DRUG DISCOVERY AND INDIAN PHARMA INDUSTRY

Indian pharmaceutical industry witnessed radical change in the R&D activity. The R&D is the key to the ulterior of the pharmaceutical sector. The advancement of medicines, its good outcomes etc paved a better path for its development. Moreover, the foreign players are showing keen interest in collaborating with India for their R&D. India has been a country of choice along with China and encouraging others in coactions. The reasons behind may be the intellectuals in our country, cheap sources. Infact they are utilizing our ingredients to get their final product. R&D work carried out in India finds better replies to the diseases occurring in tropical countries and also solutions to the unmet medical needs. This entire process of evolution took many decades. The R & D expenditure by the Indian pharmaceutical industry is around 1.9% turnover which is very much less when compared to 10-16% of foreign based companies. However, the companies tend to spend more after the introduction of Patent regime.
India has emerged as a source for carrying out the clinical trials due to availability of clinical materials in diverse areas. This is a symbiotic relationship as both are mutually benefited. Indian Pharmaceutical Industry, with its rich scientific talents, provides cost-effective clinical trial research. It has an excellent record of development of improved, cost-beneficial chemical syntheses for various drug molecules.

Several decades have passed. We enter science just to find solutions to unanswered questions. Experimentation on a single molecule may show many effects (therapeutic or adverse). We didn’t stop when the research showed null results at the same time we continued experimentation even after we lifted our winning hands. Even Nobel Laureate Sri. Venkatraman Ramakrishnan said he just knows "ribosomes" and continued his study. Definitely i think the driving force is simply the INNOVATION.
I dont think that classical drug discovery process nearly affected R&D in India. But following points may be ammended for better outcomes:
1.Wealth of novel opportunities from genomics
–How to pick the right molecules and bring them to the right patients

2. Cost and timelines of drug development
–Need to change the paradigm of drug discovery to decrease attrition and improve effectiveness

3. The potential of increased cooperation with stakeholders
–Greater public understanding, increased patient involvement and greater dialogue with regulators - in simple words its BETTER COMMUNICATION

4. The need for increased openness
–transparency of operations.
I do not say that we are completely handling the unmet needs but we are trying and improved a lot in this sector. Getting a global image is not an easy task. New minds should be involved in this arena.

Challenge is a stimulating situation we see in every field. But these are not unavoidable problems. Challenges we face commonly are the

1. Workforce: Every year many pharma graduates and postgraduates are being released. But how many of them go to R&D side and wish to make life in India?? The ratio may be 75:25. The latter are those flying to other countries. According to an estimate by the Organization of Pharmaceutical Producers of India (OPPI) more than 15% of the scientists engaged in Pharmaceutical R&D in the U.S. are of Indian origin. Number of students taking science as a major subject was 32% in the past but this has fallen to 15% now. This might be due to lesser scope in this field, lack of suitable carrer prospects in R&D or it may be due to welcome hands of infotech.

2. Base: Drug discovery is a complex process and require complex infrastructure and sophisticated equipments to carry out the process. It is not possible now to buy such huge stuff and its a cumbersome process to receive funds from Government. This is another serious bottleneck to be considered.

3. Ensuring clinical trials: All the clinical trials needs to be done effectively before letting out the product. Many animals may be required for this process. The most common problem we face is the delay in arrival of the animal. Until alternative validated approaches that are acceptable to regulatory authorities become available, we have little choice to continue testing. To ensure prompt preclinical evaluation of drug candidates, it is important to facilitate easy import of the necessary animal models for in-house research. This is another challenge being faced by many industries.

4. Regulatory environment and Handling process: The regulatory environment must provide a clear framework for operations; be it for the use of radiolabelled material for R&D, import of animal models/biological samples, clinical development etc. Currently, there are not many facilities in the country that can undertake custom radiolabelling of small organic molecules for R&D. A centralized resource might be created that will aid research organizations in sourcing radiolabelled chemicals for research. This would allow easy monitoring of the movement & use of such chemicals.

These are some of the major challanges the industry faces today. These bottlenecks can be unblocked by taking suitable measures.
For eg
1. The shortage of R&D managers in Work force can be overcome by developing a pool of R&D mangers who not only have formal training in management but also a good grasp of the drug discovery & development processes.

2. Instead buying big stuffs and waiting until funds are granted it would be better to facilitate the establishment of common resources that can be used both by the academia & the industry. This will avoid unnecessary duplication of resources and will provide ready access to those that need them. Biotech parks like the ones being set up at Hyderabad and Pune will greatly facilitate the creation of such infrastructure.

3. For prompt preclinical studies, creation of state-of-the-art animal testing facilities will provide a good alternative for research organizations that are unable to establish such facilities in-house. Infact, the first national facility for transgenic & gene knockout mice was recently inaugurated at the Center for Cellular & MolecularBiology, Hyderabad with funding from Council for Scientific & Industrial Research (CSIR) and the Department of Science & Technology (DST).
Likewise other bottlenecks or simply blocks can be lowered by taking appropriate means.

From:
Sirisha Pingali
Final year BPharmacy.

The Indian Pharma industry is now over to Rs 1,00,000 crores ($ 20 billon) and has shown tremendous progress in terms of infrastructure development, technology base creation and a wide range of products. It ranks 3rd by volume and 14th by value thereby accounting for around 10% of world’s production by volume and 1.5% by value. Globally it ranks 4th in terms of generic production and 17th in terms of export value of bulk activities and dosage forms. Consequently, India is becoming the hub for generic drug manufactures providing cost effective drugs to Indian patients as well as other countries (> 200 countries) relatively at a cheaper rates with significant quality, deserving the title as “The hero of the Poor”.. By making right investment in creating Pharma innovation hub in the country, we can reap the benefits both social and economic which also include creation of additional high value research jobs.

The major concerns with drug discovery are that it is least productive and most cost-ineffective segment with high risk/ high return activity where the risks are significantly increasing. To afford the high cost and improve performance,R&D based companies have been pursuing the strategic route of mergers and acquisitions during the last few decades. These alliances improved the finances of new entity, also complemented their therapeutic ranges, R&D pipelines and marketing strengths. However the sizes of the new companies compel them to deploy their R&D efforts and investments only in areas aimed at discovery and development of blockbusters for lucrative markets. In the process the priorities of these companies are increasingly shifting to markets rather than meeting needs. In the wake of decreasing chances for the discovery of potential blockbusters, that avenue is also shut in most cases. The new alternative largely triggered by the success of a few biotech products is to go for specialty care products catering to treatment of limited number of patients (personalized medicines) rather than for primary care for large populations.

The problem with the drug discovery process is that it is taking too much time, money and effort. Why is this happening? It is happening because we are basically always imitating the thought process and actions of the westerners who are so obsessive with respect to their thinking and actions in many fields, but especially in the field of healthcare. This obsessively precautionary type of thinking and over reaction to certain tragedies has led them to:

Fortunately for India all this has not yet happened because we are not overly obsessed about discovery of new drugs. New drugs are necessary in only certain situations say,Alzheimer's, Cancer,AIDS and others as such. In other situations need of the hour is improvement of efficacy or therapeutic effect or reduction of toxicology etc..Where new drug discovery is needed, the following procedure may be adopted.We must stop thinking that for every new molecule the entire procedure of animal toxicology i.e. Phase I- IV steps should be gone through.

