R. S. Mahwar · N. K. Verma · S. P. Chakrabarti · D. K. Biswas
Development and use of reference materials in India – status and plans
Received: 23 May 1997 / Revised: 9 July 1997 / Accepted: 12 July 1997
Abstract Reference materials development activities in India started during the period 1955–1960 for quality control in the production and use of drugs and pharmaceuticals. While the practice of import and distribution gradually accelerated in some areas, including medical, environment etc., the earliest known development of Certified Reference Materials (CRMs) within the country began with the preparation of metallurgical CRMs somewhere around 1965. A few more area-specific programs involving preparation of CRMs for quality control in the electronic industries, food and food products etc., began in the past decade. A common national program covering these activities was initiated in 1996, through organization of a national workshop on the subject and formation of a National Task Force for the development and use of reference materials in the country. The existing status and the priority needs of reference materials have been compiled by the Task Force, and a program has also been prepared for development of some of the urgently required CRMs within the country.
Introduction The earliest known use of proper reference materials in India was in the area of drugs and pharmaceuticals nearly forty years ago. The country has since then been importing reference materials for use in different areas, like drug control, environmental monitoring etc.. Some programs for the development of CRMs within the country also began in specific areas in the past three decades. This includes metallurgical CRMs and solutions of metals in high-purity water. However, the meaningful development, which led to the formulation of a common program for the development and use of reference materials in the country,
was the study conducted by the Central Pollution Control Board (CPCB) Delhi in 1990–91 to look for the world sources of the availability of reference materials for metals and organics, to help procurement of these standards by the environmental laboratories in India. CPCB is the national apex body for all environmental matters in India and its responsibilities include technical assistance to state level regulatory agencies which are in-turn responsible for the implementation of the environmental legislation in their respective states. The findings of the above study were not only documented  and made available to all the state level environmental agencies, but also presented  at the Sixth International Symposium on Biological and Environmental Reference Materials (BERM-6), held at Hawaii, USA in April, 1994. This followed organization of a national workshop on “Development and Use of Environmental Reference Materials (DUERM-1)” in February, 1996 at New Delhi, which resulted in the formation of the National Task Force for Reference Materials (REMTAF) Development and Use in India. The REMTAF has already compiled the status and plans concerning reference materials requirement and development in different areas, and also the future course of action to be taken in this regard. This paper presents details of RM programs which have occurred in the past forty years in India, details of the developments which led to the formation of REMTAF, its role and activities, the priority needs of reference materials, plans of the different agencies concerning reference materials, and details of the proposed national program for the development of CRMs in the country.
Areawise programs on reference materials Drugs and pharmaceuticals
R. S. Mahwar (Y) · N. K. Verma · S. P. Chakrabarti · D. K. Biswas Central Pollution Control Board, Parivesh Bhawan, East Arjun Nagar, Delhi-110 032, India
The Cental Drugs Laboratory (CDL), Calcutta, of the Drugs Control Department, Govt. of India, has been importing Pharmacopoeia Reference Standards (USP, BP etc.) and distributing these to the drugs testing laborato-
ries and industries, free of cost since 1960. However, the demand has increased many times and the department is trying to work out some alternatives to the practice of import and distribution for quite some time. The Drugs Controller General of India has finally constituted a sub-committee in 1996 to look into these problems, and the immediate decisions taken include, (i) identification of 143 priority items for preparation of reference standards and distribution in the country, and (ii) identification of 20 companies for preparation of these reference standards as per the prescribed standard methods. A portion of lots prepared by these companies will be analyzed by CDL, and in case meeting the required quality, it will be retained at CDL, as Indian Pharmacopoeia Reference Standards (IPRS). The rest of the materials remaining with the companies can be sold by them as Certified Working Reference Standard (CWRS). Metallurgical operation The National Metallurgical Laboratory (NML), Jamshedpur, of the Council of Scientific and Industrial Research (CSIR), Govt. of India, has been preparing certified reference materials for metallurgical purposes for about the past three decades. The certification is based on the interlaboratory testing approach, and the institute is presently in a position to offer 50 CRMs of ores, alloys, refractories, steels etc.. The CRMs which are involved in the current certification exercise include brass and iron ore.
