for OCET is its support of 
innovative science to advance CBRN countermeasure development with the 
goal of improving access to safe and effective medical countermeasures, 
should the need arise. These efforts are central to strengthening 
national preparedness and security.
    The ``Animal Rule'' (21 CFR 314.600 for drugs; 21 CFR 601.9 for 
biological products) permits animal models to be

[[Page 36278]]

used to test the effectiveness of a product when testing in humans is 
neither possible nor feasible. Under the ``Animal Rule,'' pivotal 
efficacy studies must be conducted in accordance with Good Laboratory 
Practice (GLP) regulations (21 CFR part 58). Biological threats, such 
as Ebola virus, Marburg virus, Variola virus, or Lassa fever virus, for 
which medical countermeasures are needed, require testing in high and 
maximum biosecurity level (BSL-4) laboratories. These laboratory 
environments pose daunting challenges to a researcher's ability to meet 
the requirements of GLP regulations. There has been tremendous progress 
in the development of candidate interventions over the last decade. 
However, to date there is not a single facility that is capable of 
performing pivotal studies under GLP at BSL-4. To break the current 
choke point in the development process for interventions against agents 
requiring maximum containment, it will be critical for laboratories 
with BSL-4 capacity to receive the training and develop the capability 
necessary to routinely perform pivotal studies in accordance with GLP.
    OCET seeks to support an effort to design a robust, collaborative, 
and educational program using problem-based learning techniques 
designed to bring researchers and regulators together to educate each 
other on the challenges related to these issues and to identify 
solutions that are acceptable from both scientific and regulatory 
perspectives.
1. GLP Natural History Studies in BSL-4 Laboratories
    Natural history studies are performed to establish the dose of the 
disease agent, the route of exposure, and to study the pathogenicity of 
the disease agent in the animal model. Results of these studies help 
determine which animal model best describes the disease in humans. 
Acceptance of results of these studies for regulatory decision-making 
is contingent upon these studies being conducted in accordance with 
GLP. Examples of challenges in meeting GLP requirements include 
appropriate data recording, record keeping, inspections, and equipment 
validation. Training on the development of strategies to meet GLP 
requirements in high and maximum biocontainment laboratories can be 
realized when everyone has a common understanding of the challenges and 
requirements. In such a case, the scientific validity and regulatory 
acceptance of a study can be ensured early on, reducing the need for 
repeat studies, thereby reducing the numbers of animals needed to 
address the scientific and regulatory objectives. Once the natural 
history of the disease in the animal model has been established, it can 
be used to test the efficacy of antibiotics, vaccine, or other 
therapies as described in the ``Animal Rule.''
2. GLP Animal Efficacy Studies in BSL-4 Laboratories
    Animal efficacy studies are performed in accordance with the 
``Animal Rule'' to test the effectiveness of a medical countermeasure 
against a specific threat agent in an animal model that best models the 
disease in humans. Results from these studies also help determine the 
dose of the medical countermeasure that will be effective in humans. 
Acceptance of efficacy study results for regulatory decision-making is 
also contingent upon meeting GLP requirements. To date, three 
countermeasure products have been FDA approved using ``Animal Rule''-
type studies in support of efficacy.

B. Research Objectives

1. The Role of the University of Texas Medical Branch, Galveston 
National Laboratory
    The University of Texas Medical Branch, Galveston National 
Laboratory (UTMB-GNL) is globally renowned for educational excellence 
in the sciences, medicine and research, as well as for its Laboratory 
Biosafety Training Program (LBTP). The LBTP courses are designed to 
provide training for laboratorians working at BSL-2 through BSL-4 
levels. UTMB's Institutional Office of Regulated Nonclinical Studies 
(ORNcS) provides oversight for regulated studies and regulatory 
operations. In addition to the LBTP courses, the ORNcS offers an 
extensive, high-quality GLP training program to support faculty and 
staff at UTMB that are conducting nonclinical studies to support 
product licensure, including nonclinical studies conducted in BSL-3 and 
BSL-4 laboratories. ORNcS and OCET concur that an educational gap 
exists regarding the performance challenges of conducting GLP compliant 
studies in (A)BSL3/4 environments. Both have identified the need for an 
educational opportunity designed to better link GLP regulatory 
requirements with BSL-4 laboratory work to increase the efficiency of 
FDA data review and subsequently facilitate approval of medical 
countermeasures.
2. Project Description
    This project represents a collaborative effort between OCET, the 
UTMB-GNL, and UTMB ORNcS to support scientific and regulatory 
collaboration and enhance regulatory science to advance the development 
of safe and effective antibiotics, vaccines, and other medical 
countermeasures for use by civilian and military personnel in response 
to CBRN threat agents. The goal is to develop training strategies for 
scientists to foster a thorough understanding of the challenges and 
establish collaborative classroom environments to find solutions for 
overcoming hurdles. A common understanding of the challenges and 
requirements can lead to scientific validity and early regulatory 
acceptance of a study, reducing the need for repeat studies, thereby 
reducing the numbers of animals needed to address the scientific and 
regulatory objectives. Empowered with knowledge of how to successfully 
meet GLP requirements in high and maximum biocontainment, scientists 
working in this environment and FDA staff who will be evaluating 
applications will be better able to link GLP regulatory requirements 
with BSL-4 laboratory work, thus increasing the quality of the data and 
the efficiency of data review, subsequently facilitating approval of 
medical countermeasures. This project will also lead to improved 
technical cooperation between FDA and the regulated institutions 
conducting GLP research in maximum biocontainment. The project has the 
following goals:
    a. Mutual understanding. Progress in the development of animal 
models for efficacy testing of medical countermeasures has been very 
slow as developers struggle to design and conduct studies that meet 
scientific objectives and regulatory requirements for approval. 
Progress is further slowed as developers are sometimes at a loss with 
regard to how to satisfy GLP requirements when conducting studies in 
maximum biocontainment conditions. Currently, FDA's Basic Bioresearch 
Monitoring training program used to train field inspectors who inspect 
laboratories for GLP compliance lacks specific guidance for inspection 
of BSL-3 or BSL-4 laboratories that conduct GLP studies. OCET and ORNcS 
believe one way to foster progress on this issue is by gathering 
researchers and regulators together in a nonthreatening educational 
environment to identify the challenges and needs, then work together to 
find solutions.
    b. Develop collaborations. The training opportunity will bring 
together the community of researchers involved in conducting research 
in high and maximum biocontainment laboratories, who are also 
interested in conducting ``animal rule'' studies and animal 
qualification studies to support medical countermeasure development and

