[Federal Register Volume 77, Number 168 (Wednesday, August 29, 2012)]
[Notices]
[Pages 52333-52334]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-21368]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


International Workshop on Alternatives to the Murine Histamine 
Sensitization Test (HIST) for Acellular Pertussis Vaccines: State of 
the Science and the Path Forward

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health (NIH), HHS.

ACTION: Announcement of a workshop; call for abstract submissions.

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SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM) announces an ``International Workshop 
on Alternatives to the Murine Histamine Sensitization Test (HIST) for 
Acellular Pertussis Vaccines: State of the Science and the Path 
Forward.'' This workshop, the third in a series of specialized vaccine 
workshops, will review new methods and approaches for acellular 
pertussis (aP) vaccine safety testing that incorporate innovations in 
science and technology. These scientific innovations should improve 
test accuracy, precision, and efficiency while also reducing or 
replacing the use of animals in vaccine safety testing. The goal is to 
address the path toward global validation, acceptance, and 
implementation of scientifically valid alternative methods for aP 
vaccines.
    The workshop is open to the public at no charge with attendance 
limited only by the available space; however, advance registration is 
required (see DATES). NICEATM also invites submission of abstracts for 
scientific posters for display at the workshop (see SUPPLEMENTARY 
INFORMATION).

DATES: The workshop is scheduled for November 28-29, 2012. Sessions 
will begin each day at 8:00 a.m. and will end each day at approximately 
5:45 p.m. The deadline for registration is November 16, 2012. The 
deadline for submission of poster abstracts is October 12, 2012.

ADDRESSES: The workshop will be held at the William H. Natcher 
Conference Center, 45 Center Drive, NIH Campus, Bethesda, MD 20892. 
Individuals with disabilities who need accommodation to participate in 
this event should contact Ms. Debbie McCarley at voice telephone: 919-
541-2384 or email: [email protected]. TTY users should contact the 
Federal TTY Relay Service at 800-877-8339. Requests should be made at 
least 5 business days in advance of the event.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director, 
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle 
Park, NC, 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (email) 
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530 
Davis Drive, Morrisville, NC 27560.

SUPPLEMENTARY INFORMATION:

Background

    Pertussis, also known as whooping cough, is a highly contagious 
disease caused by the bacterium Bordetella pertussis. Pertussis was one 
of the most common childhood diseases of the early 20th century and was 
once a major cause of childhood mortality in the United States. A 
whole-cell vaccine introduced in the 1940s reduced the incidence of 
pertussis by more than 80%. aP vaccines, which became available in the 
1980s, were developed in response to public concern with some common 
side effects (e.g., fever, swelling at injection site) and rare serious 
events that coincided with the use of whole-cell pertussis vaccines. 
These new generation aP vaccines contain different combinations of the 
putative protective antigens of B. pertussis bacteria (e.g., 
inactivated pertussis toxin [PTx/d], pertactin, and fimbriae) and are 
less reactogenic than whole-cell vaccines.
    Regulatory authorities require safety, potency, and purity testing 
prior to the release of each production lot of pertussis or pertussis 
antigen-containing vaccines. The murine histamine sensitization test 
(HIST) is a key safety test used to monitor residual levels of 
pertussis toxin (PTx) in vaccines. This test is performed to ensure 
that PTx has been effectively inactivated before release of vaccines 
(Corbel and Xing, 2004). However, such testing may involve large 
numbers of mice, some of which can experience significant unrelieved 
pain and distress. In addition, the HIST has technical challenges 
requiring frequent retesting, thereby increasing vaccine testing 
expense and animal usage. An international workshop organized in 2010 
\1\ by NICEATM, Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM), and their international partners 
identified the HIST as a priority for future research, development, and 
validation of alternative test methods that could further reduce, 
refine (enhance animal well-being and lessen or avoid pain and 
distress), or replace animal use for aP vaccine safety testing (Stokes 
et al., 2011).
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    \1\ International Workshop on Alternative Methods to Reduce, 
Refine, and Replace the Use of Animals in Vaccine Potency and Safety 
Testing: State of the Science and Future Directions, Bethesda, MD, 
USA September 14-16, 2010.
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    Two international workshops reviewed currently available 
alternative in vitro assays to the HIST and discussed a path forward to 
achieve their validation and adoption 2 3. The Workshop on 
Animal-Free Detection of PTx in Vaccines--Alternatives to HIST was held 
on June 9 and 10, 2011, at the Paul Ehrlich Institute, Germany. An 
International Working Group for Alternatives to HIST (previously 
designated as the ``Spiked-vaccine Working Group'') was organized to 
coordinate future studies on relevant alternative methods (Bache et 
al., 2012; Isbrucker, 2011).
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    \2\ Workshop on Animal-Free Detection of PTx in Vaccines--
Alternatives to HIST, Langen, Germany, June 9-10, 2011.
    \3\ Alternative Safety Testing Strategies for Acellular 
Pertussis Vaccines (8th World Congress Satellite meeting), Montreal, 
Canada, August 21, 2011.
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    The Alternative Safety Testing Strategies for Acellular Vaccines 
Workshop was held on August 21, 2011, as a satellite meeting to the 8th 
World Congress on Alternatives and Animal Use in the Life Sciences in 
Montreal, Canada (Isbrucker, 2011). Participants at this workshop 
further discussed and clarified regulatory agency requirements to 
achieve the acceptance of alternative methods to the HIST and agreed 
that conducting a study using spiked vaccines to compare the 
sensitivities of the HIST and in vitro assays would be important.

