The year 1997 marked India’s entry into the recombinant biotech market with its own range of biotech products. Hyderabad-based Shantha Biotechnics launched Shanvac-B, an indigenously developed hepatitis B vaccine. Since then there has been no slip back. Companies like Bharat Biotech, Biocon, Biological E, Cadilla, Dr Reddy’s Labs, Intas Pharmaceuticals, Panacea Biotec, Serum Institute and Wockhardt have not only left their mark in developing and manufacturing recombinant products in India but also intensifying the race for control of markets.

 

Until then the market was dominated by global majors. Novo Nordisk, a Danish company, became the first to introduce recombinant human insulin in India way back in 1991. Then it was Eli Lilly & Company to launch human insulin under the brand Huminsulin. These two leading names in diabetic care started catering to the needs of diabetic patients in the country by importing human insulin till Wockhardt launched its human insulin under the brand Wosulin in 2003. Later other companies like Biocon and Shreya Life Sciences entered the human insulin market by launching their products under the brand Insugen and Recosulin respectively in the second half of 2004. Now we have as many as six Indian companies with manufacturing capabilities. These companies are marketing about seven recombinant biotech products for the local as well as international market (non-regulated countries).

 

In line with global markets, the Indian market too is showing considerable growth in recombinant products. In 2003-04, the Department of Biotechnology (DBT) estimated the domestic market for recombinant therapeutics at about $90.6 million. It represents about 3.2 percent of the total Indian pharmaceutical market and 1.6 percent of the world market for recombinant therapeutics. But according to a report on Recombinant DNA Therapeutic Products published by Technology Information, Forecasting & Assessment Council (TIFAC) in 2002, the market of approved recombinant therapeutics has been estimated to be about $119 million, which is approximately 3.2 percent of the total pharmaceutical market of Rs $3.6 billion in the country. However, with IPR in place in India opportunities exist for speeding up production facilities, based on licensing and other forms of cross-border relationships for all therapeutic products approved for marketing in India, namely insulin, alpha interferon, hepatitis B surface antigen based vaccine, erythropoietin, streptokinase, and others.

 

Looking at the trends and increase in the number of reported cases of chronic renal failure in India, the erythropoietin market in the country has been on the rise. Growing at a rate of 20 percent, the EPO market was estimated at about $16.7 million. G-CSF market is about four-six million dollars and growing at a rate of 25-30 percent. Similarly the FSH market is about four-six million dollars with growth rate of 20 percent. Now the present market size for interferon is about $12 million. It is growing at rate of 30-40 percent. The insulin market in India is about $56 million and the human insulin market is growing at the rate of 40.5 percent. The present Hepatitis B vaccine market itself is about $22 million with huge growth potential. The Streptokinase market in the country is about $17 million growing at a rate of 25 percent. Considering the overall, recombinant biotech market in India at present is in the range of $100-150 million growing at a rate of 20 percent. However, considering a growth rate of 20 percent, with few exceptions, the TIFAC report observed that the market of these products would be around $214 million by 2005.

 

At present over 50 recombinant therapeutic products have been approved globally for commercial use. And one fourth of these have already made inroads into India with about 14 recombinant biotech products receiving government approval for marketing in the country. About 40 companies both Indian and multinationals are involved in one of the many activities such as R&D, importing, manufacturing and marketing of recombinant biotech products.

 

Six local companies are into real manufacturing and marketing of these products while 16 companies involved in marketing these products by importing. A few companies like Sun Pharmaceuticals and Torrent Pharmaceuticals are into contract manufacturing of recombinant products for multinationals like Eli Lilly and Novo Nordisk respectively. About 15 leading names in pharmaceuticals and biotechnology industry are investing on R&D activities related to recombinant biotech products.

 

Fourteen recombinant biotech products are available in the country. Local companies have set up the expertise to develop and manufacture seven recombinant biotech products namely Hepatitis B Vaccine, Streptokinase, human Insulin, G CSF, Erythropoietin, Human Growth Hormone and Interferon alpha 2b. The rest all are imported and marketed in India.

 

The indigenous production of these products by local companies has resulted in the drastic reduction of prices and at the same time led to increased consumption. For example, the indigenous production of Hepatitis B vaccine initiated by Shantha Biotechnics Ltd, had resulted in reduction in price of the imported vaccine from $10 per dose (in 1996) by SmithKline Beecham to an average of $3 per dose. We had a similar situation when Indian companies launched erythropoietin and insulin with their own brands after developing indigenously.

