Over the last decade outsourcing has become an important strategic issue for pharmaceutical companies due to declining R&D productivity, increased generic competition, blockbuster drugs going off-patent, rising drug development costs and fewer new drugs discoveries. Under pressure to protect their margins, innovators are outsourcing non-core activities like manufacturing of intermediates and APIs to low cost destinations like India, which is likely to gain momentum over the next decade. India currently accounts for a miniscule proportion of the US$ 27 billion global outsourcing industry and is set to capitalize on the mega opportunity.
Global scenario
Current market for outsourcing in the pharmaceutical and biotechnology industry is valued at $100 billion in 2006 growing at around 10.8 % to reach $168 billion by 2009. API manufacturing is the largest contributor to outsourcing market with a 55 % share. Clinical Research with a 35 % share of the market is the second largest segment contributing to more than one-fourth of the revenues in this industry followed closely by drug discovery and dosage form development at 25 % and 20 %, respectively.
The more established segments like API manufacture and clinical research have acquired more than 30 % share of their potential, which also reflects in their contribution to the total outsourcing revenue. However, emerging segments like basic research and developmental activities for drug substance and dosage form are yet to cross the 20 % threshold of their total potential.
Contract research
Some of the known facts in drug discovery are:
*370 Biotech medicines to treat 200 diseases are in the development pipeline from 144 companies.
*178 for cancer, 47 for infectious diseases, 26 for autoimmune diseases, 21 for HIV/AIDS.
*Of every 5,000 compounds only 5 make it to clinical trials. In spite of a sluggish economy R&D spending is on the rise.
*For the first 8 pharma companies there is 6.8 % increase in the R&D spending. Approximately $8 billion spent on R&D in 2002.
*Contrary to popular perception PDA approval time has come down from 2.4 to 1.9 years from 1960s to 1999.
All these factors have accounted for innovator companies trying to reduce cost by outsourcing components of the drug discovery process.The global pharma industry has been under pressure to bring out blockbuster drugs to strengthen its drying pipelines, as well as overcome loss of sales to generics due to best-selling drugs going off-patent. Managing the drug discovery process and technologies has become one of the top challenges faced by the global pharma industry in the recent past; herein lies the opportunity for a spate of companies focusing on contract research in drug discovery.Let us consider the threat of generics to blockbuster drugs going off-patent. In the span of five years from 2001 to 2006, about 40 blockbuster drugswith combined annual sales of $45 billion will go off-patent in the U.S. These include Merck's Zocor (off-patent in 2005; for hyperlipidemia; annual sales of $2.8 billion), Takeda-Abbot's Prevacid (off-patent in 2005; for peptic ulcers; annual sales of $3.1 billion), Bayer's Cipro (off-patent in 2003; for infections; annual sales of $1.3 billion), and AstraZeneca's Losec with sales of $4.6 billion (off-patent in 2001). Consider the R&D cost of drugs; according to a recent study by the Tufts Center for the Study of Drug Development, it takes $895 million and 10 to 15 years to get a drug to market.
The pharma industry desperately needs strategies to bring down the cost of drug discovery and outsourcing has become one of the most favored strategies being adopted globally. The most important benefit of outsourcing is that global majors can outsource processes related to biology, chemistry, screening, and lead optimization, to name a few. Many of the processes involved in drug discovery are time-consuming, laborious, and non-strategic in nature and can be outsourced to save on costs.
While it provides the global majors the much-needed cost-benefit, it is a huge opportunity for smaller companies that do not have a well-developed drug discovery program to get a toehold, making it a win-win strategy. With biotech companies joining the drug discovery race, the outsourcing of research to keep costs low, as well as gain other strategic advantages has become a high point in the last five years and is expected to gain momentum in the next decade.
