Biosafety & Regulatory Requirements For GMOs

K.K. Tripathi

Department of Biotechnology, Ministry of Science and Technology,

Outline of Presentation
Why we need Biotech crops? Biosafety issues Regulatory aspects IBSC Checklist Transgenics in Agriculture Harmonisation of Regulatory Process

Th ef ba for irst ho se f o th d a od pe ro pp ug ro h G ac M h

GM to combat malnutrition

Various Insect & Herbicide tolerant crops etc

Biotechnology contributing in Agriculture Pest management Trait improvement Increased productivity Fortification Golden rice (vitamin A rich rice) Iron and Zinc rich rice Quality Protein maize AmA1 gene in Potato

PUBLIC
Risk Communication Navigation in perpetual space

POLICY MAKERS
Risk Management Navigation in decision space

BIOSAFETY SCIENTISTS
Risk Assessment Navigation in physical space

Biosafety Information sought from GMO trials

Laboratory and Green House Trails

Back crossing methods Seed setting characteristics Germination rates Phenotypic characteristics Target gene efficacy tests Toxicity and allergenicity implications if
any during handling

Biosafety Information sought from GMO trails

Rational for the development Economic, agronomic and other benefits, and rationale of development Details of the molecular biology of GMOs Description of the host plant Source and sequence of transgenic Cloning strategy Characteristic of expression vectors Characteristic of inserted genes with details of sequences Characteristic of promoters Transformation/cloning methods of target organism Genetic analysis including copy number of inserts, stability, level of expression of transgenes, biochemistry of expressed gene products etc.
contd...

Biosafety Information sought from GMO trails Field Trial Comparison of germination rates and phenotypic
characteristics Study of gene flow Invasiveness studies Possibility of weed formation Possibility of transfer of transgenes to near relatives through out crossing Implications of out crossing Susceptibility to diseases and pests Toxicity and allergenicity implication of plants/fruits, seeds and animals studies food/feed safety evaluation Handling procedures for allergenic substances Agronomic evaluation

Regulatory Aspects for GMOs

Why Regulations are Necessary for Using GMOs and Products Thereof? GMOs) and and their products are to play important role including human and animal health care system, agriculture, industrial products, environment management Concurrently, there could be unintended hazards and risks from the use of GMOs and products thereof, if the new technology was not properly assessed before use A GMO can be safe but this can be unsafe too depending upon the trans-genes, the host organism and the environment where the GMO is being tested GMOs can be microorganisms, plants, and animals

A case-by-case analysis of the safety of each GMOs and products thereof need to be conducted to assess their safety Whenever GMOs are released in environment they require safety evaluation for humans and animals; due to this Indian Government enacted the Environment (Protection) Act in 1986 and thereafter, notified Rules & Procedures (Rules) for handling GMOs and hazardous organisms through a Gazette Notification from the Union Ministry of Environment & Forests The Rules cover all kinds of GMOs and products thereof

Steps to be followed for developing Transgenic Crops with new gene in new gene cassette
Proposal Institutional Biosafety Committee with DBT Nominee RCGMs approval for Lab & Green House Experiments & Generation of relevant data RCGMs approval for Contained open field trials & Generation of biosafety data RCGMs approval for Multi-location trials under RCGM for generation of biosafety and agronomic data Large scale field trials under GEAC & ICAR Trials for generation of biosafety and agronomic data Commercialization of seeds as per the relevant Acts & Rules

IN ORDER TO EVALUATE PROPOSALS, DBT HAS ISSUED FOLLOWING GUIDELINES Recombinant DNA Safety Guidelines, 1990 Recombinant DNA Safety Guidelines and Regulations, 1994 Revised Guidelines for Safety in Biotechnology, 1994 Revised Guidelines for Research in Transgenic Plants, 1998 Guidelines for generating pre-clinical and clinical data for rDNA vaccines, diagnostics and other Biologicals, 1999.

EPA 1986 Authorities & Administrative structure

STATUTORY BODIES
1. 2. 3. 4. 5. 6.

The Recombinant DNA Advisory Committee (RDAC): Institutional Biosafety Committee (IBSC) Review Committee on Genetic Manipulation (RCGM) Genetic Engineering Approval Committee (GEAC) State Biotechnology Coordination Committee (SBCC) District Level Committee (DLC)

RESPONSIBILITIES OF IBSC
REGISTRATION OF BIOSAFETY COMMITTEE MEMBERSHIP COMPOSITION WITH RCGM REGULAR MEETINGS AND SUBMISSION OF REPORTS REVIEW AND CLEARANCE OF PROJECT PROPOSALS FALLING UNDER RESTRICTED CATEGORY THAT MEETS THE REQUIREMENTS UNDER THE GUIDELINES TAILORING BIOSAFETY PROGRAMME TO THE LEVEL OF RISK ASSESSMENT ENSURE TRAINING OF PERSONNEL ON BIOSAFETY INSTITUTING HEALTH-MONITORING PROGRAMME FOR LABORATORY PERSONNEL ADOPTING EMERGENCY PLANS

ASPECTS TO BE REVIEWED
GENERAL CONSIDERATIONS SCIENTIFIC CONSIDERATIONS CONTAINMENT FACILITIES

GENERAL CONSIDERATIONS
STATUS OF THE ORGANIZATION ORGANIZATIONAL CAPABILITIES (SKILLED / TRAINING REQUIREMENTS) PROJECT DETAILS REQUIREMENT OF OTHER APPROVALS DOCUMENTATION ETHICAL ISSUES

STATUS OF THE ORGANIZATION

CONSTITUTION AFFILIATION BRANCHES / SUBSIDIARIES YEAR OF ESTABLISHMENT YEAR OF INITIATING rDNA ACTIVITIES YEAR OF SETTING UP IBSC

ORGANIZATIONAL CAPABILITIES
AVAILABILITY OF EXPERTISE (TECHNICAL & REGULATORY) CHAIN / HEIRARCHY IN COMMAND OF MONITORING DISTINCT ALLOCATION OF RESPONSIBILITIES SPECIALISTS IN LINE WITH COMPLEXITY OF THE PROJECT REGULATION OF STAFF MOVEMENT AND UNAUTHORISED ENTRY ACCREDIATION IF ANY (GLP, GMP, DSIR, FDA, WHO etc.

