Carving a niche

Scientific Innovation and Technology Leadership

Dr. Girish Sahni, has  been a pioneer in translating, and helping others translate, science into world-class biotechnology in the country. Since the 1990’s, Dr. Sahni and his group at IMTECH have developed four generations of an important life-saver protein drug, streptokinase, that is used as ‘clot buster’ in many cardiac and circulatory diseases.

Dr. Girish Sahni’s scientific contributions towards affordable healthcare in the country by successfully developing four generations of Streptokinase, a life-saver, essential thrombolytic (clot buster) drug for the first time in the country for treating cardiac diseases such as heart attacks is an outstanding example of translational science for societal good.

Dr. Sahni has received many awards, for example, The Vasvik Industrial award, O.P. Bhasin award, Ranbaxy award, CSIR  Technology Shield,  DBT Govt of India award for Process Development, Vigyan Ratan award of Panjab University  etc, and is a Fellow of the Indian National Science Academy (INSA), India Academy of Science (IASc., Bangalore) and the National Academy of Science (NASI, Allahabad).

Dr. Girish Sahni (born 2nd March, 1956) has been Director General of the Council of Scientific Research (CSIR) since 2015. Earlier, since 2005 he was the Director of Institute of Microbial Technology (IMTECH), a CSIR- India biotech institution. He did his B.Sc. Hons. and M.Sc. Hons from Panjab University, Chandigarh, and Ph. D. from the prestigious  Indian Institute of Science, Bangalore.

Before joining IMTECH, and CSIR,  in 1991, he pursued Post -doctoral Research in various prestigious Institutions in the USA including Univ. of California, Santa Barbara, CA; Albert Einstein College of  Medicine, New York and the Rockefeller Univ., New York, USA, where he was also Adjunct Faculty.

India’s first patented bio-therapeutic product (Clot Specific Streptokinase) invented by Dr. Sahni’s group is now in human Phase II trials. Its introduction into india and world markets is expected in 2018 and will provide a world-class drug at affordable prices.

As CSIR Director General since August, 2015 and DSIR Secretary to the Govt. of India,  Dr.  Sahni is striving to  refocus this great organization towards its original national mandate, namely using first-grade scientific knowledge to provide technological and sustainable solutions to the various extremely challenging problems facing the country and its Common Man.

Council of Scientific & Industrial Research (CSIR)

Contribution to Healthy India

Contribution to Generic Drug Industry:

Council of Scientific & Industrial Research (CSIR) has played pivotal role in making healthcare affordable to masses through technology and process provided to Generic Drug Industry in the country. Medicines are available in Indian market at much less price compared to what available globally. The Indian pharmaceuticals market increased from US$ 6 billion in 2005 to US$ 36.7 billion in 2016 and is expected to expand to US$ 55 billion by 2020. By 2020, India is likely to be among the top three pharmaceutical markets by incremental growth and sixth largest market globally in absolute size. Indian drugs are exported to more than 200 countries in the world, with the US as the key market. Generic drugs account for 20 per cent of global exports in terms of volume, making the country the largest provider of generic medicines globally and expected to expand even further in coming years. The Indian Pharmaceutical Industry today is in this place because of technologies provided by CSIR Labs such as: CSIR-IICT, CSIR-NCL, CSIR-CDRI and CSIR-IIIM.

New Drug Development:

With the advent of new patent regime in place, the focus of CSIR has now shifted to developing novel drugs and diagnostics. The main areas of R&D efforts are Infectious diseases-Tuberculosis, Malaria, Kala-azar, Typhoid; Life-style diseases-Cardio-vascular, Diabetes, Hypertension; Neuro-degenerative disorders- Alzheimer’s disease (AD) and Parkinson’s disease (PD); Osteoporosis and bone fracture etc. Novel drug development is a long drawn process involving proof of concept study, Investigational New Drugs (IND) application, Phase-I to III clinical trials, spread over 8-10 years duration. CSIR has the distinction of developing twelve out of eighteen drugs launched so far in India.

