The race to offer H1N1 flu vaccination is picking up pace. While global H1N1 vaccine manufacturers like Sanofi Pasteur, Novartis and MedImmune have begun shipping their products, Indian vaccine majors Serum Institute of India, Panacea Biotech and Bharat Biotech are likely to start human clinical trials by the year-end and the H1N1 vaccine will hit the market by March-April next year. Armed with the seed virus, scientists at domestic vaccine majors like Serum Institute of India, Panacea Biotech and Bharat Biotech are working at a frenetic pace to produce a single dose of vaccine, which induces a strong immune response in healthy adults and children.
Indian research efforts are in line with the sentiment echoed by the World Health Organisation (WHO), which has restated its confidence in the H1N1 flu vaccine, calling it the most important tool against the influenza pandemic. Mass vaccination campaigns against influenza pandemic are going on in China and Australia and will be starting soon in the United States and parts of Europe. Though mild adverse side effects such as muscle cramps or headache have been reported in some cases, WHO strongly recommends that everyone who has access to the vaccine should be immunised.
WHO declared the H1N1 influenza pandemic in June and its laboratories have provided seed virus to vaccine makers worldwide to develop vaccines. GlaxoSmithKline won government orders for its H1N1 vaccine of 440 million doses worth $3.5 billion. Sanofi Pasteur has shipped the first batch of H1N1 flu vaccine from its plant in Swiftwater, Pennsylvania, several days earlier than expected. Further shipments will follow, with a total of 75.3 million doses expected through December. Other companies manufacturing the flu vaccine include Novartis, Baxter, AstraZeneca and CSL.
It is evident that the $20-billion global vaccine market, which was earlier thought as a low-margin, low-growth industry, is currently attracting the interest of all major pharmaceutical giants. The market is presently witnessing growth rates much faster than the traditional pharmaceutical market; and with many new blockbuster potential vaccines likely to hit the market in future, the growth is only expected to increase. The biggest factor driving the vaccine market is its potential to prevent deaths due to diseases.
Healthcare analysts opine that given the H1N1 activity around the globe, it is an opportune time for pharmaceutical companies to make best use of the business opportunity by looking at vaccines. Yet, the $800-million domestic vaccine industry is pitted against various odds to reach its peak. A case in point: domestic H1N1 vaccine makers are clueless about the quantity of H1N1 vaccines the government plans to stockpile. As a result, the roadmap of the yet-to-be produced vaccine remains hazy.
Also, there is less conscious effort on the patent front. Research programmes by Indian pharmaceutical companies are not making much use of patents. While few claim that it is more like a chicken and egg scenario and mass vaccine products, especially for the pediatric use, do not deserve patents, but few others point out that there has to be a value to the research and it means business too.
Mahima Datla, chairman, Biological E says, ?Patents in the past, especially for open processes or biogenerics, were not relevant as most of the research was done by laboratories and academic institutions. Moreover, product patents in the vaccine industry for the Indian players are very hard to get. Even the awareness levels are quite low. But the scenario seems to be changing with Indian companies gearing up for process patents for vaccines.?
A major question arises. Are patents necessary at all in the vaccine industry? This is because patent infringement can happen in molecular biology, sequence, process, formulation and protein folding. Interestingly, the industry is divided. Patents on mass vaccination programmes such as the combination vaccines do not deserve respect. However, the newer vaccines targeting specifics need patent protection. Sources inform that total patents filed by the vaccine industry are less than 50 and still a major challenge for patent filing.
On a broader level, let?s look at some of the challenges in the industry. One major issue is the marketing of combination vaccines; proprietary vaccines dominate over the expanded programme on immunisation. Bharat Biotech chairman and managing director Krishna Ella says, ?For Indian manufacturers, patent is still a critical issue. It is a hard truth that global vaccine manufacturers are creating barriers. And this scenario makes it mandatory for the Indian manufacturers to patent their research. But this is not feasible with the escalating costs for patenting.?
Ella laments that there is no governmental support for the patent process. ?As for each patent, it costs over Rs 1 crore apart from maintenance cost, which is over Rs 20 lakh,? Ella adds. In his opinion, the government has to handhold with a subsidised scheme for companies that patent their products. This would also increase innovative spirit among pharmaceutical and biotech companies and there is protection around their research.
In addition, there is relatively low markup opportunity for mass-use childhood vaccines. Besides the development cost, there is substantial manufacturing fixed cost and difficulty in changing due to new regulations. In developing countries, patent-based product exclusivity is relatively rare, except on newer vaccines, and not generally on mass-use children?s vaccines.
A look at the future research programmes of Bharat Biotech reflects Ella?s renewed stress on the need for patents. The company?s pipeline comprises combination vaccines (Hepatitis-B+DPT+Hib), bio-antibiotics, combination probiotics, chikungunya vaccine and pandemic influenza vaccine. Currently, some of the programmes that are in the stage of clinical trials include malaria vaccine candidates, rotavirus vaccine candidates, anti-infectives and lysostaphin.
It?s happening at a time when big pharmaceutical companies are also pursuing research in biotech and vaccines. According to healthcare analysts, technology and regulations for vaccines are tougher than for biotech products. The option for vaccines is primarily due to promising growth globally and thanks to new diseases, which are making vaccine R&D stronger for developing preventive vaccines. The recent Pfizer-Wyeth deal for the pneumococcoal conjugate vaccine was kind of a trendsetter.
Traditionally, vaccines have consisted of weakened microorganisms. However, modern biotechnology has opened up new opportunities for fighting infectious diseases.
In the last couple of years, it has become possible to produce new types of vaccines, which consist of smaller entities of the disease-provoking microorganisms, such as proteins, peptides, and DNA. The advantages of the new vaccines are improved efficacy, less side-effects and at the same time, preventing the risk of catching the disease.
However, the scenario in India is far from encouraging. Airing his displeasure, KI Varaprasad Reddy, managing director, Shantha Biotechnics, says, ?It is purely bureaucratic apathy that prevents inclusion of many vaccines in the national immunisation programme. The government seems to be going too slow on the inclusion of combination vaccines as they have to import them.? A recent government report says that there are no indigenous combination vaccines, although there is a proposal to implement mono Hepatitis-B vaccine in the immunisation programme.
Shantha Biotechnics makes combination vaccines and claims to have the first Indian Hepatitis-B vaccine to be pre-qualified by WHO, Geneva, for supplying to UN agencies globally. The company also caters to major international markets including Asia-Pacific, Africa, CIS and Latin America.
According to Reddy, safety perceptions, downward pressure on prices, lack of effective regulatory system to facilitate timely clearance, lack of transparency and quality of vaccines could hamper Indian vaccine industry?s march. He even advocates the setting up of an Asian federation of drug administration on the lines of USFDA for the vaccine industry to tap the opportunity that exists in developed countries. Besides, poor support from national governments and venture funds for R&D in the industry and the lack of accurate long-term demand forecasting are affecting the profitability of players in the industry.
The country?s national immunisation programme covers most of the essential vaccines, like BCG, Polio, DPT, Measles, Diphtheria, Tetanus toxoid and Vitamin A. