India: Experiments With Animals: The Long Road To Preventing Animal Testing In R&D In India

Introduction

Over 100 million animals are used in laboratory experiments worldwide every year. These are only estimates; the exact number is unknown and could possibly even be higher. These animals are either killed outright in scientific procedures, or used to assess the safety and efficacy of drugs and cosmetics.

Subjecting animals to confinement, pain and cruelty through lab experiments naturally raises ethical concerns. Additionally, the significant differences between animal and human anatomy and physiology means that animal studies may not reliably predict the outcome of substances being tested on humans. For example, many potential drugs fail to show any results in humans, although they work on mice. Research suggests that the outcomes of animal studies can sometimes even be misleading. Many people, researchers among them, are now questioning the necessity of such studies, including calling for an outright ban on animal testing in some cases.

Regulators have been responsive, and a gradual shift in regulatory requirements in some jurisdictions is perceptible, including considering options for phasing out animal testing altogether. This note discusses recent developments in the United States (US), the European Union (EU) and India.

3Rs and how they work

Principles governing the use of animals in labs were laid down in 1959 by two scientists, William Russell and Rex Burch, in their book, "The Principles of Humane Experimental Technique". Their "3Rs principle" proposed in the book for the treatment of animals in research has been adopted by various regulatory bodies, including in the US, EU and India. Of the 3Rs, "Replacement" refers to methods which replace the use of animals with non-animal methods where possible; "Reduction" refers to strategies or methods to use fewer animals to obtain sufficient data or maximum information per animal thereby reducing the number of animals being used; and "Refinement" refers to adopting practices to minimize stress on animals under study.

United States

Facing increasing pressure from animal welfare organizations, the US Food and Drug Administration (FDA) sought advice from its Science Board for the development, qualification, and adoption of alternative methods for regulatory use that can replace, reduce, and refine animal testing. Recent legislation (December 2022) no longer requires new medicines to be tested on animals, unlike earlier law which said that potential drugs be tested for safety and efficacy in animals. However, the new law allows FDA to promote a drug to human trials after either animal or non-animal tests.

The US Federal Food, Drug, and Cosmetic Act also does not specifically require the use of animals in testing cosmetics for safety. Cosmetics manufacturers are advised to employ whatever testing is appropriate and effective. The manufacturer is responsible for substantiating the safety of both ingredients and finished cosmetic products before marketing.

European Union

The EU legislation "on the protection of animals used for scientific purposes" is contained in Directive 2010/63/EU. This Directive, among other things, requires marketing authorisation holders to integrate the 3Rs principle for the ethical use of animals in medicine testing across the EU.

The final aim of the Directive is to replace all animal research with non-animal methods. The European Medicines Agency (EMA) promotes the 3Rs principle through EMA's Innovation Task Force, a multidisciplinary group with members having scientific, regulatory and legal competence. It provides for discussions between regulators and drug developers to promote the 3Rs principle and discuss New Approach Methodologies to fulfill testing requirements instead of animal tests.

EU Directive 76/768/EEC ("Cosmetics Directive") provides a regulatory framework for phasing out animal testing for cosmetics purposes across the EU. It prohibits testing of a finished cosmetic product and its ingredients on animals, and also prohibits marketing of finished cosmetic products or ingredients if they are tested on animals. Exemptions may be requested by member states in exceptional circumstances. The prohibition also does not apply under EU REACH the regulation governing the manufacture and import of chemical substances) if the testing is required to determine risks to the environment or workers.

India

In India, the regulatory web is detailed and complex:

• Drugs are regulated under the Drugs and Cosmetics Act, 1940 (DC Act), the Drugs and Cosmetics Rules, 1945 (DC Rules). Read with these, the New Drugs and Clinical Trial Rules, 2019 (CT Rules), as amended in 2023, regulate clinical trials, bioequivalence studies, bioavailability studies and related matters.
• Cosmetics are regulated under the DC Act, the DC Rules, and the Cosmetics Rules, 2020 (Cosmetics Rules).
• Experimentation on animals is regulated under the Prevention of Cruelty to Animals Act, 1960 (PCA Act) and the Breeding of and Experimentation on Animals (Control and Supervision) Rules, 1998.
• The Animal Welfare Board of India and the Committee for the Purpose and Supervision of Experiments on Animals established under the PCA Act oversee animal welfare issues. The committee's duty includes taking measures to ensure that animals are not subject to unnecessary pain or suffering before, during or after experiments are performed on them.

In addition to 3Rs, India has adopted "Rehabilitation" as a 4^th R. In 2019, the Indian Council of Medical Research presented a roadmap for Indian research on non-animal technologies, recognising the need for alternatives to using animals in experimentation.

In 2014, two key amendments were made to the DC Rules: Rule 148C prohibits the testing of cosmetics on animals; and Rule 135B prohibits the import of cosmetics that have been tested on animals. After it emerged that the import ban was not being stringently followed, specific provisions for more effective enforcement were introduced in the Cosmetics Rules. Now, manufacturers and importers must mandatorily submit safety data using only non-animal assessment methods. Further, documentation demonstrating the specific methods used must also be submitted, accompanied by a self-declaration.

The CT Rules were amended in early 2023 to replace the use of animal tests in drug development. The amendment allows researchers to use non-animal and human-relevant methods, including technologies like 3D organoids, organs-on-chip, and advanced computational methods, to test the safety and efficacy of new drugs.

Future of animal testing

The changes in regulatory frameworks around the world are positive and reassuring, but a complete abolition of animal testing is yet to be achieved. In India, for example, there is still no legislative ban on animal testing for drugs, which means that the current drug approval process may not change noticeably at least in the near future. Further, although many alternatives to animal testing are available, such as cell-based assays, in silico models, computational studies, 3D organoids, organs-on-chip, and human biology-based test methods, these are still nascent. The alternatives also may have their own limitations, especially with regard to their ability in assessing toxicity. Besides the availability of alternatives themselves, it is also quite another challenge to convince scientists and researchers to switch to using non-animal methods. Clearly, a long road lies ahead, but chipping away at regulation and continuing research on alternatives may eventually lead to the use of animals in experiments being significantly reduced, if not completely eliminated.

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