Chapter 32
GLP National Status and Facilities in India for Pesticide Product Registration B. Vasantharaj David
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Jai Research Foundation, P.O. Valvada—396 108 Gujarat, India
This paper defines the principles of Good Laboratory Practice (GLP) and traces the history of GLP worldwide. In India, the usage of synthetic pesticides commenced in 1948. The history of the enactment of the Insecticides Act in 1968 and the Rules in 1971 has been outlined. In 1978, the subcommittee on pesticide toxicology was constituted under the chairmanship of Dr. Β. B. Gaitonde, and it finalized the guidelines for data requirements for registration of pesticides in India. The concept of GLP in India was initiated in 1983. The necessity for GLP laboratories in India wasfeltto promote export for Indian companies and also make available data generation to GLP at a reasonable price. GLP facilities in India established in 1992 by Rallis Research Centre and in 1996 by Jai Research Foundation have also attracted the global market. The problems and challenges in implementing GLPs in India and the prospects of GLP facilities in India are discussed.
History Good Laboratory Practice (GLP) basically aims at the philosophy of laboratories carefully documenting all activities of designing, performing and reporting safety studies on chemicals and preparations under strict monitoring by an internal independent quality assurance system thus enabling reconstruction of the studies at any time afterwards (1-2). Though laboratories observed 'Good Laboratory Practice' for years, only in the early 1970s its application to control laboratories by the Government began. In 1973, New Zealand was the first country to promulgate the Testing Laboratory Registration Act, and in March 1973 similar legislation came into force in Denmark.
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© 1999 American Chemical Society
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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279 In August 1976, the FDA released a draft set ofGLPsand the proposed GLP regulations were published on 19 November 1976 in the Federal Register. The final GLP regulations were published in the Federal Register on December 22,1978, which became a legal entity in the U.S. on 20 June 1979. On 24 October 1984 changes to the US GLPs were proposed and published as revised good laboratory practice regulation on 4 September 1987 in the Federal Register entitled "Good Laboratory Practice Regulations, The final Rule". However, proposed GLP standards relating to pesticides were published by EPA under FIFRA in April 1980 (45 FR 26373). EPA Final Regulations were enforced in November 1983 (FIFRA : 40 FR 53946). In 1987 the proposed Amended Regulations under FIFRA were issued as 52 FR 48920 (9). In 1978, the OECD set up a special program on the control of chemicals. One of the first priorities of this program was the creation of means to facilitate the generation of valid and high quality test data for the assessment of chemicals. Expert groups were set up to develop guidelines for the testing of chemicals on one hand and principles of GLP on the other. In 1981, the OECD council adopted a decision concerning the mutual acceptance of data in assessment of chemicals [C(81) 30 (final)]. The first legal measure of EEC level was the adoption of the Council Directive of 18 December 1986 on the harmonization of laws, regulations and administrative provision relating to the application of GLP principles and the verification of their application for tests on chemical substances (87/18/EEC). The second EEC measure came with the adoption of Council Directive of 9th June 1988 on the inspection and verification of GLP (88/320/EEC). In Japan, the Agricultural Production Bureau of the Ministry of Agriculture, Forestry and Fisheries introduced GLP regulations for pesticides under the Agricultural Chemicals Regulation Law, 1948 in October 1984. Indian Scenario Synthetic pesticide usage had a beginning in India with the introduction of DDT for malarial control shortly after the second world war, followed by locust control with HCH (BHC) in 1948 (J). After that the usage of pesticides increased in many areas. From the beginning, the importance was given to the effectiveness of pesticides without taking into consideration the toxic effects on their non-target areas before use. The adverse effects caused by improper handling of pesticides during manufacture, transport, storage and sale, and indiscriminate use by the farmers and other users necessitated the regulation of pesticides by registration to prevent risks during manufacture, transport, sale and use. During April and May 1958, many persons died in the states of Kerala and Tamil Nadu (Madras) as a result of food poisoning arising from contamination of food with the organophosphorus insecticide ethyl parathion. The Government of India appointed the Kerala and Madras food poisoning cases enquiry commission under the chairmanship of Justice J.C. Shah, the Judge of
