PARLIAMENT OF INDIA

RAJYA SABHA 162

DEPARTMENT - RELATED PARLIAMENTARY STANDING COMMITTEE ON SCIENCE & TECHNOLOGY,

ENVIRONMENT & FORESTS

ONE HUNDRED - SIXTY SECOND REPORT

ON

DRUGS AND PHARMACEUTICALS RESEARCH PROGRAMME INCLUDING HERBAL MEDICINES

(PRESENTED TO THE RAJYA SABHA ON THE 14TH DECEMBER, 2006)

(LAID ON THE TABLE OF THE LOK SABHA ON THE 14TH DECEMBER, 2006)

RAJYA SABHA SECRETARIAT NEW DELHI

DECEMBER, 2006/AGRAHAYANA, 1928 (SAKA)

E-mail:rsc-st @sansad.nic.in Website:http://rajyasabha.nic.in

PARLIAMENT OF INDIA

RAJYA SABHA

DEPARTMENT - RELATED PARLIAMENTARY STANDING

COMMITTEE ON SCIENCE & TECHNOLOGY, ENVIRONMENT & FORESTS

ONE HUNDRED - SIXTY SECOND REPORT

ON

DRUGS AND PHARMACEUTICALS RESEARCH PROGRAMME INCLUDING HERBAL MEDICINES

(PRESENTED TO THE RAJYA SABHA ON THE 14TH DECEMBER, 2006)

(LAID ON THE TABLE OF THE LOK SABHA ON THE 14TH DECEMBER, 2006)

RAJYA SABHA SECRETARIAT NEW DELHI

DECEMBER, 2006/AGRAHAYANA, 1928 (SAKA)

CONTENTS

PAGES

1. COMPOSITION OF THE COMMITTEE........................................................................................ (i)-(ii)

2. INTRODUCTION ................................................................................................................ (iii)

3. REPORT ..........................................................................................................................

CHAPTER I PREFACE ......................................................................................................... 1

CHAPTER II DEPARTMENT OF SCIENCE & TECHNOLOGY ........................................................... 2-6

CHAPTER III DEPARTMENT OF SCIENCE & INDUSTRIAL RESEARCH ............................................. 7-10

CHAPTER IV DEPARTMENT OF BIOTECHNOLOGY ...................................................................... 11-13

CHAPTER V MINISTRY OF OCEAN DEVELOPMENT .................................................................... 14-17

CHAPTER VI DEPARTMENT OF AYUSH ................................................................................... 18-20

CHAPTER VII GENERAL ASPECTS RELATING TO DRUG RESEARCH ............................................... 21-25

CHAPTER VIII COMMITTEES OBSERVATION/RECOMMENDATIONS ................................................. 26-32

4. ANNEXURE ....................................................................................................................... 33-36

5. MINUTES ........................................................................................................................ 57-58

COMPOSITION OF THE DEPARTMENT-RELATED PARLIAMENTARY STANDING COMMITTEE ON SCIENCE AND TECHNOLOGY,

ENVIRONMENT AND FORESTS (2006-2007)

1. Shri P.G.Narayanan –----- Chairman

RAJYA SABHA 2. Dr. Prabha Thakur #3. Vacant 4. Shri Suryakantbhai Acharya 5. Shri Bhagirathi Majhi 6. Shri Kamal Akhtar 7. Shri Saman Pathak 8. Shri Jabir Husain 9. Shri Ravula Chandra Sekar Reddy 10. Dr. Barun Mukherjee

LOK SABHA 11. Shri Jashubhai Dhanabhai Barad 12. Dr. Sujan Chakraborty 13. Shri Thupstan Chhewang 14. Shri Pankaj Choudhary 15. Shri Francis Fanthome 16. Shri Babubhai K. Katara 17. Shri A. Venkatesh Naik 18. Shri Brahmananda Panda 19. Shrimati Neeta Pateriya 20. Shri Jaysingrao Gaikwad Patil 21. Shri Pratik Prakashbapu Patil 22. Shri Bachi Singh ‘Bachda’ Rawat 23. Shri K.C. Singh “Baba” 24. Shri Kirti Vardhan Singh 25. Shri Rakesh Singh 26. Shri Aruna Kumar Vundavalli 27. Shrimati Jayaben B. Thakkar 28. Shri Akhilesh Yadav 29. Shri Mitrasen Yadav 30. Shri Sita Ram Yadav *31. Shri Rampal Singh SECRETARIAT Shri N.C. Joshi, Additional Secretary Shri R.K. Singh, Officer on Special Duty Shri Alok Kumar Chatterjee, Deputy Secretary Shri Jagmohan Sundriyal, Under Secretary Shri S. Rangarajan, Committee Officer

INTRODUCTION

I, the Chairman of the Department-related Parliamentary Standing Committee on Science & Technology, Environment & Forests, have been authorized by the Committee to present the Report on its behalf, present this One Hundred-Sixty second Report on the Drugs and Pharmaceuticals Research programme including Herbal Medicines.

2. The Department-related Parliamentary Standing Committee on Science & Technology, Environment & Forests in its meeting held on 6th June, 2005, decided to take up Drugs & Pharmaceuticals Research including herbal medicines for examination and report thereon. The nodal Ministry for Drugs and Pharmaceuticals Research programme in the Ministry of Science and Technology. Other Ministries/Departments involved in the programme are Department of Scientific and Industrial Research, Department of Biotechnology, Ministry of Ocean Development and Department of AYUSH etc. In this regard the Committee heard the Secretaries of the various Ministries/Departments like Department of Science and Technology, Biotechnology, Scientific and Industrial Research, AYUSH and Ministries of Environment and Forests and Ocean Development. In addition of the Committee also heard Director-General, Indian Council of Medical Research and Drugs Controller-General (India). The details of the representatives of various Ministries/Departments who appeared before the Committee for oral evidence are given in Annexure.

3. The Committee expresses its thanks to the Officers of the various Ministries/Departments for replying to the clarifications sought by the Members and placing before it the required material to enable the Committee to scrutinize the same.

4. In the meeting held on 6th November, 2006 the Committee considered the draft report and adopted the same.

P. G. NARAYANAN

NEW DELHI ; Chairman, 6th November, 2006 Department-related Parliamentary Standing Committee

on Science & Technology, Environment & Forests.

CHAPTER - I

l. PREFACE

1.1 With global revenue of approximately US$ 535 billion in 2005, the healthcare industry is the world’s largest industry. Over the years, the Indian drugs and pharma industry has made tremendous progress in this vital sector. The Indian Industry’s contribution stands at Rs. 50000 crores (US $10 billion). The Indian pharmaceutical sector has achieved global recognition as a low cost producer of quality drugs and formulation products. With the new patent regime coming into effect from January 2005, the Indian pharma industry and R&D sectors are reorienting themselves to face the challenges and exploit the opportunities arising therefrom.

1.2 India has demonstrated its competence in the production of bulk drugs and formulation. Indian companies export bulk and formulations to all major developed countries. The manufacturing competence and cost-competitiveness of India is unrivalled in bulk drugs and formulations. Now the country is emulating the example of information technology and climbing the pharmaceutical value chain. The country has the opportunity to do even better in drug development Biotechnology.

1.3. Further the country has endeavoured to emerge as low cost medical research hub and take an important place in global effort towards drug development. India’s strength includes availability of high-class human resource, vast scientific infrastructure, low cost-high quality clinical trials and efficient and well-established regulatory systems. India’s strength in medicinal chemistry and bio-informatics is an asset.

1.4. The diseases of importance to our country are Leprosy, Malaria, Tuberculosis, Japanese Encephilitis, Syphilis, Leishmaniasis, Filariasis, HIV/AIDS, Tetanus, Measles, Drug resistant enteric fever, Hepatitis-B, Skin disorders like Leucoderma and psoriasis, Gastrointestinal disorders like Diarrhoea and Cholera besides infections leading to Trypansomiasis and Ascariasis, Diabetes, Hypertension, Cardiovascular disorders, Dengue and other prevalent infectious diseases besides neurological diseases like dementia and Parkinson’s Disease.

1.5. The challenge to pharma research and to pharma industry lies in providing adequate medicines at affordable cost to Indian population and that too under the prevailing socio-economic conditions. At the same time, the industry has to compete globally, cost and quality wise, for exports.

1.6. One of the key objectives underlined in the Draft National Pharmaceutical Policy 2006 is to promote greater research and development in the pharmaceuticals sector by providing suitable incentives. India has a vast R&D infrastructure that includes the extensive network of national labs, academic institutes and private R&D labs. It is essential to utilize the expertise of these institutions and make them contribute not only in elimination of killer diseases but also to the development of industry and the national economy. The mettle of Indian scientists is recognized the world over, and many research laboratories in advanced countries have benefited from our national resources that could not be effectively tapped, so far. Further, research in India is far more cost-effective than it is in the west. Therefore, we could well become a source for scientific innovation.

CHAPTER - II

MINISTRY OF SCIENCE & TECHNOLOGY (DEPARTMENT OF SCIENCE & TECHNOLOGY)

2.1. The nodal Ministry for Drugs and Pharmaceuticals Research programme is the Ministry of Science and Technology. Other Ministries/Departments involved in the programme are Department of Scientific and Industrial Research, Department of Biotechnology, Ministry of Ocean Development and Department of AYUSH etc. The Committee was informed by the Secretary, Department of Science & Technology that the drug development is a long drawn process involving both risk and heavy investments. The Secretary informed that it takes twelve to fifteen years to bring out a new drug and requires nearly US $ 900 million to US $ 1.0 billion with success rate just being one in ten thousand. Despite the odds, the Secretary informed that several new chemical entities have been synthesized and important leads developed which may lead to new/novel drugs in the near future for treatment of various diseases like Tuberculosis, Malaria, Rheumatism, Cardio-vascular diseases, Cancer, Diabetes Leucoderma etc. The R&D efforts have been made both in Modern as well as Indian System of Medicine.

2.2 When the Committee enquired about the risk factor involved in pharmaceutical Research, the Secretary, Department of Science & Technology elaborated about two kinds of risk. The first risk factor is that when a lead is taken/identified, it is not that every lead results in success Half way through, finding that there are more failures than successes, it may be dropped. The number quoted is that one in 10000 studies is the success ratio. A large number of leads are tried before identifying one successful lead. A lot of money is spent for going through these 10000 studies and that has to be recovered from one success. The second risk factor is the possible side-effects. In spite of all the elaborate clinical trials, long-term side-effects are not known immediately. After sometime they become visible and then the drug has to be withdrawn from the market. These are two major risks which one faced in the industry.

2.3. The Drugs and Pharmaceuticals Research Programme (DPRP) is being managed by a Drug Development Promotion Board (DDPB) and Expert Committee. Representatives of the various concerned Ministries in ICMR, CSIR, Department of Chemicals and Petrochemicals etc. are members of the Expert Committee, besides various Industrial Representatives. Hence, there is a continuous interaction between the various departments so that no overlap of activities occurs and concerted efforts are made towards purposeful development of drugs in Modern as well as in Indian Systems of Medicines.

2.4 Infrastructure

2.4.1 Infrastructure for research and development activities in the country could be classified into two categories namely (i) infrastructure for funding R&D and (ii) infrastructure for undertaking R&D activities. Recognizing the profound influence of R&D on the prospects and opportunities for the growth of the Indian Drug Industry, a scheme titled “Drugs and Pharmaceuticals Research Programme” was initiated in DST during 1994-95 for promoting Industry-Institutional R&D collaborations in drugs and pharmaceutical sector. This programme aims at enhancing capabilities of institutions and the Indian Drugs & Pharmaceuticals Industry towards development of New Drugs in all Systems of Medicine.

2.4.2 In the category of infrastructure for funding R&D fall various government departments, such as Departments of Science & Technology; Bio-Technology; Scientific and Industrial Research; Indian Systems of Medicines and in the latter category i.e. infrastructure for undertaking R&D activities falls the scientific agencies like Council for Scientific and Industrial Research; Department of Ocean Development; Indian Council of Medical Research, Central Council for Research in Unani Medicine; Central Council of Research in Ayurveda, Central Council for Research in Yoga and Naturopathy.

2.5 Budgetary allocation for drug research

2.5.1 The Committee was informed that the Department, recognizing the profound influence of R&D on the prospects and opportunities for the growth of the Indian Drug Industry, initiated the scheme on Drugs and Pharmaceuticals Research in 1994-95 for promoting Industry-Institutional Collaboration R&D in drugs and pharmaceuticals sector. The programme aims at enhancing capabilities of institutions and the Indian Drugs & Pharmaceuticals Industry towards development of new drugs in all systems of Medicine. The specific objectives of this scheme are:

To synergise the strengths of publicly funded R&D institutions and Indian Pharmaceutical Industry in developing drugs in areas of national relevance.

To create an enabling, infrastructure, mechanisms and linkages to facilitate new drug development.

To stimulate skill development of human resources in R&D for drugs and pharmaceuticals.

2.5.2 During 2004-05, Pharmaceutical Research and Development Support Fund (PRDSF) was set-up. Under this fund, the Government has created an initial corpus of Rs. 150 crores The interest accrued on this corpus would be used for providing financial assistance to R&D projects proposed by industry/academic institutions/laboratories and also for creation of state-of-art facilities in the country, in addition to extending soft loan At simple interest of 3% per annum to non-profit making registered societies for undertaking R&D in Pharma sector. However, it was felt that with falling interest rates the interest component would not be enough to fund the activities. The Planning Commission agreed to provide Rs.150 crores for “Drugs and Pharmaceutical Research” subject to dissolution of corpus of the PRDSF.

2 5.3 It was informed by the Secretary, Department of Science & Technology that during the financial year 2005-06, continued efforts have been made extensively for promoting R&D in the Pharmaceutical Sector by financially supporting R&D projects which may lead to new drug development in the area of diseases which are of relevance to our country besides development of new drug delivery systems and veterinary drug development.

2.5.4 The Committee was further informed by the Secretary, Department of Science & Technology that the monitoring of the various projects and facilities which have completed their tenure and completed more than one year has been carried out and other miscellaneous jobs like conducting seminars, symposiums, brain storming sessions, interaction meets and expert committee meetings were also conducted during the year. During the financial year 2006-07, it is planned to continue efforts to support collaborative research projects leading to new drug development in the area of diseases which are of importance to our country.

2.5.5 Wide fluctuations were noticed in allocation made by the Department of Science & Technology for Drugs and Pharmaceutical Research. While the allocation stood at Rs 150.00 crores in B.E. 2005-06, this was reduced to Rs.105.00 crores in R.E. 2005-06 and has been increased to Rs 130.00 crores in B.E. 2006-07. The Committee has been informed that the Government created a corpus of Rs. 150.00 crore for Drugs and Pharma Research during the year 2004-05 The interest to be accrued on this corpus of the order of Rs. 9.00 crores per annum was to be utilized for drug research. During the year 2005-06, Planning Commission recommended enhanced allocation of Rs. 150.00 crores under Annual Plan and conveyed that Rs. 150.00 crores allocated for Drug & Pharmaceutical Research would he operated only after the existing corpus for Pharmaceutical Research & Development Support fund is dissolved. The Government, after adopting the entire process for seeking the approval of CCEA, dissolved the Fund on 24.01 2006. Due to this, the allocation was reduced to Rs.105.00 crores in R.E. 2005-06. The programme will be able to utilize the budget provisions of Rs.130.00 crores (2006-07) from the begining of the financial year without any procedural delay. Such a variation, it is felt, will not have any major adverse effect.