A professional body of experts from the fields of Medicinal chemistry, Pharmaceutical Technology, Toxicology and Pharmacognosy should be constituted.
All New drug Applications should go to this body. This body should have the capacity to suggest whether the company should go through the entire process or start with Phase II or Phase III trails. Based on the suggestion of this body the Drug Control of India must have the discretion to speed up the process of discovery by cutting down on certain phases of clinical trials. The NDA’s may be classified as:

The industry should allocate more budgets to R & D and should make the
R & D team multidisciplinary….

• A high percentage of this budget should go to discovery of new life saving molecules to treat AIDS, Alzheimer’s, Cancer and TB but the focus should be on such molecules that we do not have to go through the entire process of clinical trials. We focus on herbal or well known medicines or part of biological systems.
• A small percentage of the budgets should go to develop better delivery
  systems to known drugs or drugs discarded as ineffective though they are safe.
• A small percentage of the budgets should go to development of generics.

It cannot be said that the driving force before R & D is innovation; it was indeed the development of inexpensive and high quality medicines for a better health care by focusing the attention on existing modalities. Innovation must go into development of new delivery systems for existing drugs.

The post human genomic era has revolutionized the process used to identify novel molecular targets for drug discovery. Thousands of new gene sequences have been generated but only a limited number of these can be converted into validated targets likely to be involved in disease. In the industries especially the CRO’s, research is happening in the most modern way. The receptor to which the drug should bind is identified, the NCE with the necessary structure is synthesized, the tissue or cell lines with the receptor are grown/ brought and it is verified whether the drug binds to the receptor. Then the drug goes through the process of animal toxicology and clinical trials. But in most of the Universities this sophistication is still not there and research in the classical way testing and Screening is still happening, also there is no empirical evidence that new approaches will offset the pitfalls faced by the industry in area of new drug discovery.



The unmet needs to be addressed are:

1. The development/ discovery of new drugs for diseases such as Alzheimer’s, Parkinson, Cancer AIDS etc..,

2. Prediction of right species that have the same metabolism and side effects as man in pre-clinical stage.

3. Promotion of Industry- Academic collaborations.

Let us hope to reach and achieve the above needs as early as possible.

The challenges of drug discovery can be addressed by:

1. Systematically evaluating products which have been used as traditional medicines.

2. Searching and identifying new indications for existing drugs.

3. Development of chiral molecules from currently used racemates.

The Drug discovery can be made cost effective by working on:

1. To promote Acquisitions and Mergers to make R&D investments more affordable.

2. Outsource parts of drug discovery at considerably low cost.

3. By adopting a more inexpensive and less time consuming mode of clinical trials for new drugs.

Ultimately, we can reduce the bottle necks by the widespread discussion and brainstorming.

Pharmaceutical Industry in India is one of the largest and most advanced among the developing countries. It provides employment to millions and ensures that essential drugs at affordable prices are available to the vast population of India. Indian Pharmaceutical Industry has attained wide ranging capabilities in the complex field of drug manufacture and technology. From simple pain killers to sophisticated antibiotics and complex cardiac compounds, almost every type of drug is now made indigenously.

Indian Pharma Industry is playing a key role in promoting and sustaining development in the vital field of medicines. Around 70% of the country's demand for bulk drugs, drug intermediates, pharmaceutical formulations, chemicals, tablets, capsules, orals and vaccines is met by Indian pharmaceutical industry. A number of Indian pharmaceutical companies adhere to highest quality standards and are approved by regulatory authorities in USA and UK.

The pharmaceutical industry is going through a tough time due to drying
R&D pipeline, poor productivity, spiralling cost of research and cash
crunch. However, India is emerging as a favourable country for research
collaboration to provide solutions through cost competitiveness and
innovative drug discovery capabilities.Global Pharmaceutical Industry is at the crossroads. On the one side market demand for novel and better medicines is getting redefined and growing due to demographic, economic and epidemiological trends. But at the same time, pharmaceutical companies are finding it difficult to survive since they are unable to innovate and discover new molecules. The pipeline of the new drug molecules is drying fast due to poor R&D productivity, high failure rate and generic competition. Traditionally
pharmaceutical companies relied on spending big dollars on discovering possible blockbuster molecules for large patient population through internal research. However, new molecule innovation from inhouse research is declining and companies are forced to increase their R&D spending as well as to scout in licensing opportunities for new molecules.
The importance of biotech companies as an alternative source of innovative potential therapies and to fill the void has been widely noted in recent years. According to a survey published in Nature Review / Drug Discovery, based on the new approvals between January 2006 and December 2007, 65 per cent of the US FDA filing was contributed by biotech industries and mainstream pharma companies were responsible only for 35 per cent of the drugs. However, the disappointing part is that during this period 91 products failed in Phase III and 95 per cent of these failed products originated from biotech companies.
Also when it comes to new chemical entity based novel medicines, the mainstream pharma companies were two fold more successful than biotech companies. High failure rate and less innovative pipeline raise concerns on the robustness of R&D process being followed by biotech industry and is certainly not helping the drug industry to reduce its cost of discovery. The
recent economic crisis has further hit the biotech industry very hard. Recently Steven Burrill of Burrill & Company observed that
most of the biotech companies have limited cash and are pruning down their operation by reducing work forces and eliminating / limiting research and drug development projects in a desperate effort to extend their runway. This will further erode the global pipeline of the innovative products in coming years.

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered and/or designed.

Discovering and bringing one new drug to the public typically costs a pharmaceutical or biotechnology company nearly $900 million and takes an average of 10 to 12 years. In special circumstances, such as the search for effective drugs to treat AIDS, the U.S. Food and Drug Administration (FDA) has encouraged an abbreviated process for drug testing and approval called fast-tracking.
Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations. After three to six years of further clinical testing in patients, only one of these compounds is ultimately approved as a marketed drug for treatment. The following sequence of research activities begins the process that results in development of new medicines:
• Target Identification.. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
• Target Prioritization/Validation. Researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells.
• Lead Identification. A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success.
• Lead Optimization. Lead optimization compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound with the greatest. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.
• Preclinical Technology: During the preclinical development of a drug, laboratory tests document the effect of the investigational drug in living organisms (in vivo) and in cells in the test tube (in vitro).
• Chemistry Manufacturing and Controls (CMC)/Pharmaceutics: The results of preclinical testing are used by experts in pharmaceutical methods to determine how to best formulate the drug for its intended clinical use. For example, a drug that is intended to act on the sinuses may be formulated as a time-release capsule or as a nasal spray.
• Pharmacology/Toxicology: Pharmacological testing determines effects of the candidate drug on the body. Toxicology studies are conducted to identify potential risks to humans.
Results of all testing must be provided to the FDA in the United States and/or other appropriate regulatory agencies in order to obtain permission to begin clinical testing in humans. Investigational New Drug (IND)/Clinical Trial Exception (CTX)/Clinical Trial Authorization (CTA) Applications: INDs (in the U.S.), CTXs (in the U.K.) and CTAs (in Australia) are examples of requests submitted to appropriate regulatory authorities for permission to conduct investigational research. This research can include testing of a new dosage form or new use of a drug already approved to be marketed.
In addition to obtaining permission from appropriate regulatory authorities, an independent review board (IRB) must approve the protocol for testing as well as the informed consent documents that volunteers sign prior to participating in a clinical study.
Clinical testing is usually described as consisting of Phase I, Phase II and Phase III clinical studies. In each successive phase, increasing numbers of patients are tested.
• Phase I Clinical Studies: Phase I studies are the first studies conducted in humans. A small number of subjects, usually from 20 to 100 healthy volunteers, take the investigational drug for short periods of time. Testing includes observation and careful documentation of how the drug acts in the body -- how it is absorbed, distributed, metabolized and excreted.
• Phase II Clinical Studies: Phase II studies are designed to determine effectiveness and further study the safety of the candidate drug in humans. Most Phase II clinical trials are randomized, or randomly divided into groups, one of which receives the investigational drug, one of which gets a placebo containing no medication and sometimes a third group that receives a current standard treatment to which the new investigational drug will be compared. In addition, most Phase II studies are double-blinded.
• Phase III Clinical Studies: Phase III studies provide expanded testing of effectiveness and safety of an investigational drug, usually in randomized and blinded clinical trials. Depending upon the type of drug candidate and the condition it treats, this phase usually requires one to four years of testing.
After the FDA (or other regulatory agency for drugs marketed outside the U.S.) approves a new drug, pharmaceutical companies may conduct additional studies, including Phase IIIb and Phase IV studies. Late-stage drug development studies of approved, marketed drugs may continue for several months to several years.
Perhaps Pharmas should shift their R&D focus away from novel discovery and toward development areas in which they excel. These include improved formulations, compounds with superior pharmacokinetics, and analogs of known drugs with significant benefits, therapeutic agents. Enhancing potency; reducing or eliminating a side effect; limiting dosage to once-daily, enhancing bioavailability, decreasing pill size and overcoming drug resistance are changes that can result in valuable therapeutic contributions. These may not be as lucrative as new and possibly blockbuster drugs, but these products are more rational, the costs and risks in their D&D will be drastically decreased. Examples are fixed-dose combinations of drugs to treat 2 or more unrelated conditions simply because they happen to coexist in many individuals (e.g., hypertension, arthritis, diabetes, etc.). Small biotech companies can contribute more because of their small size, such companies may offer attractive alternatives.

