RECOMBINANT DNA SAFETY GUIDELINES, 1990 Department of


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RECOMBINANT DNA SAFETY GUIDELINES, 1990 Department of Biotechnology, Ministry of Science and Technology, Govt. of India

I.

INTRODUCTION

The new capabilities to manipulate the genetic material present tremendous potential and find use in many novel experiments and applications. These developments have generated a sense of concern among scientists working in biological areas and others to find ways how safely the research in the field should be carried out and means to regulate work involving pathogenic microorganisms and genes of virulence. Several countries have formulated safety guidelines and regulations for research in the field of recombinant DNA, large scale use of them in production process and their applications in the environment. Considering the possible incremental risks associated with the use of new techniques in laboratory research with pathogenic microorganisms, the National Biotechnology Board issued a set of safety guidelines for India in 1983 to ensure the safety of workers in the laboratory environment. While framing the guidelines, the Committee took into account the local factors such as resistance to infection (immunity), host parasite burden in the community, laboratory environment and chances of survival and growth of altered organisms under the tropical conditions.

Remarkable developments have ensured in the last few years in the field of genetic manipulation and the scenario has shifted from the laboratories to the market place elsewhere. In India there is a growing awareness of the commercial potential of Biotechnology and efforts are being made to promote large scale use of indigenously relevant biotechnologies. A large number of research institutions in Government, Universities and private R&D labs have active biotech programmes where research is being done in both in basic and applied fronts utilising microorganisms plant and animals, tissue culture and cell lines and on development of vaccines towards communicable diseases of both men and animals. A good deal of effort is being made in the areas of diagnostics, biofertilizers, biocides, fertility control, tissue culture of high value crops to develop technologies and useful products. The successes in indigenous research efforts would soon be translated into commercially viable technologies through clearing houses with major R&D Centres, University shops with academic institutions and by the industry itself.

The Biotechnology Safety Guidelines could never be one time exercise as knowledge is ever expanding and the Department of Biotechnology which has the mandate in this area, set up the rDNA Committee to prepare a modified draft on the basis of current scientific information and from the experience gained locally and outside the country on the use of the new technique in the area of research, possible manufacture and applications.

The guidelines cover areas of research involving genetically engineered organism. It also deals with genetic transformation of green plants, rDNA technology in vaccine development and on large scale production and dekliberate/ accidental release of organisms, plants, animals and products derived by rDNA technology into the environment. The issues relating to Genetic Engineering of human embryos, use of embryos and foetuses in research and human germ line gene therapy are excluded from the scope of the guidelines.

While preparing the revised guidelines the Committee and its sub-groups have met 4 times and have taken note of the guidelines currently in use in other countries. The evolution of the guidelines and updation have gone through the process of consultation with experts, academies, agencies and industry and the concerned Ministries with a view to gain general acceptance and broad consensus.

The guidelines are in respect of safety measures for the research activities, large scale use and also the environmental impact during field applications of genetically altered material products.

SCOPE OF THE REVISED GUIDELINES

1.

Research: The levels of the risk and the classification of the organisms within these levels based on

pathogenicity and local prevalence of diseases and on epidemic causing strains in India are defined in

the guidelines. Some of the microorganisms not native to the country have been assigned to a special

category requiring highest degree of safety. These include Lassa virus, Yellow fever virus etc.

Appropriate practices, equipment and facilities are recommended for necessary safeguards in handling

organisms, plants and animals in various risk groups. The guidelines employ the concept of physical

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and biological containment and also based upon the principle of good laboratory practice (GLP). In this context, biosafety practices as recommended in the WHO laboratory safety Manual on genetic engineering techniques involving microorganisms of different risk groups have incorporated in the guidelines (Chapter IV).

2.

Large scale operations: The concern does not diminish when it comes to the use of recombinant

organisms scale fermentation operations on large scale fermentation operations or applications of it in

the environment. As such, the guidelines prescribe criteria for good large scale practices (GLSP) for

using recombinant organisms. These include measures such as proper engineering for containment,

quality control, personnel protection, medical surveillance, etc.

3.

Environmental risks: Application and release of engineered organisms into the environment could

lead to ecological consequences and potential risks unless necessary safeguards are taken into account.

The guidelines prescribe the criteria for assessment of the ecological aspects on a case by case basis for

planned introduction of rDNA organism into the environment. It also suggests regulatory measures to

ensure safety for import of genetically engineered materials, plants and animals. The recommendations

also cover the various quality control methods needed to establish the safety, purity and efficacy of

rDNA products.