2.6 Structure of R&D Activities in India

26.1 As in most countries in the world, R&D activities are done in India by Government R&D institutions, universities, colleges, and academic institutions and by the private sector. The Government is by far the largest sponsor

of R&D in India. It was informed by the DST that the institutional sector comprising the Central and State Governments and the higher education sector accounted for 75 per cent (for Financial yealy 2002-03) of the R&D expenditure and the remaining comes from the private sector.

2.6.2 The bulk of the Central government R&D expenditure is spent through major scientific agencies such as Council of Scientific & Industrial Research (CSIR), Indian Council of Medical Research (JCMR), Department of Science & Technology (DST), and Department of Biotechnology (DBT), AYUSH, Department of Ocean Development etc. Especially after the adoption of the Resolution of Scientific Policy in 1958, a chain of national R&D laboratories have been created in India under these scientific agencies. There are about 550 Central Government R&D institutions in the country. The remaining 17 per cent of the total Central Government expenditure is spent through the ministries/departments, such as Ministry of Health & Family Welfare and the public sector enterprises within the administrative control of the concerned ministries.

2 6.3 In addition to directly performing R&D activities, for example in laboratories under CSIR. the Government provides a number of push and pull incentives to promote R&D The fiscal incentives which are currently provided by the Government, includes direct tax incentive, such as deduction of both current and capital accounts R&D expenditure from taxable income, tax holidays and indirect tax incentives such as customs duty and excise duty exemptions. Under a number of schemes administered by the Department of Science & Technology., Department of Scientific and Industrial Research (DSIR) and Council of Scientifics Industred Research the Government also provides financial (loans/grants) and other assistance to R&D performers. Most of these schemes are of recent origin. An R&D programme specifically for the pharmaceutical industry was started in the mid - 1990s.

2.6.4 According to Confederation of Indian Industry (CII), there was a time when Indian companies used to invest just 2-3% of their revenue in R&D, but of late, this figure has gone up to 10% in some cases. For instance, Gujarat based Pharma companies during 2004-05 spent Rs.205.6 crore or 9-10% of the total net sales on R&D. Similarly, Cadila Healthcare spent Rs.103 crore, or 9.2% of its total turnover. This is a healthy sign since increasing expenditure on R&D is urgently required by pharmaceutical companies not only to break new grounds in curing but also to face international competition in the coming years. It also highlighted the need to expand the R&D activities.

2.7 Process of New Drug Development

2.7.1 The drug research is resource and knowledge intensive, time consuming and full of uncertainties. It is estimated that nearly 900 million to 1 billion dollars are required to find a new molecule. It requires consistent efforts of 10 to 12 years and synthesis of thousands of molecules to see the success of one drug commercially. At the same time, there are different stages of drug development i.e. Laboratory and Animal Studies (3 to 4 years) Phase I Clinical Studies (1 year), Phase 2 Studies (2) years), Phase 3 Clinical Studies (3 years), Review by Drug Controlling Authority (2 to 3 years) where there is return on investment. Over and above, there is no guarantee for such a return. The chances of success are extremely low. There is no other industry, which can be compared with the drug industry for such a long chain of efforts and such a high risk right from the stage of discovery of the molecule in the laboratory to the stage of approval of the newly developed drug by the Drug Controller General before reaching the market place for commercial sale.

2.7.2 The country has adequate resources in terms of manufacturing base, scientific manpower and facilities to manufacture as well as to undertake R&D on bulk drugs. India has shown her strength in finding alternative route of manufacturing existing bulk drugs. This will facilitate introduction of all those drugs in the Indian market, which will be off the patent in the near future. It is expected that huge market is available from off the patent drugs.

2.7.3 Since the development cost in the country is much lower than the development cost in the advanced countries and the country has sound base, venturing development of new molecules is within our reach. This would, however, require joint efforts of the industry, institutions and the government to augment resources both financial and technical

2.7.4 The process of drug development is a long and elaborate process, which involves a variety of skills primarily from chemistry and biological sciences. To design and synthesize new promising molecules, both organic chemistry

and medicinal chemistry skills are required to identify lead compounds which have some desirable properties to achieve the target, and of optimizing the efficacy/safety of the compounds. In addition the following skills are also required:

Target identification: basic biological skill to understand how the disease works and to identify a specific target, the inhibition of which plays a crucial role in the particular disease.

Pre-clinical testing on animals and clinical trials to determine the efficacy and safety of the molecule.

2.8 Drugs and Pharmaceuticals Research Programme

2.8.1 The Department has informed that the main objective of the Drugs and Pharmaceutical Research Programme is to support industry-institutional collaborative R&D Projects and establish State-of-the Art National Facilities in all Systems of Medicine including AYUSH, in addition to extending soft loan to Pharma industries for R&D projects at the rate of 3% simple interest per annum.

2.8.2 During the last four years under this program, 42 collaborative projects, and 18 National facilities have been financially supported besides which loans were provided to 22 industries. Out of the 42 project supported so far during the last four years, 25 projects are related to the modern system of medicine, 9 are related to Ayurvedic system, 6 projects are in the Siddha system of Medicine while one project has been supported in the Unani System of Medicine, and a project is related to a veterinary product-herbal based. Among the 22 pharmaceutical industries to whom loans are provided for conducting research and development in the pharma sector, 19 projects are related to the Modern System of Medicine while 3 are related to Indian System of Medicine (Herbal).

2.8.3 Among the five industries to whom loans were provided for conducting R&D in the Pharma Sector, four Projects were related to the Modern System of Medicine while one was related to Ayurvedic System (Herbal). Financial grants have been sanctioned for conducting R&D in the Pharma Sector relating to development of new anti-tubercular compounds, novel anti-cancer agents, development of potential adjutants for Vaccines, new chemical entities as potential anti-fungal agents, novel anti-asthma agents, new drug delivery systems for sustained release of tubercular drugs, development of a novel herbal veterinary product (ectoparasiticidal), Study of Safety and Efficacy Profile of Siddha Medicine (Kodiveli) used for rheumatoid arthritis and another Siddha formulation (KARBOGI) used for lecuoderma.

2.8.4 Other Projects supported under the PRDSF Programme during 2004-05 are related to Development of Poly Lactide-co-Glycolide (PLG) for nano encapsulation of tuberculosis drugs for sustained release for drug delivery system, Development and standardization of herbal antimalarial drugs, identification and optimization of Lead Molecules for Development as anti cancer agents and Poly Lactide-co-glycolide nanoparticle based oral sustained release drug delivery system for treatment of MDR tuberculosis pre-clinical investigation in India on non-viral gene therapy of chronic wounds. Clinical and experimental evaluation of renoprotective effect of some herbal compounds. Therapeutics for would healing, Development of Botanical immunomodulators as adjuvants for improving vaccine efficacy, Development of drugs for the medical therapy of Glaucoma using natural products, Lead optimization and development of new orally active anti-malarial peroxides, Evaluation of the toxicity and Anti-Leishmanial efficacy of Liposomal Amphotericin-B (KALSOME) in mouse model, Synthesis of new chemical entities based on polyketide-derived Meacrocyclic structures and their amide-linked analogue, using sugar amino acids and related building blocks and evaluation of their anti-microbial properties, Scientific evaluation of safety and efficacy profile of a Siddha tormulation advocated in the prevention and management of Coronary heart disease besides a proposal on development of an indigenous and cost effective CD4 and CD8 count assay for HIV/ AIDS (diagnostics) etc.

CHAPTER - III

DEPARTMENT OF SCIENTIFIC & INDUSTRIAL RESEARCH

3.1 The Department of Scientific and Industrial Research has informed that the impressive growth by Indian drug industry, the share of which has reached US $ 10 billions, has been possible due to inputs of modern science and technology derived from industry and public funded R&D. CSIR is one of the constituents of this R&D infrastructure and has contributed significantly in making the Indian drug industry self-reliant.

3.2 The Committee was informed by the Secretary of the Department that R&D cost in India as compared to the west just one eighth; the manufacturing cost is one fifth; the fixed assets cost of manufacturing facility is one fourth; man power cost ranges anywhere between one-third to one-eighth and clinical study cost is just one-tenth of that in the west. The key lies in identifying the right opportunities, matching them with our strengths and relentlessly pursuing the path of making India a preferred supplier of intellectual property in the area of Pharmaceutical research & development and global leader in the sector. It is possible to leverage this factor and find ways of converting it into a source of competitive advantage.

3.3 The drugs and pharmaceuticals form a major sector of R&D in CSIR. A number of its laboratories are having world-class R&D facilities to support researches in drugs and pharmaceuticals. The major emphasis has been on discovering and developing drugs for diseases of national and global relevance. In the recent past CSIR laboratories have made valuable contributions to the industry and the society in this vital sector. These include several novel drugs, which have been successfully commercialized by the industry, and are currently marketed (e.g. Saheli, E-mal, Elubaquine, Promind, Asmon, etc.) and dozens of process technologies leading to commercial production of high-value drugs/drug intermediates (ephedrine, dextropropoxyphene hydrochloride, artemether, cetrizine, amlodipine, naltrexone, ciprofloxacin, streptokinase, etc.) and their import substitution. A recent discovery is that of a novel anti-TB molecule, which has been found after sixty years since the last molecule discovered to treat this dreaded disease.

3.4 The strengths and capabilities of CSIR in this sector lie in a network of its laboratories engaged in R&D activities and the world class research facilities established in the laboratories. In order to develop novel products, the CSIR laboratories have adopted new approaches and technologies such as molecular biology, combinatorial chemical synthesis, structural biology, genomics, proteomics, bioinformatics, etc. For this, CSIR has established several state-of-the-art facilities or upgraded the existing facilities to world class level.

3.5 In the recent years CSIR has geared itself to face the challenges by taking several measures such as priortisation of research programmes, induction of new talent and establishing linkages within CSIR and with other national agencies/ industry and creation of state-of-the-art facilities as detailed above. The projects networking of CSIR laboratories with other R&D institutions and industry is a major initiative undertaken by CSIR to capitalize on their combined strength especially in the area of new drugs discovery based on our traditional knowledge, biodiversity, marine resources etc.

3.6 The R&D programmes in CSIR laboratories include a broad-spectrum of diverse areas. The problem areas taken up cover both regional concerns as well as problems of global importance, the latter provide a major opportunity to compete internationally. Thus the priorities relating to diseases / health risk cover a mission programme on Asthma and programmes principally concerned with reproductive health (antifertility agents), tropical infections (antimalarial, antitubercular, antimicrobial agents), age related disorders (antiosteoporotic, antidementia, anti.-stress, anti-.diabetic, antidyslipidemic agents), cataract, tumors and cancers. The other programmes relate to antifilarials, hepatoprotectives, anti-ulcer, anti-inflammatory, antihypertensives, anti-arthritic, biocompatible materials, etc. The priorities relating to pathophysiology of diseases cover development of molecular targets, animal screening models, search for novel bioactive molecules and plant extracts, chemical characterization of active molecules, developmental mechanisms of action studies, novel drug delivery systems, quality control and standardization of product, process technology etc.

3.7 A network programme on bioactives, involving 21 CSIR laboratories, 13 universities and three well-known organizations Arya Vaidyasala (A VS), Kottakal; Tamil Nadu Medicinal Plant Farms and Herbal Medicine corporation Ltd (TAMPCOL), Chennaand Central Council for Research in Unani Medicine (CCRUM), New Delhi in the traditional system of medicine, is being implemented far the last five years. It involves screening of Ayurvedic formulations, plants, fungi, microbes and insects against 14 disease areas including cancer, tuberculosis, filaria, malaria, ulcer, Parkinson’s and Alzheimer diseases, to identify new lead molecules. Several new chemical entities and new herbal formulations have been discovered by the dedicated discovery groups. For example, interesting leads have been obtained on hepatoprotective cum immunomodulation as well as memory enhancement. Two entirely new anti cancer preparations in the area of women’s cancer are being developed further in collaboration with an Indian firm. Also, work on short-term toxicity of two entirely new anti-ulcer preparations has been completed and clinical trials protocols worked out.

3.8 A mission mode programme on asthma has been launched for finding a cure for this disease following the realization of CSIR’s role as a nodal player in the field due to the existing expertise in its allergy group promise shown by its herbal medicine (Asmon) developed by IICB. Studies carried out by CSIR have already led to significant increase in the understanding of the disease by its contributions in several area, viz., atopic nature of asthma, identification, purification and characterization of allergic proteins (pollen and fungal), identification of T-cell epitopes of allergens, development of in-vitro screening procedure using human endothelial cell adhesion molecules, identification of the human lung surfactant proteins in respiratory disorders, identification of SNPs (single nucleotide polymorphism) in few candidate genes for asthma, development and a mouse model of asthma.

3.9 Predictive Medicine using Single Nucleotide Polymorphism (SNPs)

3.9.1 Under this programme a consortium of CSIR laboratories have networked with other national institutions. Aims have been initiated to study polymorphism of Indian population and create SNP database with the objective to discover new SNPs in various genes of importance among Indian population to study specific genetic diseases, and to delineate structural and functional relationship to develop appropriate tools of predictive medicines.

3.10 Development of Drug targets of Pathogens

3.10.1 The objective of the programme is to identify and characterize differentially expressed genes and proteins of selected pathogenic organisms namely Mycobacterium tuberculosis, Plasmodium falciparum, Leishmania Donovan L C. albicans, A. fumigatus, V. cholerae, S. dysenteree, H. pylori.

3.11 Development of Drug Targets Using In-Silico Biology

3.11.1 The programme networks biologists and computational scientists have spread across CSIR laboratories to create and develop inhouse capability in drug target development using in-silico biology, design programmes for developing new software to enable identification of therapeutic targets, develop new tools for predicting toxicity and drug response in silica and generate qualified and trained IT professionals for pursuing research in the area of bioinformatics. Achievements under the project include discovery of new genes in the SARS virus using modern gene identification tools designed de novo and developed in house.

3.11.2 The Committee during its visit to Regional Research Laboratory (RRL) in Jammu on 16th June, 2006, obtained written responses on the application of 3-D computer graphics and simulation in in-silico biology for development and design of new drugs and the extent to which it can reduce increased dependency on animal experimentation for testing of drugs.

3.11.3 In reply the RRL has stated that use of in-vitro mammalian cell cultures are the system of choice for understanding the desired biological efficacy of test compounds in the development of therapeutic lead molecules, The in vitro systems may consist of tissue derived cells for primary culture to continuous cultures or transformed cell lines. The cell lines may mimic in functions to the tissue of origin and are used for understanding the mechanism of action of

test drugs. In this way not only our dependency on animals could be drastically reduced but it would also be cost and time-effective. The cells are also used for evaluating the toxicity of test compounds. Thus, the use of in- vitro mammalian cultures is indispensable in the early development of drugs.

