Regulatory Framework for Biosafety, Environment Protection and Biocontainment in India: From the Perspective of Biopharma R&D and Manufacturing
Research Associate, RIS
With the on-going pandemic caused due to COVID19 outbreak, the centrality of biopharmaceutical R&D and manufacturing has been quite evident. The quest for effective medicines and vaccines for treating COVID19 is going vigorously across the world. India, dubbed as “Pharmacy of the World” has also seen the exponential rise in the biopharma research and manufacturing in this period. In this scenario, it will be interesting to explore the prevailing regulatory framework for ensuring environment protection, biosafety and biocontainment requirements arising due to the biopharma R&D and manufacturing practices.
In India, the 1989 Rules under the Environment (Protection) Act, 1986 regulates the “production, manufacture etc. of drugs and pharmaceuticals and food stuffs distilleries and tanneries, etc. which make use of micro-organisms/ genetically engineered microorganisms one way or the other”.[i] Six competent statutory authorities/committees have been established to oversee the regulation[ii]. These are rDNA Advisory Committee (RDAC), Institutional Biosafety Committee (IBSC), Review Committee on Genetic Manipulation (RCGM), Genetic Engineering Appraisal Committee (GEAC), State Biotechnology Coordination Committee (SBCC) and District Level Committee (DLC).
There are four National Referral LMO Detection Labs in India viz. ICAR-NBPGR (New Delhi), PBTI (Mohali), EIA (Kochi) and DFTCML (Amravati). For the Recombinant Pharma Sector, Mashelkar Committee has given a set of recommendations in 2006, which outlined the five step-wise regulatory procedure in the form of five protocols.[iii] These five protocols dealt with the following different categories based on the usage of LMOs in the biopharma sector.
· Protocol I: Indigenous product development, manufacture and marketing of pharmaceutical products derived from LMOs but the end product is not a LMOs
· Protocol II: Indigenous product development, manufacture and marketing of pharmaceutical products where the end product is a LMO
· Protocol III: Import and marketing of Pharma products in finished formulations where the end product is a LMO
· Protocol IV: Import and marketing of Pharma products in Bulk for making finished formulations where the end product is a LMO
· Protocol V: Import and marketing of Pharma products derived from LMOs in bulk and/or finished formulations where the end product is not a LMO
For setting up of any manufacturing unit related to bulk drugs or APIs, it is mandatory to receive the “Environmental Clearance” as per the EIA Notification 2006 under the Category 5 (f).
The key environmental legislations in India are Water (Prevention and Control of Pollution) Act (1974), Air (Prevention and Control of Pollution) Act (1981), Motor Vehicles Act (1988), The Wildlife (Protection) Act (1972), The Forest (Conservation) Act (1980), Environmental (Protection) Act, (1986), Public Liability Insurance Act (1991), and National Environment Tribunal Act (1995). In the domain of biopharmaceutical sector, relevant applicable Rules under the EPA, 1986 are as follows[iv]:
· Bio-Medical Waste Management Rules, 2016
· Solid Waste Management Rules, 2016
· Hazardous and Other Wastes (Management and Transboundary Movement) Rules, 2016
· Plastic Waste Management Rules, 2016
· E-Waste (Management) Rules, 2016
The Indian biopharma industry sector has put in place mechanism in order to comply with the existing set of legislations and rules concerning the environment and biosafety requirements. For example, Biocon Ltd., India’s largest biopharmaceutical company has a Environment, Occupational Health, Safety and Sustainability Policy, which includes water management, waste management, fire safety etc. All the facilities at Biocon are ISO 14001 (environmental management system) and 45001 (occupational health and safety) Certified[v]. Similarly, Serum Institute of India has set-up Bio-Medical Waste Incinerator Plant for dealing with biomedical waste, produced during the production of drugs and vaccines. It has also established a Biomedical Bar Code system to keep stock of the biopharma materials.[vi]
In the sphere of biocontainment, the 2017 "Regulations and Guidelines on Biosafety of Recombinant DNA Research and Biocontainment" deals with the storage, import/export, large scale manufacturing, facility certification, contained use (laboratory) and disposal and emergency.[vii]
As far as the requirement of biosafety levels for ensuring biocontainment in research and large-scale activities (manufacturing) is concerned, there are following four Biosafety Levels which have been classified[viii]:
· Biosafety Level 1-4 (BL to BL4): standard research laboratory
· Biosafety Level 1-4 Large Scale (BL1 Large Scale to BL4 Large Scale): large scale (above 10 litres) research and production with Good Large Scale Practices (GLSP)
· Biosafety Level 1-4 Plants (BL1-P to BL4-P): standard plant greenhouse facility requirements
· Biosafety Level 1-4 Animals (BL1-N to BL4-N): standard whole animal facility experiments.
