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India takes first step to remove animals from drug-testing.
Relevance:
GS3/Science and Technology, GS4/ Ethics
Why in new?
An amendment to the New Drugs and Clinical Trial Rules (2023), recently passed by the Government of India, aims at stopping the use of animals in research, especially in drug testing. The amendment authorizes researchers to instead 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.
Current drug-development pipeline:
- Every drug in the market goes through a long journey of tests, each designed to check whether it can treat the disease for which it was created and whether it has any unintended harmful effects.
- For a long time, the first step of this process has been to test the candidate molecule in at least two animal species: a rodent (mouse or rat) and a non-rodent, such as canines and primates.
- However, humans are more complex creatures, and biological processes and their responses often vary from person to person as well, based on factors such as age, sex, pre-existing diseases, genetics, diet, etc. – and a lab-bred animal species reared in controlled conditions may not fully capture the human response to a drug.
- This ‘mismatch’ between the two species is reflected in the famously high failure-rate of the drug development process.
- Despite increasing investment in the pharmaceutical sector, most drugs that cleared the animal-testing stage fail at the stage of human clinical trials, which come towards the end of the pipeline.
What are the status of regulations worldwide?
- European Union: In 2021, a resolution was passed on an action plan to facilitate transition towards technologies that don’t use animals in research, regulatory testing, and education.
- United States: FDA Modernization Act 2.0 was passed in December 2022, allowing researchers to use these systems to test the safety and efficacy of new drugs.
- South Korea: A ‘Vitalization of Development, Dissemination, and Use of Alternatives to Animal Testing Methods’ bill was introduced in December 2022.
- Canada: The Environmental Protection Act was amended in June 2023 to replace, reduce or refine the use of vertebrate animals in toxicity testing.
- India: In March 2023, the government embraced these systems in the drug-development pipeline by amending the New Drugs and Clinical Trials Rules 2019. It did so after inviting comments from the people and in consultation with the Drug Technical Advisory Board, the statutory body that advises Central and State governments on drug-related technical matters.
What are the challenges?
- Developing an organ-on-a-chip system: It typically requires multidisciplinary knowledge and expertise in cell biology to recreate the cellular behavior in the lab; materials science to find the right material to ensure that the chip does not interfere with biological processes; fluid dynamics to mimic blood flow inside the micro channels; electronics to integrate biosensors that can measure pH, oxygen etc. in the chip; engineering to design the chip; and pharmacology and toxicology to interpret action of the drugs in the chips.
- Resources for research and development: Most of the reagents, cell-culture related materials and instruments are currently imported from the U.S., Europe, and Japan. There is a huge gap and opportunity in several diverse areas related to cell culture, material science and electronics, to develop an end-to-end ecosystem in India.
- Variability in the data arising from differences in lab-to-lab protocols and expertise. For example, one lab may create a system with only liver cells, while another lab attempting to study the immune system and liver may also incorporate immune cells in its liver-on-a-chip. It means there can be no ‘standard’ or ‘universal’ liver-on-a-chip to study all liver diseases.
Alternative testing modes:
- In the last few decades, several technologies have been developed using human cells or stem cells. These include millimetre-sized three-dimensional cellular structures that mimic specific organs of the body, called “organoids” or “mini-organs”.
- Another popular technology is the “organ-on-a-chip” which are AA-battery-sized chips lined with human cells connected to micro channels, to mimic blood flow inside the body.
- These systems capture several aspects of human physiology, including tissue-tissue interactions and physical and chemical signals inside the body.
- Researchers have also used additive manufacturing techniques for more than two decades.
- In 2003, researchers developed the first inkjet bio-printer by modifying a standard inkjet printer. Several innovations in the last decade now allow a 3D bio-printer to ‘print’ biological tissues using human cells and fluids as ‘bio-ink’.
- These systems promise to reshape drug-design and -development. Since they can be built using patient-specific cells, they can also be used to personalize drug-tests.
Way forward:
- To manage the complexity of recreating human tissues and organs in the petri dish, researchers often minimize the number of components required to simulate the disease being investigated.
- It is important to bring out guidelines on the minimal quality criterion and standards for these systems.
- Also, the current guidelines on animal testing requirements must be re-evaluated and revised, considering newer developments in cell-based and gene-editing based therapeutics.