3.11.4 RRL, Jammu further stated that there are lots of software available these days that can, to a great extent, simulate the drug-target interactions using computational methods. Using these software one can screen hundred thousands of compounds in a stipulated time which were out of reach or to even think in wet lab studies. Screening of such a large database of compounds using 3-d computer graphics and simulations filters out a large number of non-potent compounds at the in silico level allowing hits to be evaluated by wet lab experiments in vitro and in vivo.

3.12 Cost-effective processes for Generics

3.12.1 CSIR has made significant contribution by developing and licensing technology to industry for manufacturing of pharmaceuticals and intermediates. The generic market is highly competitive and rapidly growing. The CSIR is in a position to provide competitive technologies for drugs becoming off-patent’ besides technologies for chiral intermediates/bulk drugs of high value and new cost effective, environment friendly, catalytic processes. Processes/technologies have been developed for large number of drugs and passed on to industry for manufacture Several drug companies are manufacturing these.

3.13 New Millennium Indian Technology Leadership Initiative (NMITLI)

3.13.1 The programme envisages innovation centred S&T development to place the country as a global leader in selected niche areas in collaboration with CSIR and other institutions and industry. Projects being pursued in selected/niche areas relevant to the drugs and pharmaceuticals and herbal medicines are diagnostic kit for cancer; oral herbal formulation for treatment of psoriasis, gene based new targets and makers for cancer of head, neck, gall bladder and brain, new particle based advanced drug delivery systems for liver, cancer, diabetes etc.

3.14 New Drugs developed by CSIR

3.14.1 The new initiatives and mechanisms introduced by CSIR have led to development of a number of novel drugs. Some of these drugs have been passed on to industry for commercialisation or further development. The new drugs developed by CSIR laboratories during the last three years are:

(i) First indigenous clot buster drug (streptokinase) released to Cadila Pharma Ltd. Ahmedabad.

(ii) A new anti-TB molecule, Sudoterb released to Lupin Laboratories.

(iii) Anti-cancer agents for breast, Cervix and ovarian cancer released to lndigene, USA

(iv) Centchroman (once a week female contraceptive non-steroidal pill) to Lumen Marketing Co., Chennai,

(v) CONSAP (contraceptive cream) released to Hindustan Latex Ltd.

(vi) VIJAYSAR, a single plant based anti diabetic drug is under ulticentric clinical trials at ICMR.

(vii) A mild anti-depressant agent and an anti-diabetic agent released to Nicholas Piramal, Mumbai.

(viii) Natural Calicitrol for skin disorders released to Genova Biotechniques, Hyderabad.

(ix) Metal gluconates for calcium deficiency released to Prathista Industries Ltd., Secundrabad (AP.)

(x) Herbal drugs and nutraceuticals for anti-cough, anti-cancer, anti-bacterial, anti-diabetic, wound healing, immunomodulators, memory enhancing etc.

(xi) Antihyperglycemic, a lipid lowering agent to Cadila Pharmaceuticals,

(xii) --Arteether (antimalarial) to IPCA Laboratories,

3.15 National and International Collaboration

3.15.1 In the newly competitive R&D environment especial1y in the area of drugs and pharmaceuticals no single institution can compete globally effectively. CSIR has thus established partnerships with leading Indian R&D organisations and industry for development of drugs and pharmaceuticals. Besides the national R&D agencies/industry, CSIR labs are also partnering with leading foreign drug companies and international organisations. CSIR has active support and funding of research activities by Government department e.g. Department of Science & Technology (hepatitics vaccines, herbo mineral, immunomodulators, rheumatism, gynaecological disorders, vibrio cholerae, obesity, anticancer agents, anti-inflammatory agents, human medullary carcinoma, mycobacteria); Department of Biotechnology (national animal centre, malaria, mycobacterium fortuitum, visceral leishmaniasis, mycobacterium tuberculosis, immunomodulatory agents, protein stability, antiosteoporotic agents, kala azar, leishmania donovani, ), Department of Ocean Development (drugs from sea), Indian Council of Medical Research (hepatic amoebiasis, DNA ligase, malaria, anti-fungal peptides, antimycobacterial, anti-osteoporosis, tuberculosis, kala-azar), and Ministry of Health & Family Welfare (Antifertility) and AYUSH (herbal drugs).

3.15.2 The international funding agencies like World Health Organization, National Institute of Health, European Commission, Walter Reed Army Institute, etc. are funding some of the research schemes on malaria, Leishmaniasis, bacterial expressed P. vivax and p. cynmolgi, visceral leishmaniasis in CSIR laboratories. CSIR is having fruitful partnerships with leading Indian and foreign companies which have led to development of a number of drugs. Some of the leading industries who have collaborated with CSIR in drug development are Dabur, Nicholas Piramal, Novo Nordisk (Denmark), Ecure, ZymoGenetics (USA) etc.

CHAPTER-IV

DEPARTMENT OF BIOTECHNOLOGY

4.1 The Department of Bio-technology has informed that National policy to attract investors and promote technology transfer capability is well established for competing player and it is being continuously improved. Several large pharma companies such as Ranbaxy, Cadila, Nicolas Piramal, Reddy Laboratories etc. have already become global players, and are forging critical partnerships globally. This will effectively encourage our science capability with global technological competence and capacity for financial investment.

4.2 It is also envisaged that in near future vast majority of drugs for treatment will be off patent. Many of the useful drugs are expected to go off patent in near future. India’s R&D is adopting to the new circumstances, investment in R&D by the private sector has been substantially enhanced the public support for new product development. India will also use its knowledge in traditional medicine to develop drugs at affordable prices.

4.3 The Department is supporting R&D projects/programmes in certain institutes/centers where desired level of expertise exists on drug development and allied areas. Besides, the Indian pharma and biotech companies have adequate expertise and R&D facilities for new drug discovery, bio-therapeutic molecules, and novel drug delivery systems. R&D activities towards development of novel drugs/compounds for leishmaniasis, osteoporosis, HIV/ AIDS, malaria, tuberculosis systemic mycosis, cancer, anti thrombosis etc. have been funded by the Department and significant leads have been obtained in these diseases.

4.4 The Department has also supported programmes on genomics and proteomics for identification of genes and proteins, which could be the novel targets for drug development. A programme has been initiated towards identification and characterization of genes responsible for multi-drug resistance of Mycobacterium tuberculosis for providing a better understanding of drug resistance at IISc., Bangalore and CDRI, Lucknow. The Department has established Super Computing Facility for in silico studies in genomics, proteomics and drug design at the Indian Institute of Technology (IIT), Delhi with an aim to develop novel scientific method and new software for protein structure, prediction and active site directed drug design. Department is also supporting development of novel drug/antigens delivery systems using liposomes, neosomes, nanoparticles etc. at IICB, Kolkata; Kakatiya University, Warangal; University of Delhi (South Campus), New Delhi. Projects have also been implemented towards development and standardization of process parameters for drugs and therapeutic molecules at IICB, Kolkata; Delhi University, Delhi; Institute of Microbial Technology (IMTECH), Chandigarh; Jawaharlal Nehru University (JNU), New Delhi; University Department of Chemical Technology (UDCT), Mumbai.

4.5 The following significant research leads of the completed projects supported by Department have been transferred to industry

Various immunomodulatory compounds have been isolated from plants: Piper longum, Azadirachta indica, Tinospora cordifolia and Berberis aristata.

Significant lead compounds isolated and identified from Momordica charantia (anti-diabetic novel peptide) and Azadirachta indica (anti-gastric, hyperacidity and ulcer agents). Leads have been patented. Efforts initiated for cloning of gene for novel anti-diabetic peptide and also for technology transfer of anti-gastric/hyperacidity agents to the industry.

Significant anti-oxidant properties in methonalic extract of bark of arjun (terminalia arjuna) established. It confers protection against oxidative stress associated with subsequent myocardial ischemic reperfusion injury. Two lead medicinal plant extracts (PS-OI and PS-02) have inhibitory effect on HIV-1 reverse transcriptase (HIV-1 RT) under in vitro conditions. Preliminary studies suggest lymphoproliferative and immunomodulatory potency of PS-02. Initial efforts have been made towards developing a herbal product. The following five technologies have been transferred to the industry:

An immunomodulatory agent (berberin) from Berberis aristata to be used for septic shock in burn patients (NII, New Dehi to MIS Gufic Biosciences Ltd., Mumbai).

An improved agrotechnology for cultivation of Artemisia annua cv. Jeevan Raksha (CIMAP, Lucknow to M/S IPCA Laboratories Ltd., Mumbai). The industry has already started cultivation of A. annua cv. Jeevan Raksha In Uttaranchal state.

a nutraceutical product having immunomodulatory properties (Anna University, Chennai to M/S Parry Nutraceuticals Ltd., Chennai).

Improved polyherbal formulation for management of atherosclerosis (BHU, Varanasi TO M/S Surya Pharmaceuticals, Varanasi).

Elite hybid lines of Mucuna pruriens with improved yield and high L-Dopa content (Zandu Foundation for Health Care, Vapi, Gujarat to M/S Zandu Pharmaceuticals, Mumbai). The cultivation of these improved lines have been started by farmers in Gujarat with by-back arrangement with M/s Zandu Pharmaceuticals, Mumbai.

4.6 Cell-Culture production of Therapeutic Agents

4.6.1 Efforts are in progress towards protocol development of production of important therapeutic agents through cell culture methods such as podophyllotoxin from Podophyllum hexandrum and berberin from Coptis teeta, guggulsterones Z and E from Commiphora wightii and camptothecin from Ophiorrhyza spp. Four fast growing cell-lines of P. hexandrum capable of synthesizing podophyllotoxin devoid of a-peltatins established. Process is being scaled up in bioreactor. A bioreactor facility (20-litre capacity) set up for up scaling of cell culture production of podophyllotoxin, anthraquinones and other therapeutic agents.

4.7 Cell-based Screening

4.7.1 In vitro bioscreens developed for screening plant extracts having anti-cancer and anti-diabetic properties. Multi-institutional project is in progress on using these bioscreens alongwith modern cell signal targets to identify anti-diabetic, anti-cancer and immunomodulatory agents from plants that have been used in Indian traditional system. Screening system has been developed for screening of extracts from medicinal plants (used for amoebiosis in Indian traditional system of medicine) against Entamoeba histotytica trophozytes. Lead extracts have been identified for further standardization and product development

4.8 Isolation and Characterization of New Bioactives/Therapeutic Agents

4.8.1 Under multi-institutional project, after bio-activity based in vitro screening of 60 medicinal plants (used in Indian traditional system of medicine), a total of 35 lead molecules identified so far:

Anti-cancer-I5

Anti-diabetic-5

Immunomodulatory-I5

Two anti-cancer lead molecules (from Aegle marmelos and Phyllanthus urinaria) have been patented. Efforts are in progress for developing anti-cancer herbal product from lead extracts of Aegle marmelos, Phyllanthus urinaria and Vitex negundo

4.8.2 Following three agreements have been signed with the industries under the above project:

Anna University with Ranbaxy, Gurgaon to take data on anti-diabetic and immunomodulatory agents for further investigation including pharmacological testing, pre-clinical toxicity, clinical trials.

Anna University with Nicholas Piramal, Mumbai on anti-cancer agents for higher level of investigations.

NII with Nicholas Piramal, Mumbai for further investigations of an antiinflammatory compound isolated from Alpinia galanga towards developing an anti-inflammatory drug.

4.8.3 A new bioenhancer compound (niaziridin) has been isolated and identified from a medicinal plants which has been able to enhance in vitro activity of rifampicin by 2.5 to 3.00 folds against E.coli. Activity of niaziridin is being further investigated viz-a-via piperine An active principle (saturated fatty acid) showing significant anti-proliferative activity against Entamoeba histolytica trophozoites has been identified from Oxalis corniculata. The lead obtained is being further pursued toward development of herbal product.

4.8.4 Efforts are in progress for isolation and characterization of anti-cancer, antitubercular, anti-viral, hepatoprotective, and immunomodulatory agents from medicinal plants used in Indian traditional system of medicine.

4.9 Development of Standardized and Safe Herbal Products

4.9.1 Multi-institutional programme has been initiated for developing herbal product for inflammatory arthropathy Projects supported for developing standardized and safe herbal products for osteoporosis from the leads available in traditional system. Based on leads already available, a project has been recently initiated to develop a standardized and safe herbal product from Terminalia arjuna for left ventricular dysfunction. Clinical trials is an integral component of this project. Projects for developing standardized herbal products for hepatoprotection and diabetes-type 2 is in progress.

4.10 Pilot-Scale Process (s) Development of High Value Therapeutic Agents

4.10.1 An improved processing technology has been developed for isolation of 10-DAB from Taxus wallichiana on 1 kg dry needles/batch scale. Process for the isolation of silymarine from Silybum marianum has been scaled-up to pilot plant level (40 kg seeds/batch). An improved scaled-upprocess (10 kg/batch scale) has been developed for the isolation of camptothecin from the twigs and stem of Nothapodytes foetida.

4.11 New Initiatives

4.11.1 A programme on development of standardized herbal products for veterinary health care has been developed. A programme on genomics and metabolomics of selected medicinal and aromatic plants is being developed. The programme will aim to enhance the content of desired high value therapeutic agents in targeted medicinal and aromatic plants.

CHAPTER-V

MINISTRY OF OCEAN DEVELOPMENT (Renamed as Ministry of Earth Sciences)

5.1 Drugs from Sea

5.1.1 The National Project on “Development of Potential Drugs from Ocean” was taken up for implementation from 1990-91 with a view to harnessing the potential marine flora and fauna for extraction of drugs for medicinal purposes. The research activities include Systematic collection and identification of marine organisms, extraction and evaluation of medicinal properties of products derived from marine organisms till completion of clinical trials and development of product from the pure molecules. The nodal Institute; Central Drug Research Institute, Lucknow has been entrusted the responsibility of coordination and implementation; reconfirmation of bioactivity encountered by the other participating Institutions

5.1.2 The Ministry of Ocean Development has re-orientated this programme with the focus on Exploratory and Product Development activities, collection of wide range of marine organisms even from deep sea and islands and testing of anti-caner, anti-fungal and neurotoxic activities. The routine experiments and defined protocols both for preclinical and clinical studies are being carried. The assays for the drug/metabolite(s) concentrations in bio-samples are developed and validated as per the international guidelines.

5.1.3 The brief objectives of the programme are:

Exploratory work:

Systematic exploration of the entire coastline and collections made from deep sea as well for identification of more flora and fauna having potential for extraction of drugs and chemicals.

Large-scale collection of active materials for characterization and structural determination follow-up studies with updating of the computerized database. Assess neurotoxic potential of marine organisms vis-/t-vis developing new pharmacological tool.