Many drugs are in pipeline which need time to mature. However, some are available for manufacture under ‘Make in India’ Programme of Government of India. Some diagnostics are also available for manufacture and marketing. Further, in some cases where a product has been licensed to a new company, the companies need to be supported financially to manufacture the product in large quantity and sell into market. Incorporation of such products in Indian Health System will boost the manufacturing of these drugs and diagnostics. Thus, CSIR is ready to contribute significantly in the area of affordable healthcare through ‘Make in India’ and ‘Swastha Bharat’ Programmes of Government of India.

Following drugs and diagnostics have been developed by CSIR:

2. 1. Plasma Gelsolin Diagnostic Kit for Prematurity and Sepsis: CSIR-IMTECH has developed two mass-production ready plate based kits to estimate plasma gelsolin levels in humans. Plasma gelsolin is fast emerging as a health condition biomarker and its repletion in compromised cases is under Phase 1 and 2 trials. While, most other labs including commercial set-ups are focusing on improving bulk production of this protein, IMTECH has developed bonsai versions of this protein by structure-based insights. IMTECH successfully demonstrated the anti-sepsis properties of  miniaturized versions in LPS-induced sepsis model of mice. The kits will help in determining a quantitative measure of the sepsis. Alongside, it is being tested for predicting cases of preterm birth. Both kits come with a cell phone based application for measuring the gelsolin value and providing a prognosis on the patient status. The kits are available for license.
   2. Dip-stick for diagnosing kala-azar: The dipstick developed in CSIR-IICB is 100% sensitive and equally specific for the sero-diagnosis of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). The assay takes approximately 90 minutes where we can see the result as color bands with bare eye. It performs equally well on Indian VL and PKDL and better than commercially available rK39 strip test in Brazil. Currently a multi-centric evaluation of this device is being carried away in different VL endemic regions worldwide such as Sri Lanka, Nepal, India, Brazil and Sudan. This indigenously developed dipstick is considerably less in price than rK39 and if modify into Gold-tagged lateral flow system the time of dipstick assay could be < 5 minutes. The diagnostic is available for licensing.
   3. EHealth Centre: An initiative pursued by CSIR and Hewlett Packard, the eHealth Center (eHC) is a platform for the fourth paradigm of science, data-intensive discovery, while bringing affordable healthcare services to the doorstep of people. The eHC housed in a standard shipping container which can be quickly transported to remote areas of the country by air, rail or by land transport, is a fully integrated cloud-enabled healthcare solution that can be set up to provide affordable and preliminary healthcare in remote areas that have no immediate access to primary healthcare. The solution integrates medical instruments that collect basic patient health data with an eHC Health Cloud and enables medical diagnosis through remote consultation using built in videoconferencing options. The eHC also sets the platform for data-driven research such as disease surveillance by tracking disease patterns and risk factors. The first eHC has been successfully implemented and tested in partnership with O.P. Jindal Gramin Jan Kalyan Sansthan, 3M India, Maharaja Agrasen Medical College (MAMC) and Orion eServices at Chausala village in Kaithal district, Haryana. Over 4000 patient visits were recorded in the first 100 days of operation. The eHC was launched by the Hon’ble Minister of Science & Technology, Shri. Jaipal S. Reddy on 11 December 2012. The occasion was also graced by the key champion, Shri. Naveen Jindal, M.P., and President, O.P. Jindal Gramin Jan Kalyan Sansthan.
   4. Micro-PCR: An Indian industry with support from CSIR has developed hand-held, battery operated, MicroPCR (Polymer Chain Reaction) which detects DNA/RNA of pathogens. This device can be deployed in rural setting for diagnosis of Tuberculosis, Malaria, Dengue, Chikungunya, Hepatitis B and H1N1and data transmitted to any location for advice of an expert. The device consists of a portable unit housing a PDA (Portable Data Assistant) running a software application, the PCR chip, optical detection system and electronic Circuits controlling all aspects of the unit. This is a global product which has been patented in over 100 countries. A sample preparation device has also been developed. The product is under manufacture but company needs to be supported financially for large scale production. This device may be considered for incorporation by Ministry of Health & Family Welfare and made available at every block of the country.
   5. Diagnostic system for affordable, point of need testing to manage HIV and TB: CSIR in partnership with a company is working towards development of reliable and low cost diagnostic solutions to address unmet medical needs of TB and HIV. The initiative takes into account that the key drivers for adapting a new technology at the point of need are the presentation of the technology in an easy to use format, lower cost barrier to practice and no compromise on quality or time to result. A soft launch of the TB diagnostic kit, ReaSLR CSM Kit Ver 1.0 has been made in July 2014, whereby the kit has been made available for evaluation as well as sale. A new one step liquefaction, concentration and staining protocol has been the innovation aspect of the ReaSLR CSM Kit. Further, the HIV diagnostic kit under development, ReaSTAT CD4 Kit is ready for external validation which is being planned with Clinton Health Access Initiative. The data generated using these validation studies will be used to obtain CE-IVD (regulatory) approval. The technological solutions being developed in the project are based on dry reagent concept, the detection platforms shall be automated or quasi automated so as to meet the requirements of various outreach centers, facilitate data collection with no compromise on integrity of data or sample, and thereby enable right decision-making for disease management. Since, this development is with an industry, it needs to be supported and kits incorporated in the programmes of Ministry of Health & Family Welfare.