PROJECT DETAILS AND STATUS

OBJECTIVES SOCIO-ECONOMIC BENEFITS STAGE OF DEVELOPMENT SOURCES OF FUNDS (In-house/government organizations/ central ministries/state departments/ international organizations/industry collaboration/ national and international NGOs and any other donors) IPR AND ROYALTY ISSUES IF COLLABORATIVE, MTA/OTHER AGREEMENTS AND STATUTORY APPROVALS

Summary of Transgenic Research in Agriculture

Target Crops/ Vegetables Cotton, Corn, Mustard, Rice, Soybean, Potato, Tobacco, Coffee, Tomato, Brinjal, Cauliflower, Pea, Cabbage, Banana, Muskmelon, Pigeonpea, Chickpea, Bell-pepper, Blackgram, Chilli, Watermelon etc. Transgenes Employed Bt. toxin genes, Herbicide tolerant genes (CP4 EPSPS, Bar gene), Xa21, ctx-B and tcp of V.cholera, Chitinase, Glucanase, ACC synthase, RIP, Protease Inhibitor, Lectin, Ama-1, OXDC gene, Rabies glycoprotein gene, Bar, Barnase, Barstar, GNA gene, Vip-3 gene, Bacterial Blight Resistance gene, Osmotin etc.

Harmonization Process

Swaminathan Committee Regulatory Approvals in Agriculture

Mashelkar Committee Regulatory Approvals in rDNA Pharma

Protocol-I: For New Transgenic Event Institutional Biosafety Committee (IBSC) Review Committee on Genetic Manipulation (RCGM) Monitoring-cum-Evaluation Committee (MEC) Genetic Engineering Approval Committee (GEAC) Approval for large scale Field Trials and Evaluation Protocol** Concurrent Field trials by Company/ Institutions Involving SAUs and other State Agencies GEAC Ministry of Agriculture (DAC/ICAR ) Approval for commercial release/notification/registration of variety(ies)/hybrid(s) DAC/ICAR Ministry of Agriculture & State Governments, Post-release monitoring ICAR trials for VCU

Protocol - II: For Released Event Institutional Biosafety Committee (IBSC) Preparation/submission of application data

RCGM Case verification and Bio-safety clearance (Need based trials) Genetic Engineering Approval Committee (GEAC) Approval for large scale Field Trials and Evaluation Protocol Farmer's Field trials by Company/ Institution(s) GEAC Evaluation of data Environmental clearance of the event DAC/ICAR, Ministry of Agriculture Approval for commercial release of variety(ies)/hybrid(s) Ministry of Agriculture & State Governments, Post-release monitoring

ICAR trials for VCU involving SAUs and other State Agencies

NATIONAL BIOTECHNOLOGY REGULATORY AUTHORITY/COMMISSION In consonance with the recommendations of Both the Committees

CHAIRMAN

Apex Committee with Statutory Powers, consisting of all stakeholder Ministries/Departments

Vice-Chairman Secretariat
Agriculture Products/ Transgenic Crops Pharmaceutical/ Drugs and Industrial Products

Transgenic foods/feed

Transgenic Animals/aquaculture

The Secretariat will have Professionally competent and Experienced Technical Officers in relevant areas of specialization

Details of the Secretariat and their expertise

Agriculture Products/ Transgenic Crops Molecular biologist Plant biologist Plant Geneticist Plant breeder Agronomist Plant Ecologist Environment biologist Agriculture economist Environment biologist

Pharmaceutical/ Drugs and Industrial Products Molecular biologist Pharmacologist Toxicologist Epidemiologist Microbiologist Biochemist Analytical Chemist Physicist Environment biologist

Transgenic foods/ feed Molecular biologist Nutritionist Pharmacologist Toxicologist Epidemiologist Microbiologist Biochemist Analytical Chemist Physicist Environment biologist

Transgenic Animals/aquaculture Molecular biologist Animal Breeder Poultry Breeder Nutrition Expert Animal Pathologist Fishery Expert Pharmacologist Toxicologist Epidemiologist Microbiologist Biochemist Analytical Chemist Physicist Environment biologist

Capacity Building Needs and its Relevance Capacity building needs are considered to be the key milestones to be successfully crossed by the developing regions including at least some developing countries in the region to enable the confidence building exercise. In other words there should be societal acceptance of the technologies of living modified organisms (LMOs) and in this context capacity building needs become most relevant aspect in the safe use of LMOs

Institution Building Risk assessment capacities Involvement of stakeholders Development and strengthening of legal and regulatory structures Capacity Building Efforts- Indian expertise and experience that can be shared in the region Skills in biotechnology process and applications Human resources strengthening and development

The public should be viewed as a partner and a level of trust needs to be created. Developing this style will be a major challenge for business leaders as well as university scientists and government regulators.
The Public perception is most important in the success/failure of rDNA product and safety aspects to environment/humans/animals etc.

Thank you