REGISTRATION OF BIOPESTICIDES: CURRENT SCENARIO Biopesticides offer considerable scope as plant protection agents.

The role of microbials has expanded in crop and forest pest control with the discovery of new agents and genetic improvement in bacterial and viral pathogens and with the improvements in formulation, application options and compatibility with other interventions. The status of microbials has been periodically reviewed in India for their potential role in pest management. At present biopesticides comprise only a very small part of the crop protection sector in India.

Economic feasibility A biological control tactic with great capability to reduce pest populations may not be economically feasible, by the same token, one that has only modest impact on the target pest may be a cost effective control alternative. Biological control always results in a reduction in social costs of pest control. Social and environmental costs saved include: (a) water and soil pollution from pesticides (b) detrimental effects on non-target organisms, birds, fish, other wild life population; (c) possible health hazards associated with chemical residues and (d) development of pesticide resistant populations. The ecological and economic factors determining the feasibility of biological control interact to determine the expected net revenue to the producer from the use of a biological alternative. Ascendancy of biopesticides In the 1960s pharmaceutical companies were pioneers in the development and marketing of the biopesticides. Their interest particularly in the Bt led to the development and commercial introduction of it as a biopesticides. Currently Abbot Laboratories and Novartis combine to control 80-90% of the Bt market. Recently, agrochemical companies have taken greater interest in biopesticides. Most markets for conventional pesticides have been growing much more slowly than in the past. The procedures of re-registration and use-reduction programs have been depressing their sales. The participation in the low to medium scale biopesticides business such as natural enemies, nematodes and other products involves low-risk. Although profits may be small, the losses are likely to be

restricted. The global insecticides market was estimated at $ 8 billion in 1995. The estimated market for biopesticides was $ 380 million and upto $ 119 million for microbial insecticides. In 1991, the microbial insecticide market was estimated at $ 71 million. This represents 80% growth in four years. By 2000 AD the market for microbials is expected to exceed $ 141 million. The contribution of these microbials among the pesticides will be 1.4% (Wood Mackenzie Report, 1995). The advent of agricultural biotechnology has opened avenues for capitalists and entrepreneurs to develop innovative methods that would overcome the perceived limitations of biopesticides. Thus we see considerable research aimed at increasing speed of kill biopesticides. Biocontrol agents especially the entomophages have additional opportunities of host finding and reproduction, which make them superior to chemicals. Hence genetic improvement is given greater impetus. Today in the world the following are the biopesticides available in different trade names. Potential Biopesticides and Major Target Groups Pathogen Bacteria: Bt CryIA-G, CryIIAiC, CryIII A-D, Lepidoptera, CryIVA-D, CryIIA Simulidae B. sphaericus Viruses: NPV GV Fungi Beauvaria bassiana Metarhizium anisopliae Verticilium lecanii Microsporidia Nosema Vairimorpha Lepidoptera, Hymenoptera, Lepidoptera Coleoptera, Lepidoptera, Orthoptera Coleoptera, Lepidoptera, Orthoptera Homoptera, Thysanoptera Homoptera, Homoptera, Culicidae Coleoptera, Culicidae, Major Target Groups

Lepidoptera, Orthoptera Lepidoptera

Microbial Insecticides and Patent Protection Patent protection is crucial for a company to have serious business interest in a product. Without the ability to protect an invention, there is a risk that other companies may copy it resulting in a number of basically identical compounds/products ultimately competing against each other for the same area of business. Historically biocontrol agents works has been conducted in State Agricultural Universities and Government Laboratories. The non-proprietary nature of the products makes it more or less like a commercial business. The laws on patent differ from one country to another. The general concept in patenting require: a. the invention is new; b. it involves industrial application;

c. it is not excluded by one of a number of exclusions under the patent act. The General Agreement on Tariffs and Trade has made it more comprehensive. The 1997 Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the purpose of patent protection lists a number of international depository authorities to which nationals of the signatories to the treaty may deposit the strains of microorganisms. They will have to satisfy the disclosure requirements of their patent application. In the present scenario patenting will have to run concurrently or simultaneously while registration is being done.

Registration of Biopesticides The registration of microbial pesticides is similar in many of the countries where the agents have been developed. The processes have evolved from the existing requirements of chemical pesticides but in light of the experience have been modified to take account of the biological nature of the active ingredients involved. There are two classes of biological and biologically derived pesticides. a. Microbial Pest Control Agents (MPCAs): Pesticides referred to this category include (but are not limited) bacteria, viruses, fungi and protozoa as defined in the