Hello Friends…this is really an important discussion topic needs to be discussed with great depth as the Indian R&D system is moving towards a new shift. I would like to divide the discussion topic into 7 parts, which are as follow.
1.Current Issues with Indian R&D system
2.Progress of the R&D
3.Strategies to overcome issues
4.Importance of Innovation in R&D:
5.Ways to optimize drug discovery
6.Ways to optimize drug development
7.Optimisation of R&D –Business Model:

A RADICAL CHANGE AND A PARADIGM SHIFT TO THE R&D ACTIVITY:
1)Current Issues with Indian R&D system:
•Partnership for discovery and development of new chemical and biological entities is progressing at an even slower pace.
•Assurance of patent protection still does not come with the fortifications expected.
•Compliance with international GCP, documentation and quality of research are falling short of international standards every now and then.
•Lack of clear Indian regulatory guidelines on all areas of trial conduct, analysis and reporting is another major hurdle.
•Regulatory performance standards of trial initiation approval and review of completed trials are not publicly available and adhered to.

2)Progress of the R&D:Recently Dr.Reddys’s new molecule balaglitazone(Anti Diabetic) has completed ph-3 trails in collaboration with Rheoscience.It will be first Indian company to have own innovated molecule.Few other Indian companies also have new molecules in pipeline
3)Strategies to overcome issues:
(A)Technology strategies: Use of high-throughput technologies and R&D productivity, biologics platforms, pharma-pharma ventures for enabling technology development.
(B)Organizational structures and strategies: Restructuring R&D, emulating biotech, Building R&D through business development: M&As, collaborations, R&D strategies.
(C)Outlook for pharmaceutical R&D: Changing business models, personalized medicine, pursuing novel targets, collaboration, high-throughput strategies, translational medicine.

4)Importance of Innovation in R&D:

4(a)Focus on scientific innovation does not mean greater commercial success:

Products that are first in class based upon new targets are not necessarily more successful than products that come second, third or even fourth to market. In fact, there are many cases where first-in-class products have been eclipsed by well-marketed, effectively differentiated follower products. Zantac versus Tagamet is a famous example of second-to-market success based on clinical differentiation, aggressive pricing and marketing. Lipitor has been a hugely successful fourth-to market product

4(b)Re-thinking innovation for high performance

Pharmaceutical companies need to re-think what innovation means in the drive for enhanced productivity and high performance. Scientific innovation in Discovery is not sufficient and companies need to examine the possibilities to be innovative in every activity involved in getting a commercially valuable product to market.
The pharmaceutical industry must focus on innovating throughout the value chain to differentiate products, meeting the increasing demands of regulators and payers, and accelerating speed to market.

4(c)Innovation needs to be applied to

(a)How processes are designed and refined,- companies can adopt a ”Proof of Concept” model that focuses on rapidly generating the most salient data linked to product success.
(b)How technology is used to enable the business, - as electronic data capture, process re-optimization and more recently, the off-shoring of capabilities such as clinical data management, have all greatly improved the efficiency of trials.
(c)How the organization is structured and people and teams are managed.-

"Innovation is not about new targets, it is about successfully bringing to market a product that meets an unmet medical need.”

*Sustained innovation requires the right leadership, structure, and allocation of resources

5)Ways to optimize drug discovery

1. Learning from scientific authorities how to increase the efficiency of established scientific methods.
2. Competing for the best academic breakthroughs in molecular and cellular biology, letting biotech companies and their investors take the large risks, with pharma then funding development and marketing.
3. Collaborating over the big science problems together across the industry with government and academe to fashion the genome and proteome
4. Being free to cross all of the boundaries that define today’s silos with new suites of tools in “open source” environments that link scientists from different disciplines,
5. Submit industry scientists to the tried and true methods that used to work before the craze for
industrializing scientific research led to today’s problematic pipelines.
Drug Discovery Responses

6)Ways to optimize drug development

1. Improving efficiency to test more compounds faster by adding technologies such as electronic
medical records, biomonitors and web‐based patient recruitment tools.
2. Expanding clinical trial designs to include adaptive trials with Bayesian statistics while experimenting with fundamental method changes that can work with biomarkers and diagnostics for targeted patient populations.
3. Incorporating 24x7 biomonitoring, large‐scale exploratory INDs with rapid Phase I microdose studies moving directly to Phase III trials that support extensive Phase IV safety studies.
4. Redesigning the development cycle to enable clinicians and the FDA to fully integrate experimental science with the practice of medicine through reimbursement for trials and tests that enable a shift toward personalized medicine which accounts for the genetic, proteomic and phenotypic differences shaping healthcare outcomes
5. Encouraging a multiplicity of study designs that are matched to the different types of compounds and their intended uses so that preventive medicines, targeted drugs and blockbusters are addressed

7)Optimisation of R&D –Business Model:

1. Pharma leaders create security for investors and companies; obey the dictates of markets, which reward those companies that submit to an ordered approach in science and business.
2. Companies have the market power to take action and develop more useful innovations that offer prevention, lower the risk of therapeutic failure and provide practical solutions for major healthcare problems.
3. The industry accounts for social needs and adjusts its business practices to more effectively work together with governments and NGOs
4. The industry integrates a larger health offering with sustainable pricing models for a wider array of products and services, including generics, diagnostics, disease management, prevention and knowledge management.
5. Public esteem for pharma builds so that investors indulge industry with the capital needed for being innovative, and that means companies being free of ethical taint as they profitably improve health using interdependent global systems.