   6. Novel molecular diagnostics for eye diseases: Ocular infections are leading cause of ocular morbidity and if untreated can progress to loss of vision. Treatment of infection depends on the pathogen. And specific therapy saves people from blind ness. Most popular and well accepted method is microbial culture and smears.  However, culturing takes long time which delays treatment decisions beyond the very critical time after 72 hours by which time more than 60% patients lose vision. Moreover due to paucity of the sample culture is successful only in less than 10% of the cases. Considering the importance of the problem, CSIR undertook project and 24 signature genes of 14 pathogens were detected on DNA Chip. The test System is named as Syndrome Evaluation System or SES.  This one SES will simultaneously detect in one sample and one single test all the 15 pathogens that are known to cause dangerous eye infections. The product is available in market and needs to be adopted by Ministry of Health & Family Welfare.
   7. Natural Streptokinase: Streptokinase is an effective and inexpensive clot dissolving drug used in the treatment of myocardial infarction and pulmonary embolism and belongs to the category of fibrinolytics/clot busters which work by activating plasminogen to produce plasmin which in turn helps in dissolving the clot. The product when introduced in the market brought down the prices of imported streptokinase significantly. This product is available for re-license.
   8. Recombinant Streptokinase: The recombinant streptokinase developed does not have any traces of Streptolysin or Streptodornase (which are usually harmful) associated with natural streptokinase. Recombinant Streptokinase developed has one of the best fibrinolytic activities amongst the products currently available in the market. This product is also available in the market but available for re-license.
   9. Risorine: CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM) with Cadila Pharmaceuticals has developed for the first time a novel therapy obtained from Ayurveda named as “RISORINE” for the treatment of tuberculosis. Lead for this novel therapy is obtained from Ayurveda. Concerted research led to identification of Piperine as an active ingredient of Triktu responsible for enhancement of bioavailability.  Commercialization of Risorine has reduced cost of Rifampicin – Isoniazide containing formulation by 23%. While reducing the cost of therapy, Risorine also overcomes certain disadvantages of Rifampicin. Rifampicin is known to have decreased bioavailability over time. Risorine offers advantage of providing consistent levels of Rifampicin over entire therapy period and significant reduction in gastrointestinal side effects.
   10. Centchroman: Centchroman is a novel non-steroidal agent unrelated to any conventionally used contraceptive. This is the only anti-implantation agent approved for clinical use in the world. It offers a unique combination of weak estrogenic and potent antiestrogenic properties. Due to this subtle mix of estrogenic and antiestorgenic action it inhibits the fertilized ovum from nidation and thus prevents pregnancy, but at the same time it does not appear to disturb the other estrogen effects. The product is available in Indian market under brand name ‘Saheli’. It is part of National Family Planning Programme. This product is available for re-license.
   11. Arteether: Arteether is a semi synthetic derivative of artemisinine, the active constituent of the plant, Artemisia annua. Arteether is being prescribed to the patients as second line of treatment for chloroquine-resistant P. falciparim malaria including cerebral malaria. This drug is part of Malaria Eradication Programme. The drug is available in Indian market but available for re-license.
   12. Elubaquin: This is an anti-relapse anti-malarial for Plasmodium vivax malaria. It is unique in the sense that it does not cause Methaemoglobin toxicity in G-6PD deficient cases and is safer than Primaquine. It is being marketed as combination therapy along with Chloroquin. This drug is available for re-license.
   13. Chandonium Iodide: This drug is a neuromuscular blocker. This has rapid onset of action for endotracheal intubation for maintaining respiration during surgery under general anesthesia. Its action is rapid and reversible. The product is in the market but available for re-license.
   14. Centbucridine: Centbucridine is used as local anesthetic agent and is superior to lignocaine in many aspects. Centbucridine has been found to possess several desirable properties. As compared to lignocaine, it is 4 to 5 times more potent, its onset of action is much quicker, and the duration of action is longer. Due to its vasoconstrictor activity, it does not require simultaneous administration of adrenaline. It does not affect the cardiovascular parameters due to its moderate antihistaminic activity and is not likely to show skin sensitivity. Moreover, it can be used in patients showing hypersensitivity to lignocaine. The product is available in the market but available for re-license.
   15. Centbutindole: This drug is used for treatment of Schizophrenia. It has quicker relief and less sedation and has low extrapyramidal side effects. The drug has lesser potential of tardive dyskinesia. The drug is available in the market but available for re-license.
   16. Centpropazine: Centpropazine is a new antidepressant compound with a different pharmacological profile. The early clinical studies showed it to be safe and well tolerated in normal human volunteers. Multi-centric clinical efficacy studies were carried out in nearly 250 patients suffering from depression. These studies reveal Centpropazine to have comparable response rate with remarkably safer tolerability profile. The drug is available in the market but available for re-license.
   17. Centimizone: This drug is used for treatment of hyperthyroidism. It provides effective control of symptoms like palpitation, insomnia, hand tremors and excessive perspiration. The drug is available in the market and is available for re-license.
   18. Isaptent: This is cervical dilator drug developed from seed husk of plant Plantago ovata. It is a cheaper and safer substitute of imported Lamanaria tent. It is safe to use as it has no effect on vaginal flora. This drug is available in the market but available for re-license.
   19. Gugulipid: CSIR-CDRI has developed gugulipid, a cholesterol lowering drug taking the lead from ancient Indian system of medicine, Ayurveda. The Drug has been developed from the plant, Commiphora mukul. Drug is available in the market but available for relicense.