II.

GUIDELINES

1.

Definition of recombinant DNA: Recombinant deoxyribonucleic acid (rDNA) by definition involves

in vitro introduction of different segments of DNA (one being the vector and the others normally

unrelated DNA sequences) that are capable of replication in a host cell either autonomously or as an

integral part of host's genome and maintenance of their continued propagation. This will include all

types of cell fusion, microinjection of DNA or RNA or parts or all of chromosomes, genetic

engineering including self cloning and deletion as well as cell hybridation, transformation and other

types of virus or pathogen introduction into unnatural hosts.

The organisms involved may belong to these categories:

1. i) Intergeneric organisms ii) Well defined organisms with non-coding regulatory regions
2. i) Biological agents whose source of DNA is a pathogen ii) Organisms that are generally recognised as non-pathogenic and may imbibe the characteristics of a pathogen on genetic manipulation.

2.

Classification of a pathogenic microorganisms

2.1 The classification of infective microorganisms are drawn up under 4 risk groups in increasing order of risk based on the following parameters:
 pathogenecity of the agent  modes of transmission and host range of the agent  availability of effective preventive treatments or curative medicines  capability to cause diseases to humans/animals/plants  epidemic causing strains in India

The above mentioned parameters may be influenced by levels of immunity, density and movement of host population, presence of vectors for transmission and standards of environmental hygiene.

An inventory of pathogenic organisms classified in different groups is provided in Chapter V: A1. The scientific considerations for assessment of potential risks in handling of pathogenic organisms include the following:

i) Characterisation of donor and recipient organisms ii) Characterisation of the modified organism iii) Expression and properties of the gene product

2.2 Based on the risk assessment information, the probability of risk could be further assigned certain quantitative values (Chapter V: A7) for categorisation of experiments in terms of the following:

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i) access factor of the organism ii) expression factor of DNA iii) damage factor of the Biologically active substance

3.

Containment

Containment facilities for different Risk Groups as per the recommendations of World Health Organization (WHO)

The term "Containment" is used in describing the safe methods for managing infectious agents in the laboratory environment where they are being handled or maintained.

Purpose of containment

To reduce exposure of laboratory workers, other persons, and outside environment to potentially hazardous agents.

Types of containment

3.1 Biological containment (BC): In consideration of biological containment, the vector (plasmid, organelle, or virus) for the recombinant DNA and the host (bacterial, plant, or animal cell) in which the vector is propagated in the laboratory will be considered together. Any combination of vector and host which is to provide biological containment must be chosen or constructed to limit the infectivity of vector to specific hosts and control the host-vector survival in the environment. These have been categorized into two levels - one permitting standard biological containment and the other even higher that relates to normal and disabled host-vector systems respectively (Chapter V: A3).

3.2 Physical Containment (PC): The objective of physical containment is to confine recombinant organisms thereby preventing the exposure of the researcher and the environment to the harmful agents. Physical containment is achieved through the use of i) Laboratory Practice, ii) Containment Equipment, and iii) Special Laboratory Design. The protection of personnel and the immediate laboratory environment from exposure to infectious agents, is provided by good microbiological techniques and the use of appropriate safety equipment, (Primary Containment).

The protection of the environment external to the laboratory from exposure to infectious materials, is provided by a combination of facility design and operational practices, (Secondary Containment).

3.3 Elements of Containment: The three elements of containment include laboratory practice and technique, safety equipment and facility design.

i)

Laboratory practice and technique:

 Strict adherence to standard microbiological practices and techniques

 Awareness of potential hazards

 Providing/arranging for appropriate training of personnel

 Selection of safety practices in addition to standard laboratory practices if required

 Developing of adopting a biosafety or operations manual which identifies the hazards

ii)

Safety equipment (primary barriers): Safety equipment includes biological safety cabinets and

a variety of enclosed containers (e.g. safety centrifuge cup). The biological safety cabinet

(BSC) is the principal device used to provide containment of infectious aerosols generated by

many microbiological procedures. Three types of BSCs (Class I, II, III) are used in

microbiological laboratories. Safety equipment also includes items for personal protection

such as gloves, coats, gowns, shoe covers, boots, respirators, face shields and safety glasses,

etc.

iii) Facility Design (Secondary barriers): The design of the facility is important in providing a barrier to protect persons working in the facility but outside of the laboratory and those in the community from infectious agents which may be accidentally released from the laboratory. There are three types of facility designs: viz, the Basic Laboratory (for Risk Group I and II), the Containment Laboratory (for Risk Group III) and the Maximum Containment Laboratory (for Risk Group IV).

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4.

Bio-safety levels: It consists of a combination of laboratory practices and techniques, safety equipment

and laboratory facilities appropriate for the operations performed and the hazard posed by the

infectious agents. The guidelines for Microbiological and Biomedical Laboratories suggest four

Biosafety levels in incremental order depending on the nature of work. Additional flexibility in

containment levels can be obtained by combination of the physical with the biological barriers. The

proposed safety levels for work with recombinant DNA technique take into consideration the source of

the donor DNA and its disease-producing potential. These four levels corresponds to (P1
facilities approximate to 4 risk groups assigned for etiologic agents.

These levels and the appropriate conditions are enumerated as follows:

4.1 Biosafety Level 1: These practices, safety equipment and facilities are appropriate for undergraduate and secondary educational training and teaching laboratories and for other facilities in which work is done with defined and characterized strains of viable microorganisms not known to cause disease in healthy adult human. No special accommodation or equipment is required but the laboratory personnel are required to have specific training and to be supervised by a scientist with general training in microbiology or a related science.

4.2 Biosafety Level 2: These practices, safety equipment and facilities are applicable in clinical, diagnostic, teaching and other facilities in which work is done with the broad spectrum of indigenous moderate-risk agents present in the community and associated with human disease of varying severity. Laboratory workers are required to have specific training in handling pathogenic agents and to be supervised by competent scientists. Accommodation and facilities including safety cabinets are prescribed, especially for handling large volume are high concentrations of agents when aerosols are likely to be created. Access to the laboratory is controlled.

4.3 Biosafety level 3: These practices, safety equipment and facilities are applicable to clinical, diagnostic, teaching research or production facilities in which work is done with indigenous or exotic agents where the potential for infection by aerosols is real and the disease may have serious or lethal consequences. Personnel are required to have specific training in work with these agents and to be supervised by scientists experienced in this kind of microbiology. Specially designed laboratories and precautions including the use of safety cabinets are prescribed and the access is strictly controlled.

4.4 Biosafety level 4: These practices, safety equipment and facilities are applicable to work with dangerous and exotic agents which pose a high individual risk of life-threatening disease. Strict training and supervision are required and the work is done in specially designed laboratories under stringent safety conditions, including the use of safety cabinets and positive pressure personnel suits . Access is strictly limited.

A specially designed suit area may be provided in the facility. Personnel who enter this area wear a one-piece positive pressure suit that is ventilated by a life support system. The life support system is provided with alarms and emergency break-up breathing air tanks. Entry to this area is through an airlock fitted with air tight doors. A chemical shower is provided to decontaminate the surface of the suit before the worker leaves the area. The exhaust air form the suit area is filtered by two sets of HEPA filters installed in the series. A duplicate filtration unit, exhaust fan and an automatically starting emergency power source are provide. The air pressure within the suit area is lower than that of any adjacent area. Emergency lighting and communication systems are provided. All penetrations into the inner shell of the suit area are sealed. A double door autoclave is provided for decontamination of disposable waste materials from the suit area.

5.

Guidelines for rDNA research activities: The guidelines stipulate three categories of research

activities, These are:

5.1 Category I: Which are exempt for the purpose of intimation and approval of competent authority.
(i) The experiments involving self cloning, using strains and also inter-species cloning belonging to organism in the same exchanger group (Vide Chapter-V A4, A5).
(ii) Organelle DNA including those from chloroplasts and mitochondria. (iii) Host-vector systems consisting of cells in culture and vectors, either non-viral or viral containing
defective viral genomes (except from cells known to harbour class III, IV and special category etiologic agents listed under Chapter V: A1.

