Future of TABST and LABST in the Indian Pharmacopoeia Monographs A Humane Society International/India Workshop Report.

Humane Society International India (HSI India) organized and facilitated a workshop on the 'Future of Target Animal Batch Safety Test (TABST) and Laboratory Animal Batch Safety Test (LABST) in the Indian Pharmacopoeia (IP) Monographs'. The workshop hosted key Indian regulators from the Indian Pharmacopoeia Commission (IPC) and the Central Drugs Standard Control Organization (CDSCO), industry representatives from the Indian Federation of Animal Health Companies (INFAH), Asian Animal Health Association (AAHA), and international experts representing the European Directorate for the Quality of Medicines (EDQM), the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), and multinational veterinary products manufacturers. The workshop was organized to encourage a bidirectional flow of information and to discuss the deletion of TABST and LABST from the veterinary vaccine monographs in the IP. This workshop was built from the symposium held by Humane Society International on the 'Global Harmonization of Vaccine Testing Requirements' held in 2019. This report details the outcomes of the workshop with proposed activities to be taken up as part of the next steps for the elimination or waiving of these tests.

Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps. A workshop Report.

This online workshop Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps was organized on October 14th, 2021, by the Animal Free Safety Assessment Collaboration (AFSA), the Humane Society International (HSI), the European Federation of Pharmaceutical Industries and Associations (EFPIA), in collaboration with the International Alliance of Biological Standardization (IABS). The workshop saw a participation of over a hundred representatives from international organizations, pharmaceutical industries and associations, and regulatory authorities of 28 countries. Participants reported on country- and region-specific regulatory requirements and, where present, on the perspectives on the waiving and elimination of the Abnormal Toxicity Test. With AFSA, HSI, EFPIA and IABS representatives as facilitators, the participants also discussed specific country/global actions to further secure the deletion of ATT from all regulatory requirements worldwide.

Pathological analysis of batch safety testing of veterinary vaccines using small laboratory animals.

Batch safety tests (BSTs) of veterinary vaccines are conducted using small laboratory animals to assure the safety of vaccines according to several criteria, including clinical signs and change in body weight. Although the latter is used as an evaluation index in BSTs, there have been no reports on the internal changes that affect body weight during the test period. Therefore, we analyzed BST via pathological examination of the tested animals. Here, BSTs were performed for 176 batches using mice and 126 batches using of guinea pigs. Most of the gross findings could be classified into four lesion types (nodules, adhesions, ascites, no apparent signs), with only one vaccine inducing lesions that could not be classified into any of these four types. Histopathological examination revealed that the reactions caused by BST were pyogenic and/or granulomatous inflammation. Nodular or adhesive lesions comprised more severe pyogenic granulomatous inflammation than ascites or cases with no apparent gross lesions. These nodular or adhesive lesions were more frequently induced by vaccines that contained an adjuvant than by vaccines that did not contain an adjuvant. The cases with "exceptional" gross findings histologically presented severe necrosis of the hematopoietic system. Additional testing showed that these "exceptional" lesions were induced when a specific type of light liquid paraffin was injected along with other vaccine additives. Our results show that body weight loss and/or lesions during BST were induced by proinflammatory properties of the tested vaccines and that BST is a sensitive method for detecting unexpected effects of vaccine components.

Global harmonization of vaccine testing requirements: Making elimination of the ATT and TABST a concrete global achievement.

This one-day symposium organized by Humane Society International (HSI) brought together 18 international experts from Argentina, Brazil, China, Europe, India, Russia, South Africa and the United States to discuss the elimination of the abnormal toxicity test (ATT) from the testing requirements for human vaccines as well as the target animal batch safety test (TABST) and the laboratory animal batch safety test (LABST) for veterinary vaccines. Participants reported on country-specific regulatory requirements and, where present, the perspectives on waiver and elimination of those tests. In addition, the attendees, with HSI in the role of facilitator, moved to define the barriers to the complete elimination or waiving of these tests. This report expounds the outcomes of the symposium, and introduces a proposed roadmap - populated with country specific activities - for the elimination of these tests.

Modern science for better quality control of medicinal products "Towards global harmonization of 3Rs in biologicals": The report of an EPAA workshop.

This article summarizes the outcome of an international workshop organized by the European Partnership for Alternative Approaches to Animal Testing (EPAA) on Modern science for better quality control of medicinal products: Towards global harmonization of 3Rs in biologicals. As regards the safety testing of biologicals, the workshop participants agreed to actively encourage the deletion of abnormal toxicity tests and target animal batch safety tests from all relevant legal requirements and guidance documents (country-specific guidelines, pharmacopoeia monographs, WHO recommendations). To facilitate the global regulatory acceptance of non-animal methods for the potency testing of, e.g., human diphtheria and tetanus vaccines and veterinary swine erysipelas vaccines, international convergence on the scientific principles of the use of appropriately validated in vitro assays for replacing in vivo methods was identified as an overarching goal. The establishment of scientific requirements for new assays was recognized as a further means to unify regulatory approaches in different jurisdictions. It was recommended to include key regulators and manufacturers early in the corresponding discussions. Manufacturers and responsible expert groups, e.g. at the European Directorate for the Quality of Medicines and Health Care of the Council of Europe or the European Medicines Agency, were invited to consider leadership for international collaboration.

Incidental induction of secondary bowel disorders in guinea pigs during a batch safety test of veterinary vaccines.

Veterinary vaccines are subjected to a safety testing using laboratory animals via intraperitoneal injection per batch. From April 2010 to March 2011, 7 guinea pigs in 4 batch tests exhibited unrecoverable weight loss and/or were found dead. Six guinea pigs had developed intussusception, whereas another one had developed an intestinal obstruction consequent to adhesion. A histopathology revealed that these lesions were associated with inflammatory foci. Other animals than the 7 guinea pig also developed similar inflammatory foci but did not develop bowel disorders. In the retesting of these batches, animals did not exhibited clinical signs, though inflammatory foci were detected. The clinical signs, detected in the primary test, might be due to bowel disorders secondary to an inflammatory response, rather than toxicity.