Moving Towards Greater Regulatory Acceptance

Governments across the world, including in Canada, the United States, and the European Union, are leading the charge towards this new paradigm, coordinating together and with international partners such as the Organization for OECD and ITEM.

What are new approach methodologies (NAMs) and why are they important? Will regulatory bodies accept these new approaches during their risk assessments? How does this affect you?

There has been an increase in interest by regulatory authorities regarding the development, standardization, and implementation of NAMs as alternatives to conducting animal studies as part of safety assessments for chemical substances.

Governments across the world, including in Canada, the United States, and the European Union, are leading the charge towards this new paradigm, coordinating together and with international partners such as the Organization for Economic Co-operation and Development (OECD) and the consortium led by the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM).

+ What Are NAMs?

NAMs are broadly defined as any technology, methodology, approach, or combination of the three that can be used to replace, reduce, or refine animal toxicity testing and can allow for more rapid and effective prioritization and/or assessment of chemicals. 

These methods include, but are not limited to, computational modeling, modernized whole-organism assays, or assays with biological molecules, cells, tissues, or organs. 

A classic example of an alternative to animal testing includes the grouping and read across approach for chemical substances where the availability of data is limited to address human and/or environmental health toxicity endpoints.

Read-across involves using the available data from structurally similar substances to predict the behavior of the substance being assessed, and is based on the assumption that structurally similar substances will have reasonably similar physical–‍chemical properties, behave similarly, and elicit similar toxic effects. Another well-known and well-documented example is the skin sensitization Adverse Outcome Pathway (AOP) framework involving in chemico and in vitro assays for use in skin sensitization hazard and risk assessment.

+ Why Are NAMs important?

Planning, coordinating, and conducting animal testing in order to meet the information requirements for the regulatory safety assessment of substances is time-consuming and expensive. 

These barriers can significantly impede companies’ ability to register or notify their substances and get their products on the market, especially where the novel substance is intended for personal care products where many jurisdictions have legislated an outright ban on animal testing.

In addition to time and money, the use of animal testing can carry a societal weight that many are unable or unwilling to accept. 

For decades, there have been public calls for the reduction or outright ban on the use of animal testing for chemical safety assessments. Those calls have prompted significant advancements in scientific knowledge and technology, carving the path towards phasing out chemical testing on animals.

+ What Are the Governments Planning?

CANADA

The Government of Canada introduced amendments to the Canada Environmental Protection Act, 1999 (CEPA) under Bill S-5 (Strengthening Environmental Protection for a Healthier Canada Act), in June 2023, that recognize the need to replace, reduce, or refine the use of vertebrate animal testing for chemical risk assessments. 

The amendments support Health Canada (HC) and Environment and Climate Change Canada (ECCC) to promote the development and incorporation of alternative methods and strategies. HC and ECCC are developing a strategy within the context of CEPA and which is expected to be published alongside the Plan of Chemicals Management Priorities by June 2025. The following are key elements to be addressed under the strategy:

1. Identification and prioritization of needs for NAMs for use in chemical regulatory programs under CEPA;
2. Advancement of NAMs research and data generation to support development of methods, standardization, and translational research;
3. Promotion of harmonization, collaboration, communication, and engagement; and
4. Implementation of NAMs to reduce reliance on vertebrate animal toxicity testing in chemical regulator programs under CEPA.

UNITED STATES 

In 2016, amendments to the Toxic Substances Control Act of 1976 (TSCA) under Senate Bill 697 (Frank R. Lautenberg Chemical Safety for the 21st Century Act) were enacted into law. The amendments direct the Environmental Protection Agency (EPA) to reduce and replace the use of vertebrate animals in testing of chemicals and promote the development and timely incorporation of alternative test methods or strategies that do not require new vertebrate animal testing.

The EPA published its Strategic Plan to Promote the Development and Implementation of Alternative Test Methods within the TSCA program, which is devised around three core components:

1. Identifying, developing, and integrating NAMs for TSCA decisions;
2. Building confidence that the NAMs are scientifically reliable and relevant for TSCA decisions; and
3. Implementing the reliable and relevant NAMs for TSCA decisions.

EUROPEAN UNION

In 2007, the European Chemicals Agency (ECHA) introduced the Registration, Evaluation, Authorization and Restrictions of Chemicals (REACH) regulation (EC No 1272/2008). REACH requires that animal testing is only used as a last resort, and it promotes the use of alternative methods and approaches, including Quantitative Structure-Activity Relationship (QSAR) modeling, as far along the safety assessment as possible. 

The European Centre for the Validation of Alternative (ECVAM) of the European Commission’s Joint Research Centre was originally founded in 1991, and in 2010 its role was broadened to promote the development of new alternative test methods, establishing the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). Through the EURL ECVAM and other initiatives, the European Union aims to:

1. Foster international harmonization of regulatory testing requirements;
2. Improve animal welfare and establish the “Three Rs” principle (replacement, reduction, and refinement) when animals are needed in research in testing; and
3. Advance the research, development, and validation of alternative methods for the regulatory safety assessment of chemicals.

+ How Does this Affect You?

With the rapid scientific advancements in the development and validation of NAMs and their ever-‑increasing regulatory acceptance in chemical safety assessments, it can be difficult to know the appropriate path forward to ensure your product is assessed quickly and cost-effectively. 

While acceptance of NAMs is slowly growing across jurisdictions, a strong scientific justification, detailing and positioning any potential uncertainties of NAM-derived information, is essential to support a regulatory safety assessment.

+ We Are Here to Help

Are you looking to avoid animal testing on your product(s), but don’t know which NAMs are accepted by regulatory authorities? Do you require services related to NAMs such as commissioning testing, preparing read-across, or conducting QSAR modeling? Contact our experts at Global Standards—‍we’re here to help!

+ Useful Links 

1. https://www.canada.ca/en/health-canada/programs/consultation-strategy-replace-reduce-refine-vertebrate-animal-testing/notice-intent.html
2. https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/alternative-test-methods-and-strategies-reduce
3. https://environment.ec.europa.eu/topics/chemicals/animals-science_en
4. https://www.item.fraunhofer.de/en/press-and-media/press-releases/echa-research-project.html