In Part 1 of the CRISPR blogpost series, we outlined the science behind CRISPR technology and also illustrated its current and potential uses in India. As previously discussed, CRISPR technology, being a genetic engineering method, poses some serious concerns. These concerns are largely ethical, social, and safety related. Hence, it is pertinent to understand the regulatory regime for CRISPR in India. In this blog post, we have outlined the regulatory regime for genetic engineering in India, with special focus on CRISPR technology.
Regulatory Framework for Genetic Engineering in India
Gene editing, having gained traction globally, is the subject matter of regulatory contemplation throughout the world. India, with its experimentation with gene editing, especially in plants, also has an evolved regulatory regime catering to genetically engineered organisms, some of which have been discussed below:
Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/ Genetically Engineered Organisms or Cells, 1989
India’s regulatory framework for import, use, research and release of genetically engineered organisms, including those developed using CRISPR, is governed by theRules for Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells, 1989(“1989 Rules”), notified under the Environment (Protection) Act, 1986. Requirements under the Environment (Protection) Act, 1986, and the relevant rules are triggered especially due to the significant environmental hazards that manufacturing and use of genetically engineered organisms could have on the environment and its biodiversity and ecosystems. The 1989 Rules in this context, regulating genetically engineered organisms’ and gene technologies, emphasise on the importance of biosafety and the need for stringent regulatory measures to prevent the potential risks associated with gene editing technologies, including CRISPR.
The 1989 Rules define ‘genetic engineering’ to mean (a) the technique by which genetic material, which does not usually occur in the target cell, generated outside the organism is inserted into the said cell or organism, or (b) the formation of new combinations of genetic material by insertion of a cell into a host cell, where they occur naturally as well as modification of an organism or in a cell by deletion and removal of parts of the genetic material. This reflects the inclusion of SDN-1, SDN-2, and SDN-3 techniques within the ambit of the 1989 Rules.
Relevant Committees: The 1989 Rules provide for many committees that provide approvals for the research and handling of genetically engineered organisms, such as the Institutional Biosafety Committees (“IBSC”), the Review Committee on Genetic Manipulation (“RCGM”), and the Genetic Engineering Appraisal Committee (“GEAC”). These authorities oversee the research, development, and commercialisation of genetically engineered organisms to ensure bio and environmental safety.
Approvals: Prior GEAC approval is required to import, export, transport, manufacture, process, use or sell any hazardous microorganisms or genetically engineered organisms/ substances or cells. Production involving generation or use of genetically engineered organisms or cells shall require GEAC consent for discharging them into the environment. Further, GEAC approval is mandatory for organisations dealing with large-scale field trials or environmental release of transgenic crops. In addition to GEAC approvals, various other approvals, as mentioned in the 1989 Rules, would be applicable, basis the kind of activity being undertaking by an organisation.
At the institutional level, organisations or research institutions handling microorganism/ genetically engineered organisms are required to form an IBSC, which would be responsible for onsite evaluation, assessment and monitoring of adherence to the biosafety guidelines and proper implementation of biosafety regulatory.
Safety Assessments: Additionally, periodic safety assessments are required to monitor the impact of genetically engineered organisms on the environment. The 1989 Rules also mandate that any adverse effect observed during research must be reported immediately to the authorities to ensure prompt action and mitigation. Furthermore, comprehensive instructions on safe disposal of genetically engineered organisms to prevent any unintended release into the environment have also been provided in the 1989 Rules. These include protocols for containment, decontamination, and disposal, ensuring that all potential risks are minimised.
Guidelines for Safety Assessment of Genome Edited Plants, Department of Biotechnology
In addition to the 1989 Rules, certain additional guidelines are issued by the Department of Biotechnology (“DBT”), such as the Regulations and Guidelines for Recombinant DNA Research and Biocontainment, 2017, covering research, laboratory use, import/ export, storage, handling, manufacturing, disposal and emergency procedures for recombinant DNA. In 2022, the DBT also introduced Guidelines for Safety Assessment of Genome Edited Plants, providing regulatory compliance for biosafety assessment of genome edited plants.
National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017, and the National Guidelines for Gene Therapy Product Development and Clinical Trials, 2019
Indian Council of Medical Research’s National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017, and National Guidelines for Gene Therapy Product Development and Clinical Trials, 2019, address the ethical aspects of use of CRISPR technology in human subjects, along with other gene editing technology. These guidelines provide requirements for conducting research and clinical trials, with oversight from various committees.