Coastal monitoring The centre for Marine Analytical Reference and Standards (C-MARS), of the CSIR’s Regional Research Laboratory (RRL), Trivandrum, has prepared sea water certified for lead and cadmium through an interlaboratory testing method. The institute has plans to prepare CRMs of sea sediments and shrimp certified for toxic metals. Microbiological measurements There is no known program existing in India for the preparation of microbiological CRMs till now. However, there are a number of Microbial Culture Collection Centres established in the country. The largest among these is the “Microbial Type Culture Collection (MTCC) and Gene Bank”, established by the Govt. of India in 1986 at the Institute of Microbial Technology (IMT), Chandigarh. MTCC is presently in a position to supply nearly 2600 reference strains of actinomycetes, bacteria, fungi, yeasts and plasmids. The other major centres include the National Salmonella and Escherichia Centre (NSEC), established at the Central Research Institute (CRI) Kasauli. In addition to the reference cultures of salmonella, NSEC also supplies national reference standards (which are standardized against international reference standards) for vaccines/sera to indigenous manufacturers and their quality control laboratories free of cost. Food and food products
Environmental monitoring The Central Pollution Control Board has been importing reference standards of metals and pesticides from US, EPA, and manufacturers, such as BDH, U.K. and Promochem, Germany. A program for the preparation of standard calibration gas mixtures has also been taken up for the past five years through establishment of the “Static-Injection System (SIS)” in the CPCB’s laboratory at Delhi, with the help of experts from Hesse State Environmental Protection Agency (HLFU), Germany. The SIS system has already been commissioned, and gas mixtures of CO, NO and methane in nitrogen, and SO2 in air, have been prepared by the multimethod certification approach. The mixtures are being further subjected to the interlaboratory testing exercise. Geophysical research The National Geophysical Research Institute (NGRI), Hyderabad, a CSIR laboratory, has prepared two rock standards (granite and dolerite) through the interlaboratory testing method. Preparation of one more standard of dunite rock through participation of 25 laboratories from 17 countries is nearly complete.
The CSIR’s Central Food Technological Research Institute (CFTRI), Mysore has prepared CRMs of milk powder certified for lead, cadmium, arsenic and chromium through an interlaboratory testing method. The institute has now planned to prepare more such CRMs covering a wide range of food materials. Occupational health The National Institute of Occupational Health (NIOH), Ahmedabad, a central research institute of the Indian Council of Medical Research (ICMR), Govt. of India, has been procuring priority CRMs concerning occupational health, from IAEA, Austria, and NIST, USA. NIOH is extensively involved in internal quality assurance programs for which it has prepared AQC samples of nickel in chocolate in the past. The institute has now planned to prepare blood CRMs certified for lead and cadmium. General standards The National Physical Laboratory (NPL), New Delhi, is extensively involved in the preparation of CRMs of metals in high purity water, for the last 10 years. The CRMs
are prepared through an interlaboratory testing certification method and sold as “Indian Reference Materials” or ”Bharatiya Nirdeshaka Dravya” (BNDs).
National program Beginning of the program development process The formation of the national reference material program in India started with the CPCB’s participation in BERM-6
in 1994. The exposure and inputs received through discussions held at BERM-6 helped to identify the immediate steps the country needs: (i) taking stock of the existing situation, (ii) extensive discussions on “Preparation and Role of CRMs” among the experts, and (iii) deciding the future course of action for meeting the priority needs of reference materials in the country. CPCB, therefore, organized DUERM-1 in February 1996, at New Delhi. Although CPCB activities involve environmental measurements only, the organization of DUERM-1 1996 was made known to over 1000 organizations in the country,
Table 1 Priority needs for reference materials in India S.No. Area/Matrix 1.0 1.1
Analytes of interest
1.2 1.3 1.4 1.5
Environment Inland surface water (rivers, lakes etc.) Coastal water Ground water Industrial effluents Hazardous wastes (process wastes, sludge from ETPs etc.)