The oldest records of medicinal preparations made from plants, animals, or minerals are those of the early Chinese, Hindu, and Mediterranean civilizations in 28th century B.C.
Assessing the pharmaceutical evolution in India, I can see that India was a forerunner in traditional research. We have started developing and using our medicines back from our rich past. I should say the new generation medicines (Modern medicine) demand much different rights, ethics and standards that we have not foreseen. Our nation had morality controlled society that by law. But the new demands of world trade require law controlled communities that moralities. So we can see laws are becoming more stringent to control every minute aspect of pharmaceutical industries. In 2002 - There has been a big change in the pharmaceutical industry in both China and India. The world has been taking note of this, as future changes in the way companies of other countries look at the pharmaceutical industry. Despite the positive outlook India will lose market share in the Asian market in future. The winner, first and foremost, will be China, which will remain the No 1, as Indian companies' strategic reorientation away from generics to original preparation is still in its infancy. The sooner India manages to close the infrastructure gap, the higher growth will be in the country’s pharmaceutical industry.1 Apart from that some inherent advantages in India were its stable democracy and good legal system which was crucial for the future of pharma industry. The pharmaceutical industry in Pakistan will have to depend more on India, than China, in future to survive in the emerging global pharma scenario. Industry sources from Pakistan point out inability of Pakistan pharma industry to set up adequate infrastructure. In the pharmaceutical industry, innovation is driven by several factors. These include the cost of R&D for a new drug, sourcing the revenues for drug development. India's pharma industry is recognized as one of the low cost producers offering the same quality as that of players in the regulated market. Small scale units of pharmaceuticals are facing a tough time. With economic slowdown hitting the country, it is slowly and gradually becoming unviable for the very small players to sustain themselves. Supply chain bottlenecks are big issues in a vast country like ours. Drug discovery and manufacturing have to be changed from producing the medicines concept to supplying the medicines concept.
Pharmaceutical industry was the first branch of the economy to strongly engage in the new technology combining high-throughput experimentation with bioinformatics analysis. Medical applications step beyond trying to find new drugs on the basis of genomic data. In post-genomic era Pharmacogenomics is the revolution which helps in making individualized and cost-effective medicines.2
The pharmaceutical industry is really successful for providing abundant employment opportunities and providing essential medicines much economically. The high level of fragmentation of the pharmaceutical sector is a tough task to systematize their operations. There are more that 20,000 registered units. It has been so difficult for the authorities to control the price of thousands of medicines made from these units.
Many Indian companies maintain highest standards in Purity, Stability and International Safety, Health and Environmental (SHE) protection in production and supply of bulk drugs even to some innovator companies. India holds the lion's share of the world's contract research business as activity in the pharma market continues to explode in this region.
In India, the industry is now awaiting developments following the January draft publication of the government's National Pharmaceuticals Policy for 2006. The document contains proposals for far-reaching initiatives aimed at boosting the domestic industry's global competitiveness, as well as improving the population's access to medicines. Indian government ministers have also promised MNCs concrete action soon on speeding the patent approval process and other crucial issues, such as the definition of patentability and compulsory licensing.3

Alongside the necessary material resources, research and innovation are dependent on a framework that fosters innovation: through public attitudes, through political/legislative developments and through taxation.4
There is a need for new tools and research strategies on all fronts of drug discovery. Universities and research organizations have to build a platform of knowledge discovery and innovation. The government has to find ample funds to boost the research in independent settings.
To reduce the bottle necks we have to connect the knowledge triangle, building better cooperation between the public and private sectors and helping us deal with the biggest challenges we face, in an economically competitive and sustainable way.

India is now very well equipped with pharmaceutical law expertise, Bioethics, Clinical research and drug manufacturing. The lack in the cycle of drug development is lack of innovative research going on about drug development. If finding the drug is from trying thousands similar chemicals, the country should have thousands of research centers which are strictly controlled and funded for quality research. As this research is not done by small group of researchers the huge sum required for drug discovery is eventually distributed in many shoulders. And the new drugs won’t be as costly as now. Collaboration of the research findings from various academic sources should be the responsibility of a special ministry for health to avoid bias in research and gambling of funds. So I welcome the recent movement of the central government of India to increase the quality education and standards of research in university levels.
References:
1. Uwe Perlitz, India’s Pharmaceutical Industry on Course of Globalization, Deutsche Bank Research, Asia, April 9, 2008:1-12.
2. Biophonics, The Outlook for the Biotech Sector in the Post-Genomic Era, Business Insights, 2003.
3. KPMG, Indian Pharmaceutical Industry: Collaboration for Growth, KPMG International, 2006.
4. Humer F.B. F. Hoffmann-La Roche Ltd, to the Zürcher Volkswirtschaftliche Gesellschaft, Zurich, 16 March 2005.

Drug discovery process is a complex and time consuming aspect. In olden days, the process begins with the selection of a synthesized or extracted molecule and screening it for various activities. It is really a cumbersome job as thousands of molecules need to be screened for activity (Classical drug discovery process). India, regarding this aspect did not compete with the global countries due to poor knowledge, economic status and other reasons. We have to depend on other nations and hence making the drugs costlier. But by taking the advantage of process patent, we strived hard for the production of drugs. After 30 years, we are now in a position to manufacture drugs by ourselves and occupied 3rd position in the global market by exporting our drugs to other countries.
A revolutionary change has occurred globally in the process of discovery of new drug molecules by the advent of various sophisticated techniques like high throughput screening, robotics and computer simulations to minimize the time for the process of drug discovery. Neither the process is chemistry driven or technology driven. Rather it is the integration of both.
In the past, Investment of Indian companies in drug R&D is 0.6% of the turnover. Presently, pharma companies are spending 5% of turnover which increased 70 fold compared to 60s and 70s. The driving force behind R&D is obviously innovation. Innovation does not mean to forget the classical drug discovery. In a developing country like India, every pharmaceutical industry cannot cop up with the novel technologies of drug discovery. Only Multinational companies can afford the cost of drug discovery. With the strong co-ordination between Industry and academics, even medium scale companies in a region should step into the drug discovery process utilizing classical methods. Further, Indian industry is largely concentrating upon development of new dosage forms or ANDA s rather than on discovery of new drug molecules which requires huge investments and no guarantee of profits.
Government is encouraging the companies to undertake the job of drug discovery by providing tax exemptions, sponsoring projects through CSIR, DBT, DST. It is the responsibility of industries and academics to utilize these benefits and step more into the ‘omic’ era (proteomics, genomics) along with other countries. Emerging technologies like stem cell research, dendritic vaccines which are likely to be commercially exploitable in the near future should not be neglected. Biotechnology products are the future of R&D efforts world over and they are going to occupy 30% of R&D.
Regulatory bodies should also react as quickly as possible. They should assist the industries in the process and reduce the time for approving a drug molecule like in European countries. The time taken for an IND approval in USA is 1month whereas in India it is unpredictable. China became the first to approve the H1N1 vaccine but we have not initiated the trail at least. Similarly, DNA vaccine sponsored by the DBT is not moving forward as it completed phase-II in other countries.
Strong co-ordination between Industry, Academics and Regulatory authorities reduces the complexity in the process to some extent and encourages more and more companies to undertake the responsibility. In a report given by the organization Stratfer states that the development in India cannot be predicted in the next 10 years and no significant changes will occur. It also reports that India is very rich in resources but did not use them completely till now. There is also a need to create a strong bridge between traditional systems of medicine and pharmacy particularly with the area of drug discovery. Risorine(Rifampicin+Isoniazid+Piperine) by Cadila pharmaceuticals is a classic example which utilized traditional medicine in which the dose of rifampicin and isoniazid is reduced by utilizing the enhancing bioavailability property of piperine extracted from peppers.
India is going to be a hub of clinical trials for other countries due to more population and less cost. Global companies are outsourcing about US$ 1billion to Indian CRO in the next 3-4 yrs. We may be replaced by China in the future just as we replaced European countries. World recognized Indian pharmaceutical industries to provide generic drugs but not recognized for innovations. We have to provide also the patented products to world. Let us utilize our own natural resources of traditional system of medicine, skilled work force and prove to the global market that we are not inferior to any other country in the process of drug discovery.