Insulin

In the human insulin space there are as many as seven brands of both Indian companies and multinationals. The brands available in the country include Insugen of Biocon (2004), Huminsulin of Eli Lilly and Company India (1995), Wosulin of Wockhardt (2003), Recosulin of Shreya Life Sciences (2004), Human Mixtard of Novo Nordisk, Insuman of Aventis Pasteur, Human Mixact of USV, Mixulin of Cadila Pharmaceuticals. Most of these brands are available in vial form with different strengths ranging from 40 iu/ml-100 iu/ml. During 2003–2004 alone, as many as three companies launched human insulin products under different brands averaging at $3 per 10 ml vial. The human insulin market is growing at the rate of 40.5 percent in the insulin market.

 

Wockhardt was the first Indian company to launch the country’s indigenously developed recombinant human insulin under the brand Wosulin at $3 per 10 ml vial in September 2003. With this it became the first Indian company to launch recombinant human insulin in Asia. Even US Vitamins launched its human insulin product in 2001 but its focus remained on animal insulin. The market for animal insulin products is coming down with increase in human insulin. A year later Bangalore-based Biocon Ltd announced the launch of Insugen, the new generation bio-insulin in November 2004.  Insugen was made available to the public in 10 ml vials of 40 iu/ml for an introductory price of $2.8. Shreya Life Sciences, the Indian arm of Moscow-based Shreya Corporation too launched human insulin under the brand name Recosulin in December 2004, exactly a month after the launch of Insugen. Shreya has launched Recosulin at $3 per 10 ml vials (rate fixed by National Pharmaceutical Pricing Authority (NPPA) by importing the finished product from Bioton, Poland (manufactured using BTGC technology).

 

Besides Indian companies Eli Lilly entered the Indian insulin market a decade ago (in 1995) under the brand Huminsulin. Before that Novo Nordisk launched its human insulin product and went on to introduce insulin analogs under the brand NovoMix 30 (Premixed Insulin Analogue) and NovoRapid (Rapid Acting Insulin Analogue) for the first time in India. In August 2005, Eli Lilly & Co. India too launched its insulin analogs under the brand Humalog Mix 25-50.

 

Although there are many brands in this space from both local and multinational companies, Rajesh Nanavati, marketing controller, Biogen and Biolife, Shreya Life Sciences observed, “I don’t see any competition in the market. We want to focus on our USPs to enhance credibility for our products among patients and doctors and look for growth. Our focus is to provide better and quality product to the customers. It will help us to reach our target of $2.2 million in one year.”

 

Novo Nordisk leads the domestic market as its sales during last year stood at $24 million, followed by Eli Lilly at $1.2 million and Wockhardt with about $2 million. However, the Indian companies have to put in efforts to capture the market amid stiff competition from the established multinational companies such as Novo Nordisk, Eli Lilly and Aventis Pasteur. This is mainly because diabetes patients have been using brands of multinationals for many years.

Similarly in Erythropoietin space many brands are available in India. The companies that are marketing EPO include Shantha Biotechnics (Shanpoietin–2005), LG Life Sciences India (LG Espogen Inj), Ranbaxy (Ceriton–2003), Johnson & Johnson (Eprex), Emcure Pharma (Vintor for Nephrology/Epofer for Haematinics–2001), Wockhardt (Wepox -2001), Zydus Biogen (Zyrop), Hindustan Antibiotics (Hemax) and Intas Pharmaceuticals (Epofit and Erykine- 2005). Except Wockhardt, Shantha Biotechnics and Intas Pharmaceuticals, other Indian companies have entered into agreements with different multinationals for marketing and licensing rights to offer recombinant EPO to the Indian patients.

 

Hindustan Antibiotics has a tie-up with Elanex Pharmaceuticals, USA to manufacture and market recombinant human Erythropoietin Omega under the brand Hemax. Emcure Pharmaceuticals has been in this market with its brand Vintor since 2002 by entering into marketing and licensing agreement with Dragon Pharmaceuticals Inc., Canada for the distribution of its EPO in India. Ranbaxy too is selling Erythropoietin under the brand Ceriton since June 2003.

