DUAL USE RESEARCH OF CONCERN AND BIOSECURITY: INDIAN PERSPECTIVE

Professor C Kameswara RaoFoundation for Biotechnology Awareness and Education
Bangalore 560 004, India pbtkrao@gmail.com.

During the past year or so, there have been many significant new policy initiatives in India, in the areas of health research and biosecurity regulation of genetically engineered organisms and their products, which have a bearing on Dual Use Research of Concern (DURC). 

INFRASTRUCTURE FOR HEALTH RESEARCH
Research in life sciences related to health is carried out primarily under the aegis of the Indian Council of Medical Research (ICMR, of the Department of Health, Ministry of Health and Family Welfare, Government of India).   There are 22 National Research Institutes and six Regional Medical Research Centres under the ICMR, and a large number of Central or State Universities, autonomous research institutions, Medical Colleges and other academic institutions involved in advanced medical research. 

The research projects are financed by the Department of Health, Department of Biotechnology, Department of Science and Technology, Council of Scientific and Industrial Research, and the University Grants Commission.  Research on animal health is supported by the Indian Council of Agricultural Research in its several specialist institutions and the State agricultural/veterinary Universities.  Research in the alternative medical systems such as Ayurveda, Siddha, Unani and Homoeopathy, with a focus on indigenous medicinal plants, is funded by both the Central and State Governments.

PHARMACEUTICAL INDUSTRY
The Indian pharmaceutical industry has an export component of about 58 percent.  Its revenue stood at US$ 1.75 billion in 2007-08, a 70 per cent share of total biotech industry revenue.  About 47 per cent of the pharmaceutical revenue came from vaccines.  Of the top 20 pharmaceutical manufacturing companies in the Asia-Pacific, 14 are Indian. 

Currently, r-DNA pharmaceuticals such as HBsAg vaccine, Erythopoietin, G-CSF, α-Interferon, and Insulin are approved for manufacturing and marketing in India, while others such as GM-CSF, γ-Interferon, Interleukin, Blood Factor VIII, Streptokinase, Human growth hormone, tPA, Follicle Stimulating Hormone, and Human protein C are permitted only for marketing.

BIOTECHNOLOGY RESEARCH OF DUAL USE CONCERN IN INDIA
The r-DNA technology is being widely deployed both in the agricultural (transgenic crops) and pharmaceutical sectors.  The actual component of modern biotechnology derived biopharmaceuticals is very small, as the bulk of them are being produced through conventional technologies, but jumping on the band wagon of biotechnology, for the benefits the Government extends to biotechnology enterprises.  The cutting edge technologies posing serious dual use concerns such as synthetic biology, gene silencing or the others have yet to make their presence.  Vaccines are the major component of the Indian pharmaceuticals.  Since vaccines are administered to healthy people to prevent them from contacting a disease, dual use potential of vaccines is minimal.  Consequently, currently the quantum of R & D with dual use concerns is quite low in India.  However, this does not mean room for complacency, to delay formulation and implementation of policies and programs to monitor DURC. 

HEALTH POLICY OF THE GOVERNMENT OF INDIA
The focus of the National Health Policy is the development of drugs, vaccines and diagnostics relevant particularly to HIV, TB, malaria and emerging and re-emerging infections, through modern biotechnology.  While this continues to be the major activity of both the public and private sector R & D, there is an accelerated interest in therapeutics based in stem cells and nanobiotechnology.

The strategies and programs of health research in the country are designed to develop into a National Health Research System (NHRS) managed by a National Health Research Management Forum (NHRMF).  To facilitate this, the Government has in recent times released several policy documents with a bearing on biomedical research, the more important of them being:

a) National Health Research Policy (2007),

b) Guidelines for Stem Cell Research and Therapy (2006), and

c) Ethical Guidelines for Biomedical Research (2006).

