ICCVAM Biennial Report 2014-2015

Biologics are products derived from biological sources and used as medicines in humans or animals. Biologics can include viruses, substances derived from blood and serum, toxins, antitoxins, vaccines, and large polypeptides.

Regulatory agencies such as the U.S. Food and Drug Administration (FDA) and U.S. Department of Agriculture (USDA) require batch testing of some biologics. While the specific testing requirements vary among agencies, this testing may be used to develop appropriate labeling, ensure potency of the product when used as labeled, and/or evaluate the safety and potency of manufactured vaccines prior to sale. Some of this testing can use many animals and cause the animals pain and distress. ICCVAM agencies are working to identify methods that will refine existing testing procedures or reduce or replace animal use for biologics testing.

ICCVAM and ICCVAM Agency Activities

• ICCVAM, National Institute of Environmental Health Sciences, and FDA: NICEATM worked with ICCVAM member agencies and international partners to organize two workshops to evaluate ongoing studies of alternatives to the murine histamine sensitization test (HIST) for safety testing of acellular pertussis vaccines.
  The first workshop, Progress and Challenges in the Replacement of HIST, was held in August 2014 as a satellite meeting of the Ninth World Congress on Alternatives and Animal Use in the Life Sciences. NICEATM organized the workshop on behalf of the International Working Group for Alternatives to the HIST, a consortium of stakeholders representing government, industry, animal welfare organizations, research and regulatory institutions, and the European Directorate for the Quality of Medicines and HealthCare (EDQM). At the workshop, consortium scientists reviewed and discussed implementation of in vitro alternatives to the HIST for the testing of acellular pertussis vaccines. The workshop also provided a forum for reviewing the current framework for regulatory acceptance of a harmonized approach for alternative in vitro assays to HIST. A report from this workshop will be published in 2016.
  Discussion at the August 2014 workshop laid the groundwork for the March 2015 workshop In Search of Acceptable Alternatives to the Murine Histamine Sensitization Test (HIST): What Is Possible and Practical? This event was organized by NICEATM and the National Centre for the 3Rs (NC3Rs) in collaboration with Health Canada, FDA, EDQM, and the European Union Reference Laboratory for Alternatives to Animal Testing, and was held at NC3Rs in London. Participants in this workshop, including vaccine manufacturers and U.S. and international regulators, evaluated data from a multi-laboratory study that used a Chinese hamster ovary cell-based assay to measure pertussis toxin in reference preparations. Participants concluded that the relevance and reliability of the assay is sufficient, and recommended that vaccine manufacturers begin using the assay alongside current HIST testing to demonstrate its validity for their specific products. Participants also discussed implementing an approach that would allow manufacturers to waive testing entirely under certain circumstances. Regulatory agency representatives attending the workshop agreed in principle to this suggestion. Proceedings from the workshop will be submitted for publication in 2016.
• FDA: In June 2015, FDA accepted a cell culture-based assay as an alternative to the mouse LD50 test for potency testing of botulinum neurotoxin drug products. Acceptance of such alternatives is expected to reduce and eventually replace animal use for such testing.
• USDA: In April 2015, the USDA Center for Veterinary Biologics (CVB) updated Veterinary Services Memorandum No. 800.112, “Guidelines for Validation of In Vitro Potency Assays.” This memorandum provides guidance concerning the information a manufacturer of veterinary vaccines and other biological products should provide when submitting a new potency assay for CVB’s consideration. These guidelines apply to in vitro assays used to determine the potency of such products and provide a framework for designing in vitro potency assays and the studies needed to validate those assays. Use of in vitro assays may replace, reduce, or refine animal use for this purpose.
• USDA: In October 2015, CVB issued Notice 15-13, "Option to Remove Back-titration Hamsters from In Vivo Potency Tests for Leptospira Serogroups Canicola and Icterohaemorrhagiae." This notice describes an exemption from the titration requirement in vaccination-challenge potency assays for Leptospira serogroups canicola and icterohaemorrhagiae. The exemption could reduce animal use by 50% for potency testing on these two fractions.