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

The first hope

for food

based approach

through GM

Various Insect & Herbicide tolerant crops etcVarious Insect & Herbicide tolerant crops etc

GM to combat GM to combat malnutritionmalnutrition

Biotechnology contributing in Agriculture

Pest managementTrait improvementIncreased productivityFortificationGolden rice (vitamin A rich rice)Iron and Zinc rich riceQuality Protein maizeAmA1 gene in Potato

BIOSAFETYBIOSAFETY

PUBLICRisk CommunicationNavigation in perpetual

space

POLICY MAKERSRisk Management

Navigation in decision space

SCIENTISTSRisk Assessment

Navigation in physical space

Biosafety Information sought from GMO trials

Laboratory and Green House TrailsBack 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 trailsRational for the developmentEconomic, agronomic and other benefits, and rationale of developmentDetails of the molecular biology of GMOs

Description of the host plantSource and sequence of transgenicCloning strategyCharacteristic of expression vectorsCharacteristic of inserted genes with details of

sequencesCharacteristic of promotersTransformation/cloning methods of target organismGenetic analysis including copy number of inserts,

stability, level of expression of transgenes, biochemistry of expressed gene products etc.

contd…...

Biosafety Information sought from GMO trailsField Trial

Comparison of germination rates and phenotypic characteristics

Study of gene flowInvasiveness studiesPossibility of weed formationPossibility 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 substancesAgronomic evaluation

Regulatory Aspects for GMOs

Why Regulations are Necessary for Using GMOs andProducts 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 GMOsand 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

RCGM’s approval for Lab & Green House Experiments & Generation of relevant data

RCGM’s approval for Contained open field trials& Generation of biosafety data

RCGM’s approval for Multi-location trials under RCGM for generation of biosafety and agronomic data

Large scale field trials under GEAC & ICARTrials 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 1986Authorities & Administrative structure

STATUTORY BODIESSTATUTORY BODIES1. The Recombinant DNA Advisory

Committee (RDAC):2. Institutional Biosafety Committee (IBSC)3. Review Committee on Genetic

Manipulation (RCGM)4. Genetic Engineering Approval Committee

(GEAC)5. State Biotechnology Coordination

Committee (SBCC)6. 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/ VegetablesCotton, Corn, Mustard, Rice, Soybean, Potato, Tobacco, Coffee, Tomato, Brinjal, Cauliflower, Pea, Cabbage, Banana, Muskmelon, Pigeonpea, Chickpea, Bell-pepper, Blackgram, Chilli, Watermelon etc.

Transgenes EmployedBt. 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 ICAR trials for VCU

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

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)

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

Approval for large scale Field Trials and Evaluation Protocol Farmer's Field trials by Company/ Institution(s)

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

Transgenicfoods/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 CropsMolecular biologistPlant biologistPlant GeneticistPlant breederAgronomistPlant EcologistEnvironment biologistAgriculture economistEnvironment biologist

Pharmaceutical/Drugs and Industrial ProductsMolecular biologistPharmacologistToxicologistEpidemiologistMicrobiologistBiochemistAnalytical ChemistPhysicistEnvironmentbiologist

Transgenic foods/feedMolecular biologistNutritionistPharmacologistToxicologistEpidemiologistMicrobiologistBiochemistAnalytical ChemistPhysicistEnvironmentbiologist

Transgenic Animals/aquacultureMolecular biologistAnimal BreederPoultry BreederNutrition ExpertAnimal PathologistFishery ExpertPharmacologistToxicologistEpidemiologistMicrobiologistBiochemistAnalytical ChemistPhysicistEnvironmentbiologist

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