Collection, extraction and biological evaluation of 150 species, and evaluation of biologically potential organisms, leading to possible development of new drug (s).

5.2 Product Development

Isolation of biuoactive constituents and development as possible drugs.

Development of suitable models for biological activity in certain priority areas.

Undertaking regulatory pharmacology and toxicology of 2-3 extracts. Initiation of clinical trials for drugs.

Development of herbal drugs from the samples and marketing.

5.3 Industrial participation in Drug Development and Marketing

5.3.1 During the Tenth Plan, the main activities include further investigation and release of new drugs developed from marine flora and fauna evaluated so far. The schedule/milestones of programme have been worked out in detail and are being implemented with respect to various activities listed below:

A. Activities identified for product development:

i) Anti-diabetic

ii) Anti-hyperlipidaemic

Exploration work:

i) Collection of new organisms.

ii) Repeat collection of active organisms for confirmation of activity.

iii) Large-scale collection of active materials for follow-up studies.

iv) Characterization and structural determination of the active materials.

v) Upgradation/additions of “in-vitro” and “in-vivo” test models for screening will continue.

vi) Strengthening of information technology using database and other facilities will continue.

vii). HRD training in bioassay and chemical analysis.

5.3.2 In addition to the above developmental and ongoing activities, the following new activities are being carried out:

Introduction of new in-vitru test systems, enzymes assays and receptor binding studies, which will facilitate rapid biological screening and determination of possible mechanism of action of active compounds.

Development of new models for evaluation of wound healing specially healing of ischemic and immuno compromised wounds and expression/lack of expression of new proteins during healing process, molecular target based medium screening of antimyocobacterial activity, adaptogenic, anxiolytic, antiaging, memory & learning improvement & test system to evaluate reverse transcriptase inhibition.

5.3.3 The nature has continuously provided mankind with structurally diverse arsenal of pharmacologically active compounds. Some of these have been utilized as effective drugs or have served as lead molecule for the development of novel synthetic drugs. The oceans are the source of a large group of novel chemical entities and the serious attempts to tap the vast potential of marine organisms as a source of bioactive compounds that may be utilized as drugs started in late 1960s. Now there are more than 10,000 compounds isolated from various marine organisms from a humble beginning 40 years ago. Recently a number of compounds have been identified and that are undergoing at various phases of clinical trial mostly for the treatment of cancer. Details of some the strategic drugs are given below:

5.4 Antidiabetic Drug (CDR-134):

5.4.1 CDR-134 is a crude extract derived from a mangrove plant (halophyte) which grows only in coastal regions of Andaman & Nicobar Islands, Orissa, Tamil Nadu and Sundarban areas. This was initially subjected to detailed antidiabetic activity bioevaluaiton, a dose of 250 mg/per kg was found to be effective in streptozotacin model in rat. It was found safe in regulatory pharmacology studies. The chronic toxicity studies' of preparation was also found safe in rodents but when tested in monkeys quite a few of them died and the post mortem report indicated faecolith formation in large intestine as cause of death. This prompted to further fractionate the extract to optimize the antidiabetic activity and at the same time remove the toxic component causing harmful effect. The results were very encouraging and the efforts gave good dividends as the epicarp. extract (D-123) possess antidiabetic activity while mesocarp (D-125 proved to be an antidiarrhoeal preparation. The fruit seed 50 percent ethanolic extract showed promising antidislipdemic activity in hamster model.

5.4.2 Quality control parameters using HPTLC and HPLC finger printings of its solvent extractions have been developed, sulphated ash content and its acid insoluble ash content, loss on drying had been standardized. HPLC method for the estimation of 0-123 active marker (Gedunin) had been developed. Further other 12 markers also have been identified. The antidiabetic fraction was found safe in four standard genotoxicity assays comprising reverse mutation, chromosomal aberration both in vitro and in vivo and micronucleus assay.

5.4.3 The pharmacology and regulatory toxicity studies of D-123 were again carefully undertaken and found safe. This new preparation after necessary regulatory approval was taken up for phase-/clinical trial . The phase-/trial was completed on 31 volunteers and found safe. Now multiple dose efficacy clinical trial has been planned.

5.5 Antidyslipedemic Product (CUOl/002/004)

5.5.1 The puffer fish oil (PFO) has consistently produced lipid lowering activity in various models. The safety pharmacological studies clearly demonstrated its wide margin of safety in various organ systems. The chronic toxicity studies in rodents at 2.5-10 fold higher doses administered for 90 days were also devoid of any gross or microscopic abnormalities. The chronic toxicity studies of PFO in healthy young rhesus monkeys for 90 days also indicated that it did not affect the body, weight nor any change in texture of skin or mucosal membranes. Further the haematological parameters, blood biochemistry, liver and kidney functions were within physiological limits of normalcy. There was a 15-20% decrease in serum cholesterol and triglyceride levels in all the treated groups of monkeys at one month of treatment of PFO, which remained at lowered level upto the end of the study. Thus the antidyslipidemic product is quite safe on chronic administration. The bioactivity, regulatory and toxicity data is being compiled for obtaining DCGI permission for Phase-I clinical trial in humans.

5.6 Antihyperglycemic Agent (CDR-134-D123-F194)

5.6.1 Antihyperglycemic agent (CDR-134-D-123-F-194) is derived from a mangrove angiospermic plant which grows in the inter-tidal regions of the coastal line in Andaman & Nicobar, Orissa, Tamil Nadu and Sundarban areas. The antidiabetic dose of 0-123 is reasonably high hence it limits its acceptability for use in humans. This prompted to further fractionate it and the chloroform fraction F-194 exhibited significant glucose lowering profile with nearly one-fourth dose of D-123. This fraction (FI94) is now being developed as a better substitute for D-123. The detailed antihperglycemic bioactivity in SLM, STZ and db/db mouse model has been completed and effective dose worked out.

5.6.2 The chloroform fraction also showed the presence of eight compounds and these have been structurally identified. The compound K-211 was found to be significantly active though less than F-194, hence, it was decided to take up F-194 for further development. The regulatory pharmacology of F-194 indicates its safety in all the test systems used. A 10 days toxicity studies in rodents also showed that the F-194 is safe. Further, chronic toxicity studies for 30 days have been initiated.

5.7 Antidyslipidemic Cum Antihyperglycemic Agent (CDR-267-F-018)

5.7.1 The ethanolic extract of fruits of CDR-267 showed promising antihyperglycemic activity in STZ and db/db mice, The extract was found to be a potent lipid lowering agent in hamster model Both the bioactivities have been localized in the chloroform fraction (F-018). Eight pure substances have been obtained from FO 18 but only K-30 has shown mild bioactivities In view of the poor activity in pure substances obtained, it was decided to pursue F018 in the product form in view of its dual bioactivities. The safety pharmacological profile is under examination and regulatory toxicity studies are also underway for developing a novel antihyperglycemic cum lipid lowering agent.

5.8 Other Active Leads

5.8.1 Twelve pure substances from CDR-181 were also isolated but as no significant bioactivity was observed, they have been dropped from further development. A new (CDR-258-A001) antifungal and spermicidal agent was discovered and pure compound was. isolated There was some interesting lead in the area of CNS diseases as a new NIO-450-K030 has shown significant anxiolytic activity.

CHAPTER -VI

DEPARTMENT OF AYUSH

6.1 Herbal Medicines

6.1.1 Medicinal plants are being utilized in the preparation of various modern durgs. The effectiveness of this system is contingent upon the proper use and sustained availability of genuine raw materials. There is growing importance in traditional health system in providing health care for a wider population Due to side effects of synthetic products, herbal medicinal products are gaining popularity in the world market. In spite of well practiced knowledge of herbal medicines and availability of large number of medicinal plants, the share of India in the global market is not satisfactory.

6.1.2 Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha &Homoeopathy (AYUSH) deals with the Ayurveda, Siddha, Unani & Homoeopathy systems of medicine and Yoga Naturopathy as drugless therapies. The medicines of these systems have major portion of plant based materials. About 95% medicine have only plant based ingredients and remaining 5% have also mineral and metallic compounds. Department of AYUSH has identified a few priority areas like quality education, R&D, development of medicinal plants for raw material and to ensure good quality standard of drugs.

6.1.3 Standardization and quality control of AYUSH drugs is one of the top priority areas of AYUSH Department. The Department has identified short-term and long terms strategies to ensure the quality ASU Drugs. As a long-term strategy, the Department has taken up the fundamental work of developing Pharmacopoeial monographs which emphasize on identity, purity and strength of AYUSH drugs. This work is being carried out with the help of Pharmacopoeia Committees separately set up for Ayurveda, Siddha, Unani & Homoeopathy comprising the experts of Botany, Chemistry, Phyto-Chemistry and Pharmaceutical Chemistry of respective systems of medicines. The scientific work on the monographs is carried out by Pharmacopoeial Laboratory for Indian Medicines (PLIM), and Homoeopathic Pharmacopoeial Laboratory (HPL), both at Ghaziabad. To develop pharmacopoeias of plant based drugs used in AYUSH system require high scientific work on Botany, Chemistry and Phyto-Chemistry and therefore, the work was outsourced to 30 laboratories belonging to Council of Scientific & Industrial Research (CSIR), Universities, Central Council for Research in Ayurveda & Siddha (CCRAS), Central Council for Research in Unani Medicine (CCRUM) and other eminent scientific institutions in the country. These laboratories have helped to develop 150 monographs on single drugs. Presently 20 Laboratories are working to develop standard operative processor (SOP) of manufacturing process, Pharmacopoeial standards and shelf life studies of Ayurveda Siddha Unani Drugs.

6.1.4 The Department has achieved the first target of publishing official formularies and Pharmacopoeias which acts as mandatory guidelines for the manufactures to prepare medicines. Accordingly National Formulary for Ayurveda 2 volumes, for Unani 3 volumes and for Siddha 1 volume have been published. These formularies contain the composition of the formulations, the proportion of the ingredients, method of preparation indications and dose etc. The work for more volumes is continuing.

6.1.5 An other important landmark in the Ayurveda Siddha Unani drug development is the publication of the Pharmacopoeial monographs. The Official Pharmacopoeias describing identity, purity and strength of single drugs has been published. Ayurveda Pharmacopoeias of India 4 volumes has been published and 5th volume is under publication. Unani Pharmacopoeias of India one volume and Homoeopathic Pharmacopoeias in 8 volumes have been published. This is a scientific work of continuous nature and the Department is allocating sufficient budgetary provision as well as monitoring these activities regularly

6.1.6 The main R&D work on drugs development Programme of AYUSH system is carried out through its Research Councils i.e. Central Council for Research in Ayurveda & Siddha (CCRAS); Central Council for Research in Unani Medicine (CCRUM) and Central Council for Research in Homoeopathy (CCRH). These Councils are carrying out

research in the field in the clinical research, drug research literary research and survey & cultivation of medicinal plants. All these activities are inter-related and help in the validation and development of drugs of AYUSH system.

6.1.7 The Department is undertaking R&D activities relating to drug development under 2 programmes. One relates to development of Pharmacopoeial Standards of Ayurveda, Siddha & Unani drugs on identity, purity and strength, developing SOP of manufacturing process and studying shelf life of ASU medicines. This activity is carried out through Pharmacopieial Laboratory for Indian Medicine (PLIM) and homoeopathy Pharmacopieial Laboratory (HPL) at Ghaziabad. 20 other CSIR institutions, universities and CCRAS laboratories are also engaged in this activity. They have been given the annual targets for the 3 year programme. SOPs of about 100 formulations has been worked out and the work is going on for different batches and different drugs.

6.1.8 Central Council for Research in Ayurveda and Siddha is carrying out research on 19 disease conditions, which is a part of long term programme. The following new areas were focused as drug related research in the last 3 years:

An Oral contraceptive-Pippalyadi Yog is in the clinical trial phase-III-at AIIMS, New Delhi, PGI, Chandigarh, and JIPMER, Pondicherry. Drug standardization work, toxicity studies and biological activities of 8 coded drugs have been carried out. These drugs are :

Coded drugs Indication

Ayush Rasayana B Rasyana for elderly persons

Ayush osteo Osteoporosis and fracture healing

Ayush Liv Hepatitis A, B&C (Kamala)

Ayush Manas Mental Retardation in Children (Manas Mandata)

Ayush SL Filariasis (Morbid cases of Slipada)

Ayush QOL2 Supportive therapy for the improvement of

quality of life in HIV / AIDS and cancer patients

Ayush RP Sickle cell Anaemia

Ayush M Migraine

6.2 Extra Mural Research Scheme

6.2.1 The Department has implemented a Central Scheme to support project based R&D activities on priority areas identified for the purpose in accredited medical and scientific institutions. The research findings of such projects lead to validation of claims and acceptability of the AYUSH approach and drugs. The aims and objectives of the Scheme are:

(i) To develop evidence based support on the efficacy of AYUSH remedies and therapies;

(ii) To generate evidence on safety, standardization and quality of AYUSH products;

(iii) To facilitate the validation of relevant and promising practices and skills of traditional health practitioners and to further develop their utility for public benefit;

(iv) To retrieve and revive the rare classical literature and historical aspects of AYUSH;

(v) To investigate the fundamental principles of Indian Systems of Medicine;

(vi) To generate a data base on various aspects of AYUSH practices;

(vii) To generate data on Heavy metals, pesticides residues, microbial load, Safety/Toxicity etc. in the raw drugs & finished ASU & H drugs.;

(viii) To utilize appropriate technologies for development of single and Polyherbal/herbo-mineral products to make it globally acceptable.

(ix) To develop the products those have IPR potentials to attract national/multinational pharmaceutical complanies;

(x) Human Resource Development especially to inculcate Scientific aptitude and expertise relation to AYUSH systems.

The Scheme was initiated in the 9th Plan and so far 67 different projects have been supported.

6.3 Clinical Evaluation Of Herbal Remedies And Medicinal Plants

6.3.1 For the herbal remedies and medicinal plants that are to be clinically evaluated for use in the Allopathic System and which may later be used in allopathic hospitals, the procedures laid down by the office of the Drugs Controller General of India for allopathic drugs should be followed. This does not pertain to guidelines issued for clinical evaluation of Ayurveda, Siddha or Unani drugs by experts in those systems of medicine, which may be used later in their own hospitals and clinics. All the general principles of clinical trials described earlier pertain also to herbal remedies. However, when clinical trials of herbal drugs used in recognised Indian Systems of Medicine and Homeopathy are to be undertaken in Allopathic Hospitals, association of physicians from the concerned system as co-investigators / collaborators / members of the expert group is desirable for designing and evaluating the study.

CHAPTER- VII

GENERAL ASPECTS RELATING TO DRUG RESERACH

7.1 Use of animals for Drug Research

7.1.1 The recent international trends in research demand rational use of animals and utilization of emerging alternative technologies and approaches. The objective is to develop alternative/ internationally accepted animal models and transgenic and knockout animals for drug research and introduce cell-based system

7.1.2 According to animal activists, any animal research project implies a potential violation of widely subscribed moral norms and values. The breeding of animals under caged conditions, feeding them prepared diets, handling them for experiments and sacrificing their lives are violations of biological species-specific life. Inducing pain, causing suffering, anxiety, stress or impairing their psychological well-being are abuses which deviate even more from the norm of reverence to life. Induction of heritable deviations of the wild type genome-transgenic animals, genetically modified organisms, presents the latest class of violation against the normal norm.

