DEVELOPMENT OF BIOSAFETY REGULATIONS FOR GENETIC ENGINEERING

● The first successful use of genetic engineering, also referred to as recombinant DNA (rDNA)

technology was accomplished in 1973.

● Recognizing that this novel technology is beneficial but could also pose some risks, scientific

community-initiated discussions on the need for regulating this technology in 1975 at a

meeting in Asilomar, California.

● A set of voluntary guidelines regarding the cautious use of recombinant technology and any

products resulting from that technology were recommended at Asilomar.

● In 1976, guidelines for laboratory work using genetic engineering techniques were issued by

the US National Institute of Health followed by involvement of other regulatory offices in

USA to effectively regulate genetic engineering in USA.

● Initially, the regulations of rDNA technology focused on the technology and biosafety

concerns were primarily towards safety procedures for recombinant DNA work within the
laboratory. The objective was to ensure that researchers were taking proper steps to contain
organisms that potentially posed a risk to themselves or human health. By the end of 1980s
the focus shifted to the end products besides the technology as rDNA technology began to
produce organisms and products thereof that were useful as commercial products in
healthcare and agriculture.

● In 1982, the Organization for Economic Cooperation and Development (OECD) released a

report on the potential hazards of releasing Genetically Modified Organisms (GMOs) into the
environment as the first transgenic plant was being developed.

● A report on "Recombinant-DNA Safety Considerations" was published by the OECD in 1986

(also known as the "blue book"), which set out the first international safety guidelines for the
use of recombinant DNA organisms in industry, agriculture and the environment.

● From 1986, biosafety regulations applicable to biotechnological products and activities have

been developed in various countries as well as at international level.

● A national biosafety framework to regulate production and release of GMOs is considered

essential in any country with a biotechnology programme.

● Regulatory frameworks aim to ensure that safety of genetically engineered (GE) plants is

comparable to safety of conventionally produced plants.

 ● More recently, the establishment of a biosafety regulatory framework was triggered in several

developing countries, when Cartagena Protocol on Biosafety came into force.

● The regulatory framework in India was initiated in 1989 in response to commencement of

research and development in biotechnology in India.

REGULATORY SYSTEM IN INDIA

The Environment (Protection) Act, 1986 is an umbrella legislation implemented by the Ministry of
Environment, Forest & Climate Change that provides a holistic framework for protection and
improvement to the environment. Pursuant to sections 6,8 and 25 of the EPA, 1986 and with a view to
protecting the environment, nature and health, in connection with the application of gene technology
and microorganisms, the Rules for the Manufacture/ Use/ Import/Export and Storage of Hazardous
Microorganisms, Genetically Engineered Organisms or Cells (Rules, 1989) have been notified under
the Environment (Protection) Act, 1986. These rules are the apex rules for regulation of all activities
related to genetically engineered organisms and products thereof. In addition, there are other acts,
rules and policies which are also applicable to these organisms.

KEY FEATURES OF RULES 1989

The Rules, 1989 are very broad in scope, essentially covering the entire spectrum of activities
involving GMOs and products thereof including sale, storage, exportation, importation, production,
manufacturing, packaging, etc. These rules cover areas of research as well as large scale applications
of GMOs and its products and apply to:

● Manufacture, import and storage of microorganisms and gene technological products.

● Genetically engineered organisms/ microorganisms and cells and correspondingly to any

substances and products and foodstuffs, etc., of which such cells, organisms or tissues hereof
form part.

● New gene technologies in addition to cell hybridization and genetic engineering.

Competent Authorities

These rules are implemented by the Ministry of Environment, Forest & Climate Change (MOEF &
CC), the Department of Biotechnology (DBT), Ministry of Science & Technology, Government of
India and State Governments. Six competent authorities and their composition and roles have been
notified under the rules.

1. Recombinant DNA Advisory Committee (RDAC)

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 2. Institutional Biosafety Committee (IBSC)
3. Review Committee on Genetic Manipulation (RCGM)
4. Genetic Engineering Appraisal Committee (GEAC)
5. State Biotechnology Coordination Committee (SBCC)
6. District Level Committee (DLC)

Various sub-committees and Expert committees are set up by RCGM and GEAC on a case by case
basis and comprise of experts from various disciplines drawn from public sector institutions to
prepare and review various guidelines and biosafety data. Central Compliance Committees are also
set up for monitoring of confined field trials on case by case basis.

1. Recombinant DNA Advisory Committee (RDAC)

● Is constituted by DBT

● Review developments in biotechnology at national and international level and recommend

suitable and appropriate safety regulations for India in r-DNA research, use and applications

● Was set up in 1990 and prepared Recombinant DNA Safety Guidelines, 1990.

