HEALTHCARE, DRUGS & PHARMACEUTICALS

CSIR has geared itself to face the challenges in the Healthcare, Drugs and Pharmaceuticals sector by taking several measures such as prioritization of research programmes, creation of state-of the- art facilities, induction of new talent and most importantly, establishing linkages within CSIR and with other national agencies/industry.

The projects networking CSIR laboratories, other R&D institutions, and industry to capitalize on their combined strength include those on: new drugs based on our traditional knowledge, biodiversity, marine resources, search for new molecular targets for selected pathogens, in-silico biology, predictive medicine, new animal models and animal substitute technologies, etc.

Recent advances in biology such as genome sequencing have opened up unlimited opportunities in medicine. After deciphering sequence of genes (structural genomics), it is now possible to elucidate their function (functional genomics).  Ultimately it is believed that through proteomics, new disease markers and drug targets can be identified that will help design products to prevent, diagnose and treat disease. Technologies of combinatorial synthesis and high-throughput screening (HTS) offer the potential to speed up the pace of drug research and reduce the time and cost of investment in drug discovery. All these tools and techniques and research disciplines are now being applied in current R&D programmes of many CSIR laboratories in order to become internationally competitive.

That CSIR has made valuable contributions to the industry and the society in this vital sector are amply reflected by the development of several novel drugs, which have been successfully commercialized by the industry, and are currently marketed (Saheli, E-mal, Elubaquin, Promind, Asmon, etc.), and dozens of process technologies leading to commercial production of high-value drugs/drug intermediates (l-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 for this dreaded disease.  The molecule, Sudoterb reduces the treatment time to 2 months from 6-8 months and has lesser side effects.

MANDATE

CSIR’s composite mandate in the sector covers a large spectrum of activities, and it may be summed up as: Broad-based, multi-disciplinary research — basic, exploratory and applied — in order to develop suitable knowledge-based products, processes and interventions; to investigate and advise on abatement and control of environmental and industrial health hazards; and to provide testing and analytical services, contract research, consultancy, information services and training for development of human resource. The products developed, viz., new drugs, diagnostics, vaccines, herbal medicines, nutraceuticals, inventions, devices and gadgets for monitoring air, water, food contaminants/adulterants, will comply with international regulatory requirements, quality and standards.”

CORE COMPETENCE

CSIR laboratories at the forefront of drugs and pharmaceutical research and the expertise available are as follows:

 Labs

Areas of Core Competence

Central Drug Research Institute (CDRI, Lucknow)

Drug discovery to development, synthetic/natural product chemistry, combinatorial chemical synthesis, molecular modelling, HTS, structural biology, broad-based biological screening, pharmacology, pharmaco-kinetics, toxicology, phase I clinical studies, chemical and fermentation technology, quality control and standardization, proteomics, medicinal chemistry, molecular and cell biology, pharmacology, and phytochemicals/herbal drugs/nutraceuticals research.

 

Indian Institute of Chemical Biology (IICB, Kolkata)

Synthetic/natural products/medicinal chemistry, infectious diseases, cellular physiology, drug designing, molecular modelling, molecular biology, biotechnology, cell signals for oncogene expression and metabolic diseases, immunology, human genetics, genomics, proteomics, bioinformatics, molecular and cell biology, pharmacology, phytochemicals/nutraceuticals.

 

Indian Institute of Chemical Technology (IICT, Hyderabad)

Synthetic and natural products chemistry, chemical /process engineering, combinatorial/medical chemistry, asymmetric synthesis for chiral drugs, custom synthesis, computer-aided modelling and drug design, glyco-therapeutics, peptides and peptido-mimetics, enzyme mimics (drug delivery systems), pharmacology, pre-clinical toxicity pharmacokinetics, toxicology, phytochemicals/herbal drugs/nutraceuticals research, quality control and formulation.

 

Indian Institute of Microbial Technology (IMTECH, Chandigarh)

Molecular and cell biology, microbial genetics, immunology, structural biology, protein engineering, fermentation technology, culture type depository, microbial gene bank, bioinformatics, proteomics, molecular and cell biology.

 

Institute of Genomics and Integrative Biology (IGIB, Delhi)

Genomics & Molecular Medicine, Predictive medicine, Genome Informatics (in-silico biology), Bio-informatics, Pathway modelling, Proteomics structural biology, Comparative Genomics & Gene Expression, Immunology and molecular genetics of respiratory disorders including allergy, Nucleic Acids & Peptides, Bioactive molecules of medicinal importance.