Contract work in basic research has evolved from low-end research activities to more value-added high-end research. The numbers of alliances formed for basic research collaboration are growing steadily; however, most of them are concentrated in the pharma and biotech hubs of U.S. and Western Europe. Alliance activity in Asia, Eastern Europe, and Latin America is growing; however, growth lags the U.S. and Western Europe. Growth of outsourcing continues to be fueled by the need for drug developers to contain costs and speed products to market, increasing globalization of pharmaceutical and biotech firms, and technological demands from drug developers. Reputation for research quality and thoroughness, speed to project completion, and strong client relationships are the key to success in research partnering. Domain expertise as an entry barrier is restraining contract research partnering opportunities. Availability of top of the line infrastructure and manpower is a defining factor for success in drug discovery contract research. Understanding and respecting sanctity of patents is critical for growth.Outsourcing in basic drug discovery occurs mainly in the following 10 segments: Broad-based screening, oncology infectious diseases, genomic targets, chemistry, central nervous system disorders, cardiovascular system disorders, gene therapy, autoimmune/ inflammation, metabo-lic diseases.
In the period from 1997 to 2004, these 10 segments accounted for cumulative alliance payouts of $8.02 billion. Genomics, Broad-based screening, oncology, and are the three segments exhibiting higher payouts than the remaining segments. In all the segments, big pharma is the largest outsourcer, accounting for more than 50 % of the payouts on an average. In the cardiovascular disease segment, big pharma dominated completely with 92.3 % share. For the period 1997 to 2004, the autoimmune/inflammation and CMS segments, mid-size pharma was prominent with a share of 37.4 % and 24.1 %, respectively. In the oncology and metabolic segments, big biotech is prominent with a share of 21.1 % and 29.1 %, respectively. Outsourcing by biotech companies has been minimal in the autoimmune/ inflammation segment for the period 1997 to 2004.
The global contract research market was worth $18.7 billion with a YOY growth rate of 14.7 %. This represents a significant 23 % of the total global R&D expenditure currently being outsourced. The market is expected to grow to $47 billion at a faster pace in the period 2006 to 2011(at a CAGR of 16.6 %) when compared to the projected global R&D spend. India's drug discovery outsourcing market amounted to just $ 470 million in 2005. But it is expected to grow 30% a year, hitting $ 800 million by end 2007.
Clinical research
Clinical research is the second largest segment, which is being outsourced with nearly a 35% share of the outsourcing activity. The global CRO market was worth $ 15.2 billion in 2005 with a YOY growth rate of 23%. The market includes services provided to the pharmaceutical and biotechnology companies in the clinical development process for innovative molecules (NCEs) as well as generics. Specifically these services would be clinical, bio-analytical, bio-statistical, data management services, biomarkers, regulatory submissions, medical writing, and site management services for the four phases of clinical development of a NCE and the bio-analytical/bio-equivalence services for generics. Phase I Ib-l 11 is the single largest segment in the global CRO market accounting for 40 % of the total market revenue. The segment is also the most established component of clinical development that has seen earliest outsourcing efforts from companies primarily to:
*Tap expertise in patient recruitment and monitoring.
*Leverage cost and skill advantages offered by Site Management Organizations (SMOs) for multi-site trial management
*Leverage cost and skill advantages in bioanalyses
However, the segment exhibiting highest YOY growth is that of biomarkers. The clinical leverage provided by biomarkers in predicting probable end points and challenges drives this segment to be a significant contributor in the next decade and is expected to revolutionize the way early clinical development will be conducted.
Phase I and IV are expected to maintain the pace of growth with the current focus on ADR monitoring and more rigorous evaluation in early clinical development.The bioavailability/ bioequivalence (BA/BE) outsourced market was worth $1.56 billion with a in 2005 with a YOY growth of 16.8 %. A robust pipeline of patent expiries in the forecast period, potential growth in authorized generic efforts and technology enhanced generics are expected to drive the growth in this market. Most of the outsourcing in this segment is currently on a project basis and has not evolved towards a preferred partnership model.
India, with second largest population in the world, and with every sixth patient in the world being an Indian, is going through an upheaval economically, socially and scientifically. Increasing globalization has brought about fundamental changes in the way clinical trials are conducted here. Increased awareness of Good Clinical Practices (GCP) requirements, stronger desire of international acceptability of research done in India has brought favorable changes in the attitude of clinicians in India towards participation in clinical trials. Investigators are eager to take part in GCP clinical trials and are also willing to adhere to constraints of the protocol.