2. Institutional Biosafety Committee (IBSC)

● Is mandatory for each organization involved in Recombinant DNA (rDNA) activities.

● Comprises of the Head of Institute, three or more scientists engaged in rDNA work, a medical

expert and a member nominated by DBT.

● Responsible for ensuring adherence to RDNA Safety Guidelines, experimentations carried out

at designated locations as per approved protocols and prepare onsite emergency plans
according to manuals / guidelines of RCGM.

● Serve as a nodal point for interfacing with other Regulatory Committees regarding ongoing

research within the institutions.

● Review experiments falling in risk category III or above and recommend to RCGM.

3. Review Committee on Genetic Manipulation (RCGM)

● Is a Regulatory Body functioning in DBT

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 ● Comprises of Members from DBT, Indian Council of Medical Research, Indian Council of

Agricultural Research, Council of Scientific and Industrial Research and other experts from
multi-disciplinary fields in their individual capacity.

● Responsible for bringing out manuals / guidelines specifying procedures for conduct of GMO
research, use and industrial applications with a view to ensure environmental safety and lay
down procedures restricting or prohibiting production, sale, import and use of GMO as
mentioned in the Schedule of Rules 1989.

● Authorized to review all ongoing rDNA projects and approve experiments falling in risk

category Ill and above with appropriate containment and permit import of GMOs / transgene
for research purposes.

● Authorized to recommend GM crop field experiments (BRL I) at multi locations in an area of

up to 1 acre per site.

4. Genetic Engineering Appraisal Committee (GEAC)

● Is the apex Regulatory Committee functioning in MoEF & CC.

● The Committee is chaired by Special Secretary / Additional Secretary of MoEF & CC and co-

chaired by an Expert nominated by DBT and comprises of Members from Ministry of

Industrial Development, DBT, Department of Atomic Energy. Member Secretary is an
official of MoEF & CC.

● Expert Members also include nominees of Director General, Indian Council of Agriculture

Research, Director General Health Services, Plant Protection Adviser, Directorate of Plant
Protection, Quarantine and Storage, Chairman, Central Pollution Control Board and three
outside experts in individual capacity. The Committee may co-opt other Members / Experts as
necessary.

● Authorized to review, monitor and approve all activities involving large scale use of

hazardous micro-organisms and recombinant research and industrial production including

import, export, transport, manufacture, use or sale of GMOs and products thereof from an
environmental angle.

● Authorized to review, monitor and approve proposals relating to release of genetically

engineered organisms and products into the environment including experimenting field trials
with specific conditions for containment.

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5. State Biotechnology Coordination Committee (SBCC)

● Is a Regulatory Committee set up in each State where research and applications of GMOs are

contemplated

● The Committee is chaired by Chief Secretary of the State and comprises of Secretaries from

the State Department of Environment & Forest, State Department of Health, State Department
of Agriculture, State Department of Industries and Commerce, State Department of Public
Works, Chairman, State Pollution Control Board and Experts in the field of microbiology and
pathology as Members. The Committee may co-opt other experts/ members as necessary.

● Empowered to inspect, investigate and to take punitive action in case of violations of statutory

provisions through the nodal Department and the State Pollution Control Board or the
Directorate of Health / Medical Services.

● Authorized to review periodically the safety and control measures in various

industries/institutions handling genetically engineered/hazardous organisms.

● Serve as a nodal point at State level for coordinating activities related to GMOs in the State

with the Central Ministries including monitoring of conditions stipulated by the

RCGM/GEAC.

6. District Level Committee (DLC)

● Is a Regulatory Committee set up in each District where research and applications of GMOs

are contemplated.

● The Committee is headed by District Collector of the District and comprises of Factory

Inspector, Representative of State Pollution Control Board (SPCB), Chief Medical Officer,
District Agriculture Officer, Representative of Public Health Engineering Department,
Commissioner, Municipal Corporation and Technical Experts in the field of microbiology and
pathology as Members. The Committee may co-opt other experts/members as necessary.

● Authorized to monitor and inspect the safety regulations in installations engaged in the use of

genetically modified/ hazardous organisms and its applications, formulate information charts,
identify hazards and risks associated with each of these installations and coordinate activities
with a view to meeting emergency.

● Serve as a nodal point at district level for coordinating activities related to GMOs in the

District with the SBCC and GEAC including monitoring of conditions stipulated by the
RCGM / GEAC.

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Approvals and Prohibitions Under Rules, 1989

● No person shall import, export, transport, manufacture, store, process, use or sell any GMOs,

substances or cells except with the approval of GEAC

● Use of pathogenic organisms or GMOs or cells for research purposes shall be allowed in

laboratories or inside laboratory areas notified by MoEF & CC for this purpose under the
EPA, 1986.