Fly ash Sediments (rivers, lakes, coastal)
Soils Industrial/vehicular emissions, ambient air
Industrial raw materials and products Metallurgical products
Oil and petroleum products
Drugs and pharmaceuticals
Mineral acids and caustic soda
Food, food products
4.0 4.1 4.2 4.3 4.4
Agriculture Produce Fertilizers Biofertilizers Compost, manure
Environment Industrial effluents, emissions, solid/hazardous waste Inland surface water including sediments Ground water Ambient air Coastal water, sediments Soil/rocks Industrial raw materials and products Metallurgical products Oils, petroleum products Drugs, pharmaceuticals Food, food products Agriculture Biological Biomedical Microbiological General Solutions of trace metals Pure pesticides, PAHs, PCBs etc. and their solutions Gas mixtures
covering almost all areas of analytical measurements, to all the participants of BERM-6, and to all the organizers of BERM-7 (for their suggestions and inputs). The program included 50 paper presentations on various aspects related to reference materials and an exhibition of over 100 catalogues/documents (including proceedings of BERM-5 and BERM-6) concerning reference materials. Over 120 delegates from 70 organizations participated in the workshop, and the major decisions taken at the workshop included the formation of REMTAF. Formation, role and status of the activities of REMTAF A National Task Force has been set up in June 1996, comprising (i) an international advisory group of experts from the world’s leading organizations of the area including ISO, Switzerland, AOAC, International, USA, NIST, USA, IRMM, Belgium etc., (ii) a national advisory group of the directors of national premier research institutes in the country, and (iii) a working group of individual experts actively involved/interested in the area. The overall objectives of REMTAF are: – development, harmonization and promotion of the use of CRMs in various areas in the country, – collection, collation, compilation and dissemination of information covering various aspects of reference materials, and – Development of a national data base on reference materials at CPCB, Delhi, and establishment of its international traceability. REMTAF had its first meeting on September 25, 1996 at the CPCB’s office in Delhi. The priority needs of refer-
ence materials compiled in the meeting are summarized in Table 1. The meeting also identified 12 nodal agencies as well as formulated the tasks to be performed by these agencies for taking up problems of reference materials in different areas. The areawise distribution of these agencies is shown in Table 2. The first meeting of the nodal agencies was organized on March 03, 1997 at CPCB Delhi. The modus operandi for preparation of CRMs of immediate priority needs in different areas, and the possible sources for funds to be approached, were discussed in detail. It was agreed that CPCB will prepare a comprehensive proposal covering preparation of about 10 priority CRMs through the nodal or other competent agencies. This comprehensive program for the development of CRMs for the country is expected to start by the end of 1997.
Concluding remarks Preparation of CRMs in India, although begun over three decades ago, is so far limited to some specific areas, like metallurgical, geophysical, and solutions of metals in high purity water for general purposes. The country has established a Reference Materials Task Force at the national level in 1996 to consolidate the sporadic efforts in different areas for the preparation of CRMs and formulate a national program for the development and use of reference materials. The priority needs for reference materials have been compiled, the future course of action to meet these needs including preparation of some CRMs within the country has been formulated, and a comprehensive project for the preparation of CRMs in India is expected to start within the year 1997.
295 Acknowledgements The authors wish to thank, (i) Dr. M.K. Mazumdar of CDL, Calcutta; Dr. L.P. Pandey of NML, Jamshedpur; Dr. P.K. Govil of NGRI, Hyderabad; Dr. C.S.P. Iyer of RRL,Trivandrum; Dr. T. Chakrabarti of IMT, Chandigarh; Dr. (Mrs.) J. Sokhey of CRI, Kasauli; Dr. V. Prakash of CFTRI, Mysore; Dr. C.B. Pandya of NIOH, Ahmedabad; Dr. K. Lal of NPL, New Delhi; and all the REMTAF members concerned for providing the necessary details on the reference material activities of their respective institutes which have been summarized in the paper, and (ii) Mr. Shriance Jain and Mr. Subhash Chand of CPCB Delhi, for their help in compilation of this information.
References 1. Mahwar RS (1992) International Directory of Suppliers and Dealers of Standard Reference Materials for Measurement of Metals and Organics, Publication No. LATS/8/1992 of Central Pollution Control Board, Delhi, India 2. Mahwar RS (1995) Fresenius J Anal Chem 352:188