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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280 the High Court of Bombay at that time, to inquire into and report on the circumstance under which the food stuff came to be contaminated and the preventive measures to be taken against similar occurrences in the future. The long term measures suggested by the commission envisaged the enactment of legislation to regulate manufacture, sale, storage, transport, distribution and use of pesticides (insecticides, fungicides, herbicides, etc.) in the country. The occurrence of these poisoning cases due to pesticides were not the only ones: there were many cases thereafter. In 1968 an act, "The Insecticides Act, 1968" was accorded the President's assent on September 2, 1968, but became enforceable on October 31, 1971. During 1978, a subcommittee on pesticide toxicology, chaired by Dr. B.B. Gaitonde, which was constituted by the Registration Committee of the Central Insecticides Board, Ministry of Agriculture, New Delhi, finalized guidelines for data requirements for registration of pesticides in India and protocols for generating toxicity and chemistry data for pesticide registration. The data were generated by Universities, National Laboratories, and reputed laboratories like the Jai Research Foundation, the Rallis Research Centre, and the Fredrick Institute of Plant Protection and Toxicology. Necessity for GLP Laboratories in India In 1991, the EEC Council Directive 91/414/EEC was issued concerning the placement of plant protection products on market, and required that the member states could not authorize a plant protection product unless certain requirements were satisfied in accordance with uniform principles provided for in Annex VI of that document. The aim of the directive was to establish and harmonize the data requirements in all the EC member states with respect to authorization of plant protection products. About 89 active substances were scheduled for review under commission regulation EEC No. 3600/92. Indian industries, having shown capabilities for process development for various pesticide molecules, posed a threat to international manufacturers on quality and price. However, they faced problems for export as they had to invest heavily in order to generate data in compliance with Good Laboratory Practices (GLP) from laboratories abroad for registration purposes. Further, due to recent export policies, apart from the agrochemical and pharmaceutical industries, even the dye manufacturers are in need of laboratories certified to GLP. The need for Good Laboratory Practices (GLP) in India was thus felt. GLP in India The concept of GLP in India was initiated during 1983 and published in the official gazette. This concept is also similar to OECD principles of GLP, giving scope of definition, testing facilities, management, personnel, QA program, SOPs, facilities for handling test substance and their control, test system, equipment, maintenance and calibration of equipment. However, no major progress was made toward implementing this concept (4).
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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281 During November 1994, a workshop on GLP was organized by the Hindustan Levers Limited and the Council of Scientific and Industrial Research, Government of India at New Delhi. The workshop recommended the establishment of an Indian GLP monitoring and certifying agency. However, there was no progress. During December 1995, a one day workshop on GLP (Good Laboratory Practices - an Introduction and Update) was organized at Jai Research Foundation (JRF) where scientists, industrialists and academia from all over India participated. On March 22, 1997, a program was held at JRF when Nigel J. Dent of Country Consultancy, U.K., and Dr. Theo Helder of the Ministry of Health, Welfare and Sport, the Netherlands, gave a talk on Quality Assurance and GLP monitoring, respectively. On February 8, 1997, a seminar on GLP was organized by the Fredrick Institute of Plant Protection and Toxicology (Fippat), Padappai, which was chaired by Dr. R.L. Rajak, Plant Protection Advisor to the Government of India, and Mrs. Rose Brookes, Quality Assurance Manager, CSL, Hutton, York, delivered the key note address. It was resolved that the Director of the Central Insecticides Laboratory and his team would take the initiative for creating a national GLP inspection authority. On August 30, 1997, Fippat organized another meeting in which Dr. David Moore, Chief of the GLP Monitoring Authority, U.K., delivered a key note address, and experts from the Department of Science and Technology (DST), Central Insecticides Laboratory and Indian Council of Medical Research participated. The meeting recommended creation of a national GLP Monitoring Authority under the DST and suggested a delegation to meet the Secretary, DST, in this regard. During the late 1980s, the Department of Science and Technology, Government of India, set up the National Coordination of Testing and Calibrating Facilities (NCTCF). Thereafter, in 1992, it was felt necessary to align the Indian Laboratory Accreditation program to international norms. In the same year, the National Accreditation Board for Testing and Calibration Laboratories (NABL) in the place of NCTCF was formed, which is in line with ISO/IEC Guide 25 (1990) and also aims to bring the criteria in line with requirements of Europe as in EN 45001 (1989). NABL maintains its linkages with die international bodies like International Laboratory Accreditation Conference (ILAC) and the Asia Pacific Laboratory Accreditation Co-operation (APLAC) by participation in their conferences. The testing and calibration in India are being accreditated by NABL at present. Though private laboratories are being accredited by NABL, it is envisaged in the near future that national laboratories may also be required to fall in line with NABL accreditation. GLP Facilities in India In India, very few laboratories, except the Jai Research Foundation (received GLP certification in 1996 from the Veterinary Public Health Inspectorate, GLP Section, pursuant to the Netherlands GLP Compliance Monitoring Programme, Ministry of Health, Welfare and Sport, State Supervisory Public Health Service, Government of