Regards,
G.Sailesh, M.pharm
Bapatla college of pharmacy, Bapatla

Indian Pharma industry is now $ 20 billon and even more with multiplying progress in terms of development, in maintaining a technology base and in bringing quality products. Globally it ranks 4th in terms of generic production and 17th in terms of export value of bulk activities and dosage forms. India growing exponentially in terms of business is set to bring a drastic change in the present existing scenario hoping to provide tremendous job potential to all the young Indians

The major concerns with drug discovery are that it is least productive and most cost-ineffective segment with high risk/ high return activity where the risks are significantly increasing. According to the present scenario, it is hard to say that innovation is the driving force before R&D, but can be partly said that innovation can be the key and the urge to come up in the existing market can be the cause. On the other hand, it is evident that unfortunately there are no innovators in India since 1947 as on date, but have grown up in the global market due to the ease in the system followed in Govt. of India. Previously, there was only process patent that was implemented in India, where many pharmaceutical companies brought drug molecules and manufactured them in various other processes possible, such that they cannot be made liable under the process Patent Act. Since, the system existing in India till 2005 was not made strictly, manufacturer found it hard to invent a new molecule since it would take nearly 12 to 14 years for a drug molecule to come out into the existing market. So attempt was made from manufacturers bringing out business angle into picture, brought drug molecules and synthesized them in means possible. This may be the cause where innovation might not have originated into the brilliant brains of India. But due to the Product Patent Act that was brought out in 2005, marketing of drugs from foreign market was made tight, and was made tough time for all the manufacturers following the route. Then came renaissance in the Indian Pharma world, where researchers were given bigger platform and innovation was valued giving it higher priority to sustain. Hope to see great innovators bringing out wonderful life saving molecules in the upcoming days.

Though we are in the Post Human Genomic Era, many challenges faced and had been overcome, but we still find loopholes in the existing processes being done. To discuss about the affect that has been to classical drug discovery in this new millennium, it is only minimal because all the basic screening and quality tests going on now-a-days in industries follow principles mainly of classical drug discovery though there has been many developments in technologies. There is nothing like one coming in and phasing out the other, each one has their equal importance but may imply its effect only to a certain extent. Coming to present day new drug discovery process we owe a lot to the global pharma community, as they have provided ultramodern technologies to make our processes much simpler, but unfortunate thing to be thought is we don’t have even one industry making all the so called modern equipments to make ourselves self-sufficient. We have been importing them from different countries but only to a limited extent because of the higher costs. Then comes the question, why a higher cost to India, the reason for this is difficulty in maintaining the service personnel. Only a few industries and hardly some of the universities use this modern equipment and companies manufacturing equipment find it hard to make business, implies higher costs. There has been a paradigm shift from classical to modern drug discovery process, absolutely but there has been no considerable change in the system governing. Measures can be made by the Govt. of India where industries can be brought out to manufacture modern equipment that can be ancillary to the present pharmaceutical industries where employment potential can be generated and dependence can be minimized. Coming to our achievement to traverse from the conventional or classical to modern drug discovery process, neither we have completely achieved nor under-developed, but on the middle banks, the only cause being “Avoid risk bearing”, whenever new comes into picture, risks come into existence, only the risk bearer can achieve in most cases. A major drawback modern drug discovery unraveled involves the difference in the stages of process designed, where a multi-step process of classical drug discovery has been replaced with a single-step in modern drug discovery, still a single step process has its limitations that can be overcome by conventional process though tedious.

India is still failing to procure sufficient needs; all the unmet needs being evident to all, measures to overcome are like:
• Establishing Academia-Industry collaborations to keep industrialists and students afresh, also to equip students with latest upcoming technologies, thereby providing a chance for development of academia.

Regards,

K.S.KUMAR UPADHYAYULA
University College of Pharmaceutical Sciences,
Andhra University,
Visakhapatnam.

The Indianpharma industry is verymuch attractive for all foreign and worldwide pharma companies consequently, india is becoming the hub for generic drug manufacturer providing costeffective drugs to Indian patients and also for other countries ,relatively at a cheaper rates with better quality .
India has emerged as a source for carrying out the the clinical trials due to availability of various clinical materials in different areas.the Indian pharmaceutical industry provides a cost effective clinicasl trial research.it has an excellent record of development of cost beneficial clinical drug synthesis.
The advancements in modern-day cellular imaging, along with genomic information, has allowed scientists to probe deeper into the underlying mechanisms of cellular functions, effects of protein transcription, cell pathway signaling, and ultimate fate of the cell's life cycle all in an effort to better understand the developmental processes and finding treatment or even cure of human diseases. It has been a little more than a decade since automated fluorescent microscopy image analysis or better known as High Content Screening (HCS) was introduced to the scientific community, but the approach has been occurring for almost 20 years, the knowledge and lessons learned over this time has provided an insight of where the technology is today and what to expect in the coming years.
Today, almost every pharmaceutical company has implemented some version of HCS into the drug discovery process, as well as many biotechnical firms with the promise of identifying new drug target indications, validating targets, and use in small compound drug discovery, toxicity assessment, biomarker identification, and pre-clinical studies. Academia institutions have also invested in HCS, initially in core centers, but now the technology is branching out into well-funded departments. The approaches are similar to the pharmaceutical industry but at a much lower throughput except for a few NIH-funded small molecule compound and RNAi screening centers. Academic centers are utilizing the technology in basic science programs to extract large amounts of cellular data information to better understand cell functions and mechanisms of actions in developmental biology and target-based identification in diseased tissue. The continued effort and synergy between academia and industry should lead to new discoveries which for scientists are the ultimate goal.
The Indian pharma industry is over to $20 billion and has shown tremendous improvement in terms of technology base creation and a wide range of products .it ranks 3 by volume and 14 by value .globally it ranks 4 in terms of generic production .
The productivity of the pharmaceutical industry in delivering new medical entities (NMEs) has been stagnating over the past decade in spite of exponential increase in R&D investment. This situation is having significant impact on the Pharma business at large, which has exhibited significant market capitalization losses likely to exacerbate in the next 5 years as patent protection (estimated at $50-60 billions) due to expire. Moreover, loss of revenues due to removal from the market of 'block buster' drugs due to safety concerns (e.g., vioxx) and restrictive labeling warning (e.g., PPAR gamma modulators for diabetes) confounded by heightened restrictive regulatory labeling for new drugs (e.g., cardiovascular safety requirements for diabetes drugs) are adding significant challenges. Overall, the new financial and regulatory environments over the unacceptable attrition rate in realizing NMEs, likely contributed to the recent bouts of mergers and acquisitions within leading Pharmaceutical industries (e.g., Merck-Schering Plough, Pfizer-Wyeth, Roche-Genentech). Consequent to such events, Pharma R&D continues to shrink along with loss of tenth of thousands of highly educated, trained, skilled and experienced professionals, many to leave the industry altogether. This spiral of detrimental events could further lead to stagnation and failures in realizing NMEs.

From RCP

Function and alignment of Translational Scientists within RD- from Early Discovery to POC.