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5.2 Category II: Those requiring prior intimation of competent authority.
(i) Experiments falling under containment levels II, III and IV. (ii) Experiment wherein DNA or RNA molecules derived from any source except for eukaryotic viral
genome may be transferred to any non-human vertebrate or any invertebrate organisms and propagated under conditions of physical containment PC1 and appropriate to organism under study. (iii) Experiments involving non pathogen DNA vector systems and regeneration from single cells. (iv) Large scale use of recombinants made by self cloning in systems belonging to exempt category (e.g. E.coli, Saccharomyces, and B. subtilis)
5.3 Category III: Those requiring review and approval of competent authority before commencement.
(i) Toxin gene clonings : A list of toxins classified based on their potential toxicity is listed in Chapter V - A6. The number of plasmid toxin gene clonings at present going on are only three viz. B. subtilis and B. sphericus toxin genes are cloned in B. subtilis and cholera toxin genes and B. thuringiensis crystal protein genes cloned in E.coli K12. These toxins gene cloning are being done under PC1 and BC 1 Containment conditions. All toxin gene cloning experiments producing LD50 less than 50 ug/kg of body weight of vertebrates (Chapter V-A6) or large scale growing may be referred to Institutional Biosafety Committee (IBSC) for clearance.
(ii) Cloning of genes for vaccine production: e.g. Rinderpest and leprosy antigens. Rinderpest has been classified under Risk Group II in view of the common incidence of the disease in India, though it is listed under special category in the Centres for Disease Control & National Institute of Health (CDC-NIH) system. Similarly, leprosy afflicts a large segment of population which calls for concerted programme to control the disease by vaccination and detection at early stages through immunodiagnostic tests. The containment should be decided by Review Committee on Genetic Manipulation (RCGM) on a case by case basis on experiment utilising DNA from non-defective genomes of organisms recognised as pathogen. In view of no demonstrated risk from handling free M. laprae antigens, inactivated whole cells as well as antigens can be assigned to Risk Group I. The details of the rDNA technology in development of vaccines for human and animal health giving containment conditions for observance of safeguards in large scale operations are given in Chapter V-B.
(iii) Cloning of mosquito and tick DNA experiments should be prescribed on a case by case basis since these are natural vectors for certain endemic viral and parasitic diseases.
(iv) Genes coding for antibiotic resistance into pathogenic organisms which do not naturally possess such resistance.
(v) Introduction into cultured human cells of recombinant DNA molecules containing complete genes of potentially oncogenic viruses or transformed cellular genes.
(vi) Introduction into animal cells of unidentified DNA molecules derived from cancer cells or in vitro transformed cells.
(vii) Experiments involving the use of infectious animal and plant viruses in tissue culture systems. (viii)Experiments involving gene transfer to whole plants and animals. (ix) Cell fusion experiments of Animal cells containing sequences from viral vectors if the sequence
lead to transmissible infection either directly or indirectly as a result of complementation or recombination in the animals. For experiments involving recombinant DNA of higher class organisms using whole animals will be approved on case by case following IBSC review. (x) Transgenosis in animal experiments : Transgenosis method is used to transform animal cells with foreign DNA by using viruses as vectors or by microinjection of DNA into eggs and pre-embryos. The expression of an inserted gene can be influenced both by the regulatory sequences associated with the gene and the sequences present at the site of integration of host genome. At present, there is no way to control where a gene is inserted into the chromosome of either an animal or plant cell. Yet this site of insertion can affect not only the expression of the interested gene but also the regulation of the host cells- DNA e.g. by non-specific activation of cellular protooncogenes. (xi) All experiments involving the genetic manipulation of plant pathogens and the use of such genetically manipulated plant pathogens would require approval of competent authority (IBSC). (xii) Transfer of genes with known toxicity to plants using Agrobacterium tumefaciens or other vectors. Attempts are under way using Ti-plasmid, A. tumefaciens and other vectors to transfer toxinencoding genes that enable plants to make their own insecticide, resist infections or tolerate a variety of environmental stresses. Case by case clearance is needed though exemption may be made for the use of well characterized vectors and non-toxic genes. (xiii)In case of plant viruses, permission may be obtained only when it is known that there is a chance of non-species specific spread of infection to plants that could produce changes in pathogenicity,
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host range or vector transmissibility. The growth of whole plants, propagation of genetically manipulated organisms in plants, regeneration of plants from cells transformed by manipulated plant pathogen vector would require containment conditions that are elaborated in Chapter V: C2. (xiv)Experiments requiring field testing and release of rDNA engineered microorganisms and plants (Chapter V: C3). (xv) Experiments involving engineered microbes with deletions and certain rearrangements. (xvi)Diagnostics: No major risk can be foreseen on diagnostics involving in vitro tests. But for diagnostics involving in vivo tests, specific containment levels have to be prescribed on case by case basis. For example, tuberculin moiety could be cloned and used for in vivo hypersensitivity test as a diagnostic method. (xvii)Gene therapy for hereditary diseases of genetic disorders.