 

Regional Research Laboratory (RRL-Jammu)

Agrotechnology, synthetic (chiral) and natural product chemistry, herbal drugs, select biological screening, bioprospecting, microbial biodiversity for industrially useful enzymes, genetic fingerprinting, identification/authentication of medicinal plants, fermentation technology, quality control and standardization of herbal drugs, establishment of medicinal plants gene bank, bioinformatics, pharmacology phytochemicals/herbal drugs/nutraceuticals research. 

 

Central Institute of Medicinal and Aromatic Plants (CIMAP, Lucknow)

Agrotechnology of economically important herbs, process technology for phytochemicals, herbal drugs, nutraceuticals, genetic finger printing of plants/herbs, plant bioinformatics, genetic improvement, bioprospecting, molecular and cell biology, quality control and formulation.

 

Centre for Cellular and Molecular Biology (CCMB, Hyderabad)

Advanced molecular and cell biology, biotechnology, sperm-associated proteins/fertility-potential of sperm, DNA-fingerprinting, signal transduction, eye diseases, hepatitis vaccine, microbial genetics, transgenics, anti-microbial proteins, genomics, proteomics molecular and cell biology

 

National Chemical Laboratory (NCL, Pune)

Synthetic chemistry, tissue culture, biotechnology, industrial microbiology, nanoparticle technology, smart polymer gels, chemical/process engineering, process/enzyme/fermentation technology, combinatorial chemistry, medicinal chemistry, quality control and formulation

 

Institute of Himalayan Bioresource Technology (IHBT, Palampur)

Identification, collection, isolation and characterization of plants and microbes chemical and molecular characterization of bioactives, genomics, tissue culture, agro-technology of medicinal plants, phytochemicals/herbal drugs/nutraceuticals research, and chemical/process engineering

 

Industrial Toxicology Research Centre (ITRC, Lucknow)

In vitro test systems for bio-evaluation/identification of molecules or neurological disorders and antioxidant activity, complete toxicity evaluation in small animals; identification and action mode of hazardous toxicants/pollutants, diagnostics for toxicants/pollutants; safety evaluation/preventive measures for environmental/industrial hazards, and quality assessment of drinking water

 

National Botanical Research Institute (NBRI, Lucknow)

Pharmacognosy, ethnopharmacology, herbal drugs (authentication, standardization, characterization), nutraceuticals, agro-technology of medicinal plants, plant bioinformatics, genetic characterization and genetic improvement of economically important plants, proteomics, transgenics, molecular and cell biology, pharmacology, phytochemicals/herbal drugs, quality control and formulation

 

Central Salt & Marine Chemicals Research Institute (CSMCRI, Bhavnagar),

Bioactives from plants, cultivation of desert economic plants and their value addition, sea weed cultivation, phycocolloids and marine microbes, biotechnology, synthetic chemistry and drug intermediates desalination water treatment technology for pure water for drinking, low sodium and plant/herbal salt

 

Regional Research Laboratory (RRL, Jorhat).

 

Bioactives from plants, drugs and drug intermediates, isolation and characterization of active molecules and analytical services

 

National Institute of Oceanography (NIO, Goa)

Collection and identification of marine flora and fauna, biological screening (antimicrobial, anticancer, oxytocic, anti-inflammatory, anti-fouling cytotoxic, antimalarial, antiosteoporotic antiviral, immunomodulatory) and marine natural product chemistry for the identification and structure elucidation of active molecules

 

Regional Research Laboratory (RRL-Thiruvananthapuram)

 

Synthesis of drugs/drug intermediates, natural product isolation, biological screening, chemical finger printing, herbal drugs, nutraceuticals, bioprocess/enzyme technology and phytochemicals.

Central Food Technological Research Institute (CFTRI, Mysore)

Nutraceuticals, health-promoting effects of spices/herbs/foods (antioxidants, digestion-stimulants, anti-inflammatory), traditional remedies, food-safety/nutritional toxicology, nodal codex food laboratory, animal and plant cell culture, PCR probes and biosensors, phytochemicals/nutraceuticals research, quality control & formulation, toxicology and bioprocess/enzyme/fermentation technology

 

Central Leather Research Institute (CLRI, Chennai)

Controlled drug delivery systems, collagen-based biomaterials, skin biology

 

Central Glass and Ceramics Research Institute (CGCRI, Kolkata

Ceramic membrane technology based water purification technologies, Ceramic based bio-medical implants

National Environmental Engineering Research Institute (NEERI, Nagpur)

Water purification, diagnostic kits etc.

