AFSA-EFPIA Workshop 2021
The workshop aimed to assess the lingering barriers, to reach a shared agreement on further concrete actions to make the deletion of the test a global concrete achievement. International organisations and funding bodies, industry and its associations, and regulatory stakeholders are invited to share their view and discuss the respective experiences in a multi-stakeholder environment.
Continuing the discussion on the deletion of the ATT remains a key priority for many stakeholders. Despite multiple successful examples of deletions and exemptions (e.g. Europe, USA, Canada, Brazil, Argentina, and partially India and Japan), and WHO’s clear recommendations, a meaningful number of regulatory authorities have yet to evolve in their perspective regarding this test. Cooperation, information exchange and dialogue are still needed to assist regulators in evaluating and embracing change.
Building from the results of HSI Symposium (Rome, 2019) and on the IABS Congress (Bangkok, 2019), bring together a wider but specific range of key international and local stakeholders— including new ones with a keen interest in vaccine innovation and increased accessibility through diminished reliance on in vivo testing—to strategically agree on the way forward to the elimination of the ATT from the regulatory requirements for vaccines and biologicals.
Review and update barriers and difficulties hindering the elimination of the ATT in some key regions/countries that are still undecided on the evaluation or implementation of this opportunity.
Identifying concrete action to speed up the decision towards the elimination of the ATT.
- The Global Challenge of Post Approval Changes (PACs)
- The European Directorate for the Quality of Medicines & Healthcare (EDQM)
Read the Workshop report in Biologicals: Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps. A workshop Report, Biologicals, 2022.
ATT Global Requirements
|USA||Deleted (2015)||Revocation of General Safety Test Regulations That Are Duplicative of Requirements in Biologics License Applications (link)|
|Canada||No longer required (2007)||As of 2007, requests to delete the General Safety Test (GST) for approved vaccines were accepted, and the GST was not required for new vaccine authorizations.|
|Europe||Fully Deleted (2019)||1998 – Deleted for batch release from > 80 other monographs; complete removal from monographs for veterinary medicines, human sera and immunoglobulins, diphtheria, tetanus and pertussis vaccines and moved to the production section for other relevant human medicines.
Decision taken by the European Pharmacopoeia Commission during the 159th plenary session (Strasbourg on 21-22 November 2017) to delete all remaining ATT entered into force on January 1st, 2019 (link)
|Argentina||Partially Deleted (2018-)||Deleted from all human vaccines. Deletion activities ongoing for other biologicals products. Revision of the Argentinian Pharmacopoeia (7th Edition, 2003) ongoing. Volume 1. Chapter: 360. ENSAYO DE TOXICIDAD ANORMAL|
|Brazil||Partially deleted (2019- )||Brazilian Pharmacopoeia 6th Edition (only one exception: required for monograph “Meglumine antimoniate, injectable solution”)|
|India||Deleted from most of the specific monographs of human vaccines (2020- )||IP 2018, Amendment List 06 of July 22nd, 2020 (link) delete ATT for all listed products (human vaccines). In IP 2022, ATT requirement remains for new human vaccines and for 12 other products (Sterile bags; Chorionic gonadotrophin injection; Menotropin; Protamine sulphate injection; Streptokinase; Streptokinase injection; Urokinase; dried human anti-haemophilic fraction; human albumin; human normal immunoglobulin; human plasma protein fraction; recombinant streptokinase injection).|
|South Africa||Not performed (end of 2018)||Viviani et. al (2020)|
|Russia||Required (waiver possibilities)||Russian Pharmacopoeia Edition XIV. OFS:1.2.4.0004.15. Аномальная токсичность. Государственная фармакопея Российской Федерации. XIII изд. Т. 1. М.; 2015. Government Decree No. 1510 (2019) ‘On the Procedure of Batch Release of Medicinal Products for Human Use’|
|China||Required (waiver possibilities)||Chinese Pharmacopoeia 2020. Chapter 1141. 异常毒性检查法|
|Japan||Partially waived (2020)||Amendment Act (2020) of the Minimum Requirements for Biological Products (link). Waiver from some products: Influenza HA vaccine, Japanese encephalitis vaccine, Haemophilus influenzae type B (Hib), pneumococcal polysaccharide vaccine (PPSV23).
April 28th 2022: ATT are no longer needed to ensure the safety of vaccines, including recombinant VSV, HPV and HBV vaccines.
|South Korea||Deleted (2022)||Amendment to the Regulation on Approval and Review of Biologicals Products (link)|
|Indonesia||Required (waiver possibilities)||Indonesian Pharmacopoeia 6th Edition (2020). Vaksin, page 64: “Toksisitas Abnormal Memenuhi syarat Uji toksisitas abnormal seperti yang tertera pada Uji Reaktivitas secara Biologis in-vivo <251>, kecuali dinyatakan lain dalam monografi.”
Product specific waivers have been granted to manufacturers (2022)
|Thailand||Deleted||WHO 69th Expert Committee on Biological Standardization held from 29 October to 2 November 2018 (link).
Manufacturers report that ATT is still requested but waivers are granted depending on the type of products (vaccine vs antivenom).
|Mexico||Required (waiver possibilities)||Review of the pharmacopeia for ATT deletion planned for 2023.|
|Malaysia||Required||Not performed, manufacturers’ request for waivers pending authorities’ decision|
|Pakistan||Required||Not performed, manufacturers’ request for waivers pending authorities’ decision|
|Egypt||Required||Not performed, manufacturers’ request for waivers pending authorities’ decision|
|Turkey||Required (waiver possibilities)||Manufacturers reported acceptance of waiver request|
|Myanmar||Required||Manufacturers’ request for waivers pending authorities’ decision|
|Philippines||Required||Manufacturers’ request for waivers pending authorities’ decision|
|GCC – Cooperation Council for the Arab States of the Gulf||Required||Manufacturers’ request for waivers pending authorities’ decision|
|Iran||Required||Manufacturers’ request for waivers pending authorities’ decision|
|Kenya||Required||Manufacturers reported acceptance of waiver request|
|Zambia||Required||Manufacturers reported acceptance of waiver request|
|Nepal||Required||Manufacturers reported acceptance of waiver request|