Indian GMO Regulations and implications on New Plant Breeding Molecular Technologies

Transcription

1 Indian GMO Regulations and implications on New Plant Breeding Molecular Technologies S.R. Rao, Department of Biotechnology, Ministry of Science & Technology, India Presented at International Workshop for Regulation of Animal Biotechnology in Jaipur, India, October, 2014

2 Today s Topics GMO dilemma Regulatory frame work - Scope Principles of scientific risk assessment Current Status of GMOs Research on transgenic plants and RNAi Regulatory approach for NPBMT Future plans

3 GMO dilemma PUBLIC POLICY FRAME WORK ACTUAL PUBLIC RISK ASSESSMENT ACTIVISTS

4 GMO dilemma Promotional Precautious India Pakistan Bangladesh Preventive Prohibitive Sri Lanka Nepal Bhutan

5 Complexity with Research Development and Commercialization of Transgenics Discovery Development Commercial use Public acceptance Basic Research Translati on phase Breeding Development Environment Protection Act 1986 Field testing Rs 30M 30M 30M 20M Varietal release Cultivation yrs Variety release breeders- foundation- certification of seeds Farmers Consumers

6 Regulatory frame work - Scope ENVIRONMENT PROTECTION ACT 1986 RULES FOR THE MANUFACTURE, USE/IMPORT/EXPORT AND STORAGE OF HAZARDOUS MICROORGANISMS/ GENETICALLY ENGINEERED ORGANISMS OR CELLS New Delhi, The 5th December, 1989 Applicable to: The import, export, transport, manufacture, process, use or saleofgmosanduseofgmosforresearch Authorization for production of genetically modified microorganisms, plants and animals Approval for deliberate or intentional release of GMOs into the open environment Approval for production, sale and import of foodstuff, ingredients in foodstuff including processing aid which may contain GMOs or cells

7 Regulatory frame work - Scope ENVIRONMENT PROTECTION ACT 1986 RULES FOR THE MANUFACTURE, USE/IMPORT/EXPORT AND STORAGE OF HAZARDOUS MICROORGANISMS/ GENETICALLY ENGINEERED ORGANISMS OR CELLS New Delhi, The 5th December, 1989 Applicable to: Procedures for obtaining approvals in different conditions Conditions of approval of GMOs Mechanism for supervising the implementation of term and conditions given with authorization for commercial use Penalties that can be levied for non compliance of measures forsafeuseofgmosandproductsthereof Redress mechanism through National Environment Appellate Authority

8 Regulatory frame work - Scope DEFINITIONS In these rules unless the context requires. Gene Technology means the application of the gene technique called genetic engineering, include self cloning and deletion as well as cell hybridisation; Genetic engineering means the technique by which heritable material, which does not usually occur or will not occur naturally in the organism or cell concerned, generated outside the organism or the cell is inserted into said cell or organism. It shall also mean the formation of new combinations of genetic material by incorporation of a cell into a host cell, where they occur naturally (self cloning) as well as modification of an organism or in a cell by deletion and removal of parts of the heritable material;

9 Regulatory frame work - Scope Statutory Bodies National Level Genetic Engineering Appraisal Committee (GEAC) Final Approval environmental release for Ministry Environment and Forests of National Level Review Committee For Genetic Manipulation (RCGM) Scientific risk assessment of plants, animals, biopharma, microbes and Guidelines Ministry of S&T Department of Biotechnology State Level State Biotechnology Coordination Committee (SBCC) Local monitoring and compliance 29 State governments Institute universit y/compan y level Institutional Biosafety Committee (IBSC) with Nominee of RCGM R&D and Contained Experiments Ministry of S&T Department of Biotechnology

10 Expertise in RCGM (about 36 members) including interministerial nominations Mandate : Scientific Risk assessment of all recombinant products and recommendation to GEAC /DCGI etc

11 Regulatory frame work - Scope Guidelines Recombinant DNA Safety Guidelines, 1990 Plants Guidelines for research in transgenic plants & evaluation of transgenic seeds, plants and plant parts, 1998 Guidelines for the conduct of confined field trials of regulated, GE crops, 2008 Guidelines and protocols for food and feed safety assessment of GE crops, 2008 Standard Operating Procedures for confined field trials 2008 Biosimilars and rdna medical products Under preparation Animals Insects Oxitec Mosquito; Silkworm Trees RNAi

12 Regulatory frame work - Scope Guidelines Category I Self cloning using strains and also inter-species cloning belonging to organism in the same exchanger group which are exempt from intimation and approval. Category II Experiments falling under containment levels II, III and IV require prior intimation of Competent Authority and include (details of each containment level have been provided separately in the guidelines). Category III Review and approval of Competent Authority before commencement of genetic engineering experiments in which foreign gene is incorporated