Challenges :
 Interest in foreign pharma R&D:
According to an estimate by the organization of pharmaceutical products of India, more than 15% of the scientists engaged in pharmaceutical R&D in the U.S. are of Indian origin.
It is may be because of higher salaries offering in the foreign .
 Drug discovery is a complicated and required complex infrastructure and high technical instruments to carryout the process.
 Ensuring: the clinical trials need to be done effectively before letting out the product .until alternative validated approaches that are acceptable to regulatory authorities is available, we don’t have more chances to continue tests .
 Regulation and handling : the authorities that are regulating must provide aclear frame work for operations ,import of animal models biologicals etc..
It can not be said that driving force is always innovation. Innovation is discovering the new things but it is not the zeal of discovering a new one but the scientist have to give answer to the problems which are existing already such as AIDS, SWINEFLU, ALZHEIMERS, CANCER etc.. of course sometimes it may innovation also .

We can unblock certain bottlenecks by taking some measures such as:
 There is a need of providing high salaries for professionals in R&D in all companies and other labs, to avoid migration of Indians from India to other countries.
 A highly skilled professionals have to be employed who are well grasping of drug development and discovery process.
 Better to facilitate the establishment of common resources that can be used by both academia and the industry. This may avoid unnecessary duplication of resources .
 We must know that there is no need for every molecule the entire process of animal toxicology ,i.e. phase 1 -4 /5 should be gone through .
 The pharma industries should allocate more budgets to R&D and
 A high percentage should be go to discovery of new lifesaving drugs to treat AIDS, SWINFLU , ALZHEIMERS, CANCER, etc.

India is gaining importance as a manufacturer of pharmaceuticals on a large scale. According to the statistics, the nominal sales between ‘96 & ‘06 were up 9% p.a. as against +7% for the global market of the world as a whole. Since the end of 1980’s, India has been exporting more pharmaceuticals than it imports.
The above data indicates the growing share of India in the global market. This has been possible by the growing demand of medicines in the market due to the growing population. The manufacturers are now interested not only in copying the patented products, but are investing in the ever-growing market of Indian Pharmaceuticals.
Drug discovery is described as “The process of developing a novel therapeutic agent into a marketable drug”. Yes! Surely, the driving force before R&D is innovation, BUT this seems to be a bit incomplete. In my opinion, it is “INNOVATION FOR A CAUSE”. This is so because; the driving force is the force, which not only initiates but also helps in carrying out the task. Whenever it is the cause (i.e. the disease to be cured), the innovation is done (in the modern approach). The new or the established targets are the causes for the innovation and therefore, the entire R&D is directed towards that particular target.
The Classical Drug Discovery was based on the multi-targeted or serendipitous discovery. It was THEN correct to say that: Driving force for R&D is innovation. Homer Adkins correctly says for those times as:
“Basic research is like shooting an arrow into the air and, where it lands, painting a target.”
However, in modern approaches we have been concentrating on a “target”. This target is the causal organism or specific entities, which cause diseases and infection to the living organisms. As correctly stated in the words of Zora Hurston:
“Research is a formalized curiosity. It keeps on poking or prying with a purpose”.
The approach for doing so, may be at the molecular or physiological levels. Therefore, in this case, the Classical Approach has been abandoned or say, less practiced due to the failure of many drug discovery approaches, which were time consuming and led to heavy cost losses.
In my opinion, the Modern approach has brought a revolutionary change in the area of Drug discovery. This is so because, during multi targeted drug discovery, the chances of failure were very high leading to a decrease in the number of investors and researchers. Now, with the upcoming of the selected target approach, the cases of failure had been greatly reduced, since the automated and statistical approach gives us an idea about the correlation between the target & the lead compound. Thus, minimizing efforts and proving to be cost effective.
Now, the question that arises for we Indians is: How far have WE reached in utilizing the Modern Approach of R&D? The answer is: The booming sales of India indicate that we have gone through many changes and advancements, which has brought a change in the mind set of Indians. This is so because; before 2005, when the Patents’ Amendment Law was implicated in India, the Indian Industries used to make the Generic drugs in lots. With the Process Patent, the manufacturers have to get through the 20 years for implying even the Generic version of the patented drug. Therefore, the manufacturers now are interested in getting their R&D set up in India itself. The new Act has given them also an excellent opportunity to make extensive profit for the product they would launch in the market as a patented product.
We are still striving hard to meet the unmet needs of our country as well as for the global market. Even with the significant progress made in genomic and proteomic techniques, it is still fraught with perils and missteps, resulting in a potentially expensive and somewhat unpredictable “fishing expedition”. Advances in medicine had been a lot in this 21st century, with which many diseases are discovered, leading to the invention of new medicines. It has been estimated that the cost of putting up a new drug in the market is in excess of $ 200M. so, first of all the manufacturers don’t go for new inventions due to such high costs & unavailability of innovative minds, & even if they go, they do not have a profit of their expectations as Ours is a Developing Nation, where 100’s of people die due to lack of medication. Therefore, an unfortunate truth for we Indians is the availability & cost of medicines is not such that we could meet the needs of common person.
We’re a developing nation and as being so, there persists a lot of opportunities to make a strong stand in the pharmaceutical market. The hidden talents have to be discovered. James Watson rightly said:
“Formula for breakthroughs in research: Take young researchers, put them together in virtual seclusion, give them an unprecedented degree of freedom and turn up the pressure by fostering competitiveness.”

Many approaches can be followed in order to make the drug development cost effective such as:
1. On the part of Manufacturers or Developers:
• Selecting the appropriate target and thus, a suitable led compound.
• Going for Rational Drug Design, instead of Random Screening.
2. On the part of the Government:
• Harmonization of Marketing authorizations for different countries, i.e. developing a Centralized Marketing by the ICH.
• Modification of laws regarding Patent protection.
By the application of “Receptor Theory” and several others, it is possible to select the appropriate target. The advancement in pharmacology, medicine and drug development should go hand-in-hand for eliminating the bottlenecks. Also, the development of new dosage forms have paved the way of introducing newer drugs in the market in a cost effective manner.
At the end, I would like to sum up the philosophy of developing drugs by two quotes: first, “Chance favors the prepared minds” and “What we work on today, others will first think of tomorrow”.

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Now a days the word DEVELOPMENT has been found to be synonymous to our country “INDIA “ I suppose in every field ,but as far as our PHARMA FAMILY was concerned it proved to be the best fit meaning to it. Now it is in a frontrunner position to reach its goals. But in order to do so we need to overcome the various problems that act as bottlenecks to our DEVELOPMENT. With low-cost manufacturing, high-quality research and manufacturing facilities and educated personnel, the Indian pharmaceutical industry presents both a competitive threat and partner opportunities.
As these words are being written down, the world is going through extraordinary times, with a financial crisis not experienced since the world wars. Markets are in turmoils and uncertainty is part of many businesses and industries. Several financial analysis are available for us to read, but the content often difficult to digest. The recession has badly affected many industries who are now desperately seeking help, such as the car industry. But what will be the specific impacts of the economic recession on the biotech and pharmaceutical industry. The pharmaceutical and health-care industry have historically been relatively immune to economic turndowns, because illness doesn't take a vacation. Yet, with the ongoing recession, financial support will be reduced. Therefore, like in other industries, it is expected that the most affected by the reduced availability in funding will be the early stage biotech and pharmaceutical companies who need funding.
Apart from such deviating situations it still got success in keeping up it’s own fame and even more with an increased growth rate also.

 India is the world’s fourth largest producer of pharmaceuticals by volume, accounting for around 8% of global production.

 In value terms, production accounts for around 1.5% of the world total.