Herbal Drugs: In India herbal drugs find a major share amongst all the officially recognized systems of health care. Although there is no separate category of herbal drugs or dietary supplements, as per the Indian Drugs Act, but there is a vast experiential-evidence base for many of the natural drugs. With changing lifestyle and sedentary habits, degenerative diseases are taking alarming proportions and require long term treatment/ management. Current therapies involving the use of allopathic medicines have innumerable side effects and therefor herbal drugs find an important place for their management and cure. Taking advantage of the India’s rich biodiversity, a significant amount of basic and clinical research has been carried out on the medicinal plants and their formulations and newer herbal preparations, with the state-of-the-art methods in a number of CSIR’s institutes which have significantly contributed to the area of herbal drugs and transferred the knowledge to the industry. Few of the herbal technologies than can be utilized for “Swastha Bharat’ and “Make in India” Programmes of Government of India are as follows:

BGR-34: CSIR has developed an anti-diabetic herbal formulation from a combination of extracts derived from six plant species mentioned in Ayurvedic literature. The formulation, NBRMAP-DB, was scientifically validated for efficacy in animal models. The product shows anti-oxidant protection activity along with nephoprotective, hepatoprotective and dislipidemic activities to the benefit of diabetic patients. The product was dedicated to the nation by Hon’ble Vice President of India, Shri M. Hamid Ansari on 22.02.2014 at Vigyan Bhavan, New Delhi. It was licensed on non-exclusive basis to AIMIL Pharmaceuticals Pvt. Ltd., New Delhi. The company conducted clinical trial on BGR-34 at Aggarwal Dharmarth Hospital Society, New Delhi. The company has launched the drug in parts of North India. The market response has been encouraging. Ongoing studies on over 50 patients for last over more than 9 months, further revealed that, used in pre-diabetic or mild conditions, BGR-34 used as monotherapy has been found to effectively manage blood glucose homeostasis. In chronic, severe cases, used as an adjuvant therapy to synthetic antidiabetics, BGR-34 has been found to help improve management of diabetes while helping check or reduce total dependence on allopathic drugs, which otherwise increases with the span of time. Thus, BGR-34 even helps significantly reduce the total daily cost of diabetes management on one hand while improving the much needed quality of life and reduce fatigue in type-II diabetic patients on the other hand without any untoward effects. Further with its valuable hepatoprotective, nephroprotective and dislipdemic activities, it also helps in reducing the side effects of synthetic drugs.