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
282 The Netherlands) and the Rallis Research Centre (received GLP certification in 1992 from the German Health Ministry, BGVV) conduct studies in accordance with international GLP principles. Contract Services. Today, the facilities compliant with GLP in India can offer contract services on the following:
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Bioefficacy including phytotoxicity and compatibility meeting Good Field Practices Physico-chemical analysis Residue studies Environmental fate studies Metabolism studies Toxicology including acute, subchronic and chronic studies; genetic and reproductive toxicology Ecotoxicology Biomonitoring exposure of workers
Third Party Laboratory Accreditation. Quality Assurance Services, Australia, an independent body, has certified three laboratories in India viz., Jai Research Foundation, Vimta labs. Ltd. (for toxicology and chemistry) and Gharda Chemicals Ltd. (for chemistry) as complying with the requirements of GLP. The implications, status and significance of such third party accreditation in relation to international acceptance of the study data is not fully understood. Problems and Challenges The problems and challenges one has to face in implementing GLPs in India are outlined briefly. GLP Certification and Monitoring. At present no GLP certification and monitoring system exist in India. However, recently the Adviser from The Department of Science and Technology (DST) has been impressed on the need to create a GLP monitoring Authority in India and hopefully it should take shape soon. In India, the registration of pesticides comes under the Ministry of Agriculture, and the guidelines for data generation have been laid out by the B.B. Gaitonde committee appointed by the Ministry of Agriculture. In order to have a GLP monitoring system implemented in India it is essential that the existing protocols defined by the Dr. B.B. Gaitonde committee and approved by the Ministry of Agriculture be required to be statutorily revised to fall in line with the international guidelines. Recently, the Ministry of Agriculture has constituted committees to address these concerns. The Indian laboratories have to cope with certain difficulties, such as, power cuts; irregular supply of basic items like quality animal feed supported by feed analysis reports; obtaining the services of Veterinary pathologists experienced in
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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283 rodent pathology; difficulty in getting animals of required age and weight within short time frames from the Indian suppliers (a herculean task to get an import license for the animals from abroad); difficulty in getting certain instruments calibrated as calibration facilities are limited in India; problems faced in explaining to Indian sponsors the time and investment needed to generate data in compliance with GLP; sometimes adequate basic information on test substances is not provided by the sponsors and must be obtained before commencement of the study; and delays in obtaining the permits from the Central Insecticides Board for importing samples from abroad. Prospects in India Many Indian companies will have the opportunity to utilize the facilities and expand their export market. Being competitive in price will attract a considerable amount of contract work from sponsors from different countries whose cost of data generation is highly prohibitive or who do not have laboratories that comply with the GLP standards. The capability of providing the complete acute toxicology studies and the physico-chemical and analytical chemistry services would make contract facilities in India indispensable, competitive and attractive. Many pharmaceutical R&D labs also have started implementing GLP programs for in-house evaluations of new drugs. The Government of India, in the near future, will probably insist that data generated in Indian laboratories follow GLPs. Under these circumstances, the GLP facilities will become indispensable in the country. The Government of India soon will be establishing an Inspectorate for monitoring and certifying laboratories for GLP compliance. Acknowledgments Thanks are due to Mr. R.D. Shroff, President, and Mrs. Sandra R. Shroff, VicePresident, JRF, for encouragement and support in the establishment of a GLP program in JRF and for providing the opportunity to attend the conference at Cancun, Mexico. Literature Cited 1. 2.
3. 4.
Good Laboratory and Clinical Practices; Carson, P.A; Dent, N.J., Eds.; Heinemann Newnes, 1990, pp 390. Broad, R.D; Dent, N.J. An introduction to good laboratory practice (GLP) in Good Laboratory and Clinical Practices; Carson and Dent, Eds.; Heinemann Newnes; 1990; p 3-15. David, Β. V. Pesticide Industry in India. In Indian Pesticide Industry, David, B.V., Ed.; Vishvas Publications, Madras, 1981, pp 1-36. Kanungo, D. Good Laboratory Practices (GLP) - an Introduction and Update -training programme at JRF on 4th December 1995 - Inaugural address. Indian J. Environ. & Toxicol.; 5(2): pp 49-50.
In International Pesticide Product Registration Requirements; Garner, W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
