S.R. Rao,

Department of Biotechnology ,

Ministry of Science & Technology, India

Indian GMO Regulations and implications on New Plant Breeding

Molecular Technologies

Presented at International Workshop for Regulation of Animal

Biotechnology in Jaipur , India , October , 2014

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

PUBLIC POLICY

RISK ASSESSMENT

ACTIVISTS

FRAME

WORK

ACTUAL PUBLIC

GMO dilemma

GMO dilemma

Promotional

Precautious

Preventive

Prohibitive

India

Pakistan

Bangladesh

Sri Lanka

Nepal

Bhutan

Basic Research

Translation phase

Breeding Development

Field testing

Varietal release

Cultivation

Discovery Development Commercial

use Public

acceptance

Variety release

breeders-

foundation-

certification of

seeds

Farmers

Consumers

3 5 7 10 yrs

Rs 30M 30M 30M 20M

Complexity with Research Development and Commercialization

of Transgenics

Environment

Protection Act

1986

Regulatory frame work - Scope

ENVIRONMENT PROTECTION ACT 1986RULES 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

sale of GMOs and use of GMOs for research

�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

Regulatory frame work - Scope……

ENVIRONMENT PROTECTION ACT 1986RULES 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

for safe use of GMOs and products thereof

�Redress mechanism through National Environment

Appellate Authority

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;

Regulatory frame work - Scope

Regulatory frame work - Scope…… Statutory Bodies

National

Level

Genetic Engineering

Appraisal

Committee (GEAC)

Final Approval for

environmental

release

Ministry of

Environment

and Forests

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

Expertise in RCGM (about 36 members) including inter-ministerial nominations

Mandate : Scientific Risk assessment of all recombinant products and recommendation to

GEAC /DCGI etc

Plants

Guidelines for research in transgenicplants & evaluation of transgenicseeds, plants and plant parts, 1998

Guidelines for the conduct of confinedfield trials of regulated, GE crops, 2008

Guidelines and protocols for food andfeed safety assessment of GE crops,2008

Standard Operating Proceduresfor confined field trials 2008

Biosimilars and rDNAmedical products

Under preparation

Animals

Insects

Oxitec Mosquito; Silkworm

Trees

RNAi

Recombinant DNA Safety Guidelines, 1990

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

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

Regulatory frame work - Scope…… Guidelines

Molecular/protein Characterization

Environmental SafetyFood 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

Principles of scientific risk assessment

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

Specific information and data requirements for the Food & Feed Safety and Environmental Risk Assessment of GE plants

Category of Information/Data Requirement India

Arg

entin

a

Australia

Can

ada

Philip

pin

es

Japan

S. A

frica

EU

US

A

Host information X X X X X X X X X

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

GM Food Safety Evaluation

Marvin 2014

Current Status of GMOs

Research Institutions/

Companies engaged

Universities 50

Research

Institutions

45

Companies 140

Total 235

Year Healthcare Agriculture

2007 202 668

2008 348 617

2009 355 367

2010 388 390

2011 511 452

2012 394 450

2013 374 277

Total 2572 3221

Application reviewed

2007-2013

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 & Osteoblastsproliferation

• Follicle Stimulating Hormone for reproductive disorders

Current Status of GMOs - Approved

Impact of Technology on Cotton in India

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

CONTROL

ODC 22

ODC 27

ODC 32

SAMDC 22

SAMDC 24

SAMDC 56

SAMDC 70

ADC 25

ADC 93

Line no.