7.1.3 According to antivivisectionists, toxicity testing in animal do not confirm to good science practice. This is the most controversial of all animal procedures because many people believe that it is unnecessary to test many of the compounds. Although not all animals used in toxicity suffer (eg control or low dose groups), a significant number do, because the intention of toxicity testing is to induce adverse effects in some of the animals. These tests are intended to identify which organs of the body, may be susceptible to damage by a particular chemical.

7.1.4 The ultimate goal of any animal welfare measure is the elimination of all experiments on animals that are likely to cause pain or distress. But this can be only be a dream at present since new and new diseases keep coming up and sometimes eliminating one may give way to another. So the next best measure is to think of strategies that can eliminate the use of higher mammals altogether or at least reduce the number as much as possible. The importance of this approach lies in its combination of animal welfare considerations along with good science and best practices.

7.1.5 India enacted an animal law as early as 1960’s called the ‘Prevention of Cruelty to Animals Act’ amended in 1982 which provided for the prevention of cruelty to animals in general. Under Chapter 4 of the same Act there is provision for the control of experimentation on animals. The act also provides for the constitution of an Animal welfare board to take care of the welfare of animals in general, and also provides that the Animal Welfare Board constitute a Committee for the Control and Supervision of Experiments on Animals. This Committee is empowered to take care of the legal and ethical aspects of experimental animals being used in research and enact preventive measures wherever there is violation of the law. The CPCSEA issued a Gazette Notification in December 98 called “Breeding of and experiment on Animals (Control) and (Supervision) Rules, 1998” and its amended notification in February 2001.

7.1.6 Another area of concern is the use of large animals like cats, dogs and monkeys for experimental work. Unlike Western countries, there are very few animal facilities in the country, where controlled captive breeding is undertaken for these animals. With the longer duration of gestation, weaning and limited litter size (especially in monkeys) in these animals, enough animals cannot be raised by these limited animal facilities for many of the experimental needs of the country.

7.1.7 Since It is imperative that some selected studies and safety evaluation of certain drugs need to use cats, dogs, primates and other large animals, a programme for their captive breeding have to be initiated. This is very much true for primates and there is a need to establish 2 or 3 national centres of excellence to breed primates in captivity and to undertake work related to reproductive biology, disease problems, behavioural status and population dynamics. We should try to preserve and facilitate the growth of a sustained populations of different species of primates unique to our country These centres should be large enough to meet the genuine needs of the work involving the use of primates.

7.1.8 During its interaction with Departments of Biotechnology and Ocean Development, the Committee was informed that there were problems in importing animals for pre-clinical trials. While the country is fast appearing as a low cost

hub for clinical trials, researchers have to go abroad for pre-clinical trials. This not only increases the cost of research here but also cuts down the comparative advantage India has in pharmaceutical research.

7.1.9 The Committee during its interaction with Department of Ocean Development was informed that in January 2002, the Department made requests for clearances of monkey trials for anti-hyperlipedemic drugs. But final clearances could only be obtained in February 2004 and that too for dogs. They have stated that such instances are demoralizing for the scientists and should not be allowed to happen in future. The time-gap for obtaining clearances should be reduced as far as possible.

7.1.10 Secretary, Ministry of Environment and Forests assured the Committee that new guidelines adopted by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), which have become operational after 20th December, 2004, have effectively addressed the above concerns. Since then there has not been a single case in any court in India and not one complaint has been received by the Ministry or the CPCSEA either from the animal activists or medical researchers.

7.2 Golden Triangle Partnership (GTP) Scheme (AYUSH, CSIR & ICMR Partnership)

7.2.1 The Golden Triangle Partnership Scheme is a new initiative by AYUSH, CSIR and ICMR and has been devised as an integrated technology mission for the development of Ayurveda using the latest scientific tools and technology with specific budgetary support. These departments will work together to achieve the objectives of (i) safe, effective and standardized classical Ayurvedic products for the identified disease conditions; (ii) developing new Ayurvedic medicines effective in disease conditions of national/global importance; (iii) utilizing appropriate technologies to develop single and poly-herbal mineral products. To start with diseases have been prioritized for which safe and effective ayurvedic products are to be developed in a time bound manner These are:

i. Rasayana (Rejuvenators/Immunomodulators) for healthy ageing.

ii. Joint disorders

iii. Memory disorders

iv. Menopausal syndrome

v. Bronchial allergy

vi. Fertility & infertility

vii. Cardiac disorders (cardio-protective & anti-arteriosclerosis)

viii. Sleep disorders

ix. Irritable Bowel Syndrome (IBS)

x. Vision disorders

xi. Urolithiasis & Benign Prostrate Hypertrophy (BPH)

xii. Malaria/Filaria/Lieshmanissis

xiii. Diabetes

7.2.2 The Department in collaboration with CSIR and ICMR have undertaken a Golden Triangle Project from 2005-06 onwards with budget provision of Rs.15 crore in current year for setting up integrated technology mission for scientific validation of classical, Ayurveda, Unani and Siddha drugs and development of new drugs of contemporary relevance. 14 disease areas and safety evaluation of Bhasmas/herbo mineral formulations have been identified for R&D. In the first phase five task forces have been constituted respectively for Rasayana, Urolithiasis/BPH, joint disorders, sleep disorder, and cardiac disorders/atherosclerosis. The task forces have identified clinical conditions where gaps of treatment exist and corresponding formulations recommended by the experts for scientific validations and relevant R&D. These formulations have been forwarded to CSIR with details of the ingredients and references for taking up

standardization and safety evaluation studies. A working group of experts from different disciplines has also been constituted to recommend to the Government of India regarding modes and modalities of undertaking safety evaluation of Bhasmas and Herbo mineral preparations under Golden Triangle Project.

7.2.3 The Department is also involving reputed Ayurveda/Siddha/Unani companies in safety evaluation studies of Herbo-Mineral formulations under the Golden Triangle Project with collaborative involvement of Council of Scientific and Industrial Research and Indian Council of Medical Research.

7.3 New Patent Regime and Drug Research

7.3.1 The country has crossed the threshold of a new patent regime, which has become effective for the pharmaceutical sector from January 1, 2005, that is after completion of the ten years’ transitory period, under the TRIPs. This has started a new chapter as patents on products also, in addition to patents on processes, in the pharmaceutical sector would be granted. This will necessitate innovation and invention and make reverse engineering inadequate. R&D will have to be taken up in the right earnest. Researchers have to apply their creative skills to producing new inventions. The Pharmaceutical industry will have to focus its resources and efforts on value-added innovation and development of new drugs.

7.3.2 The Indian Patent Act of 1970, did not have the system of patenting “products” in the pharmaceutical sector. Only process patents were recognized. By virtue of this, Indian Pharmaceutical Industry was able to adopt different processes and thus manufacture a product, which was earlier invented elsewhere in the world. This helped in various drugs being available in one therapeutic group, and thereby, also helped in making the prices competitive and cheap. But fallout of this system has been that it has not encouraged investments on basic Research and Development (R&D) in the Indian Pharmaceutical Sector, as desired. It is understood that while on an average, companies spend 15-16 per cent of their sales turnover on R&D in the U.S and Europe, in India, it is between 1-2 per cent only.

7.4 Public Private Partnership for Development of New Drugs In India

7.4.1 A significant change which has taken place in India in recent years is a particular form of Public-Private Partnership (PPP). Traditionally, CSIR laboratories such a CDRI did not have much interaction with the pharmaceutical industry so far as R&D for new drugs was concerned. Neither the MNC’s nor the Indian companies were interested in the drugs developed by the publicly funded laboratories. In the previous patent regime, the Indian companies actually were more interested in developing processes for the new drugs and so far as this activity is concerned, the Indian companies did collaborate with the CSIR laboratories. The situation has now changed with the Indian companies starting R&D for NCEs.

7.5 Increase in Human Resource in S&T

7.5.1 Science and Technology are the drivers of economic growth, and science education is the backbone of all Science & technology efforts in any country. The role of scientific manpower is critical and there exists a close relationship between human resources in Science & Technology and economic growth. For socio-economic development it is essential to evaluate how this pool of skilled human resource is utilized.

7.5.2 The Committee was informed that in the last decade while improvement in infrastructure has been on a reasonable scale, a critical mass of scientific leaders has not been achieved so far specially in the non-engineering sectors. This is causing a severe obstacle at a time when innovation is required on an unprecedented scale, following the introduction of the new IPR regime. The current decision making process is fragmented and the different Ministries involved do not have a synergistic view of the policy of scientific leadership creation. An additional concern is the declining interests of students in taking up science as a career.

7.5.3 As per the Indian Science Report (2005) the national literacy level has increased from 42.4% in 1991 to 59.7% in 2004. The percentages of students in science at different levels of education are approximately between 25 and 30. Of

the 48.7 million graduates and higher degree holders (excluding diploma holders) approximately 25% have a science background. Out of the 39.2 million graduates 22.3% are from science; out of 9.3 million postgraduates 19.4% are from the science stream; and out of 0.3 million doctorates-33% are with a science background.

7.5.4 A matter of concern however is that in 2000-01, of the 8.44 million students enrolled at graduate/post graduate level only a little over 1% enrolled for Ph.D. The interest in science gradually declines from classes 6-8 to 11-12 (22%-13.4%). One of the reasons attributed to this is the increased dissatisfaction with the teaching quality and the lack of interest in the subject. To attract the best students to S&T, we need to begin early. It is therefore essential to analyze the problem and find solutions starting from primary level education right upto Ph. D/Post Doc. The main factors which require attention are:

* Adequate resources/infrastructure

* Content and quality of teaching/teachers

* Building an evidence based system of job opportunities

* Allowing greater mobility in knowledge related jobs

* Motivation/incentives

7.6 Adverse Drug Reactions (ADR)

7.6.1 In response to a written querry on adverse drugs reaction and monitoring of the same, the RRL Jammu has stated that the physician should take into consideration the genetic make up of the patient and prescribe the drug accordingly. ADR can be monitored using molecular biology tools. They also stated that they had developed major programme on bioenhancers and bioefficacy enhancers and the objective of the study was to reduce the drug intake by increasing the bioavailability of drug by increasing its bioefficacy of drug. In either condition, the drug intake would reduce thereby reducing the Adverse Drug Reaction (ADR).

7.6.2 When asked about the role of comprehensive Adverse Drug Reaction (ADR) Pharmaco Vigilance Monitormg Programme in reducing the number of cases relating to illness and deaths among patients, the RRL Jammu replied that Pharmaco Vigilance Programme was absolutely necessary to monitor ADR since it was a process of keeping strict watch on a drug released after Phase III studies for human use. Adverse Drug Reactions, reported or noticed were properly studied by clinicians and scientists together to properly document such adverse activities and were passed on to the regulatory agencies for further necessary action

7.7 Nano Technology and its Role in Drug Development & Research

7.7.1 The Committee during its meeting with Agarkar Research Institute at Pune on 28th September, 2005, inter-alia held discussions on the role of nanotechnology and its usefulness in the development of various drugs. The Committee was apprised that an important research work was being done in the Institute in this connection and the results of nano technology was also being confirmed regarding the extent of its usefulness for drug development. Apart from this, certain other Institutes like Sree Chitra Tirunal Institute of Medical Sciences, Bose Institute and National Chemical Laboratory were also undertaking considerable research in the field of nanotechnology and a detailed plan was also being developed to harness the basic usefulness of nanotechnology in various fields.

7.7.2 The RRL Jammu while responding to a written querry of the Committee on the role of nano-technology for drug research and development, replied that Dip-pen nanolithography can create arrays of antibodies that retain their ability to bind to their biological substrates. Nano-structured hydrophobic Active Pharmaceutical Ingredients (APls) hence improve oral bioavailability in vivo models to assess the formulability of engineered powders to improve the chances of clinical success and commercialization of poorly soluble new chemical entities (NCEs) and APls. Nanoscale constructs can serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutics and thereby reducing undesirable toxicities of chemotherapeutic agent.

CHAPTER - VIII

COMMITTEE’S OBSERVATIONS/RECOMMENDATIONS

8.1 The Committee is of the opinion that central focus of drug research should be to develop drugs mainly to fight common diseases like tuberculosis, leprosy, kalazar, malaria, diarrhoea, dysentery, stress related disorders, thoracic diseases, cholera, etc , particularly prevalent among poorer sections of society lacking purchasing power. The Committee feels that strategic public investment by Govel’l1ment in the field will be the right answer since such investment in drugs will primarily be undertaken with the objective of providing drugs to the poor at low cost without profit motive.

8.2 During the course of evidence, the Committee has been informed by the Secretaries of Departments of Biotechnology and Scientific and Industrial Research that despite India being a low cost hub for drug development, drugs remain unaffordable by the poor. This requires further intervention by the Government.

8.3 The Committee also notes that major chronic diseases like blood pressure, diabetes, Asthma etc. have treatments in the nature of control and not cure. With the growing incidence of young population getting affected by such life style diseases and the continuation of life-long medication to control such diseases, the Committee, even while recognizing the complexity of the affliction, is of the view that we should start looking for cures, keeping in mind the increasing number of such patients, their decreasing quality of life and the side-effects of the medicines.

8.4 The Committee hopes that the procedural complexities will become thing of the past. Drug research being a long-drawn and costly affair, the funds should be provided on a long-term basis and without spreading them too thin. Collaboration with industry is a good idea in not only sharing of risk but also for commercial viability of the product. Besides, there is a need to continue focus on diseases, which acquire epidemic proportions in backward areas.

8.5 During the course of evidence, Secretaries of the Department of Biotechnology and the Ministry of Ocean Development highlighted the need for meaningful networking, besides focused research. The Committee, after hearing officials of various Departments, has felt the need for a more focused approach. What is required is concentration on our core competencies and focus areas where results can be excellent rather than doing too many things without fruitful achievements. The Committee is of the view that due to lack of coordination between different departments and inter departmental research groups/institutes, repetition of work often results wastage of time and money. The Committee, therefore, emphasizes for strong coordination among the various departments/ research institutes to increase efficiency in drug research.

8.6 The Committee was informed that development of a new molecule involves about US $1 billion and 10-12 years time, with lot of uncertainties. So, considering the current pharmaceutical scenario, strategies must be designed to have medicines for common diseases within a short time span and for this Government should concentrate on developing new molecules as a long-term strategy.

8.6.1 On herbal research, as a short term strategy, there is a need to develop medicines to combat most prevalent diseases like Gastric problems, Arthritis, Diabetes, Stress Related Disorders, Thoracic Diseases, etc., for which a well thought strategy requires to be evolved. Time bound research on herbal drugs may be a suitable option. It was informed that a large number of ISM drugs are being used for a long time, having no acute toxicity. But long-term toxicity on these drugs must be established. A few more experiments could be done in scientific manner to make it more meaningful. Public sector units may be utilized for production of these drugs for mass consumption.