6.

Large scale experiments: Large scale production of bio-molecules from genetically engineered

microorganisms have not just been taken up in the country. However, the use of recombinant

organisms in large scale operations is expected in the near future.

6.1 In the guidelines, experiments beyond 20 litres capacity for research as well as industrial purposes are included in the category of large scale experimentation/operations.

6.2 For such activities it is recommended that one should seek approval of the competent authority as described in Chapter-III. In order to seek approval it will be necessary to furnish the relevant details in a prescribed format on the lines suggested by GEAC.

6.3 For good large scale practice (GLSP) as well as levels of containment, the following principles of occupational safety and hygiene will be applied.

i) to keep work place and environment exposure to any physical, chemical or biological agent to the lowest practicable level;
ii) to exercise engineering control measures at source and to supplement these with appropriate personal protective clothing and equipment when necessary ;
iii) to test adequately and maintain control measures and equipment ; iv) to test when necessary for the presence of viable process organisms outside the primary physical
containment ; v) to provide training of personnel vi) to formulate and implement local code of practice for the safety of personnel.

6.4 The following safety criteria are to be compiled with for good large scale practice:

i) The host organism should not be a pathogen, should not contain adventitious agents, and should have an extended history of safe use, or have built-in environmental limitations that permit optimum growth in the bioreactor but limited survival with no adverse consequences in the environment.
ii) The vector/insert should be well characterised and free from known harmful sequences; the DNA should be limited in size as much as possible to perform the intended function; should not increase the stability of the recombinant in the environment unless that is a requirement of the intended function; should be poorly mobilisable; and should not transfer any resistance markers to microorganisms not known to acquire them naturally if such acquisition could compromise the use of a drug to control disease agents in human or veterinary medicine or agriculture.
iii) The genetically manipulated organism should not be a pathogen and should be assessed as being as safe in the bio-reactor as the host organism, and without adverse consequences in the environment (Chapter V:B2)

6.5 The physical containment conditions that should be ensured for large scale experiments and production activities are given in Chapter V: B1.

7.

Release to the environment:

7.1 Depending on the types of organisms handled and assessment of potential risks involved appropriate containment facilities must be provided to ensure safety of worker and to prevent unwanted release in the environment.

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7.2 Biowastes resulting from laboratory experiments, in industrial operations should be properly treated so that the pathogenicity of genetically engineered organisms are either destroyed or rendered harmless before disposal in the environment. Special facilities should be created for disposal of experimental animals. All refuse and carcasses must be incinerated. Exemption/relaxation of safety measures on specific cases may be considered based on the risk assessment criteria.

7.3 For planned release of organisms into the environment, the following points should be taken into consideration: i) Geographical location, size and nature of the site of release and physical and biological proximity to man and other significant biota. In case of plants, proximity to plants which might be cross pollinated. ii) Details of target ecosystem and the predicted effects of release on that ecosystem. iii) Method and amount of release, rate frequency and duration of application. iv) Monitoring capabilities and intentions: how many novel organisms be traced, e.g. to measure effectiveness of application. v) Onsite worker safety procedures and facilities. vi) Contingency plans in event of unanticipated effects of novel organisms.

It is important to evaluate rDNA modified organism for potential risk prior to application in agriculture and environment. Prior to introduction of micro-organisms, properties of the organism, the possible interaction with other disease causing agents and the infected wild plant species should be evaluated. An independent review of potential risks should be conducted on a case by case basis prior to application. Details of points to be taken into account for risk assessment of genetically altered organisms while making proposals for release applications are given at Chapter V:D1. The bio-hazard evaluation of viral, bacterial, insecticidal agents for field applications are provided in Chapter V:C4. Development of organisms for agricultural or environmental applications should be conducted in a stepwise fashion, moving where appropriate, from the laboratory to the growth chamber and green house under containment conditions and good laboratory practice. It should be done under expert advice of competent authority with regard to the area to be covered taking into account the experimental design and condition of isolation. Release of any strain for field testing should be done with the permission of Genetic Engineering Approval Committee (GEAC) as mentioned at Chapter III.

Though, manipulation of plants under containment would not require regulatory clearance of GEAC, testing of altered plant material in the environment however should follow regulatory guidelines seeking experimental field use permit from GEAC even though prima facie, plant material appears safe to test under containment conditions. License for large scale release in case of genetically engineered plants tested pathogens is required.