13 Regulatory frame work - Scope Guidelines The approach to formulation of new Guidelines or for review or revision of protocols, guidelines of safety assessment of GM crops in India at national level is: to examine all the available peer reviewed research publications and documented experiences followed by wide ranging consultation at multiple level of stakeholders to arrive at consensus documents for wider adoption and harmonisation of practices at global level

14 Principles of scientific risk assessment Food Safety Molecular/protein Characterization Environmental Safety Food and feed safety assessment and the environmental risk assessment are separate and distinct evaluations and share some common elements of information through the molecular characterization of the GM organism and characterization of expressed, transgenic proteins

15 Specific information and data requirements for the Food & Feed Safety and Environmental Risk Assessment of GE plants Description of the genetically engineered plant Biology of the non-transgenic host plant Donor organism information Molecular characterization Bio-informatic analysis: potential toxicity and allergenicity Expression of introduced protein(s) Compositional analysis Acute oral safety limit study Pepsin digestibility assay Protein thermal stability Sub-chronic feeding study in rodents (if required) Livestock feeding study (if required) Inheritance of introduced trait Stability of introduced trait Reproductive and survival biology Impact on non-target organisms

16 GM Food Safety Evaluation Category of Information/Data Requirement India Host information X X X X X X X X X Argentina Australia Canada Philippines Japan S. Africa EU USA Donor information X X X X X X X X X Molecular characterization X X X X X X X X X Characterization of expressed protein X X X X X X X X X Nutritional composition X X X X X X X X X Potential toxicity of novel protein(s) X X X X X X X X X Potential allergenicity of novel protein(s) X X X X X X X X X

17 Marvin 2014

18 Current Status of GMOs Research Institutions/ Companies engaged Universities 50 Research Institutions 45 Companies 140 Total 235 Year Application reviewed Healthcare Agriculture Total

19 Current Status of GMOs -Approved Plants Bt Cotton from Monsanto, USA Bt Cotton from IIT, Kharagpur Bt Cotton from Biocentury, China Bt Cotton from Metahelix, Bangalore Bt Cotton from CICR, Nagpur Biopharma Human insulin for diabetes Hepatitis B Vaccine Human growth hormone Streptokinase for acute myocardial infraction Teriparatide(Forteo) for Osteoporosis Platelet Derived Growth Factor (PDGF) for Bone marrow induction & Osteoblasts proliferation Follicle Stimulating Hormone for reproductive disorders

20 Impact of Technology on Cotton in India

21 70 R&D projects in 15 crops for development of GM crop varieties in public sector institutions/ universities for improvement of productivity, quality, pest and disease resistance, water use efficiency and salinity Tomato with improve quality parameters and shelf life Lycopene (mg/100g) CONTROL ODC 22 ODC 27 ODC 32 SAMDC 22 SAMDC 24 SAMDC 56 Line no. SAMDC 70 ADC 25 ADC 93 Rice with water use efficiency Groundnut with virus disease resistance 3/06/2010 Hyderabad

22 Research on transgenic plants in Public sector CROP Cotton Corn Brinjal Mustard Rice Potato Sorghum Groundnut Chickpea Castor Cabbage Rubber Okra Cauliflower Tomato Papaya Watermelon TRAITS Tolerance to insect pests and herbicides Tolerance to insect pests and herbicides Tolerance to insect pests Tolerance to abiotic stress, Male sterile lines Tolerance to insect pests, herbicides and abiotic stress Male sterile female inbred lines Tolerance to late blight disease; Delayed sweetening Tolerance to insect pests Tolerance to tobacco streak virus and Aspergillus Tolerance to abiotic stress & insect pests Tolerance to insect pests Tolerance to insect pests and herbicides Tolerance to abiotic stress Tolerance to insect pests Tolerance to insect pests and herbicides Tolerance to insect pests, peanut bud necrosis virus and leaf curl virus Delayed ripening Tolerance to PRSV Tolerance to WBNV

23 RNAiScience & Technology Aiming to foster innovations and promote translational research in collaboration with industries, to address issues related to health, agriculture, and food environment using RNAi science/technology approaches. genome wide RNAi factors in various organisms to manipulate the RNAi potential l cellular factors responsible for disease susceptibility or resistance using genome wide RNAi pathways for mirna biogenesis and function in animal and plants molecular process for various diseases/metabolic / processes in animal or plant model Profiling,, prediction and manipulation of mirnas for development and stress pi RNA biogenesis and function Search for mirna biomarkers for known diseases & Developing genome wide shrna libraries Chemical synthesis of stable small RNAs and their target specific delivery Developing transgenic with economic traits using RNAi approach Development of RNAi based diagnostics and therapeutics for important diseases