 

MAJOR ACCOMPLISHMENTS 

Knowledge-based Products/Technologies Developed and Basic Findings

CSIR has earned the distinction of developing 11 out of the 16 new drugs developed in India. It has developed cost effective and innovative processes for around 25 generic drugs, standardization of over 50 herbal drugs and devised new diagnostic tools. The production of over 25 drugs/drug intermediates, technologies for which have been developed and successfully commercialized, is valued at around Rs 600 million annually. Several of these drugs are exported and save net foreign exchange through export substitution. Some of the major accomplishments are as follows:

Products Commercialized
Products Available for Licensing/Commercialization
Diagnostic Kits/Probes
Enzyme Mimics from CSIR

·        Cyclodextrin-based chemosensors have been developed as ‘artificial receptors’ for molecular recognition of organic compounds, which may find use in the detection of drugs.

·        Dynamic kinetic resolution has been achieved using cyclodextrins under supramolecular catalysis for the first time to get single enantiomer from the racemic substrates.  The strategy is being used to develop single enantiomer drugs.

·        Cyclodextrin based drug delivery systems have been developed for rifampicin to improve its bioavailability in fixed dose combinations.

Products Developed/Under Development
TeTechnologies Licensed/Commercialized

 

Technologies Available for Licensing/Commercialisation

·                    Generic drug technologies: Lacidipine, losartan-K doxazocin, mefloquin, pyrazinamide, pentazocine, nitrazepam, o-aminobenzophenone, vitamin-B6.

·                    Transgenic flies for drug screening.

·                    Heterogeneous catalysts for preparation of aryl propanoic acid used as intermediate in the synthesis of ibuprofen and naproxen.

·                    Know-how for urokinase, used for dissolving blood clot.

·                    Custom made peptides.

·                    Process for isolation of cyclosporin A from marine fungus, Fusarium nivale.

·                    Technology for gene delivery using cationic amphiphiles.

·                    Processes for the preparation of reconstituted collagen substratum, reconstituted collagen sponge, transparent soft collagen film, novel fibrin sponge, and novel cross-linked collagen sheet have been developed for medical applications.

·                    Technologies for the preparation of hepatoprotective agents, immunomodulators, anti-diabetic and anti-arthritic agents.

·                    Technology for phytopharmaceuticals viz. Colchicine, Colchicoside, Silymarin, Boswellic acids, Diosgenin, 16-DPA, Berberis hydrochloride and Rutin.

·                    Seapath: A bio-informatics software tool for identifying adhesin and adhesin-like proteins useful for developing new therapeutics.

·                    Gene-decipher.  A bio-informatics software tool for identifying protein coding DNA sequences useful as potential drug targets.

·                    A rapid method of enzyme linked immuno-sorbent assay (ELISA).

·                    Monitoring of BOD and COD.

    ·     Rapid method for estimation of chemical oxygen demand (COD)

    ·        A reusable immobilized microbial formulation for use in BOD analysis.

    ·        BOD Sensor: Immobilized microbial consortium useful for rapid and reliable BOD estimation.

·                    Know how for biological neutralization of alkaline industrial effluents.

Technologies Developed/Under development

·                    IICT has taken up the improvement in the process for Ranitidine, Omeprazole, and Ciprofloxacin to realize maximum conversion, replacement of hazardous intermediates and solvents.

·                    Studies to understand the structure function aspects of staphylokinase (SAK) and develop its new variants carrying functional units of both SAK and streptokinase (SK) in order to generate new molecule with improved properties.

·                    Preparation of cell beads BOD sensor, useful for instant BOD estimation

·                    A biological process for colour reduction of pulp and paper effluent

·                    Preparation of an immobilized microbial consortium for the treatment of phenolic wastewater.

·                    An aerobic biological method of removing total dissolved solids from tannery wastewater.

·                    A novel method for preparing novel anti-hypertensive molecules.

·                    Detection of pathogenic Mycobacteria in clinical specimens

·                    DNA based diagnostic methods for prediction of predisposition to certain diseases:

·                    A method for the detection of predisposition to High Altitude Pulmonary Edema

·                    A method of detecting predisposition to atopic disoders by screening for human (Stat 6) gene variants

·                    A method of detection of SP-A2 gene variants useful for prediction of predisposition to pulmonary tuberculosis

·                    Genetic variants of human Transforming Growth Factor BetaI (TGFBI) and prediction of immunological disorders.

·                    Detection of MBL gene variants useful for prediction of predisposition to bronchial asthma with allergic rhinitis.

·                    Pharmacogenomics (Variable Drug response)

§         A method for predicting an individual’s bronchodilatory response to a beta agonist.

§         Novel allelic variant of CYP2C19 associated with drug metabolism.

·                    Immobilization/bioassay of biomolecules:

·                    A simple, efficient and accelerated method for enzyme catalyzed in vitro modification and synthesis of Nucleic acid using microwave irradiation.

·                    A significant breakthrough in chemical degradation of diosgenin, a major raw material used in the synthesis of corticosteroids, sex hormones and anti-fertility compounds. 