PROMOTION OF BIOTECHNOLOGY IN HEALTH RESEARCH
The Government of India has taken several policy initiatives to encourage involvement of both the public and the private sector in modern biotechnology based health research.  The more important of them are:

a) Small Business Innovation Research Initiative (SBIRI) to encourage pre-proof-of concept research and innovation with potential for commercialization,

b) Biotechnology Industry Partnership Programme (BIPP) aimed at generating IPR and allowing the industry partner to retain IPR at the same time protecting the interests of the public sector partners, and

c) Biotechnology Industry Research Assistance Council (BIRAC) to act as an interface between the public and private sectors catalyzing R & D and innovation, and to manage BIPP and SBIRI.

BIOSECURITY REGULATORY FRAMEWORK
The biosecurity regulatory regime of India stems from the Environment (Protection) Act, 1986 (Rules of 1989) that stipulated rules and procedures for the ‘manufacture, import, use, research and release of genetically engineered organisms and their products’.  The regulatory regime is jointly implemented by the Ministry of Environment and Forests and the Department of Biotechnology (Ministry of Science and Technology), with interventions from the Ministries of Agriculture and of Health and Family Welfare, wherever appropriate.

India’s biosecurity regulatory regime for genetically engineered products is among the most stringent in the world, operating through a coordinated activity of four major competent authorities:

a) Recombinant DNA Advisory Committee (RDAC

b) Institutional Biosafety Committees (IBSC),

c) Review Committee on Genetic Manipulation (RCGM), and

d) Genetic Engineering Approval Committee (GEAC). 

The RDAC and the RCGM are under the Department of Biotechnology while the GEAC is with the Ministry of Environment and Forests.  All the Committees have due representation of diverse stakeholders and the scientific community. 

The RDAC, the eyes and ears of the Government, reviews national and international developments in biotechnology to advise the Government on policy imperatives.

Every organization involved in research in any area of modern biotechnology functions under the supervision of an ISBC specifically constituted for an area of research in that institution.  ISBCs are the first and most crucial phase in designing, evaluating and monitoring biosecurity regime.  ISBCs are the stage for recognition of DURC and to regulate the intent, content and direction of research.  The Department of Biotechnology has issued a detailed handbook on the functions and role of the ISBC as per the ‘Recombinant DNA Safety Guidelines, 1990’ and the ‘Revised Guidelines for Research in Transgenic Plants and Guidelines for Toxicity and Allergenicity Evaluation of Transgenic Seeds, Plants and Plant Parts, 1998’.

The RCGM is involved in biosecurity clearance on the recommendation of the ISBC.  The Indian Council of Agricultural Research conducts biosecurity evaluation of agricultural products and the Drug Controller General of India (being reorganized as the Central Drug Regulatory Authority) is involved in biosecurity clearance of medical products.  A large number of public research institutions generate and evaluate biosecurity data for a wide range of parameters and advise the appropriate regulatory Committee. 

In addition, it is mandatory to constitute State Biosafety Coordination Committees (SBCCs) and District Level Committees (DLCs), to locally supervise compliance of statutory biosafety requirements.  
NEW POLICY INITIATIVES ON BIOSECURITY REGULATION
Based on a couple of decades of experience in implementing a biosecurity regulatory regime, the representations from different stakeholders and the criticism faced by the present regulatory regime, the Government of India has initiated several policy changes rooted in the new ‘National Biotechnology Development Strategy’ (NBDS, 2007).  The most significant change emerging out of the new policy is the establishment of the ‘National Biotechnology Regulatory Authority’ (NBRA, 2008), for which a statutory ‘National Biotechnology Regulatory Bill, 2008’, drafted after extensive consultation with diverse stakeholders, is in processing.  Till the new policy falls in place, the current GEAC based regulatory system would continue.

The NBRA, retaining the sound and time tested segments from the current procedures, will function interacting with an Inter-Ministerial Advisory Board and a National Biotechnology Advisory Council.  The NBRA will have:

a) Risk Assessment Unit,

b) three Regulatory Branches (one for each of  i) Agriculture, Fisheries and Forestry, ii) Human and Animal Health and iii) Industrial and Environmental Applications), each functioning as a single window clearance mechanism for the relevant sector, and

c) several cross-sectorial offices, all feeding and advising the NBRA.

A very large number of public sector research organizations relevant to each stream/product will undertake biosecurity evaluation and recommend for appropriate action to the NBRA, through the appropriate Regulatory Branches.

