India takes first step to remove animals from drug testing

Subject: Science and technology

Section: Biotechnology

Purpose of the New Drugs and Clinical Trial Rules (2023) Amendment:

The amendment, passed by the Government of India, aims to eradicate animal usage in drug research, prioritizing non-animal and human-relevant approaches.
Researchers are now empowered to employ technologies like 3D organoids, organs-on-chip, and advanced computational methods for drug safety and efficacy evaluation.

Traditional Drug Testing and Limitations:

Conventional drug testing involves assessing candidate molecules in at least two animal species, including rodents and non-rodents.
These methods often fail to capture human-specific responses due to intricate variations in genetics, age, sex, and pre-existing conditions.
The drug development process exhibits high failure rates during human clinical trials, underscoring the discrepancy between animal testing and human outcomes.

Exploration of Alternative Testing Methods:

Researchers are increasingly shifting focus towards technologies that more accurately emulate human biology and predict human responses.
These advancements encompass organoids (miniaturized human organs),
- organs-on-chip (microfluidic devices mimicking human physiological conditions), and
- 3D bioprinting of human tissues.
Personalization of drug testing using patient-specific cells is a promising facet of these methods.

Global Regulatory Evolution Towards Non-Animal Testing:

The European Union introduced an action plan to transition away from animal-based methods in research, regulatory testing, and education.
The U.S. FDA Modernization Act 2.0 facilitates the use of non-animal systems for testing new drug safety and effectiveness.
South Korea‘s ‘Vitalization of Development, Dissemination, and Use of Alternatives to Animal Testing Methods’ bill.
Canada’s amendment to the Environmental Protection Act underscores global momentum.

India’s Embrace of Non-Animal Testing Methods:

India amended the New Drugs and Clinical Trials Rules 2019 in March 2023 to incorporate non-animal methods.
Public comments and consultation with the Drug Technical Advisory Board informed this decision.

Challenges Faced by India in Implementing Advanced Testing Methods:

The development of organ-on-a-chip systems necessitates diverse expertise across fields like cell biology, materials science, fluid dynamics, electronics, engineering, pharmacology, and toxicology.
Indian academia and industry require specialized training and human resources to bridge these interdisciplinary gaps.
Proposals to establish institutes akin to the Wyss Institute in Boston could bolster India’s capability in emulating human biology.

Indigenous Resource Limitations Impacting Adoption:

Import reliance for essential reagents, cell-culture materials, and instruments from the U.S., Europe, and Japan presents challenges.
India has an opportunity to develop a self-sustaining ecosystem in areas related to cell culture, material science, and electronics.

Addressing Variability and Standards in Advanced Testing Methods:

Variability in data outcomes stems from discrepancies in lab protocols and expertise.
Guideline development for minimal quality criteria and standards is crucial to ensure consistency.
Reevaluation of existing animal testing requirements is imperative in light of evolving cell-based and gene-editing therapeutics.

Explaining Key Concepts: Organoids, Organs-on-Chip, and 3D Bioprinting:

Organoids:
- Miniature 3D structures replicating specific organs from human cells.
- Brain organoids for studying neural development and disorders like autism.
Organs-on-Chip:
- Microfluidic devices with human cells mimicking organ functions.
- Lung-on-chip for studying lung diseases and toxin effects.
3D Bioprinting:
- 3D printing using bio-inks of cells and fluids.
- Printing functional liver tissue for drug testing and regenerative medicine.
Advantages:
- Better drug testing accuracy compared to animal models.
- Personalized medicine potential based on individual characteristics.
Challenges:
- Refinement for accurate organ replication.
- Standardization and validation for reliable results.
Examples:
- Heart-on-Chip: Simulates heart tissue behavior for disease and drug studies.
- Kidney Organoids: Model kidney development, diseases, and drug toxicity.
- Skin Bioprinting: Constructs for cosmetic testing and potential grafts.

Drugs Technical Advisory Board (DTAB):

DTAB serves as the supreme statutory decision-making authority concerning technical aspects of drugs within the nation.
It is established in accordance with the Drugs and Cosmetics Act of 1940.
DTAB operates under the umbrella of the Central Drugs Standard Control Organization (CDSCO), which operates within the Ministry of Health and Family Welfare.

Central Drugs Standard Control Organization (CDSCO):

CDSCO is India’s top regulatory authority for pharmaceuticals and medical devices.
Established under the Drugs and Cosmetics Act, 1940.
Operates under the Directorate General of Health Services (DGHS) in the Ministry of Health and Family Welfare.
Mandate and Functions:
- Ensures safety, efficacy, and quality of drugs, cosmetics, and medical devices.
- Reviews new drug approvals, clinical trials, and import/export licenses.
- Regulates manufacturing, sale, distribution, labeling, and packaging.
- Monitors adverse reactions, conducts post-market surveillance.
- Collaborates with state authorities, industry, global regulators.