Accelerating Global Deletion of the Abnormal Toxicity Test

ATT Deletion Workshop - AFSA

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.


  1. 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.

  2. 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. 

  3. Identifying concrete action to speed up the decision towards the elimination of the ATT. 

An overview of the work that has been undertaken and is still needed to delete the obsolete, animal-based Abnormal Toxicity Test (ATT) from biologicals product testing worldwide.

Video also available with voiceovers in:

ATT Global Requirements

Country Status Reference
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: 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 28
th 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).
Taiwan Required  
Vietnam Required  
Mexico Required (waiver possibilities) Review of the pharmacopeia for ATT deletion planned for 2023.
Chile Required  
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
Saudi Arabia Required   
Laos Required   
Cambodia Required  
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
Ghana Required  
Nigeria Required  
Zimbabwe  Required  
Nepal Required Manufacturers reported acceptance of waiver request
Uganda Required  
Uzbekistan Required  
Ukraine Required  
back to top