[[Page 52334]]

    Several in vitro assays have been developed, or are currently under 
development, with the aim of finding an alternative method to the HIST 
for monitoring residual PTx activity in aP vaccines. The International 
Working Group for Alternatives to HIST is coordinating the acquisition 
and distribution of aP vaccine samples from manufacturers to research 
laboratories for generation of data using in vitro methods to evaluate 
vaccines spiked with a known amount of PTx. Data from the various 
alternative assays will be presented at the upcoming workshop and will 
form the basis for identifying in vitro methods for future assessment 
in the next international collaborative study.
    The following methods will be evaluated and may be used to generate 
data to be presented at the upcoming workshop:

1. Binding assay: used to assess the amount of PTx/toxoid binding 
activity to the glycoprotein fetuin
2. Enzymatic assay: monitors the residual ADP-ribosylation of the PTx/
toxoid
3. Cell-based assays: monitor the generation of cAMP or decrease in 
cellular ATP following exposure to PTx
4. Genetic assays: determine potential genomic markers of PTx activity

    This workshop will provide a forum to discuss and review the in 
vitro protocols and available data from the International Working Group 
for Alternatives to HIST study and will suggest future collaborative 
projects using prepared materials. The workshop will also review 
additional new methods and approaches for aP vaccine safety testing 
that should improve test accuracy, precision, and efficiency while also 
reducing or replacing the use of animals in vaccine safety testing. 
Finally, the workshop will address the path toward global validation, 
acceptance, and implementation of scientifically valid alternative 
methods for aP vaccines.

Preliminary Workshop Agenda and Registration

    Registration information, draft agenda, and additional meeting 
information are available on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/meetings/HISTWksp-2012/HISTWksp.htm) and upon 
request from NICEATM (see FOR FURTHER INFORMATION CONTACT).

Call for Abstract Submissions

    NICEATM and ICCVAM invite the submission of abstracts for 
scientific posters to be displayed during this workshop. Guidelines for 
the submission of abstracts are available at http://iccvam.niehs.nih.gov/meetings/HISTWksp-2012/HISTWksp-AbstractSubmit-508.pdf. Abstracts must be submitted by email to [email protected]. 
The deadline for abstract submission is October 12, 2012. The 
corresponding author will be notified regarding the abstract's 
acceptance within 21 working days of the submission deadline. 
Guidelines for poster presentations will be sent to the corresponding 
author with notification of acceptance.

Background Information on NICEATM and ICCVAM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that require, use, 
generate, or disseminate toxicological and safety testing information. 
ICCVAM conducts technical evaluations of new, revised, and alternative 
safety testing methods and integrated testing strategies with 
regulatory applicability and promotes the scientific validation and 
regulatory acceptance of testing methods that more accurately assess 
the safety and hazards of chemicals and products and that reduce, 
refine, or replace animal use. The ICCVAM Authorization Act of 2000 (42 
U.S.C. 285l-3) established ICCVAM as a permanent interagency committee 
of the NIEHS under NICEATM. NICEATM administers ICCVAM, provides 
scientific and operational support for ICCVAM-related activities, and 
conducts independent validation studies to assess the usefulness and 
limitations of new, revised, and alternative test methods and 
strategies. NICEATM and ICCVAM welcome the public nomination of new, 
revised, and alternative test methods and strategies applicable to the 
needs of U.S. Federal agencies. Additional information about ICCVAM and 
NICEATM can be found on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).

References

Bache C, Hoonakker M, Hendriksen C, Buchheit K-H, Spreitzer I, 
Montag T. 2012. Workshop on Animal Free Detection of Pertussis Toxin 
in Vaccines--Alternatives to the Histamine Sensitization Test. 
Biologicals 40: 309-311.
Corbel MJ, Xing DK-L. 2004. Toxicity and potency evaluation of 
pertussis vaccines. Exp Rev Vaccines 3: 89-101.
Isbrucker R. 2011. Alternative safety testing strategies for 
acellular pertussis vaccines. ALTEX Proceedings, 1/12, Proceedings 
of WC8; 77-80.
Stokes WS, Kulpa-Eddy J, McFarland RM. 2011. The International 
Workshop on Alternative Methods to Reduce, Refine and Replace the 
Use of Animals in Vaccine Potency and Safety Testing--Introduction 
and Summary. In: International Workshop on Alternative Methods to 
Reduce, Refine, and Replace the Use of Animals in Vaccine Potency 
and Safety Testing: State of the Science and Future Directions 
(Kulpa-Eddy J, McFarland R, Stokes WS, eds). Procedia Vaccinol 5: 1-
15.

    Dated: August 20, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-21368 Filed 8-28-12; 8:45 am]
BILLING CODE 4140-01-P