8.6.2 Compilation of a compendium & conducting clinical trial, which is a long term strategy, must also be evolved. Although work is progressing in different parts of India, in a bid to search and isolate effective plant

medicines, there is a lack of co-ordination among the groups. This often leads to many miscommunications, work repetitions, use of different contradictory methods of study, and missing out on important information. By having good networking among these groups much time, effort and cost could be saved. For this, there is a need for a standard data bank on the study conducted on traditional medicine and information gathered. It would be useful to compile a compendium of plants and herbs of traditional medicinal value for easy reference and standard data. More emphasis should be given on herbal research focusing on development of drugs for the diseases commonly prevailing in the country.

8.6.3 On the Non Herbal research, isolation of a new lead molecule and designing of Novel Drug ‘Delivery System (NDDS) can be done. Also, the classical methods involving extraction, isolation, identification, characterization, pre clinical & clinical trials could be considered. As a short term strategy, Developing NDDS is the easiest way to compete in the present patent regime involving low capital investment. Patent expired drugs could be considered for developing NDDS to enhance its bioavailability, safety and efficacy. It will take lesser time than that of developing new molecule.

8.6.4 In the Long term strategy emphasis should be given for the development of new molecule. Though this is the area to compete in the world market, it is a tough process and only a few companies could venture out for this project. However, it is a fact the some of the Indian companies are investing even 10 per cent of the turnover in drug research. A few successes have already been achieved in this regard. Government funded laboratories should frame long term research schemes for developing new molecules.

8.7 The Committee recommends that an audit report on drug development be prepared. The audit should include the organizational structure, time taken and expenditure since inception of the project/research and the outcome of the research including productivity and effectiveness of the product. This audit be completed within eight months and a report be made available by August /September 2007.

8.8 The Committee is concerned about safety of herbal preparations as far as their metallic components and toxicity is concerned. The problem of standardization and validation of drugs has not been resolved yet. This needs to be done as early as possible so as to avoid recent instances which highlighted that some of the Indian medicines, samples of which were collected in foreign countries, contained metallic contents above permissible limits. Such instances underline the importance of regulatory mechanism and genuine certification.

8.9 Quality control of raw materials is the prime concern in manufacturing herbal products. Quality control of finished products especially polyherbal products is a great concern, which requires to be resolved. Quality of medicines of herbal origin mainly depends on quality of raw materials. Presently, a major part of the raw materials are procured from wild origin, having almost no control on parameters of cultivation, collection and content of active constituents etc. Controlled cultivation could be a crucial parameter of the quality control. If Good Cultivation Practice & Good Harvesting Practices are developed and implemented raw materials of good quality can be ensured. European Guidelines for Good Agricultural Practice (G.A.P.) of Medicinal and Aromatic Plants, Good Agricultural and Collection Practice for Medicinal Plants (GACP), Japan, Good Agricultural Practice for Traditional Chinese Medicinal Materials, People’s Republic of China etc. have been published for this purpose. Recently World Health Organization has also published Good Agricultural & Collection Practice (GACP) which could be practised in case of cultivation and collection of medicinal plants.

8.10 The Committee is of the view that quality control of herbal drugs has not been developed sufficiently, especially for combination product. Research on developing standardization methods involving modern instrumentation is urgently required. Though a few attempts have already been made, more emphasis is required in this area. Monographs of more plants require to be incorporated in the existing Ayurvedic Pharmacopoiea. More stringent specifications, including use of sophisticated instruments, are to be incorporated. Research & development of marker compounds & Metabolomics are the order of the day and stress must be laid in this area.

8.11 The Committee also feels that ISM products are generally compared with herbal products from abroad. The Committee is of the opinion that lack of adequate scientific data has been a serious lacuna in the field of such comparisons. Hence, there is a need, in the opinion of the Committee, for developing comprehensive database for providing a strong impetus to promote research in ISM plants and raw materials as finished products. The Department of Science and Technology, therefore, should initiate a plan to control the quality and rigours of such work so that the standard of ISM medicines could be sufficiently raised to bring them in a comparable position with the herbal medicines from abroad and could be popularised in the Indian pharmaceutical market.

8.12 The Committee is further given to understand that a number of countries like Germany, France, Canada, U.S.A. and China are registering standardised plant extracts of proven clinical efficacy and safety option from natural source as herbal drugs or dietary supplements. However, in spite of the fact that India has a vast resource of drugs of natural origin, the country is unable to tap effectively the vast world market primarily because it is not having a satisfactory system of quality control and registration of ISM and herbal drugs. The Committee is, therefore, of the opinion that on account of the increasing number of herbal drugs, multiple procedures and practices including registration of the patenting, etc., it may be necessary to create a separate division/cell to regulate the quality of such drugs and provide proper focus on related aspects of drug development. The Committee, therefore, recommends that a proper system of registration with acceptable standards and quality control needs to be put in position in order to derive the maximum benefit from herbal drugs.

8.13 When the Committee enquired from the Department of AYUSH about procedure/mechanism to get feedback about the efficacy of a medicine for a particular disease, the Committee was informed that Central Council for Research in Ayurveda & Siddha (CCRAS), is adopting good clinical practice guidelines and WHO guidelines along with Ayurveda and Siddha guidelines for standardized research for evaluation of efficacy of treatment of all the patients for a particular disease. The Committee was further informed that as far as the Central Council for Research in Unanai Medicine(CCRUM) is concerned, there is a third party assessment system about the efficacy of different drugs in clinical research and general OPD programme. Each Clinical Research Unit has been provided with the services of bio-statistician. Central Council for Research in Homoeopathy has an elaborate system for ‘Drug Proving’ which is the essence of Homoeopathy. It is now observing the effect of a particular homoeopathy drug on the health of individuals. The Committee is not satisfied with the procedure adopted by various Departments regarding feedbacks on efficacy of drugs developed by them. The Committee would like the concerned Departments to generate easily comprehensible and effective data regarding the efficacy of various developed drugs which might be of help both to the medical practitioners as well as to the patients while making a choice regarding administration of drugs.

8.14 The Committee observes that with the introduction of patent laws, the Indian pharmaceutical companies and research organizations have been prompted to speed up their research activities for development of new drugs. However, there were complaints from the scientific community regarding restrictions on the use of animals for research purpose. With the inordinate delay and unrealistic demands in the process of getting clearance for animal experimentation, the research activity has become a victim of animal activism. The guidelines laid down by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) have in some cases stalled major research in the field. While some of the institutes and private pharmaceutical companies have done their studies abroad at higher cost, the government funded institutes find it difficult to pursue their research. The CPCSEA should initiate steps to provide quick approvals and make the system more transparent. The Committee hopes that this will be effective in checking irrational delays and saving precious man-hours of quality research.

8.15 The Committee also recommends that if the above-mentioned guidelines are found effective, they should be incorporated in the Prevention of Cruelty to Animals Act and in the relevant rules thereunder. The

Committee also feels that the scientific community needs to be adequately informed about the new guidelines so that projects which have been hanging in balance for want of approval can be taken up in right earnest. Moreover, it was reported to the Committee that restriction on the use of animals is putting inordinate delay in research activities. The Committee, therefore, feels that there is a need for rethinking about the composition of CPCSEA. More representatives from scientific community needs to be inducted which can lead to finding a rational solution of eliciting maximum scientific results with minimal animal specimen usage considering animal welfare.

8.16 The Committee feels that in-vitro experimentations should be encouraged more to avoid testing of drugs on animals and use of 3-D computer graphics by downloading lead molecule structures from protein data bank and then modifying the same accordingly to the software to design new treatments through new drugs should be given more emphasis so that minimum number of animals are used for drug testing. The in-vitro method and computer simulation could be taken as a preliminary test for drugs prior to their confirmation on animals.

8.17 The Committee would, therefore, like to conclude that since thousands of animals suffer and die during drug development testing every year and while experiments on animals cannot be 100 per cent relied upon to produce valid results, particularly about the toxicity effects on humans, the drug testing policy needs to be reviewed in such a manner as to devote more attention and resource to alternative forms of drug testing instruments like in-vitro experimentation.

8.18 The Committee is of the view that an ideal regime of intellectual property rights has to strike a balance between the private incentives for innovators and the public interest of maximizing access to the fruits of innovations. This balance is reflected in article 27 of the 1948 Universal Declaration of Human Rights, which recognizes that “Everyone has the right to the protection of the moral and material interest resulting from any scientific, literacy or artistic production of which he is the author” and that “Everyone has the right... to share in scientific advancement and its benefits”.

8.19 The Committee feels the need to promote public private partnership in order to increase funding for frontier areas of scientific and technological research in drug development. The Committee is of the view that in the world of stiff competition and expensive nature of research activity, Industry has to be involved at least at the late stage which is much more expensive than the principal research stage. Public research has to strike a balance between Principal research and late stage research. The Small Business Research Initiative (SBRI) model has been a huge success in US and Israel and the same could be experimented in India.

8.20 The Committee is of the view that inculcating scientific temper among the school children is the need of the hour to attract more students in opting science as their career which may bring more human resource in the research field. Moreover, to check the declining trend in students’ preference to opt science as their career, the curriculum for science at all levels should keep pace with developments in the sphere of science education, particularly experiment based and skill based learning strategies. Besides, there is a need for more interaction between the Universities and public funded research institutes so that the supply and quality of human resource needed for high-end research is maintained. The Committee strongly recommends improving and integrating the university system and improving the quality of human resource in research. Moreover, the present funding for research activities’ is limited only to few universities involved in drug research. The Committee is of the opinion that more universities should be funded to bring more talent in the field of scientific research.

8.21 The Committee is of the considered view that the Human resource development policy for the Science & technology sector should be to create science leaders in diverse disciplines and to make it easy for Indian Post Doctoral and mid career scientists to return home. The way to address this could be to create a National pool of at least 1000-1500 central pool of jobs with central support to attract the best scientists from overseas and retain the good scientists who are attracted overseas. These scientists could be placed at the Centers of Excellence, University Science Centers, etc. based on their area of specialization and could be engaged in research full time.

The details regarding their cadre controlling authority, career growth, mobility/remuneration pattern etc. need examination.

8.22 The Committee also feels the need of devising flexible ways of hiring young scientists and reversing brain drain. During its interaction with the Department of Biotechnology, Ministry of Ocean Development and AYUSH, the Committee was informed about the need for creating incentives for scientists who presently worked on fixed salaries and lacked good promotion scheme. Different methods/criteria were being presently followed by ICMR, CSIR etc. in promotional schemes which needed to be streamlined.

8.23 The Committee during its interaction with officials of Department of Biotechnology and Ministry of Ocean Development has been informed about the prevailing red-tape and regulatory bottle-necks which delay commercialization of drug products. The Committee is of the opinion that de-bureaucratization of Science & Technology institutions should be ensured and their academic autonomy assured.

8.24 The Committee while agreeing with the observation of Regional Research Laboratory (RRL) Jammu on Drug Delivery System feels that knowledge in the field of Proteomics, Genomics and Bio- Technology should be harnessed in such a manner that could be designed for developing impressive drug delivery mechanism with precision. Drug Delivery Technique can enable patients to derive optimum benefits from different drugs administration. The Committee feels that innovative Drug Delivery System will not only increase the safety and efficacy level of the drugs but it can also improve the overall performance of a drug. The precision drug delivery system can offer additional advantages, such as easy administration of drugs, increased patient compliance, decreased side effects and considerable reduction in the cost of the development of drugs. The Committee is of the opinion that emphasis should be given on developing Novel Drug Delivery Systems (NDDS) e.g., Nanotechnology, Liposome, Transdermal Drug Delivery System (TDDS) etc. which is a feasible area for India to play in the Global market in the new patent regime, apart from its therapeutic advantages.

8.25 The Committee feels that following two things need to be done to deal with the adverse drug reaction cases:

(a) A comprehensive Adverse Drug Reaction Pharmaco Vigilance Monitoring Programme should be formulated and should be implemented under capacity building project; and

(b) The Adverse Drug Reaction Monitoring should be of high quality, done through a special unit manned by experts.

8.26 The Committee would like to draw the attention of the Department of Science & Technology to the important role of Nanotechnology in the field of drug development and research. The Committee strongly feels that under the aegis of the Department of Science & Technology, Institutes like Agarkar Research Institute, Bose Institute, Advanced Research Centre and Powder Metallurgy and New Materials, Sree Chitra Tirunal Institute of Medical Sciences and RRL, Jammu should try to develop, in joint collaboration, national nano-missions so that the basic tools of nanotechnology could be beneficially exploited and utilized in a productive way for developing new drugs with precision technology.

8.27 The Committee would like to draw the attention of the Department of Science and Technology that the Ministry of Earth Sciences has essentially worked on shoreline mangrove plantation and puffer fish extracts. These research projects could be handled by the CSIR and the Ministry of Earth Sciences focus on Ocean flora /fauna for research studies and examine whether organism found in the deep sea and remote areas (arctic region) could be the source of medicinal products. The Ministry of Earth Sciences may prepare a feasibility study report for this project based on data available from various sources located in remote region.

8.28 The Committee appreciates the Golden Triangle Partnership Scheme which is a new initiative by AYUSH, CSIR and ICMR. This scheme should be pursued with all seriousness to-

develop safe, effective and standardized herbal products for identified diseases,

develop new herbal medicines effective in disease conditions of national/ global concern,

utilize appropriate technologies to develop single and poly-herbal mineral products.

8.29 The Committee in its 146th report opined “that the traditional medicine is popular, accepted and used by most of the country’s population. Moreover, there is growing importance in traditional health systems in providing health care for wider population. Inspite of the Department’s efforts in formulating Golden Triangle, there is a need for giving boost to the herbal medicines. The Committee feels that with the abundant resources of medicinal plants all over the country, there is a need to set up an Herbal Research and Development Institute in a location where all the variation of our biodiversity can be tapped.” The Committee reiterates its earlier recommendation and feels that development of drugs of herbal origin needs specialized manpower having a modern mind set. This Institute will not only depend on classical theory of ISM, but will also have scientific basis and approach.

8.30 The National Institute of Pharmaceutical Education and Research (NIPER), an autonomous body set-up under the aegis of Ministry of Chemicals and Fertilizers, is a national level Institute in pharmaceutical sciences with the objective of becoming a centre of excellence for advanced studies and research in pharmaceutical sciences and toning up the level of pharmaceutical education and research by training the future teachers, research scientists and managers for the industry and profession. The Committee feels that the potential of this premier institute should be utilized efficiently for drug research in the country.

ANNEXURE

ANNEXURE

LIST OF REPRESENTATIVES FROM THE VARIOUS MINISTRIES/DEPARTMENTS WHO APPEARED BEFORE THE COMMITTEE FOR ORAL EVIDENCE.