24 First demonstration of RNAi-based protection against a plant DNA virus Infected Only traces of viral DNA were detected in recovered blackgram plants Recovered Dilution (fold): 5 Poogin MM, et aal Nature Biotechnology 21: About 35 projects develop transgenics through RNAi approachout Total plant of DNA total 120 Infected Recovered projects Plasmid DNA A (nanograms) Bombarded leaves Semi-quantitative PCR Leaf: lower upper lower upper

25 National Agriculture Research System 100 Research National Institute/ centres 80 in crops and 20 in animal Sciences 42 agriculture Universities 16 vet Universities

26 Problem formulation is methodology that allows the organization of the risk assessment in logic way case- by case In this step the risk assessment is where the protection goals are clearly outlined as well as assessment end points Relevant available information is compiled to address key questions Facilitates an initial risk characterization to establish : If the risk characterization can be completed with available information If more information is necessary If more information is necessary, the problem formulation allows The development of clear analysis plan The identification of information needed to facilitate decision making

27 Approach to NPBT -Problem formulation is methodology that allows the organization of the risk assessment in logic way caseby case In this step the risk assessment is where the protection goals are clearly outlined as well as assessment end points Relevant available information is compiled to address key questions Facilitates an initial risk characterization to establish : If the risk characterization can be completed with available information If more information is necessary If more information is necessary, the problem formulation allows The development of clear analysis plan The identification of information needed to facilitate decision making

28 Future plans : reforms in current system Task Assigned by RCGM/GEAC Secretariat Chief Scientific Officer (F) Biologicals Agriculture Scientist (Biologicals) Scientist (Agriculture) Scientist- Pharmacology Toxicology Biochemistry Microbiology Veterinary Pharmacology Molecular Biology/Genetics Fermentation Technology Pharma. Biotechnology Drug Regulatory Affairs Analytical Chemistry Scrutiny & Evaluation of Dossier/Application Report Preparation Internal Risk Assessment unit to assist statutory bodies Presentation before the RCGM to facilitate regulatory decision making

29 BIOTECHNOLOGY REGULATORY AUTHORITY OF INDIA Inter-Ministerial Governing Board Chief Regulatory Officer, Agriculture, Fisheries & Forestry Division Regulatory & Policy Unit Scientific Advisory Panels (as needed) Chairperson, BRAI & 2 full time & 2 part time members Product Ruling Committee Chief Regulatory Officer, Industrial & Environmental Applications Division Regulatory & Policy Unit Scientific Advisory Panels (as needed) National Biotechnology Advisory Council Environment Appraisal Panel Chief Regulatory Officer, Human & Animal Health Division Regulatory & Policy Unit Scientific Advisory Panels (as needed) Risk Assessment Unit Core Characterization: Molecular Biologist; Microbiologist; Chemist; Toxicologist; Bioinformatics; Statistics Animal Biotechnology: Physiologist; Pathologist; Nutritionist; Animal Breeder; Veterinary Scientist; Fisheries/aquaculture scientists Plant Biotechnology: Physiologist; Pathologist; Entomologist; Agronomist; Plant Breeder Human Health Biotechnology: Immunologist; Epidemiologist; Pharmacologist; Clinical scientist Industrial & Environmental Biotechnology:Ecologist; Environmental biologist; Industrial microbiologist; Analytical chemist Cross-Sectoral Offices National & International Policy Coordination Unit Communication & Outreach Unit Legal Unit Monitoring, Compliance & Accreditation Unit Capacity Building & Training Unit State Biotechnology Advisory Committee NEW LEGISLATION Economic Bhutan Analysis Unit 29

30 The Supreme Court of India, for the first time, on September 22, 2006, issued an interim verdict banning all field trials of genetically modified (GM ) crops in the country and slammed its regulatory mechanism. Discovery Basic Research Supreme court may say otherwise Translatio n phase Complexity with Research Development and Commercialization of Transgenics Commercial Development use Breeding Development Field testing Rs 30M 30M 30M 20M Supreme court constituted committee of five experts in Interim report recommended ban on field trials, heard and stayed for detailed report with induction of one more experts Varietal release Variety release breeders- foundation- certification of seeds Public acceptance Cultivation yrs Farmers Consumers Bhutan 30

31 Thanks My Group DR RajaLaksmi, DR Nitin Dr Amit and MR Sunil