Lycopene (m

g/1

00g)

Tomato with improve quality parameters and shelf life

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

Rice with water use efficiency Groundnut with virus disease resistance

3/06/2010 Hyderabad

Research on transgenic plants in Public sector

CROP TRAITS

Cotton Tolerance to insect pests and herbicides

Corn Tolerance to insect pests and herbicides

Brinjal Tolerance to insect pests

Mustard Tolerance to abiotic stress, Male sterile lines

Rice Tolerance to insect pests, herbicides and abiotic stress

Male sterile female inbred lines

Potato Tolerance to late blight disease; Delayed sweetening

Sorghum Tolerance to insect pests

Groundnut Tolerance to tobacco streak virus and Aspergillus

Chickpea Tolerance to abiotic stress & insect pests

Castor Tolerance to insect pests

Cabbage Tolerance to insect pests and herbicides

Rubber Tolerance to abiotic stress

Okra Tolerance to insect pests

Cauliflower Tolerance to insect pests and herbicides

Tomato Tolerance to insect pests, peanut bud necrosis virus and leaf curl virus

Delayed ripening

Papaya Tolerance to PRSV

Watermelon Tolerance to WBNV

RNAi Science & 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

Infected

lower upper lower upper

Infected Recovered

Dilution(fold):

255

125625

525

125625

525

125625

525

125625

Plasmid

DNA A(nanograms)10.1

0.010.001

Total plant DNA

Leaf:

Recovered

Bombarded leaves

Only traces of viral DNA were detected in recovered

blackgram plants

Semi-quantitative

PCR

Poogin MM, et aal 2008. Nature

Biotechnology 21:131-132

First demonstration of RNAi-based protection against a plant DNA

virus

About 35 projects develop

transgenics through RNAi

approach out of total 120

projects

42 agriculture Universities

16 vet Universities

National Agriculture Research System

100 Research National Institute/ centres

80 in crops and 20 in animal Sciences

�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

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

Approach to NPBT -Problem formulation is methodology that allows the organization of the risk assessment in logic way case-

by case

Task Assigned by RCGM/GEAC Secretariat

Chief Scientific Officer (F)

Biologicals Agriculture

Scientist (Biologicals ) Scientist (Agriculture )

Scrutiny & Evaluation

of

Dossier/Application

Report Preparation

Presentation before the RCGM to facilitate regulatory decision making

Scientist-

Pharmacology

Toxicology

Biochemistry

Microbiology

Veterinary Pharmacology

Molecular Biology/Genetics

Fermentation Technology

Pharma. Biotechnology

Drug Regulatory Affairs

Analytical Chemistry

Future plans : reforms in current system

Internal Risk Assessment unit to assist statutory bodies

Chairperson, BRAI &

2 full time & 2 part time membersInter-Ministerial Inter-Ministerial

Governing Board

National Biotechnology

Advisory Council

Environment Appraisal PanelProduct Ruling CommitteeProduct Ruling Committee

Chief Regulatory Officer, Industrial

& Environmental Applications

Division

Chief Regulatory Officer, Industrial

& Environmental Applications

Division

Regulatory & Policy UnitRegulatory & Policy Unit

Scientific Advisory

Panels (as needed)

Scientific Advisory

Panels (as needed)

Chief Regulatory Officer,

Agriculture, Fisheries & Forestry

Division

Regulatory & Policy Unit

Scientific Advisory

Panels (as needed)

Scientific Advisory

Panels (as needed)

Regulatory & Policy Unit

Chief Regulatory Officer,

Human & Animal Health

Division

Cross-Sectoral Offices

National & International

Policy Coordination Unit

Communication & Outreach Unit

Legal Unit

Monitoring, Compliance

& Accreditation Unit

Capacity Building & Training Unit

Economic Analysis Unit

Risk Assessment Unit State Biotechnology

Advisory CommitteeCore 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 chemistBhutan 29

BIOTECHNOLOGY REGULATORY AUTHORITY OF INDIA

NEW

LEGISLATION

Basic Research

Translation phase

Breeding Development

Field testing

Varietal release

Cultivation

Discovery Development Commercial

use Public

acceptance

Variety release

breeders-

foundation-

certification of

seeds

Farmers

Consumers

3 5 7 10 yrsRs 30M 30M 30M 20M

Complexity with Research Development and

Commercialization of Transgenics

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.

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

Bhutan 30

Supreme court may say otherwise

Thanks

My Group

DR RajaLaksmi, DR

Nitin Dr Amit and

MR Sunil