SL No. Date of Meetings Witness

1 2 3

Department of Science & Technology

1. 05.07.2005 1. Prof V.S. Ramamurthy, Secretary

2. Shri K.P. Pandian, J.S. & F.A

3. Dr. Laxman Prasad, Scientist ‘G’

4. Dr. G.J. Samathanam, Scientist ‘F’

5 Dr. (Mrs.) S.N. Khan, Scientist ‘F’

Department of Bio- Technology

2. 05.07.2005 1. Dr. M.K Bhan, Secretary

2. Shri U.N. Behera, Joint Secretary

3. Shri K.P. Pandian, J.S.& F.A.

4. Dr. S. Natesh, Scientist ‘H’

5. Dr. K.K. Tripathi, Scientist ‘G’

6. Dr. (Mrs.) Seema Wahab, Scientist ‘G’

7. Dr. T.S. Rao, Scientist ‘F’

8. Shri S. Sinha, Scientist ‘F’

9. Dr. (Ms.) Renu Swarup, Scientist ‘F’

10. Shri Virendra Kapoor, Deputy Secretary

Department of Scientific & Industrial Research

3. 20.09.2005 1. Dr. R.A. Mashelkar, Secretary

2. Dr. C.M. Gupta, Director, CDRI

3. Dr. J.S. Yadav, Director, IICT

4. Dr. G.N. Qazi, Director, RRL

5. Dr. R.R. Abhyankar, Adviser, DSIR

6. Dr. S.N. Sharma, Head, RDPD, CSIR

7. Dr. D.Y. Rao, Head, TNBD, CSIR

8. Dr. Rajinder Prasad, Head, ISTAD, CSIR

9. Dr. J.S. Khan, Scientist, CSIR

Ministry of Ocean Development

4. 21.09.2005 1. Dr. P.S. Goel, Secretary,

2. Shri S.K. Das, Scientist ‘G’

3. Shri Ajai Saxena, Director

4. Dr. Ram Raghubir, CDRI, Lucknow

Department of AYUSH

5. 28.10.2005 1. Shri Shiv Basant, Joint Secretary

2. Dr. S.K. Sharma, Adviser, Ayurveda

3. Dr. S.P. Singh, Adviser, Homeopathy

4. Prof A.A. Ansari, Adviser, Unani

5. Shri Bala Prasad, Director

6. Dr. G.S. Lavekar, Director

7. Dr. Khalid Siddiqui, Director

8. Dr. C. Naik, Director

9. Dr. B.T.C. Murthy, Director

10. Dr. D.C. Katoch, Dy. Advisor

Ministry of Environment & Forests

6 10.01.2006 1. Dr. Prodipto Ghosh, Secretary

2. Shri Naresh Dayal, Additional Secretary

3. Shri D.D. Verma, Joint Secretary

Drugs Controller-General of India

7. 30.01.2006 Shri Ashwani Kumar, Drugs Controller General (India)

Indian Council of Medical Research

8. 10.02.2006 1. Prof N.K. Ganguly, Director-General, ICMR

2. Dr. Vasantha Muthuswamy, Senior

Deputy Director-General (BMS)

3. Dr. S.D. Seth, Chair (Pharmacology), ICMR

4. Dr. A.K. Gupta, Deputy Director-General &

Chief, Traditional Medicine Unit

5. Dr. Vijay Kumar, Additional Director-General

MINUTES

XVIII EIGHTEENTH MEETING

The Conm1ittee met at 11.00 A.M. on Tuesday, the 5th July, 2005 in Committee Room ‘B’, Ground Floor. Parliament House Annexe, New Delhi.

PRESENT

1. Shri P.G.Narayanan –– Chairman

RAJYA SABHA

2. Prof Saif-ud-Din Soz

3. Shri Dilip Singh Judev

4. Shri Birabhadra Singh

5. Smt. Kum Kum Rai

LOK SABHA

6. Dr. Sujan Chakraborty

7. Shri Pankaj Chaudhery

8. Shri Anantrao Gudhe

9. Shri Babubhai Katara

10. Shri A. Venkatesh Naik

11. Shri Brahmananda Panda

12. Shrimati Neeta Pateriya

13. Shri Bachi Singh Rawat

14. Shrimati Jayaben Thakkar

15. Shri V. Aruna Kumar

SECRETARIAT

Shri R.K.Singh, Officer on Special Duty

Shri Alok Kumar Chatterjee, Deputy Secretary

Shri CB.Rai. Under Secretary

Shri S. Rangarajan, Committee Officer

Shri Girija Shankar Prasad, Committee Officer

2. * * *

3. The Committee then considered its future programme and decided to take-up for its consideration the following subjects in order of priority (i) Drugs & Pharmaceutical Research Programme with particular reference to Herbal Research (ii) *** (iii) *** (iv) *** . The Committee also directed the Secretariat to obtain relevant information/papers on the first two subjects, in the first instance from the concerned Ministries/Departments.

4. The Committee then adjourned at 11.55 A.M.

XIX NINETEENTH MEETING

The Committee met at 11.00 A.M. on Tuesday, the 5th July, 2005 in Committee Room ‘B’, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G.Narayanan –– Chairman

RAJYA SABHA 2. Prof Saif-ud-Din Soz 3. Dr. Prabha Thakur 4. Shri Nand Kishore Yadav 5. Shri Ravula Chandra Sekar Reddy 6. Shrimati Kum Kum Rai 7. Shri Birabhadra Singh

LOK SABHA 8. Shri Anantrao Gudhe 9. Shri A. Venkatesh Naik 10. Shri Brahmananda Panda 11. Shrimati Neeta Pateriya 12. Shri Bachi Singh Rawat 13. Dr. Ramlakhan Singh 14. Shri V. Aruna Kumar 15. Shri Francis Fanthome

SECRETARIAT Shri R.K.Singh, Officer on Special Duty Shri Alok Kumar Chatterjee. Deputy Secretary Shri C.B. Rai. Under Secretary Shri S. Rangarajan. Committee Officer Shri Girija Shankar Prasad, Committee Officer

WITNESSES REPRESENTATIVES OF THE DEPARTMENT OF SCIENCE & TECHNOLOGY 1. Prof V.S. Ramamurthy, Secretary 2. Shri K.P. Pandian, J.S. & F.A. 3. Dr. Laxman Prasad, Scientist ‘G’ 4. Dr. G.J. Samathanam, Scientist -F’ 5. Dr. (Mrs.) S.N. Khan, Scientist ‘F’

REPRESENTATIVES OF THE DEPARTMENT OF BIO-TECHNOLOGY 1. Dr. M. K. Bhan, Secrctary 2. Shri U. N. Behera, Joint Secretary

3. Shri K.P. Pandian, J.S. & F.A.

4. Dr. S. Natesh, Scientist ‘H’

5. Dr. K.K. Tripathi, Scientist ‘G’

6. Dr. (Mrs.) Seema Wahab. Scientist ‘G’

7. Dr. T.S. Rao, Scientist ‘F’

8. Shri S. Sinha, Scientist ‘F’

9. Dr. (Ms.) Renu Swarup, Scientist ‘F’

10. Shri Virendra Kapoor, Deputy Secretary

2. At the outset the Chairman welcomed the Secretary and other representatives of the Department of Science & Technology and requested the Secretary to make a presentation on the aspects related to the Drugs and Pharmaceuticals Programme, including Herbal Medicines. The Secretary made a visual presentation of the Programme of the Department and explained the different activities under the programme. The Members then sought clarifications on points arising out of the presentation. The Secretary replied to them.

The officials then withdrew.

3. The Committee, thereafter, adjourned at 12.20 P.M. for tea and re-assembled at 12.45 P.M. to hear the Secretary, Department of Biotechnology.

4. The Chairman welcomed the Secretary and other representatives of the Department of Biotechnology and requested the Secretary to make a presentation on the aspects related to the Drugs and Pharmaceuticals Programme, including Herbal Medicines. The Secretary made a visual presentation of the Programme of the Department and explained the different activities under the programme. The Members then sought clarifications on points arising out of the presentation. The Secretary replied to them.

The officials then withdrew.

A verbatim record of the proceedings was kept.

5. The Committee then adjourned at 1.45 P.M.

II SECOND MEETING

The Committee met at 3.00 P.M. on Monday, the 29th August, 2005 in Committee Room ‘E’, Basement, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G.Narayanan –– Chairman

RAJYA SABHA 2. Prof Saif-ud-Din Soz 3. Shri Birabhadra Singh

LOK SABHA 4. Shri Jasubhai Dhanabhai Barad 5. Dr. Sujan Chakraborty 6. Shri Anant Gudhe 7. Shri A. Venkatesh Naik 8. Shri Brahmananda Panda 9. Shrimati Neeta Pateriya 10. Shrimati Jayaben Thakkar

SECRETARIAT Shri R.K.Singh, Officer on Special Duty Shri Alok Kumar Chatterjee. Deputy Secretary Shri C.B. Rai. Under Secretary Shri S. Rangarajan. Committee Officer Shri Girija Shankar Prasad, Committee Officer

2. The Committee considered its future programme And recalled that in the meeting held on 6th June, 2005, it had identified the subject matter of Drugs and Pharmaceuticals Research including Herbal Medicines for its examination. In this regard, it heard the views of the Secretaries of the Department of Science & Technology and Department of Bio-technology, in its meeting held on 5th July, 2005. The Committee decided to hear the views of the Secretaries of other two departments, namely, Department of Scientific & Industrial Research and Department of Ocean Development on 20th and 21st September, 2005 respectively.

3. The Committee further decided to undertake study visit to Mumbai, Pune and Goa from 26th September to 4th October, 2005 to examine the aspects related to Drugs & Pharmaceuticals Programme including Herbal Medicines by visiting some of the Drugs & Pharmaceuticals Labs. The Committee also decided to utilize the opportunity to visit, at the places of visit, certain institutes/bodies/centers etc., falling within the administrative control of the Ministries/Departments attached with the Committee, to acquaint itself with their functioning and also to analyse problems being faced be them. The committee directed the Secretariat to take necessary action accordingly.

4. The Committee than adjourned at 3.30 p.m. to meet again at 3.00 p.m. on Tuesday, the 20th September, 2005.

III THIRD MEETING

The Committee met at 3.00 P.M. on Tuesday, the 20th September, 2005 in Committee Room A, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G.Narayanan –– Chairman

RAJYA SABHA

2. Prof. Saif-ud-Din Soz

3. Shri Birabhadra Singh

LOK SABHA

4. Dr. Sujan Chakraborty

5. Shri Francis Fanthome

6. Shri Anant Gudhe

7. Shri A. Venkatesh Naik

8. Shri Brahmananda Panda

9. Shrimati Neeta Pateriya

10. Shri Adhalrao Shivaji Patil

11. Shri Bachi Singh ‘Bachda’ Rawat

12. Shrimati Jayaben Thakkar

13. Shri SitaRam Yadav

SECRETARIAT

Shri Alok Chatterjee, Deputy Secretary

Shri C.B.Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

REPRESENTATIVES OF THE DEPARTMENT OF SCIENTIFIC & INDUSTRIAL RESEARCH

1. Dr. R. A. Mashelkar, Secretary

2. Dr. C.M. Gupta, Director, CDRI

3. Dr. J.S. Yadav, Director, IICT

4. Dr. G.N. Qazi, Director, RRL

5. Dr. R.R. Abhyankar, Adviser, DSIR

6. Dr. S.N. Sharma, Head, RDPD, CSIR

7. Dr. D.Y. Rao, Head, TNBD, CSIR

8. Dr. Rajinder Prasad, Head, IST AD, CSIR

9. Dr. J.S. Khan, Scientist, CSIR

2. The Chairman welcomed the Secretary and other representatives of the Department of Scientific & Industrial Research and requested the Secretary to make a presentation on the aspects related to the Drugs and Pharmaceuticals Programme, including Herbal Medicines. The Secretary made a visual presentation of the Programme of the Department and explained the different activities under the programme. The Members then sought clarifications on points arising out of the presentation. The Secretary replied to them.

The officials then withdrew.

A verbatim record of the proceedings was kept

3. The Committee then adjourned at 5.10 P.M. to meet again at 11.00 A.M. on Wednesday, the 21st September, 2005.

IV FOURTH MEETING

The Committee met at 11.00 A.M. on Wednesday, the 21st September, 2005 in Committee Room ‘C’, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G.Narayanan –– Chairman

RAJYA SABHA

2. Prof. Saif-ud-Din Soz

3. Shrimati Kum Kum Rai

LOK SABHA

4. Dr. Sujan Chakraborty

5. Shri Pankaj Choudhary

6. Shri A. Venkatesh Naik

7. Shri Brahmananda Panda

8. Shrimati Neeta Pateriya

9. Shri Adhalrao Shivaji Patil

10. Shri Bachi Singh ‘Bachda’ Rawat

11. Dr. Ramlakhan Singh

12. Shrimati Jayaben Thakkar

13. Shri D. Venugopal

SECRETARIAT

Shri Alok Chatterjee, Deputy Secretary

Shri C.B. Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

REPRESENTATIVES OF THE DEPARTMENT OF OCEAN DEVELOPMENT

1 . Dr. P.S. Goel, Secretary

2. Shri S.K. Das, Scientist ‘G’

3. Shri Ajai Saxena, Director

4. Dr. Ram Raghubir, CDRI, Lucknow

2. The Chairman welcomed the Secretary and other representatives of the Department of Ocean Development and requested the Secretary to make a presentation on the aspects related to the Drugs and Pharmaceuticals Programme, including Herbal Medicines. The Secretary made a visual presentation of the Programme of the Department and explained the different activities under the programme. The Members then sought clarifications on points arising out of the presentation The Secretary replied to them.

3. During the course of discussion, the Committee also discussed the process of obtaining clearance in respect of animal trial in connection with medical research for drug development. The Secretary informed the Committee that it is mandatory to get clearance from the Committee for the purpose of Control and Supervision on Experiments on Animals (CPCSEA), which is a part of animal welfare division of the Ministry of Environment & Forests. He further informed that the CPCSEA, however, restrict the use of animals for medical research and takes much time to grant the approval for animal experimentation needed for drug development. The Committee expressed its serious concern over the problem and decided to take up the matter for discussion in its future meetings

The officials then withdrew.

4. The Committee also decided to call the Secretary of the Department of AYUSH and representatives of Indian Council of Medical Research; National Institute of Pharmaceutical Education & Research; Committee for the purpose of Control and Supervision on Experiments on Animals (CPCSEA) and Drug Controller General of India to hear their views on the subject matter of Drugs Pharmaceutical Programme.

A verbatim record of the proceedings was kept.

5. The Committee then adjourned at 12.45 P.M.

V FIFTH MEETING

The Committee met at 11.00 A.M. on Friday, the 28th October, 2005 in Room No. 63, First Floor, Parliament House, New Delhi.