 The Indian pharmaceutical industry directly employs around 500,000 people and is highly fragmented. While there are around 270 large R&D based pharmaceutical companies in India, including multinationals, government-owned and private companies, there are also around 5,600 smaller licensed generics manufacturers, although in reality only around 3,000 companies are involved in pharmaceutical production.

 Most small firms do not have their own production facilities, but operate using the spare capacity of other drug manufacturers.

 Amongst Global pharmaceutical producers, India ranks 4th in volume terms and 13th in value terms

 Indian pharmaceutical market - USD7.42 billion in 2006 (Growth rate 12.9% over previous year).

 Domestic market contributed USD2.61 billion and exports touched USD 4.81 billion (65% of the market).

 About 65% of bulk drugs and 6% of formulations are imported and balance requirements met from domestic manufacturing.

 Out of the total formulation sales, about 90% is accounted by generics, balance being patented drugs.

 Generics segment grew by 13% to USD5.89 billion in 2006. Patented drugs sale was USD389.36m in 2006 growing at a rate of 18.9% over previous years.

However, new molecule innovation from in-house research is declining and companies are forced to increase their R&D spending as well as to scout in-licensing opportunities for new molecules.

VAST TALENT POOL TO SUPPORT DISCOVERY:

Research outsourcing is a matter of trust and since this trust has already been built through chemistry and clinical services, CROs in the country are confident that pharmaceutical companies would be willing to outsource more value-added services. As a result, Indian CROs are fast moving up the value chain from order takers to problem solvers and value co-creators. The initial concerns like intellectual properties and regulatory issues are gradually being addressed through reforms in law as well as through sensitivities shown by CROs to address them upfront. Companies are expanding into other disciplines like pharmacology, cell biology and pharmacokinetics. Though India is considered weak in biology research, the country has an impressive number of biological scientists. According to IMA India’s estimations, every year India produces half a million graduates in biological sciences, biotechnology and bioinformatics and awards more than a quarter million postgraduates and 1,500 PhDs in the biosciences. India has a thriving generic, formulation and bulk drug industry but lagged behind in developing skills to support discovery-oriented innovative research. As a result, the discovery-focussed biology research remained at a nascent stage. However, after upholding the Intellectual properties agreement (TRIPS) and commitment to recognize product patents, for last decade or so Indian companies have invested in innovation-led drug discovery and produced a reasonable talent pool in biological sciences. As the opportunities are increasing, the number of US trained Indian scientists including biologists are returning to India and being recruited by Indian CROs.

INITIAL SUCCESS STORY:

Based on these strengths India has staked its claim to become a frontrunner in innovation-led collaboration leading to intellectual property generation through discovery research and are ahead of their Chinese counterparts as reported in the recently published report sponsored by Kauffman Foundation. On the ground Indian CROs have closer collaboration with established pharmaceutical companies for discovering drugs rather than limiting themselves to provide services and are hoping to get a bigger pie in intellectual properties. The pace at which these discovery collaborations are being established indicate that Western Pharmaceutical Industry is relying more on India for their brain power and source of innovative research rather than for cost cutting measures. Time will tell if Indian CROs and pharmaceutical companies can prove themselves. However, initial milestones awarded to some of these collaborations indicate that Indian scientists have not disappointed their western counterparts. Drug discovery research and development in India comprises collaborative research, basic drug discovery and development and contract services. Due to increasing cost of developing a new drug and risks involved in the process, companies are looking to mitigate risks involved. One of the recent trends is the de-merger of R&D units to unlock values.

Apart from such developments the various forma of challenges are there in front of us to overcome with a good planning, different methods, changed laws, after all the first and foremost one is the courage and unity to achieve our goals.

CHALLENGES:

Challenges facing the industry revolve around manpower and early stage funding. There is severe paucity of trained personnel, the only solution being recruiting fresh graduates and training them on the job. Such a situation leads to rampant poaching of trained people from other companies.
R&D in the pharma industry is multi-faceted and draws upon the expertise of molecular biologists, synthetic and analytical chemists, genomics and proteomics specialists, pharmacologists and medical practitioners. Closely associated with these are regulatory and quality assurance functions. However, according to industry sources, pharma companies find a huge dearth of skilled resources in the critical areas of early stage drug discovery as compared to chemistry or analytical chemistry wherein the talent is easily available.
A considerable challenge faced by the industry is venture capital (VC) funding, which in India is severely limited. Funding pertains to private equity (PE) players that invest when the candidate reaches the development phase. The focus is more towards the 'D' rather the 'R' in R&D. Most venture capitalists are unwilling to invest in biotech R&D. Rather, they want to fund companies whose products and markets are clearly identified or commercialization of technologies already developed.

THOUGHTFUL REMIDIES:

Such are only some of the challenges being faced by pharma industry to go on freely for R&D programmes.Regarding these challenges some of my ways of facing the challenges are:

 A recent trend of de-risking the business model along with unlocking value from the drug discovery program has started making headlines. Drug majors including Ranbaxy Laboratories, Sun Pharmaceuticals and Nicholas Piramal India Limited (NPIL) have already hived off their R&D divisions into separate entities. Even Dr Reddy's Laboratories (DRL) has followed the same path, but in a slightly different manner. The drug maker has floated Perlecan Pharma in collaboration with ICICI Venture and CVC to take care of its novel drug business.

 In order to get such skilled persons in R&D department the education system should be made much more skill oriented from bachelors degree onwards rather than a mere theory oriented.

 The training programmes are the best forms to have this manpower that too skilled manpower to get them at low expenses of salary.

 In order to have the funding either from government or other companies or in the form of ventures, we have to wait for some time until a stable economy is attained after the crisis situation, though the industry (generic drugs) is not at all effected by crisis, a temporary effect is poised on the development of R&D branch of company.

 By integrating and rewriting the GOVERNING LAWS to discover a drug or a molecule by a company, such that the cost of drug discovery is reduced which can affordable by most number of companies.

Last but not the least is the courage and unity in our PHARMA FAMILY of INDIA can make India number one in the world with in no time.

"FUTURE IS OURS"
(PHARMACY=HEALTH=WEALTH)

With regards,

shilpa.sambana
st ann's college of pharmacy
cantonment,vizianagaram.

INTRODUCTION:
• Drug discovery involves the identification of novel molecules which have therapeutic potential and developing them into viable drugs for the treatment of human diseases. In the process, which involves constant interactions between the academia, industry and regulators, a wide variety of preclinical and clinical studies are carried out to prove the predicted therapeutic efficacy of the agent.

• The main goal is to have a more efficacious and much safer drug for the concerned disease and both treatment as well as prophylaxis is in view. Classical as well as non-conventional experimental procedures are performed in both animals and humans by highly specialized personnel aimed at devising relevant strategies for specific diseases in specific situations, thus addressing the challenges of ensuring maximum drug efficacy and safety.

• Needless to mention, the pharmaceutical industry has a crucial role to play in drug discovery and development. The Indian Pharmaceutical industry is one of the largest and most rapidly expanding industries in the world. It is 20 billion dollar industry and globally it ranks 4th in terms of generic production and 17th in terms of export value of bulk activities and dosage forms.

R&D: A DRIVING FORCE
• In recent years there has been a radical shift in the attitude and policies of pharma industry and the focus has been on new and sustainable drug development strategies. The emphasis has been on both preclinical and clinical development of new molecules, with special reference to national health needs.