 

Wockhardt has been manufacturing and marketing EPO under the brand Wepox and selling at $17 /2000 iu/ml lowest among its competitors. At the launch of EPO product, Habil Khorakiwala, chairman, Wockhardt Ltd noted, “By pricing it at this level, we have made EPOX therapy significantly more affordable to Indian cancer and kidney failure patients. This will increase the usage of this drug in India and will be within the reach of many more patients.” Intas Pharma too launched its EPO product in July 2005 under the brand name Epofit for nephrology and Erykine for oncology spaces. Intas is selling these two brands in four strengths at 20 percent lesser than the innovative brands available in the market. 

 

Janssen-Cilag CRF, a business division of Johnson & Johnson, was amongst the first to launch a successful biotech drug in India namely Eprex. Eprex in a short span of five years has become the largest selling brand of Janssen-Cilag India. LG Life Sciences India Pvt Ltd another multinational has been marketing EPO under the brand LG Espogen Inj. It is looking at setting up its own production and R&D units in India to innovate, manufacture and build export business to other SAARC, Middle East and African countries. Considering the opportunity with few serious players, Hyderabad-based Hindustan Bio Sciences Ltd (HBSL) and New Delhi-based Kee Pharma Limited are also looking at entering this niche market. HBSL proposes to launch the EPO in the Indian market under the brand “Eposino” targeting mainly the middle and lower income group patients unlike similar drugs in the market, such as Eprex of Johnson & Johnson, Hemax of Hindustan Anti Biotech and Zyrop of Zydus Biogen, which, it says, were expensive.

 

The Indian EPO market was estimated at $7.8 million in 2001. The EPO market has been growing at a rate of 20 percent. Last year it has increased to $13.4 million and this year it was estimated at about $16.7 million.

 

Commenting on the possibility of a price war in this space, R Chandrasekaran, Vice President Marketing, Biotech/Oncology, Intas Pharmaceuticals Ltd, said, “We don’t initiate any price war in this niche market. Our focus will be to provide good service and better quality product to the customers. Companies like Johnson & Johnson and Ranbaxy with their well established names are doing well in the market. Intas will have an edge in this niche market as its products are targeted at oncology and nephrology.”

India known as the vaccine hub of the world has many local companies, which have actually developed recombinant human Hepatitis B vaccine and are selling the same in the domestic market at affordable prices. As pointed out earlier, with the launch of Shanvac B, India entered the manufacturing phase of recombinant biotech products in 1997. A year later Bharat Biotech International launched Revac B. Then in 2000, Wockhardt joined the team of manufacturers of recombinant biotech products in India with launch of its first recombinant biotech product Biovac B.

 

In 2004, Biological E too launched its hepatitis B vaccine under the brand Bevac B. The other Indian players in this business include Panacea Biotec (Enivac HB), Serum Institute of India (Gene Vac-B), and VH Bhagat Life Sciences (Hepagen Plus) introduced its hepatitis B vaccine in 2000.

 

Even multinationals like LG Chemicals (LGEuvax B Inj), and GlaxoSmithKline India (Engerix-B) have their own brands in hepatitis B vaccine market. In all we have over 10 brands available in India.

 

Looking at the competition in the Hepatitis B vaccine market in India, which is growing at a rate of 20 percent, S Kalyanasundaram, Managing Director, GlaxoSmithKline Pharmaceuticals Ltd said, “For different reasons Indian companies unlike multinationals, who have very large portfolio, have their own marketing strategies. They manage it quite well.”

 

The present Hepatitis B vaccine market is estimated to be about $22 million. As the government plans to include hepatitis B vaccine under the national immunization program, many government agencies and non-government organizations are supporting/ pushing the growth of the market in India.

 

“The market is growing in terms of volume. But in terms of value it is taking a slow trajectory path mainly because some agencies are selling the vaccine free of cost,” observed N Jiva, product manager, Zydus Biogen.

In the Streptokinase space too, India has a couple of brands marketed by local companies.  Bharat Biotech International and Shantha Biotechnics, both from Hyderabad launched their brands under the name Indikinase in 2003 and Shankinase in 2004 respectively. Apart from these, Knee Pharma from New Delhi is also into this space. Dr Krishna Ella, chairman and managing director of Bharat Biotech while launching Indikinase said, “By manufacturing indigenously, we can bring down the cost of this drug, which has been all along imported into India. The recombinant Streptokinase scores over its non-recombinant counterpart in many respects, the most significant one being able to prevent excessive bleeding compared to the existing products.”  In 2003 the market for Streptokinase in the country was valued at over $14.5 million growing at a rate of 25 to 30 percent. Considering this, the present the Streptokinase market will be about $17 million. Cadilla Pharmaceuticals has STPase. Cadilla’s streptokinase brand is a purified preparation of Streptokinase produced through bacterial fermentation.

