International Workshop on Alternatives to the Murine His­ta­mine Sensitization Test (HIST) for Acellular Pertussis Vaccines: Progress and Challenges in the Re­placement of HIST

Sunday, 24 August, 2014

Pertussis, also known as whooping cough, is a highly contagious bacterial disease. Pertussis was once a major cause of childhood mortality, but widespread vaccination has decreased its incidence substantially.

Regulatory authorities require 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 performed to ensure that pertussis toxin in acellular pertussis vaccines has been effectively inactivated. However, such testing uses many mice, some of which can experience significant unrelieved pain and distress. In addition, the HIST has technical challenges requiring frequent retesting, increasing vaccine testing expense and animal use.

This workshop organized by the International Working Group for Alternatives to the HIST, a consortium of interested stakeholders representing government, industry, animal welfare organizations, research and regulatory institutions and the EDQM, will bring together scientists involved in this collaboration to review and discuss the implementation of in vitro assays as alternatives to the HIST for the testing of acellular pertussis vaccines. The workshop will also provide a forum for reviewing the current framework for regulatory acceptance of a harmonized approach for alternative in vitro assays to HIST, in the context of recent international progress in the development of such alternative assays.

Additional Information:
Due to kind sponsorship from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) the workshop is free and open to the public, with attendance limited only by the space available. Because of space limitations, pre-registration is strongly recommended.

Register for the upcoming meeting here.

Lunch will be provided.

The workshop is being organized by the International Working Group on Alternatives to the HIST a consortium of interested stakeholders representing government, industry, and research institutions.

Time:
9:30–16:15

Place:
Hotel Hilton Prague, room Tyrolka

Contact:
Juan Arciniega, DSc (Center for Biologics Evaluation and Research – CBER, U.S. FDA)
juan.arciniega@fda.hhs.gov

Organized by:

NICEATM National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods
NC3Rs National Centre for the Replacement, Refinement and Reduction of Animals in Research
ICCVAM Interagency Coordinating Committee on the Validation of Alternative Methods
EURL ECVAM European Union Reference Laboratory for Alternatives to Animal Testing
Health Canada  
EDQM European Directorate for the Quality of Medicines and HealthCare

Sponsored by:

NC3Rs National Centre for the Replacement, Refinement and Reduction of Animals in Research

Workshop Objectives:

  1. Discuss the implementation of in vitro assays as replacements for the murine histamine sensitization test (HIST) for acellular pertussis (aP) vaccines on the basis of the consistency approach (i.e., the efficient functioning of a Quality System since the product licensing, involving process and testing validation. This approach ensures that the licensed manufacturing produces batches that are consistent with those that fulfilled the criteria of quality, safety and efficacy defined for the batches included in the marketing authorization):
    1. For licensed/registered products: Discuss the importance of Relevance of an in vitro assay to replace the HIST from the product profile of an aP vaccine – The high-level element that, along with Reliability, is required to validate a method.
    2. For new products: Discuss the requirements leading to the inclusion of one or more in vitro assays as replacements for the HIST in the product profile for licensing/registration.
  2. Discuss the necessary framework for regulatory acceptance of a harmonized approach that uses in vitro assays instead of the HIST.
  3. Discuss recent international efforts towards the development of in vitro assays to replace the HIST.

Draft Agenda

09:30–09:45 Welcoming Remarks, Announcements, and Introductions
Juan Arciniega, DSc, Center for Biologics Evaluation and Research (CBER), U.S. FDA
Katie Lidster, PhD, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), United Kingdom
Warren Casey, PhD, National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), NIH, USA
09:45–10:05 Prague, Pertussis, and Vaccines
Roman Prymula, PhD, Czech Vaccinology Society, Czech Republic
Peter Sebo, PhD, Czech Academy of Science, Institute of Microbiology, Czech Republic
10:05–10:25 The Road to Prague 2014
Richard Isbrucker, PhD, Health Canada
10:25–11:45 Session 1
The Murine Histamine Sensitization Test (HIST)

Co-chairs:
Leslie Wagner, Center for Biologics Evaluation and Research (CBER), U.S. FDA
Blaise Descampe, DVM, GSK, Belgium
10:25–10:45 Introduction
10:45–11:45 Roundtable Discussion
11:45–12:45 Lunch
12:45–13:15 Animal Use for the HIST and the Impact of In Vitro Alternatives
Coenraad Hendriksen, PhD, IntraVacc, Netherlands
Marieke Hoonakker, IntraVacc, Netherlands
13:15–13:30 Discussion
13:30–15:10 Session 2
In Vitro Assays as Replacements for HIST: Challenges to Regulatory Acceptance

Co-chairs:
Sue Nelson, PhD, Sanofi Pasteur, Canada
Richard Isbrucker, PhD, Health Canada
13:30–13:40 Introduction
13:40–15:10 Roundtable Discussion
15:10–15:25 Break
15:25–16:15 Final Discussion, Conclusions and Recommendations
Juan Arciniega, DSc, Center for Biologics Evaluation and Research (CBER), U.S. FDA
Warren Casey, PhD, National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), NIH, USA
16:15 End of Meeting