PRESENT 1. Shri P.G. Narayanan –– Chairman

RAJYA SABHA

2. Prof Saif-ud-Din Soz

3. Shri Nand Kishore Yadav

4. Shri Ravula Chandra Sekar Reddy

5. Shrimati Kum Kum Rai

6. Shri Birabhadra Singh

7. Dr. Chhattrapal Singh Lodha

LOK SABHA

8. Dr. Sujan Chakraborty

9. Shri Francis Fanthome

10. Shri Anantrao Gudhe

11. Shri A. Venkatesh Naik

12. Shri Brahmananda Panda

13. Shri Adhalrao Shivaji Patil

14. Shri Bachi Singh ‘Bachda’ Rawat

15. Shri K.C. Singh ‘Baba’

16. Shri Rakesh Singh

17. Dr. Ramlakhan Singh

18. Shri D. Venugopal

19. Shri Aruna Kumar Vundavalli

SECRETARIAT

Shri R.K.Singh, Officer on Special Duty

Shri Alok Chatterjee, Deputy Secretary

Shri C. B. Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

REPRESENTATIVES OF THE DEPARTMENT OF AYURVEDA, YOGA & NATUROPATHY, UNANI, SIDDHA AND HOMOEOPATHY (AYUSH)

1. Shri Shiv Basant, Joint Secretary

2. Dr S.K. Sharma, Adviser Ayurveda

3. Dr. S. P. Singh, Adviser, Homeopathy

4. Prof. A.A. Ansari. Adviser, Unani

5. Shri Bala Prasad, Director

6. Dr. G.S. Lavekar, Director

7. Dr. Khalid Siddiqui, Director

8. Dr. C. Naik, Director

9. Dr. B.T.C. Murthy, Director

10. Dr. D.C. Katoch, Dy. Advisor

2. * * *

3. The Chairman informed the Committee that due to pre-occupation of the Secretary of the Department of AYUSH and on her request, he had permitted the Joint Secretary, Shri Shiv Basant to express the Department’s views on the Drugs and Pharmaceuticals Programme including Herbal Medicines.

4. The Chairman, then, welcomed the Joint Secretary and other representatives of the Department of AYUSH and requested the Joint Secretary to make a presentation on the Programme. The Joint Secretary and other officials of the Department made a visual presentation of the Programme of the Department and explained the various ongoing and proposed activities under the programme. The Members then sought clarifications on points arising out of the presentation. The officials replied to them.

The officials then withdrew.

A verbatim record of the proceedings was kept.

5. * * *

6. The Committee adjourned at 1.15 P.M.

VIII EIGHTH MEETING

The Committee met at 3.00 P.M. on Tuesday, the 20th December, 2005 in Room No. 121 (Committee Chairman's Room), First Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G. Narayanan — Chairman

RAJYA SABHA

2. Prof. Saif-ud-din Soz

3. Dr. Prabha Thakur

4. Shri Ravula Chandra Sekar Reddy

5. Smt. Kum Kum Rai

LOK SABHA

6. Dr. Sujan Chakraborty

7. Shri Jasubhai Dhanabhai Barad

8. Shri Adhalrao Shivaji Patil

9. Shri K.C. Singh ‘Baba’

10. Shri Rakesh Singh

11. Shri Aruna Kumar Vundavalli

SECRETARIAT

Shri R.K.Singh, Officer on Special Duty

Shri Alok Kumar Chatterjee, Deputy Secretary

Shri C. B. Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

2. * * *

3. * * *

4. The Committee, then, decided to hear the oral evidence of the representatives of the Ministry of Environment and forests in respect of control and supervision on experiments on Animals for the purpose of Drugs and Pharmaceutical Research, in its next meeting to be held on the 10th January, 2006. The Committee also decided to hear the Drugs Controller General of India and representatives of Indian Council of Medical Research in the matter in its future meetings.

5.The Committee then adjourned at 4.35 P.M.

IX NINTH MEETING

The Committee met at 2.00 P.M. on Tuesday, the 10th January, 2006 in Committee Room ‘A’, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G. Narayanan — Chairman

RAJYA SABHA 2. Shri Ravula Chandra Sekar Reddy 3. Shrimati Kum Kum Rai 4. Shri Birabhadra Singh

LOK SABHA 5. Dr. Sujan Chakraborty 6. Shri Pankaj Choudhary 7. Shri Francis Fanthome 8. Shri Anant Gudhe 9. Shri A. Venkatesh Naik 10. Shrimati Neeta Pateriya 11. Shri Adhalrao Shivaji Patil 12. Shri Bachi Singh ‘Bachda’ Rawat 13. Shrimati Jayaben Thakkar 14. Shri Sita Ram Yadav

SECRETARIAT Shri R.K. Singh, Officer on Special Duty Shri Alok Chatterjee, Deputy Secretary Shri C.B. Rai, Under Secretary

REPRESENTATIVES OF THE MINISTRY OF ENVIRONMENT AND FORESTS 1. Dr. Prodipto Ghosh, Secretary 2. Shri Naresh Dayal, Additional Secretary 3. Shri D.D. Verma, Joint Secretary

2. The Chairman welcomed the Secretary and other representatives of the Ministry of Environment & Forests and requested the Secretary to clarify certain points regarding experimentation on animals for medical research and aspects relating to conservation of medicinal plants under the Drugs & Pharmaceuticals Programme. The Secretary gave clarifications on the points raised by the Chairman. The Members then sought clarifications on points arising out of the presentation. The Secretary replied to them.

2A. A verbatim record of the proceedings was kept.

3. The Committee then decided to hear the Drugs Controller General of India at its next meeting to be held on the 25th January, 2006 to hear his views on the subject.

4. The Committee then adjourned at 3.10 P.M.

X TENTH MEETING

The Committee met at 11.00 A.M. on Monday, the 30th January, 2006 in Committee Room ‘A’, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G.Narayanan — Chairman

RAJYA SABHA

2. Shri Ravula Chandra Sekar Reddy

3. Shri Birabhadra Singh

LOK SABHA

4. Dr. Sujan Chakraborty

5. Shri Francis Fanthome

6. Shri Anant Gudhe

7. Shri Bachi Singh ‘Bachda’ Rawat

8. Shri Rakesh Singh

9. Dr. Ramlakhan Singh

9. Shri D. Venugopal

SECRETARIAT

Shri R.K. Singh, Officer on Special Duty

Shri Alok Chatterjee, Deputy Secretary

Shri C.B. Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

REPRESENTATIVE OF THE OFFICE OF DRUGS CONTROLLER GENERAL (INDIA)

Shri Ashwani Kumar, Drugs Controller General (India)

2. * * *

3. * * *

4. The Chairman then welcomed the Drugs Controller General (India) and requested him to make a presentation on the aspects related to the Drugs and Pharmaceuticals Research, including Herbal Medicines. The Drugs Controller General made a visual presentation on the role of his office on the subject and explained the various activities under the programme. The Members then sought clarifications on the points arising out of the presentation. The Drugs Controller General replied to them.

The official then withdrew.

4A. A verbatim record of the proceedings was kept.

5. The Committee then decided to hear the Director General, Indian Council of Medical Research at its next meeting to be held on the 10th February, 2006. It also decided to have an internal discussion on the same day on the Wild Life (Protection) Amendment Bill, 2005, which has been referred to the Committee by the Hon’ble Chairman, Rajya Sabha for examination and report.

6. The Committee then adjourned at 12.30 P.M.

XI ELEVENTH MEETING

The Committee met at 11.00 A.M. on Friday, the 10th February, 2006 in Committee Room ‘C’, Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G. Narayanan — Chairman

RAJYA SABHA

2. Shri Ravula Chandra Sekar Reddy

3. Shri Birabhadra Singh

LOK SABHA

4. Dr. Sujan Chakraborty

5. Shri Pankaj Chaudhary

6. Shri Francis Fanthome

7. Smt Neeta Pateriya 8. Shri Bachi Singh ‘Bachda’ Rawat

9. Shri K.C. Singh ‘Baba’

10. Dr. Ramlakhan Singh

11. Jayaben B. Thakkar

SECRETARIAT

Shri R.K. Singh, Officer on Special Duty

Shri Alok Chatterjee, Deputy Secretary

Shri C.B. Rai, Under Secretary

REPRESENTATIVES OF THE INDIAN COUNCIL OF MEDICAL RESEARCH

1. Prof. N.K. Ganguly, Director-General, (ICMR)

2. Dr. Vasantha Muthuswamy, Senior Deputy Director- General(BMS)

3. Dr. S.D. Seth, Chair (Pharmacology), ICMR

4. Dr. A.K. Gupta, Deputy Director-General & Chief, Traditional

Medicine Unit

5. Dr. Vijay Kumar, Additional Director-General

2. The Chairman welcomed the Director-General and other representatives of the Indian Council of Medical Research and requested the former to make a presentation on the aspects related to the Drugs and Pharmaceuticals Research, including Herbal Medicines. The Director-General made a visual presentation on the role of ICMR on the subject and explained the various activities under the programme. The Members then sought clarifications on the points arising out of the presentation. The Director- General replied to them.

The officials then withdrew.

2A. A verbatim record of the proceedings was kept.

3. The Committee, thereafter, adjourned at 1.00 P.M. for tea and reassembled at 1.20 P.M.

4. * * *

5. The Committee, then, adjourned at 2.15 P.M.

II SECOND MEETING

The Committee met at 11.00 A.M. on Wednesday, the 27th September, 2006 in Committee Room ‘A’ Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri Bachi Singh ‘Bachda’ Rawat —— In the Chair

RAJYA SABHA

2. Dr. Prabha Thakur

3. Shrimati Viplove Thakur

4. Shri Suryakantbha Acharya

5. Shri Bhagirathi Majhi

6. Shri Kamal Akhtar

7. Shri Saman Pathak

8. Dr. Barun Mukherjee

LOK SABHA

9. Shri Pankaj Choudhary

10. Shri Francis Fanthome

11. Shri A. Venkatesh Naik

12. Shri Brahmananda Panda

13. Shrimati Neeta Pateriya

14. Shri Pratik Prakashbapu Patil

15. Dr. Ramlakhan Singh

16. Shrimati Jayaben B. Thakkar

17. Shri Mitrasen Yadav

18. Shri Sita Ram Yadav

SECRETARIAT

Shri R.K. Singh, Officer on Special Duty

Shri Alok Chatterjee, Deputy Secretary

Shri S. Rangarajan, Committee Officer

2. In the absence of the Chairman, Shri Bachi Singh ‘Bachda’ Rawat chaired the meeting.

3. The Committee took-up for consideration its draft One Hundred Sixty-second Report on Drugs & Pharmaceuticals Programme including herbal medicines. After some discussion on the said report, the Committee observed that there is a need to seek some more clarifications regarding certain points and it, hence, directed the Secretariat to obtain further clarifications from the Ministry of Earth Sciences and Department of Science & Technology. * * *

4. The Committee then adjourned at 11.40 A.M. to meet again on Monday, the 16th October, 2006.

III THIRD MEETING

The Committee met at 11.00 A.M. on Monday, the 16th October, 2006 in Committee Room ‘A’ Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G. Narayanan –– Chairman

RAJYA SABHA 2. Shri Suryakantbha Acharya 3. Shri Bhagirathi Majhi 4. Shri Saman Pathak 5. Dr. Barun Mukherjee

LOK SABHA 6. Dr. Sujan Chakraborty 7. Shri Pankaj Choudhary 8. Shri Francis Fanthome 9. Shri A. Venkatesh Naik 10. Shri Brahmananda Panda 11. Shrimati Neeta Pateriya 12. Shri Jaysingrao Gaikwad Patil 13. Shri Pratik Prakashbapu Patil 14. Shri Bachi Singh ‘Bachda’ Rawat 15. Shri K.C. Singh “Baba” 16. Shri Aruna Kumar Vundavalli 17. Shri Mitrasen Yadav 18. Shri Sita Ram Yadav

SECRETARIAT Shri R.K. Singh, Officer on Special Duty Shri Alok Kumar Chatterjee, Deputy Secretary Shri C.B. Rai, Under Secretary Shri S. Rangarajan, Committee Officer

2. The Committee took-up further consideration of draft One Hundred Sixty-second Report on Drugs & Pharmaceuticals Programme including herbal medicines. After some discussion on the said report, some members suggested to add/ modify certain recommendations in the report. The Committee directed the Secretariat to do the needful.

3. * * *

4. The Committee then adjourned at 12.05P.M. to meet again at 11.00A.M. on Monday, the 6th November, 2006.

IV FOURTH MEETING

The Committee met at 11.00 A.M. on Monday, the 6th November, 2006 in Committee Room ‘B’ Ground Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri Bachi Singh ‘Bachda’ Rawat — In the Chair.

RAJYA SABHA

2. Dr. Prabha Thakur

3. Shri Suryakantbha Acharya

4. Shri Bhagirathi Majhi

5. Shri Jabir Husain

6. Dr. Barun Mukherjee

LOK SABHA

7. Dr. Sujan Chakraborty

8. Shri Thupstan Chhewang

9. Shri Pankaj Choudhary

10. Shri Francis Fanthome

11. Shri A. Venkatesh Naik

12. Shri Brahmananda Panda

13. Shrimati Neeta Pateriya

14. Shri Pratik Prakashbapu Patil

15. Shri Aruna Kumar Vundavalli

SECRETARIAT

Shri R.K. Singh, Officer on Special Duty

Shri C. B. Rai, Under Secretary

Shri S. Rangarajan, Committee Officer

2. In the absence of the Chairman, Shri Bachi Singh ‘Bachda’ Rawat chaired the meeting.

3. The Committee took-up further consideration of its draft One Hundred Sixty-second Report on Drugs & Pharmaceuticals Programme including herbal medicines. Some members suggested certain modifications in the report which were carried out. The Committee, thereafter, adopted the report.

4. The Committee then adjourned at 12.45 P.M.

V FIFTH MEETING

The Committee met at 3.00 P.M. on Tuesday, the 12th December, 2006 in Room No. ‘63’, First Floor, Parliament House Annexe, New Delhi.

PRESENT 1. Shri P.G. Narayanan —— Chairman

RAJYA SABHA

2. Shri Bhagirathi Majhi

3. Shri Saman Pathak

4. Shri Ravula Chandra Sekar Reddy

5. Dr. Barun Mukherjee

LOK SABHA

6. Shri Francis Fanthome

7. Shri Brahmananda Panda

8. Shri Aruna Kumar Vundavalli

9. Shrimati Jayaben B. Thakkar

10. Shri Mitrasen Yadav

11. Shri Sita Ram Yadav

SECRETARIAT

Shri R.K. Singh, Officer on Special Duty Shri Alok Kumar Chatterjee, Deputy Secretary Shri J. Sundriyal, Under Secretary Shri S. Rangarajan, Committee Officer

2. * * *

3. The Committee decided to present *** the 162nd report which was adopted by it in its meeting held on 6th November, 2006. The Committee authorized its Chairman and in his absence Shri Ravula Chandra Sekar Reddy to present the reports in Rajya Sabha and to lay the copies of the reports on the table of Lok Sabha by Shri Francis Fanthome and in his absence by Shri Brahmananda Panda.

4. * * *

4. The Committee then adjourned at 3.40 P.M.