• In view of the new patent rules, the focus had to be shifted to indigenously generated products and technology. Drug discovery is a two-edged sword in that risks are to be taken in the hope of rewards. Hence, innovations are not only desirable but mandatory to meet the constantly evolving challenges in this highly competitive field.

• Several new approaches to drug discovery have been adopted over the years and these have been incorporated into the R&D activities of the pharmaceutical industry. In order to do so, the pharmaceutical houses have increased their financial commitments in this direction and as a result both in-house and outsourced biomedical research has flourished.

• Classical pharmacological experiments have had to take the back seat in the wake of rapidly emerging research methodology of cellular and molecular biology like systems biology (omic technology) approach (genomics, proteomics, metabolomics, transcriptomics), , high throughput screening, cell assay techniques, etc.

A PARADIGM SHIFT
• What has happened in the process is that classical pharmacological approach has suffered. Further, the fact that history had shown that, most new drugs developed earlier were merely by a process of serendipity further compounded the problem.

• The traditional in vitro and in vivo pharmacological assays were no longer considered rational and effective. It is however being realized that the modern lead-target concept for drug development may not be the only answer to our drug discovery and development problems.

• In spite of increased expenditure on new drug development research and development, the number of new drug approvals has remained relatively less. Too add to this, the completion of the human genome project has not delivered the desired results in that not many novel leads and targets have surfaced. It is therefore apparent that alternative strategies need to be devised.

• A paradigm shift therefore is always in the offing and the possibility of near radical changes could be contemplated in the interest of new and life saving molecules for meeting the pressing national health needs. The unmet needs thus have to be given top priority and strategies need to be adopted to ensure that India can still emerge as one of the leading players in the global arena of drugs and pharmaceuticals.

REDUCING THE BOTTLENECKS:
• Another area that needs to be looked at seriously is the development of drugs from natural resources. The new international regulatory laws have now made it mandatory that we concentrate on our indigenous resources for drugs as these are not only cheaper but have a strong, time tested scientific logic working for them.

• Natural product have always been India`s strong point and our traditional systems of medicine viz. Ayurveda, Unani, Siddha, etc. have used many plant based products for several hundreds of years with documented beneficial effects in some intractable diseases.

• It is interesting to note that several life saving drugs that have stood the test of time in modern medicine, are from herbal sources eg. Yet, surprisingly, this area of drug discovery and development has been totally neglected and we have placed an enormous amount of trust and faith in the chemically synthesized molecules. There is therefore a dire need to promote research aimed at drug discovery and development in the area phytopharma-ceuticals. The Indian pharmaceutical industry should seriously consider in investing in this area by using the modern scientific methodology. Some initiative has already been taken by the government agencies and a cooperative and collaborative atmosphere has been created.

Conclusion - A BRIGHT FUTURE
• Taken together, the fact remains that in spite of the tremendous potential in the area, India has not made desirable progress in the area of drug discovery and development, which is not only overdue but very much on course. It has to be realized that drug discovery and development is a highly specialized and multidisciplinary activity.

• Some of the factors like, the Process-product patent laws, low R& D costs, abundance of natural resources and highly skilled professionals, are in India`s favor. The stakeholders, viz, the academia, the industry and the government (regulator) need to realize the immense potential that India holds and for becoming the global leader in this area.

• More organized interactions need to take place between the academia and the industry, and here lies the nidus for effective drug discovery and development. Bottlenecks will always be there, but by adopting a positive scientific and logical approach the Indian pharmaceutical industry can effectively overcome them in the interest of drug discovery and development.

Drug Discovery and Indian Pharmaceutical Industry.
First of all I would like to thank the committee members for giving such a challenging topic for group discussion.
Before embarking upon a discussion on the role of Indian pharmaceutical industry in the development of drugs for the world market, we just understand basic process related to drug development and discovery process.
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered and/or designed.
In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery. A new approach has been to understand how disease and infection are controlled at the molecular and physiological level and to target specific entities based on this knowledge.
The process of drug discovery involves the identification of candidates, synthesis, characterization, screening, and assays for therapeutic efficacy. Once a compound has shown its value in these tests, it will begin the process of drug development prior to clinical trials

The drug discovery process incorporates several distinct phases each requiring a dedication of time and resources.
Basic Science: At the basic science level, scientists discover information about individual chemicals and biological processes.
Drug Discovery: As the drug discovery process proceeds, the focus narrows as scientists develop specific chemicals and study their effects on identified disease targets. This requires sophisticated chemistry and testing on animal models of disease.
Drug Development: Finally, when a chemical is found to impact a specific target, human testing is conducted through clinical trials to show the safety and efficacy of the chemical so it may be approved by the FDA as a drug.Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery. Information on the human genome, its sequence and what it encodes has been hailed as a potential windfall for drug discovery, promising to virtually eliminate the bottleneck in therapeutic targets that has been one limiting factor on the rate of therapeutic discovery. However, data indicates that "new targets" as opposed to "established targets" are more prone to drug discovery project failure in general.
This data corroborates some thinking underlying a pharmaceutical industry trend beginning at the turn of the twenty-first century and continuing today which finds more risk aversion in target selection among multi-national pharmaceutical companies. It should be appreciated that drug discovery is an arduous task that could be a decade-long effort and that success is not always guaranteed. Indian pharmaceutical industry’s attempts to discover new drug entities are no exception.
The critical factors driving the global pharmaceutical industry to look for newer strategies are based on hard facts stemming from decade-long experiences. These may be one or more of the combinations as stated below:

• High cost of drug development in the Western countries.
• Patent expiration of blockbuster drugs
• Hurdles in carrying out clinical trials.

India is on the threshold of drug discovery research where the next few years are going to be critical in terms of delivery. Investors and pharma business owners have adopted a wait and watch attitude ruminating on whether or not to make a long term commitment. Most Indian pharmaceutical companies have spent the past decade in identifying strengths and weaknesses and shaping their business portfolios. In doing so, the companies have indulged in many appropriate but diverse activities including bulk drugs, formulations, generics, novel drug delivery systems, new chemical entities and biotechnology products. The coming decade will see these companies focusing on their strengths and leveraging opportunities in selected areas of research and development.

In view of the increasing drug development costs, two to three different models have evolved in the past 5-10 years.
(I) Contract research and development activities, where bigger pharma outsource specific tasks (e.g. pre-clinical studies, animal studies or clinical trials) in the drug development process to smaller speciality companies. A number of Indian companies have positioned themselves to cater to such needs wherein a portion of the drug development process can be handled satisfactorily and the results achieved in a timely fashion.
(II) The offshore activities that merely started as manufacturing hubs in India have in due course emerged into clinical research or basic R&D units. Examples of this model include Pfizer, Novartis and AstraZeneca.

Figure 1. Research and development expenditures in the pharmaceutical industry.
Nearly 50% of the $31 billion (2002 figures) expended by major pharmaceutical companies fall within the preclinical and early clinical (phase 1 and 2) categories,
There are many forces that have contributed to the current scenario: (i) a series of product recalls (ii) continued increase in the prices of new drugs (iii) increased, perhaps unrealistic expectations regarding the safety of current and future drugs and (iv) decreased productivity despite heavy expenditure in the discovery and development of innovative drugs. Therefore, it is clear that a new strategy is required to discover and develop new drugs at a cost that allows major pharmaceutical companies to address unmet medical needs in a timely and cost-effective manner. India and China are seemingly at the forefront to offer such an opportunity.

Pragati Mukund Amin
M.G.V.M’S.S.P.H.College of Pharmacy
L.V.H. Marg.Malegaon Camp, Malegaon.
Pin -423105. Maharashtra

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