8.

Import and shipment:

8.1 The import or receipt of etiologic agents and vectors of human and animal disease or their carriers is subject to the quarantine regulations. Permits authorising the import or receipt of regulated materials for research (e.g. toxin genes, hybridomas, cell cultures, organelle) and specifying conditions under which the agent or vector is shipped, handled and used are issued by the Review Committee on Genetic Manipulation while large scale imports for industrial use are regulated by Genetic Engineering Approval Committee and are mentioned in Chapter III. Safety testing may be required to ensure that it is far from risk.

8.2 The Inter-State shipment of indigenous etiologic agents, diagnostic specimens and biologicals products is subject to applicable packaging, labeling and shipping requirements specified for etiologic agents. Packaging and labeling requirements for Inter-state shipment of etiologic agents are summarised and illustrated in the rDNA booklet. All such shipments would need the clearance of Institutional Biosafety Committee mentioned in Chapter III.

9.

Quality control of biologicals produced by rDNA technology: The general regulations normally

applicable for biologicals are applicable to the recombinant DNA products. The specific relevant

aspects to a particular product should be discussed with the appropriate Government Agency on a case

by case basis.

9.1 A new license for the product or drug application would be required on products made of recombinant DNA technology even if the product is considered to be chemically and physically similar to the naturally occurring substance or previously approved product produced in conventional system.
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9.2 A recombinant DNA product demonstrated to be identical to normally occurring substance would not require toxicological and pharmacological data if the information is already available at dose levels of intended use but fresh clinical trials will be necessary on all such products.
9.3 The booklet prescribes the various control methods needed to establish the safety, purity and efficiency of rDNA products (Chapter V: B4).
9.4 Animal feeds: The prevention of food adulteration Act 1954 make it an offence to sell any material for use as a feeding stuff containing any ingredient which is deleterious to animals.
The use of stilbesterol, vitamin B12, antibiotics, direct or indirect sources of nitrogen such as urea and its derivatives, amino acids as additives in forage and animal feed to enhance nutritive effect are in practice. The possibilities of introduction of products derived by biotechnological process such as single cell protein, enzymes and also the growing interest in probiotics i.e. living organisms that are fed to animals to improve performance and use of micro-organisms as silage aids may find means to improve the overall health of animals. The control of these products is the same in principle whether they are produced by chemical or biotechnological process provided the purity criteria are met.
The products derived from animals for human consumption such as meat and milk should be free from any contaminants or residue effect resultant on the use of feed stuffs containing additives produced by biotechnological processes.
Figure 1: Importation and inter state shipment of human pathogens and related materials

Fig.1.1: Diagram illustrate packaging and labeling of etiological agents in volumes of less than 50 ml.

Fig.1.2: Diagram illustrate packaging and labeling of etiological agents in volumes of less than 50 ml.

Fig.1.3: Specify the colour and size of the lable which shall be affixed to all etiologic agents. Informating on any provisions of this regulatory requirements may be obtained from Institutional Biosafety Committee (IBSC)
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III. MECHANISM OF IMPLEMENTATION OF BIOSAFETY GUIDELINES

For implementation of the guidelines it is necessary to have an institutional mechanism to ensure the compliance of requisite safeguards at various levels. The guidelines prescribe specific actions that include establishing safety procedures for rDNA research, production and release to the environment and setting up containment conditions for certain experiments. The guidelines suggest compliance of the safeguards through voluntary as well as regulatory approach. In this connection, it is proposed to have a mechanism of advisory and regulatory bodies to deal with the specific and discretionary actions on the following:
a. Self regulation and control in the form of guidelines on recombinant research activities; and b. Regulation of large scale use of engineered organisms in production activity and release of organisms in
environmental applications under statutory provisions.

The institutional mechanism as proposed for implementation of guidelines is shown in organogram in Figure 2. Mainly it consists of the following:-
i) Recombinant DNA Advisory Committee (RDAC) ii) Institutional Biosafety Committee (IBSC) iii) Review Committee on Genetic Manipulation (RCGM) iv) Genetic Engineering Approval Committee (GEAC)

Scope and functions of advisory committee and statutory body

1.

Recombinant DNA Advisory Committee (RDAC): The Committee should take note of

developments at national and international levels in Biotechnology towards the currentness of the

safety regulation for India on recombinant research use and applications. It would meet once in 6

months or sooner for this purpose.