[[Page 36279]]

approval. In some cases, similar research is being conducted in 
different laboratories for the same medical countermeasure need. 
Participants will be encouraged to share experiences and join in 
collaborations to prevent duplication of research and avoid repetition 
of failed efforts and otherwise join in support of each other to attain 
shared goals and facilitate countermeasure development and approval.
3. Continuing Education--Areas of Focus
    a. GLP in high and maximum containment.--This portion of the 
training will be a joint UTMB/FDA effort, with UTMB providing the 
course foundation and FDA offering the field inspector perspective. 
Lecture examples would include a GLP Refresher, Good Documentation 
practices, Internal GLP Audits, Equipment Validation and Calibration, 
and Effective SOPs. Lectures could be followed with practical exercises 
pointing out specific challenges in meeting GLP requirements that have 
been encountered in BSL-3 and BSL-4 studies conducted at UTMB.
    b. The ``Animal Rule.''--FDA will provide an overview of the 
regulations for approval of new drugs and biologics based on evidence 
of effectiveness from studies in animals, including the status of FDA's 
draft document entitled, ``Guidance for Industry: Animal Models--
Essential Elements to Address Efficacy Under the Animal Rule'' dated 
January 2009 (Draft Guidance) and the animal model qualification 
process.
    c. Animal welfare.--This portion of the training will review animal 
welfare laws, policies guidelines and requirements, including lectures 
and discussions on the role of the veterinarian, determination of 
humane endpoints, and use of supportive care measures in BSL-4 studies.
    d. Telemetry.--Use of telemetry for remote monitoring of routine 
clinical parameters, such as body temperature, heart rate, respiration 
rate, and blood pressure is a helpful and sometimes an essential tool 
for conducting studies in BSL-4 laboratories. An entire half-day will 
be devoted to teaching what is available and how to implement telemetry 
techniques into BSL-4 studies.
4. Dissemination of Successful Enhancements to the Regulatory Science 
and Regulation of Animal Rule Studies for Medical Countermeasure 
Development
    UTMB and OCET will collaborate to incorporate any new FDA guidances 
and educational tools into the training program as new measures are 
developed (e.g., drug development tool guidance, updates to GLPs).

C. Eligibility Information

    As work in regulatory science for medical countermeasure 
development progresses, OCET and UTMB anticipate additional 
collaboration through seminars and training programs, particularly in 
the areas of GLP in maximum and high biocontainment laboratories, 
training FDA field inspectors how to effectively conduct GLP 
inspections in a high or maximum biocontainment laboratories, and 
training laboratorians and regulators in how to work in high or maximum 
biocontainment laboratories. With the financial and scientific support 
from FDA, UTMB is uniquely qualified to undertake these activities, 
given its mandate as an educational and scientific institution, its 
high visibility as a pioneer in implementing GLP in maximum and high 
biocontainment laboratories, and its access to worldwide scientific and 
regulatory expertise. UTMB has demonstrated a GLP reporting structure 
and large animal in vivo GLP BSL-4 expertise. In addition, the FDA/UTMB 
training program will be accessible to researchers at all other 
university, government, and private organizations.

II. Award Information/Funds Available

A. Award Amount

    Only one award will be made.
    OCET anticipates providing in FY2012 up to $150,000 (total costs 
include direct and indirect costs) for one award subject to 
availability of funds in support of this project. The possibility of 
four additional years of support up to $600,000 of funding is 
contingent upon successful performance and the availability of funds.

B. Length of Support

    The timeframe for this project is 5 years from the award date of 
the initial application.

III. Paper Application, Registration, and Submission Information

    To submit a paper application in response to this FOA, applicants 
should first review the full announcement located at (http://www.fda.gov/EmergencyPreparedness/MedicalCountermeasures/default.htm). 
(FDA has verified the Web site addresses throughout this document, but 
FDA is not responsible for any subsequent changes to the Web sites 
after this document publishes in the Federal Register). Persons 
interested in applying for a grant may obtain an application at http://grants2.nih.gov/grants/funding/phs398/phs398.html. 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.
     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 Bohler, Office of 
Acquisitions and Grants Services (HFA-500), 5630 Fishers Lane, Rm. 
1078, Rockville, MD 20857.

    Dated: June 12, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-14741 Filed 6-15-12; 8:45 am]
BILLING CODE 4160-01-P