·                    CDRI and Bharat Biotech International Ltd., Hyderabad, are collaborating under NIMTECHU project for the development of Lysostaphin as a drug for treatment of staphylococcal infection.

·                    A biocatalytic kinetic resolution method has been developed for the preparation of enantiomerically pure (S)-(+) –flurbiprofen in more than 99% purity.  At present, sales of these drugs are permitted as racemates.  A collagen membrane has also been prepared for use in periodontal surgery.

·                    CGCRI has developed a new process for the recovery of low sodium salt (mixture of NaCl and KCl).

·                    Developing anti-diabetic marketable products of plant origin.

·                    End to end technology of Tinospora cordifolia for the production of standardized extract.

·                    Up-scaling and standardizing the process for the production of enriched extract of 1,25-dihydroxy Vitamin D3 from a plant source as an anti-psoriasis agent.

Basic Findings

·                    Combinatorial facilities have led to synthesis of libraries with several ‘hits’ and ‘lead compounds’ from 3-isoxazoles, glycoconjugates of galacto-pyransylated amino alcohols and thiazine-thiones.

·                    The formulation of a novel hemiacetal during ‘Baylis-Hillman’ reaction of substituted aldehydes (substitutes of 5-isoxazole carboxaldehyde and substituted benzaldehydes) with cyclohexenone has been established for the first time.

·                    Discovery of the underlying mechanism of drug resistance in Mycobacteria reveals a multi-drug-resistance pump in M. smegmatis, which is often used as a model system for M. tuberculosis, holds promise in developing a detection system for drug-resistant Mycobacteria.

·                    Bioactive lead molecules have been identified with potential for developing antifungal and anti-asthmatic drugs.

·                    Identification of Protein tyrosine phosphatases and Protein kinase F of M. tuberculosis as potential drug targets.

·                    Studies of smart polymer gels, have demonstrated for the first time that a fine balance between hydrogen bonding and hydrophobic interactions is responsible for transformation from swollen to the collapsed state.  The ‘intelligent’ response of such gels can be utilized in novel applications such as controlled drug delivery.

·                    A drug target inositol-1 phosphate synthase enzyme has been identified in tuberculosis bacillus.  This enzyme has already been cloned and expressed at IMTECH and efforts are on to overexpress it so that an assay for high throughput screening of chemical libraries can be set up.

·                    Studies at IMTECH on structural elements in streptokinase (SK), which confer high affinity to this protein for plasminogen, has led to a comprehensive model to explain the mechanism of action of SK. 

·                    Human lung surfactant proteins SP-A and SP-D have been identified as therapeutic agents for Aspergillosis and other respiratory allergic and infectious diseases for the first time. 

·                    Studies on selected genotypes of opium poppy have led to development of genotypes with high thebine, codeine and narcotine contents.

Future Prognostics

Recent advances in molecular biology, sequencing of human genome, computational biology, protein sciences, development of nanotechnology and electronics have given rise to a wave of new disciplines aided and supported by new laboratory techniques and tools. The recent advances in genomics and proteomics are providing new insights into the better understanding of living functions and their possible use in abatement of diseases and health risks. While automation of various techniques and use of computers has increased efficiency, accuracy and speed, the magnitude of data generated poses problems of storage, analysis and interpretation. 

With initial success of bio-ceramic research, efforts are directed to develop different types of innovative implants and devices, drug delivery systems, sensors, tendons, ligaments, artificial organs etc. As a part of programme of technology demonstration a few projects funded by DST, New Delhi and National Drinking Water Mission are planned to be pursued viz. a) setting up iron-removal plants in N-E States and West Bengal; b) fabrication of high-capacity ceramic membrane module and arsenic removal plants for attachment to contaminated deep tube wells; c) standardization and up-scaling of manufacturing process of multi-channel ceramic elements required for designing high capacity arsenic removal plants.

While the picture on the discovery front looks grim, new approaches emerging in therapeutic arena pose yet another challenge to chemotherapy. Though genomics opens new opportunities to develop safer drugs, the use of drugs developed in post-genomic era will be restricted in use. The application of pharmacogenetics will lead to designing of drugs based on the genetic make-up of a given population with the result that such drugs will have use only in a sub-set of patient population, that is, a restricted market compared to the current blockbuster drugs which capture huge markets. The targeted drugs will be, however, more effective, safer and would take lesser time for development. The recent developments in biology, which are expected to cause far-reaching impact on conventional therapy in future, are ‘gene therapy’ and ‘stem cell research’.

It is envisaged that in the near future, the biotechnology market, a sizeable percentage of which comprises biopharmaceuticals, will open up yet wider. India has an immense opportunity in the pharma sector in the areas of product development and licensing, contract research, knowledge-based services and routine quality S&T services in order to serve the country’s long term S&T and economic interests.