The specific terms of reference for Recombinant Advisory Committee include the following :
i) To evolve long term policy for research and development in Recombinant DNA research. ii) To formulate the safety guidelines for Recombinant DNA Research to be followed in India. iii) To recommended type of training programme for technicians and research fellows for making
them adequately aware of hazards and risks involved in recombinant DNA research and methods of avoiding it.

2.

Implementation Committees:

2.1 Institutional Biosafety Committee (IBSC)

Institutional Biosafety Committee (IBSC) are to be constituted in all centres engaged in genetic engineering research and production activities. The Committee will constitute the following:

(i) Head of the Institution or nominee (ii) 3 or more scientists engaged in DNA work or molecular biology with an outside expert in the
relevant discipline. (iii) A member with medical qualifications - Biosafety Officer (in case of work with pathogenic
agents/large scale use). (iv) One member nominated by DBT.

2.2 The Institutional Biosafety Committee shall be the nodal point for interaction within institution for implementation of the guidelines. Any research project which is likely to have biohazard potential (as envisaged by the guidelines) during the execution stage or which involve the production of either microorganisms or biologically active molecules that might cause bio-hazard should be notified to IBSC. IBSC will allow genetic engineering activity on classified organisms only at places where such work should be performed as per guidelines. Provision of suitable safe storage facility of donor, vectors, recipients and other materials involved in experimental work should be made and may be subjected to inspection on accountability.

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The biosafety functions and activity include the following:

i) Registration of Bio-safety Committee membership composition with RCGM and submission of reports. IBSC will provide half yearly report on the ongoing projects to RCGM regarding the observance of the safety guidelines on accidents, risks and on deviations if any. A computerised Central Registry for collation of periodic report on approved projects will be set up with RCGM to monitor compliance on safeguards as stipulated in the guidelines.
ii) Review and clearance of project proposals falling under restricted category that meets the requirements under the guidelines. IBSC would make efforts to issue clearance quickly on receiving the research proposals from investigators.
iii) Tailoring biosafety programme to the level of risk assessment. iv) Training of personnel on biosafety. v) Instituting health monitoring programme for laboratory personnel.

Complete medical check-up of personnel working in projects involving work with potentially dangerous microorganisms should be done prior to starting such projects. Follow up medical checkups including pathological tests should be done periodically, at least annually for scientific workers involved in such projects. Their medical records should be accessible to the RCGM. It will provide half yearly reports on the ongoing projects to RCGM regarding the observance of the safety guidelines on accidents, risks and on deviations if any.

vi) Adopting emergency plans.

3.

Review Committee on Genetic Manipulation (RCGM): The RCGM will have the following

composition:

i) Department of Biotechnology ii) Indian Council of Medical Research iii) Indian Council of Agricultural Research iv) Council of Scientific & Industrial Research v) Three Experts in Individual capacity vi) Department of Science & Technology

The RCGM will have the functions:

i) To establish procedural guidance manual - procedure for regulatory process with respect to activity involving genetically engineered organisms in research, production and applications related to environmental safety.
ii) To review the reports in all approved ongoing research projects involving high risk category and controlled field experiments, to ensure that safeguards are maintained as per guidelines.
iii) To recommended the type of containment facility and the special containment conditions to be followed for experimental trials and for certain experiments.
iv) To advise customs authorities on import of biologically active material, genetically engineered substances or products and on excisable items to Central Revenue and Excise.
v) To assist Department of Industrial Development, Banks towards clearance of applications in setting up industries based on genetically engineered organisms.
vi) To assist the Bureau of Indian Standards to evolve standards for biologics produced by rDNA technology.
vii) To advise on intellectual property rights with respect to rDNA technology on patents.

3.1 The RCGM would have a Research Monitoring function by a group consisting of a smaller number of individuals (3 or 4). The monitoring group would be empowered to visit experimental facilities in any laboratory in India where experiments with biohazard potential are being pursued in order to determine the Good Laboratory practice and conditions of safety are observed.

3.2 In addition, if the RCGM has reasons to believe that there is either actual or potential danger involved in the work carried out by any laboratory (which might or might not have obtained prior clearance for the project), the monitoring group would be empowered to inspect the facility and assess the cause of any real or potential hazard to make appropriate recommendation to the RCGM. RCGM would be empowered to recommend alteration of the course of experiments based on hazard considerations or
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RECOMBINANT DNA SAFETY GUIDELINES, 1990 Department of