As per Frost & Sullivan analysis current outsourced clinical trial activity in India is at around $118 million and is estimated to go up to $379 million by 2013. Just 800 people are full time employees, while an additional 1,500 people work as site staff. The total number of patients undergoing clinical trials is close to 10,000. The clinical trials legislative requirements are guided by specifications of schedule Y of the Drugs and Cosmetics Act in India. Recently, the Ministry of Health, along with DCGI and Indian Council for Medical Research (ICMR) came out with draft guidelines for research in human subjects. These are essentially based on the Declaration of Helsinki, WHO guidelines and ICH requirements for GCP. The Department of Science and Technology has taken the initiative for establishing quality requirements by setting up the National Board for Accreditation of Testing and Calibration Laboratories for clinical and diagnostic laboratories (NABL).
India has more than 50 contract / clinical research organizations (CROs) with many pharmaceutical companies having their own CROs, conducting trials in close to 80 government and private hospitals. MNCs like Aventis, Pfizer and Novartis are already outsourcing their global clinical trials to India. Indian companies such as Doctor Reddy's Labs and Biocon have made significant investments in R&D infrastructure and have partnered with MNCs for contract research and licensing of the R&D pipeline.
Contract manufacturing
Large pharmaceutical companies increasingly turn to contract manufacturing organizations (CMOs) solely to achieve efficiencies in cost, capacity and time-to-market, or to obtain a specific expertise not available in-house. Today, these factors still play a role, but now the most dynamic driver behind the use of CMOs in the pharmaceutical industry rapidly is becoming the unique, innovative, and state-of-the-art process and production technology they offer. More and more pharma companies are leaning towards outsourcing to concentrate on marketing their products, without spending time in drug discovery and the process of manufacturing. This applies to those virtual companies that exist by the simple fact they can rely on contract manufacturers and researchers.
As per Frost & Sullivan research the worldwide revenue for contract manufacturing and research for the pharmaceutical industry was estimated at $100 billion in 2004 and is expected to increase at a CAGR of 10.8 % to $168 billion in 2009.
Contract manufacturing of prescription drugs for 2004 was estimated at $26.2 billion, and is expected to rise to $43.9 billion by end of 2009. Contract manufacturing of OTC and nutritional products is the largest and fastest growing segment, expected to rise at a CAGR of 11.3 % to $102 billion by 2009. The contract research market is expected to reach $21.9 billion by 2009, rising at a CAGR of 8.6 % from $14.5 billion in 2004.
The global pharmaceutical contract manufacturing market for finished dosage formulation has been traditionally strong in North America and Europe. North America accounted for 50.5 % of the global pharmaceutical contract manufacturing market followed by Europe and Asia. Due to the outsourcing boom in Asia, contract manufacturing has been witnessing significant growth in finished dosage formulations, active pharmaceutical ingredients (API's) and intermediates. The global pharmaceutical contract manufacturing market is segmented into injectables, solid and liquid dosage forms spanning across North America, Europe, and Asia. Injectables are expected to show the highest growth during the next five years. Solid dosage forms represented 47.0 % of the global market in 2004. Liquid dosage forms are projected to grow the slowest during the next five years.
The demand for specialized technologies and services such as sterile products, biopharmaceuticals, and lyophilization is likely to drive the market to a significant extent. Within the contract-manufacturing segment, that for the cardiovascular drugs is the largest among all other application categories with worldwide revenue of about $2.56 billion in 2004, it is rising at a CAGR of 8.7 % through the next five years. Analgesics seem to be rising at the highest pace in the contract manufacturing business with the expected annual average growth rate of 11.9 % over the period from 2005 2010.
Many CMOs have gone far above and beyond the immediate needs of their customers to create innovative homegrown processes and to implement the latest, technologically advanced equipment-technology that frequently surpasses that available at Big Pharma's own facilities. The total cost of pharmaceutical production includes not only the cost of building new plants. It includes the cost to maintain them, stay up-to-date on equipment advances, and to maintain a workforce of highly-skilled operators with more than just the knowledge to run them, but with the expertise and experience necessary to continually update and improve them.
