Replacing a long used test method with advanced and sustainable alternatives needed multiple steps and constant dialogue. Credit: bymuratdeniz/Getty Images
India recently abolished an outdated test in use for over 50 years to prove the safety of veterinary vaccines.
The Target Animal Batch Safety Test (TABST), which involved injecting high doses of vaccines into animals to observe their reactions, has been officially scrapped. The test would typically be passed if the animal survived or showed no adverse effects.
With this decision, India, the world's largest vaccine supplier, aligns itself with countries like Brazil, Europe, Canada, the US, and Japan, which have also abandoned the test, provided vaccine manufacturers adhere to established international quality standards.
The move follows similar action in 2020 when India removed the Abnormal Toxicity Test (ATT) from almost all vaccine requirements. The ATT was used to check for non-specific contaminants in human vaccines and other biological products like antivenoms. The decision to eliminate these tests reflects growing concerns about their relevance, given that they often don’t provide clear information about potential contaminants and can yield inconsistent results.
These animal tests were originally developed in the early 1900s, a time when quality control for vaccines was not as advanced as it is today. However, the industry has since evolved, with modern vaccine manufacturers required to meet strict quality control standards and consistency measures. These are often guided by international organizations like the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products and The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).
By following these rigorous guidelines, the risk of contamination during vaccine production is significantly reduced, making additional animal tests like TABST and ATT unnecessary. India's decision is seen as a positive step towards more ethical practices in vaccine production, while still ensuring the safety and effectiveness of vaccines.
Despite the shift in scientific consensus, getting rid of these outdated animal tests wasn't easy. Several hurdles stood in the way, such as the industry's reliance on older, well-established methods, which made it hard to accept new approaches. There was also a lack of global coordination, limited communication between vaccine makers and regulators, and concerns about the technical challenges of adopting new methods.
India eventually overcame these obstacles through extensive discussions involving Indian and global vaccine manufacturers, regulators, and other key stakeholders.
ATT and TABST are not the only animal-based assays that test batch safety of vaccines. The Rabbit Pyrogen Test is another such, in which the vaccine is injected into healthy adult rabbits to detect the presence of fever-causing substances (pyrogens). However, this is also a qualitative test that does not provide any insights on the nature of the pyrogen.
Recognising its limitations, the IPC introduced the in vitro Bacteria Endotoxin Test (BET) in 2014. This test uses the blood lysate of horseshoe crabs, which coagulates in the presence of pyrogens, offering a more precise and convenient method for detecting these substances in samples.
New test methods based on synthetic reagents or human cells can provide more sustainable and accessible alternatives. This can enable an uninterrupted global supply chain for testing of drugs, medical equipment, waters, and vaccines. For example, the Monocyte Activation Test (MAT) is an in vitro pyrogen test based on human cells, where monocytes (present in human blood) elicit an immune response upon contact with pyrogens which can be detected using a quantitative assay.
This method has been incorporated as a compendial method in European Pharmacopeia since 2009, and IPC also introduced a new chapter on MAT in 2018.
The abolition of TABST also brought to fore the crucial need to understand how technology can better serve the requirement of regions and its manufacturers; and have constant extensive dialogues with vaccine manufacturers, supply chain companies and regulators.