● Any person operating or using GMOs for scale up or pilot operations shall have to obtain

permission from GEAC.

● Deliberate or unintentional release of GMOs shall not be allowed.

● Production in which GMOs are generated or used shall not be commenced except with the

approval of GEAC.

● All approvals shall be for a period of 4 years at first instance renewable for 2 years at a time.

● GEAC shall have powers to revoke approvals in case of:

a) Any new information on harmful effects of GMOs.

b) GMOs cause such damage to the environment as could not be envisaged when approval was given.
c) Non-compliance of any conditions stipulated by GEAC.

Supervision and penalties

● The GEAC has the authority to supervise the implementation of terms and conditions laid
down in connection with the approvals accorded by it through the SBCC/DLC/SPCB or any
person authorised by the GEAC.

● If an order is not complied with, there is provision for imposing penalties including

immediate intervention by the SBCC/ DI-C in order to prevent damage to the environment,
nature and health without issuing any orders at the expense of the person responsible for such
damage.

● The GEAC may fix fees to cover the expenses incurred by the authorities in connection with

approvals, examinations, supervision and controls.

Exemption

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MoEF & CC has the authority to exempt an occupier handling a particular GMO from the provisions
of Rules, 1989 (7-11). The following activities/products are exempted from the purview of Rules,
1989:

● Indigenous product development, manufacture and marketing of recombinant pharmaceuticals

derived from organisms falling under Risk Group I & ll.

● Import and marketing of products derived from LMOs as drugs/ pharmaceuticals in bulk and/

or finished formulations (therapeutic proteins) where the end product is not an I-MO.

● Bt cotton hybrids containing approved events under the 'Event Based Approval Mechanism'.

Procedure for Approval of Confined Field Trials and Environmental Release of GE Plants
APPLICABLE GUIDANCE

Rules, 1989 are implemented by competent authorities through a series of biosafety guidelines with a
view to minimise any adverse impact that the GMOs and product thereof would have on the
environment as well as human and animal health.

1. RDNA Safety Guidelines, 1990

● Provide guidelines for R&D activities on GMOs, transgenic crops, large-scale production and

deliberate release of GMOs, plants, animals and products into the environment, shipment and
importation of GMOs for laboratory research.

● The research activities are classified into three categories based on the level of the associated

risk.

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 Category-I: Experiments involving self-cloning using strains and also inter-species cloning
belonging to organisms in the same exchanger group.
Category-II: Experiments falling under containment levels II, III and IV
Category-III: Experiments involving toxin gene cloning, cloning of genes for vaccine
production, and other experiments

● The levels of risk and classification of the organisms within these categories have been

defined in these guidelines.

● Appropriate practices, equipment and facilities necessary for safeguards in handling

organisms, plants and animals in various risk groups have been recommended.
2. Revised Guidelines for Research in Transgenic Plants, 1998

● Provide guidance for recombinant DNA research on plants including the development

of molecular and field evaluation of transgenic plant.

● Deal with import and shipment of GE plants for research purposes.

● Include complete design of a contained greenhouse suitable for conducting research

with transgenic plants.

● The GE experiments on plants have been grouped under three categories and

appropriate containment measures have been prescribed.

● Also include information to be generated on biosafety aspects of the transgenic

plants.
3. Guidelines & Standard Operating Procedures (SOPs) For Confined Field Trials of Regulated,
Genetically Engineered (GE) Plants, 2008.

● Provide guidance on conduct of confined field trials of regulated GE plants.

● Include procedures on filling the application form for seeking approval of CFTs from

regulatory authorities.

● SOPs have been provided to ensure quality and safety at each stage of the CFT. These

include SOPs for transport, storage, planting and harvest.

● Recording formats have been provided for proper and uniform documentation during

the conduct of the trials.

● Provide guidance for the monitoring of confined field trials.

● Comprehensive glossary of terms used in the context of CFTs has also been provided.

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4. Guidelines for the Safety Assessment of Foods Derived from Genetically Engineered (GE)
Plants, 2008

● Provide guidance on principles and steps on food safety assessment of GE plants

● Developed by Indian Council of Medical Research (ICMR) based on guidelines and

principles of Codex Alimentarius Commission, 2003

5. Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in
India, 2012

● Guidelines prepared by Central Drugs Standard Control Organization (CDSCO) and

DBT to lay down the regulatory pathway for a similar biologic claiming to be similar
to an already authorized reference biologic.

● The guidelines address the regulatory pathway regarding manufacturing process and

quality aspects for similar biologics.

● These guidelines also address the pre-market regulatory requirements including

comparability exercise for quality, preclinical and clinical studies and post-market
regulatory requirements for similar biologics.