India, with second largest population in the world, and with every sixth patient in the world being an Indian, is going through an upheaval economically, socially and scientifically. Increasing globalization has brought about fundamental changes in the way clinical trials are conducted here. Increased awareness of Good Clinical Practices (GCP) requirements, stronger desire of international acceptability of research done in India has brought favorable changes in the attitude of clinicians in India towards participation in clinical trials. Investigators are eager to take part in GCP clinical trials and are also willing to adhere to constraints of the protocol.
As per Frost & Sullivan analysis current outsourced clinical trial activity in India is at around $118 million and is estimated to go up to $379 million by 2013. Just 800 people are full time employees, while an additional 1,500 people work as site staff. The total number of patients undergoing clinical trials is close to 10,000. The clinical trials legislative requirements are guided by specifications of schedule Y of the Drugs and Cosmetics Act in India. Recently, the Ministry of Health, along with DCGI and Indian Council for Medical Research (ICMR) came out with draft guidelines for research in human subjects. These are essentially based on the Declaration of Helsinki, WHO guidelines and ICH requirements for GCP. The Department of Science and Technology has taken the initiative for establishing quality requirements by setting up the National Board for Accreditation of Testing and Calibration Laboratories for clinical and diagnostic laboratories (NABL).
India has more than 50 contract / clinical research organizations (CROs) with many pharmaceutical companies having their own CROs, conducting trials in close to 80 government and private hospitals. MNCs like Aventis, Pfizer and Novartis are already outsourcing their global clinical trials to India. Indian companies such as Doctor Reddy's Labs and Biocon have made significant investments in R&D infrastructure and have partnered with MNCs for contract research and licensing of the R&D pipeline.
Contract manufacturing
Large pharmaceutical companies increasingly turn to contract manufacturing organizations (CMOs) solely to achieve efficiencies in cost, capacity and time-to-market, or to obtain a specific expertise not available in-house. Today, these factors still play a role, but now the most dynamic driver behind the use of CMOs in the pharmaceutical industry rapidly is becoming the unique, innovative, and state-of-the-art process and production technology they offer. More and more pharma companies are leaning towards outsourcing to concentrate on marketing their products, without spending time in drug discovery and the process of manufacturing. This applies to those virtual companies that exist by the simple fact they can rely on contract manufacturers and researchers.
As per Frost & Sullivan research the worldwide revenue for contract manufacturing and research for the pharmaceutical industry was estimated at $100 billion in 2004 and is expected to increase at a CAGR of 10.8 % to $168 billion in 2009.
Contract manufacturing of prescription drugs for 2004 was estimated at $26.2 billion, and is expected to rise to $43.9 billion by end of 2009. Contract manufacturing of OTC and nutritional products is the largest and fastest growing segment, expected to rise at a CAGR of 11.3 % to $102 billion by 2009. The contract research market is expected to reach $21.9 billion by 2009, rising at a CAGR of 8.6 % from $14.5 billion in 2004.
The global pharmaceutical contract manufacturing market for finished dosage formulation has been traditionally strong in North America and Europe. North America accounted for 50.5 % of the global pharmaceutical contract manufacturing market followed by Europe and Asia. Due to the outsourcing boom in Asia, contract manufacturing has been witnessing significant growth in finished dosage formulations, active pharmaceutical ingredients (API's) and intermediates. The global pharmaceutical contract manufacturing market is segmented into injectables, solid and liquid dosage forms spanning across North America, Europe, and Asia. Injectables are expected to show the highest growth during the next five years. Solid dosage forms represented 47.0 % of the global market in 2004. Liquid dosage forms are projected to grow the slowest during the next five years.
The demand for specialized technologies and services such as sterile products, biopharmaceuticals, and lyophilization is likely to drive the market to a significant extent. Within the contract-manufacturing segment, that for the cardiovascular drugs is the largest among all other application categories with worldwide revenue of about $2.56 billion in 2004, it is rising at a CAGR of 8.7 % through the next five years. Analgesics seem to be rising at the highest pace in the contract manufacturing business with the expected annual average growth rate of 11.9 % over the period from 2005 2010.