SDN-1 & SDN-2 Exemption for Genome Edited Plants
Genetic engineering using SDN-1 and SDN-2 technique results in modification of the genetic material in such a manner that no foreign genetic material is inserted at the target site and this is referred to as ‘gene editing’, whereas, in SDN-3, a foreign genetic material is introduced in the cell, which creates a ‘genetically modified organism’ (GMO).
While the 1989 Rules provide for the overarching regulation of genetic engineering in India, the Ministry of Environment, Forest and Climate Change (“MoEFCC”) under Rule 20 of the 1989 Rules has issued an exemption for genome edited plants, falling under the category of SDN-1 and SDN-2 via its memorandum dated March 30, 2022[1]. This step aligns with the global trend of exempting SDN-1 and SDN-2 gene-edited plants from extensive regulatory scrutiny on account of lack of introduction of foreign DNA in these techniques. Pursuant to the said exemption, field trials of crops developed “free of exogenously introduced DNA” (i.e. created using SDN-1 and SDN-2 CRISPR techniques) would be permitted to undergo open field trials, leading to their commercial release. This exemption could be made use of only when the IBSC confirms that no foreign DNA is present in the plant. However, genetically engineered plants that are the result of SDN-3 technique, on account of being ‘GMO’, would still require approvals under the 1989 Rules.
Building upon the exemption so created, DBT issued Guidelines for Safety Assessment of Genome Edited Plants, 2022[2], providing a roadmap for the development of genetically edited plants in India, emphasising upon the biosafety concerns and regulatory pathways to be adopted. The regulatory pathway for genetically edited plants using CRISPR, falling under SDN-1 and SDN-2 is as follows:
- Research and Development Phase: The development of genetically edited plants must be conducted under containment conditions, regulated by IBSCs, which would ensure that the research organisation complies with biosafety guidelines. The research and development of genome-edited plants are to be conducted under containment as per the Regulations & Guidelines for Recombinant DNA Research and Biocontainment, 2017.
- Exemption from 1989 Rules: Once the genetically edited plant is confirmed to be free from foreign DNA, the IBSC may grant it exemption from the 1989 Rules. The IBSC must submit the relevant data and minutes of the meeting to the RCGM for information. The data requirements include confirmation of genome editing at the target locus/ loci using DNA sequencing, evidence of absence of exogenously introduced DNA, and phenotypic data, etc.
- Further Development and Commercialisation: After receiving exemption, further development, evaluation, and release of genetically edited plants as new varieties or hybrids are governed by other applicable laws and regulations. For instance, this could include guidelines and regulations of the Food Safety and Standards Authority of India (FSSAI) for food safety assessment, the Ministry of Agriculture and Farmers’ Welfare for agricultural practices, etc.
Conclusion
The regulatory regime for CRISPR technology in India reflects a balanced approach, promoting scientific innovation while ensuring biosafety. The exemption of SDN-1 and SDN-2 genome-edited plants from stringent regulations marks a significant step towards commercialisation of gene-edited crops, aligning with global trends. In India, where BT-Cotton is the only commercialised genetically engineered crop, such relaxations could pave the way for commercialisation of more genetically edited plants.
Some issues that could impede CRISPR growth in India could be the overlapping authorities and multiple regulations creating a complex and confusing regulatory landscape, despite the comprehensive rules and guidelines established by the MoEFCC and DBT. This regulatory muddle can lead to delays in approvals and inconsistencies in enforcement, hindering the progress of CRISPR research and application. Further, clear guidelines are required to regulate the ethical standards to be employed for CRISPR use in India. Ensuring that gene technology is accessible and affordable for all, not just the privileged few, is another consideration. Another factor could be the tackling of anti-genetic engineering market forces that see the development of genetically edited crops as a threat.
As India continues to harness the potential of CRISPR technology, robust regulatory frameworks will be essential to ensure safety, efficacy, and ethical use of gene-edited crops. Establishing comprehensive guidelines for ethical oversight, ensuring transparency through informed consent, public engagement and post-trial responsibilities are crucial steps towards a robust regulatory framework. The development of such a framework, informed by global practices, can pave the way for responsible and innovative use of CRISPR technology.
* The Authors were assisted by Sneha Smriti (Intern)
For further information, please contact:
Biplab Lenin, Partner, Cyril Amarchand Mangaldas
biplab.lenin@cyrilshroff.com
[1] MoEF&CC Office Memorandum F. No. C -12013/3/2020-CS-III dated 30.03.2022
[2] https://dbtindia.gov.in/sites/default/files/Final_%2011052022_Annexure-I%2C%20Genome_Edited_Plants_2022_Hyperlink.pdf