NATIONAL GUIDELINES FOR BIOLOGICAL DISASTER MANAGEMENT
The Government of India has constituted a statutory body, the ‘National Disaster Management Authority’ (NDMA), under the Disaster Management Act, 2005.  The NDMA has in August 2008 released ‘National Guidelines for Biological Disaster Management’ (NGBDM), to deal with natural and manmade biological threats and emergencies.  The guidelines relate to:

a) Legislative framework,
b) Capacity development,
c) Biosecurity measures,
d) Standardized documentation,
f) Development of critical infrastructure,
g) Mechanism for public health response,
h) Management of pandemics, and
j) International cooperation.

Both the Central and State Governments are required to set up appropriate Biological Disaster Management Authorities in course of time.

AWARENESS OF DURC
Though India has supported the 2005 Inter-Academy Panel Statement on Biosecurity, awareness of the term and import of DURC is alarmingly low even among the scientific circles, as also reflected by its absence from any of the official and scientific documents.  However, the terms bioterrorism and biowarfare are used occasionally in India, but in broad general terms.  The recent biological disaster management guidelines will in course of time enhance levels of awareness, but of only biowarfare and bioterrorism in conventional contexts. 

The identification and monitoring of DURC is presently dependent upon the level of awareness of the IBSCs, which is patchy.  There is no concern and/or mechanism now in place for the funding agencies to identify projects with DURC implications or for the journal editorial system to identify them at the stage of peer review.  The levels of awareness at the funding and publication stages certainly need to be addressed, keeping in view the international consensus that there should be no restrictions on the kind of research one undertakes or on international communication of advances in science, but intent on only the identification of the risk and means of mitigating it. 

CHANNELS OF OUTREACH
Enhancing awareness of DURC through the media may not elicit the intended positive response, as the Indian media seem to regard only the macabre as newsworthy and facts are not news.  An interview I gave on DURC to Deccan Herald (an English daily), published on July 14, 2008, got the facts near right, but had a sensational title ‘Andromeda Strain, Made on Earth’, resulting in several phone calls asking me ‘why do scientists undertake such risky research?’
 
The response from the Indian biotech business to an article on infectious diseases and DURC (Harvey Rubin and C. Kameswara Rao, May 2008), in Biospectrum, a biotech business magazine with a very wide circulation in Asia, was lukewarm.  The article circulated via e-mail to the big wigs of the Indian pharmaceutical biotech industry drew a blank. 

Another article by Harvey Rubin and me is under protracted consideration for over five months, by Current Science, India’s premier science journal, which hopefully will draw the attention of the scientific community to DURC, if accepted.

Three lectures, I have delivered this year on biopharmaceuticals with a prominent DURC component, elicited a better response from the audience composed of teachers, graduate students and research scholars of biological sciences.   This sector would serve as an effective means of enhancing levels of awareness of DURC in the developing countries, on a long term basis.

Workshops designed to address different target groups of audience separately are likely to have a better reach and response, though financing them is a hurdle.  A workshop on bioterrorism conducted by our Foundation in Bangalore several years ago is still being referred. 

Notwithstanding the past disappointing experience, DURC outreach through diverse media is still the most important necessity, however tardy the progress may be.

THE NEED FOR AN INTERNATIONAL DOCUMENT
A comprehensive consensus document, jointly prepared by international scientific bodies such as the US National Science Advisory Board for Biosecurity, World Health Organization and national science academies, to impress upon the developing countries on the need for urgent measures to handle DURC at different levels, from the initial research proposal to commercialization, is a desideratum.  Such a document will aid the national regulatory authorities, such as the Indian NBRA, to develop policy involving both the public and private sectors and the rules for its implementation.  The document will promote awareness of DURC among the system and medical administrators both at the National and States levels for effective implementation of official provisions and among the general public to be forewarned for an orderly and coordinated response without hitting the panic button. 

*The Foundation for Biotechnology Awareness and Education is a Registered non-profit organization working since January 2001, to enhance levels of awareness, and standards of education, of modern biotechnology.