Many CMOs have gone far above and beyond the immediate needs of their customers to create innovative homegrown processes and to implement the latest, technologically advanced equipment-technology that frequently surpasses that available at Big Pharma's own facilities. The total cost of pharmaceutical production includes not only the cost of building new plants. It includes the cost to maintain them, stay up-to-date on equipment advances, and to maintain a workforce of highly-skilled operators with more than just the knowledge to run them, but with the expertise and experience necessary to continually update and improve them.areas in which Indian firms are attracting new business. Ranbaxy has two ongoing collaborative research programs. An anti-malarial molecule, Rbx 11160, is being developed in collaboration with the Medicines for Malaria Venture (MMV), Geneva and a collaborative research program with GlaxoSmithKline pic (GSK). Nicholas Piramal India Ltd. (NPIL) runs a clinical research unit and does contract synthesis as well. This involves lead optimization of compounds prepared in very minute amounts. Other large companies like Zydus Cadila and Dr Reddy's all have either active programs or intentions of entering the area of CRAMS.
CRAMS are an important area for some medium-sized pharma companies. For example, Shasun Chemicals and Drugs positions itself as an "integrated research and manufacturing solutions provider". Divi's Laboratories, a similar sized pharmaceutical company, has been associated with innovative multinational companies for contract research and custom synthesis.
Besides these pharma companies there are also specialized contract research organizations (CROs) in the pharma sector, which do just outsourced research. Some are international CROs, like Quintiles, which came to India in 1997. It has facilities in Mumbai, Ahmedabad and Bangalore, with close to 900 people.
Biotech companies also show a lot of prominence in terms of opportunities available to them. Most biotech companies are built on a contract or collaborative research model. Syngene, which is a subsidiary of Biocon, carries out contract research for drug discovery. Syngene has a three-year agreement to carry out research projects to support new drug discovery and development, primarily in the early stages and involving small molecules in the areas of oncology and cardiovascular disease with Novartis. Avesthagen has established itself as an RPO - a research process outsourcing company. It works on a collaborative model with partners in development and shares the Intellectual Property rights. Avesthagen is into agricultural research and medical research of plants and spanning across genomics, proteomics, sequencing, and metabolics. Reliance Life Sciences does contract clinical research and chemistry and biology research.
India has strong chemistry and regulatory skills, which have helped it emerge as a top destination for research and development. India's cost of manufacturing is 30-40 % lower as compared to western countries and its labor cost is 1/7th of that of the USA. India has the highest number of US PDA approved plants outside the USA and has 6 times the number of trained chemists as the US, available at 1/1 Oth of cost. Already MNCs like AstraZeneca, Merck, GSK, Solvay, Eli Lilly and others have started sourcing products from India. MNCs are likely to scale up operations gradually as they get more experienced with Indian partners.
Although India scores over China on most fronts, the Chinese companies pose a significant threat to India. Over the years, Chinese companies have been aggressive in filing DMFs. Chinese companies have filed over 60 DMFs in 2005 as compared to 40 in 2004. Over the next 2-3 years, Chinese companies are likely to move up the value chain by venturing into high-end intermediates and formulations. Leveraging on its low cost advantage and strong government, backing China poses a significant threat of making major inroads into the US market as well as commanding a better share of the CRAMS industry. Other Asian countries like Taiwan and Korea could also pose a threat to Indian companies.
India is likely to account for 3-4 % of the global contract outsourcing industry. From the above estimates, it is evident that the Indian CRAMS story has just scaled the 'tip of the iceberg' and 'sky is the limit' for the companies that have ventured into this space. Its competencies in providing growth solutions cover a broad range of markets in and within industries like:Life Science Molecules , Food Ingredients and Nutraceuticals, Plastics and Polymers, Specialty and Fine Chemicals Adhesives and Sealants, Printing Inks, Agrochemicals.
(Source: Frost & Sullivan & FICCI report)