 

In the Human Growth Hormone space, we have both multinationals and Indian companies marketing their brands. None of the Indian companies are manufacturing this drug locally. The brands available in India include Humatrope of Eli Lilly & Company (India), LG Eutropin Inj from LG Chemicals, Saizen from Serum Institute of India and Norditropin NordiLet from Novo Nordisk.

 

In Granulocyte Colony Stimulating Factor (G-CSF) space, Indian companies like Intas Pharmaceuticals and Dr Reddy’s Labs have set up the facilities to manufacture this drug. Intas Pharma launched G-CSF product under the brand Neukine in 2004 and Dr Reddy’s Labs sells Grastim. Emcure Pharma (Emgrast) and Kee Pharma too are marketing G-CSF. “The Indian market for G-CSF is very small. It is estimated to be about $5.5 million growing at the rate of 25-30 percent,” said R Chandrasekaran, Vice President Marketing, Biotech/Oncology, Intas Pharmaceuticals Ltd.

 

In Interferon space, India has a couple of brands from both multinationals and local companies. Shantha Biotechnics is the only Indian company that has been manufacturing Interferon alpha under the brand Shanferon. However, companies like Zydus Biogen, LG Chemicals, Fulford India, an affiliate of Schering-Plough, USA, Glenmark Labs are marketing the drug under Zavinex, LG Intermax alpha Inj, INTRON A and Markferon respectively. Launched in April 2002, Shanferon is claimed to be the only Interferon Alpha 2b in the world to be cloned and expressed in Pichia pastoris, a eukaryotic new generation host, having immense advantages over prokaryotic E. coli host. Giving stiff competition to multinational brands, Shantha Biotechnics garnered 20 percent market share in a $6.7 million interferon market in the first of product launches in 2003. The present market size for interferon is about $12 million. It is growing at rate of 30-40 percent. “The doctors are convinced about the drug and the technology used. But with no insurance scheme in place, higher costs are coming in the way of growth of the market in India,” noted Jiva of Zydus Biogen. 

 

There are also other recombinant products available in the country. The hemophilia patients are receiving the Blood Factor VIII drug not at chemist shop but though Hemophilia Federation of India, a non-profit organization working for the cause of hemophilic patients across the country. Off the 70,000 odd patients less than 40 percent of them are affordable to use the drugs. While some patients are not at all aware of the availability of these drugs. In Follicle Stimulating Hormone (FSH) India has only two brands in recombinant space i.e., from LG Chemicals under the brand LG Follimon Inj and other one from Pune-based Serum Institute of India Ltd under the brand Gonal-F. Similarly in Tissue Plasminogen Acticator and in Alpha Drotrecogin, German Remedies and Eli Lilly & Company (India) have their brands.  

The success stories of Shantha Biotechnics and Bharat Biotech, which developed their products using the funds from Technology Development Board (TDB), have pressed the other companies to develop recombinant therapeutic products indigenously. Shantha received $4.6 millionfor two projects, one on Hepatitis B vaccine and other one on interferon alpha 2b. Similarly Bharat Biotech received financial assistance from TDB for development and commercialization of recombinant Hepatitis B vaccine and streptokinase. It got $3 million aid for these two projects.

Over the last few months, there has been a sleuth of launches. Bharat Biotech has announced Regen D, a recombinant epidermal growth factor for diabetic ulcers and for burns and skin grafts. Shantha Biotechnics announced its four-in-one vaccine, Shantetra, a single vaccine for protecting children against four life-threatening infections including diphtheria, tetanus, pertussis and hepatitis B. Similarly, Serum Institute has announced an indigenous DTP and Hepatitis B combination vaccine, Q-Vac. Serum Institute also announced the launch of its unique rabies vaccine, Rabivax claimed to be the only indigenously developed Human Diploid Cell (HDC) rabies vaccine in India. It is being priced at $6.5 (against the imported cost of $26.8). Others like Indian Immunologicals are likely to launch their range of human biologicals too. Looking at the growth of the recombinant market and recombinant drugs going off patent as many as 15 pharmaceutical firms in the country have drawn up plans for large-scale commercial production of recombinant therapeutic proteins. The aggregate investment in this segment in the next five years would be about $111 million.