The practices, procedures, design and construction of each such research facility varies according to the Biosafety Level category it belongs to. The biology lab in university/college represents the most simple BSL-1 Category, while the labs in biopharma companies/specialised research centres, which deals with infectious materials and biological agents, belong to the high BSL-3 or BSL-4 Category. In the case of BSL-3 and BSL-4, the entry is strictly prohibited for anyone who is not authorised. These labs are specially designed and constructed in a separate/isolate building in order to ensure only inward directional airflow and limited access. The personnel working in these are supposed to wear a full-body, air-supplied, positive pressure suit.[ix] In addition to this, the biohazard waste generated in these laboratories must be segregated into three waste categories (White, Red and Yellow) before disposal.
In order to simplify registration, modification, renewal etc, a single window information portal “Indian Biosafety Knowledge Portal (IBKP)” in the domain of Biosafety has been recently launched by the Department of Biotechnology.[x]
The main aim of IBKP is to reach out to researchers, industry and other stakeholders to provide latest scientific information and regulatory guidance related to authorization of GMOs/LMOs and products thereof. It is an interactive online web portal for transactions in dealing with Review Committee on Genetic Manipulation (RCGM) serviced by Department of Biotechnology under Rules 1989 of Environment (Protection) Act 1986. The portal provides information on[xi]:
· Relevant Acts and Rules related to Biosafety of GMOs/LMOs in India
· Biosafety, Biocontainment guidelines, Check lists, etc.
· Database on various ongoing research activities on GMOs/LMOs and products thereof in the country including scientific Risk Assessment and Risk Management Plans;
· Linkages to international developments and scientific information;
· IBSC registrations/renewals and annual compliance records
The portal also facilitates online submission of forms for Import/Export, R&D projects, Pre-clinical toxicity of recombinant DNA derived Biosimilars and Investigational New Drug, event selection trials, Biosafety Research Level 1 trial, etc. including online tracking of the application status.
From the above, it is clear that that the regulatory framework and institutional architecture to regulate the biopharma-related research, development and manufacturing in India to ensure that the required measures and tools to ensure environmental protection, biosafety and biocontainment are very much in place. A better supervision and coordination among the stakeholders will greatly help in checking any unintended negative consequences/accident in the labs endangering the lives of the researchers and scientists working there as well as the environment.
[ii] Ahuja, Vibha. 2018. “Regulation of Emerging Gene Technologies in India”. BMC Proceedings. 12 (Suppl 8). 14.
[iii] Chimata, M.K. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Regulatory Framework for Environment Protection in India - Biopharma Sector Perspective” on 1st October 2020.
[iv] Kamyotra, J.S. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Regulatory Framework for Environment Protection in India - Biopharma Sector Perspective” on 1st October 2020.
[v] Rao, A V K. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Regulatory Framework for Environment Protection in India - Biopharma Sector Perspective” on 1st October 2020.
[vi] Kshirsagar, R. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Regulatory Framework for Environment Protection in India - Biopharma Sector Perspective” on 1st October 2020.
[vii] Jain, N.K. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Biosafety and Biocontainment Requirements for Biopharma Research and Manufacturing” on 15th October 2020.
[viii] Gowda, L.R. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Biosafety and Biocontainment Requirements for Biopharma Research and Manufacturing” on 15th October 2020.
[x] Agarwal, S. 2020. Presentation made during Webinar organised by National Biopharma Mission on “Biosafety and Biocontainment Requirements for Biopharma Research and Manufacturing” on 15th October 2020.