• • – Picroliv: Hepato-protective agent of plant origin. Picroliv (6 and 12.5 mg/ kg ) has shown efficacy comparable to silymarin ( 10 and 20 mg/ kg ). It has also antiviral and immune-stimulant activities. Picroliv is devoid of any significant CNS and CVS, autonomic and other systemic activity. Picroliv has excellent therapeutic index. Phase I and II clinical trials have been conducted and the drug has shown no side effect and is well tolerated. The technology is available for deployment.
  • – Standardized Herbal Formulation as Memory Enhancer: A quality herbal preparation has been developed from B. monnieri which has been standardized in terms of its bacosides contents. During efficacy and safety studies the Brahmi extract was found safe and efficacious for improving the long-term memory. This formulation is available in market and is available for further licensing.
  • – Diabetes: CDR134D123 developed in herbal mode with Anti-hyperglycemic activity. DG, CCRAS approval is awaited for inclusion of the plant in the Extra Ayurvedic Pharmacopeia to avail marketing permission in herbal mode. Product is available for licensing.
  • – Arthritis: A standardized Ayurveda based formulation comprising three herbs has been developed as equivalent to standard modern medicine (Celecoxib) in efficacy, but better in safety and quality of life parameters, for treatment of symptomatic knee osteoarthritis. The formulation was selected after a series of studies involving permutation and combination of test formulations comprising pre-selected botanicals based on pre-clinical. The formulation has been manufactured in accordance with GMP and a complete product master file that provides details of quality assurance and pharmaceutics is maintained. The formulation is available for licensing.
  • – Hepatocellular Protection: Standardized poly-herbal formulation comprising hydro-alcoholic extracts of twelve herbs has been developed and scientifically validated through preclinical studies and multi-centric clinical studies in limited number of patients. The formulation is efficacious in wide spectrum of liver diseases and showed reduction in acute phase inflammatory response and bilirubin in hepatitis B, protection against toxemia in patients on AKT therapy. Studies show hepato-protection, with better clinical recovery and quality of life parameters. The formulation is available for licensing.
  • – Natural Calcitriol: A process for the extraction of an enriched extract of calcitriol from a plant has been developed. Calcitriol is physiologically active form of Vitamin D3, which plays an important role in uptake of calcium in intestine and bones. The drug has therefore an important role in osteoporosis and skin disorders like psoriasis.  The technology for the production of the extract has been scaled up to the pilot plant scale and transferred to industry. The company had already started the production of the extract for marketing in India. The technology is available for further licensing.

• – Phalsa Juice: Grewia asiatica L. is commonly known as Phalsa. The plant grows both in tropical and subtropical climates. Pleasant sherbet or squash is prepared from the fruit pulp by mixing it with sugar and used as an astringent, astringent, stomachic and cooling agent. CSIR-IIIM, Jammu has developed cultivation technology for irrigated and rain-fed conditions and developed an unique product from its ripen fruits as ‘Phalsa juice- Shivalik Health drink’ from the pulp of ripen fruits. The juice is rich in crude fibre, Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6 ¬, Vitamin B12 and Vitamin C. The product is available for licensing.

Ayurgenomics:

In Ayurveda texts, though the principles of phenotypes in health and disease states are extremely well described, they are not readily decipherable and hence its potential has not been appreciated by modern genomic researchers. According to Ayurveda individual’s basic constitution (Prakriti) describes its predisposition and prognosis to disease status and also the treatment for disease and lifestyle regime. In Genomics, individual’s basic constitution is decided by its genetic makeup which indirectly reflects the levels of various biochemical parameters in individual which states its Health status. We aimed at establishment of high correlation of Prakriti with genomic signatures by isolating DNA, RNA and Plasma from the blood sample. It is anticipated that this approach of Ayurgenomics would allow development of surrogate methods for cost effective screening of predisposed individuals in the population. This would result in development of an integrative approach to systems biology for disease and health state.