40CFR162 of the EPA. The guidelines apply to all MPCAs used as pest control agents that are naturally occurring, but also those strains that are improved either by natural selection or by deliberate genetic manipulation. b. Biochemical Pest Control Agents (BPCAs): They generally fall into four functional categories. Semiochemicals, hormones, natural plant regulators and enzymes. The testing protocols here is different compared t the former category as in the former the case the MPCAs may survive and reproduce in the environment and may infect or cause disease in other living organisms where as in the latter case there is no self replicating properties. The first microbial pesticide Bacillus popilliae was registered in 1948. During the late 1960s and early 1970s there was general awareness on the intangible benefits the users can derive with the microbial pesticides which led to the synthesis of public driven research on microbial pesticides. As early as 1978, at an EPA symposium Viral Pesticides: Present Knowledge and Potential Effect on Public and Environmental Health the need for sensitive identification and detection methods for microorganisms as well as quality assurance provisions were clearly identified. Rogoff (1982) has reviewed the development of guidelines for the registration of microbial pesticides in various countries. Guidelines are available including those developed by the European Economic Community (EEC, 1980), the International Organization for Biological Control of Noxious Animals and Plants regarding Baculoviruses, fungi and bacteria and the Environment Protection Agency of the USA. In the UK the Pesticides Safety Directorate and the Health and Safety Executive administer the registration of all pesticides, including the microbial pesticides. The EPA guidelines involve a tier testing approach. The first tier provides a maximum challenge and progression to a further tier is necessary if as hazard is detected in the first tier Betz et al.(1989) summarized the requirement under the US law for full as well as experimental use permit. The data requirements were

Product analysis Tier I: Toxicology Tests Tier II. Environmental Fate Tier III. Ecological effects and Tier IV. Simulate and/or actual terrestrial or aquatic field studies.

Indian Scenario In India pesticide manufacturing requires registration of the product with the Central Insecticides Board Registration Committee, Department of Plant Protection and Quarantine, Ministry of Science and Technology, Government of India. Under the section 9(i) of the Insecticides Act 1968 any person desiring to import or manufacture an insecticide included in the schedule annexed to the Insecticides Act, has to apply for the registration of the product to the Registration Committee. Different kinds of classifications are in practice in India for the registration of plant protection agents. 1. Provisional Registration (Section 9(3)b of the Insecticides Act) Any product that needs to be registered for the first time in India can be applied under this section, wherein the required data need to be submitted except for long-term studies. A conditional registration will be granted under this special approval for even commercializing the product. A time span of two years will be given at the time of registration before which the entire data pending henceforth should be generated and submitted. 2. Permanent Registration(Section 9(3)b of the Insecticides Act) Once the entire pending data on long-term basis is generated the same may be submitted the based on which the permanent registration will be granted. This makes commercialization of the product automatically eligible. The generation is valid till further review.

Recently Indian market has been flooded with bacterial preparations for use in agriculture and public health. The data requirement for registration of Bacillus thuringiensis and B. sphaericus for pest control and vector control has alone been approved by the CIB&RC as per the approval of the government in its notification No.7-5/91-CR.II dtd.7.10.91 of the Secretary, CIB &RC. The schedule has in expression not included the viruses. Accordingly the manufacturer is required to submit the data for the following categories: Part A A. Chemistry/Product Characteristics 1. Physicochemical specifications and composition 2. Systematic name and strain 3. Common name 4. Natural occurrence of the organism, its relationships with other species and history 5. Manufacturing process 6. An appropriate test procedure and criteria used for the identification such as morphology, biochemistry and or serology/immunology 7. Method of analysis B. Bioefficacy Laboratory Tests: For registration of microbial pesticides LC50 or LD50 values for each test insect species should be generated. The data is required from

DST/ICAR/CSIR/ICMR and SAUs etc. for the purpose C. Toxicity 1. Single exposure/pathogenicity 2. Repeated exposure/pathogenicity 3. Supplementary toxicity/pathogenicity D. Processing, Packaging and Labeling 1. Manufacturing process

2. Packaging 3. Labels and Leaflets Part B B. Data requirements for the registration of formulated material 1. Physical and chemical properties 2. Quantities of active ingredient 3. Name and type of the formulation 4. Nature and quantities of the diluent 5. Purpose and identity of the non active ingredients 6. Stability of product and effect of temperature and storage conditions on biological activity 7. Method of analysis B. Bioefficacy tests: Laboratory Tests: For registration of microbial pesticides LC50 or LD50 values for each test insect species should be generated. The data is required from DST/ICAR/CSIR/ICMR and SAUs etc. for the purpose C. Field Tests: The data on the bioefficacy based on two seasons/two years trials under different agroclimatic conditions in form of published/authentic data is required to be submitted. E. Information on phytotoxicity F. Data on persistence G. Data on residues H. Compatibility I. Time of application J. Data on non-target organisms.

The implications In India the estimated demand for the biopesticides is increasing day by day. Due to the effort of the Industries Bt has been registered and introduced into the market. However, the NPVs are not included in the schedule. The requirements for the NPVs of Helicoverpa armigera and Spodoptera litura is enormous and estimated at 4.26x1023 and 1.59x1023POBs respectively even to fulfil the requirements of 10% cropped area (Sathiah and Jayaraj, 1996). In the absence of any registration, which will enforce the manufacturers to follow stringent measures, it becomes needless to state that the quality will be sacrificed on one hand and will lead to the introduction of spurious and substandard products in the market on the other. Ultimately the agents while striving to establish as an alternative for exploitative chemicals will be weaned away from the market. Also there are instances when the BV preparations produced elsewhere in other countries tested for hazardous nature were found to contain harmful microorganisms like Shigella, Salmonlella etc. These reports underscore the need for registration Future Thrust The registration of BVs is pending in India for quite some time. Principally the SAUs and Research Institutions of GOI have carried out the researches on the BVs. This suggests that the registration can not be expected to be done by the Industries where the data development is totally lacking. Following the USDA model a situation may arise wherein the State and Central sponsored Institutes may take up the registration.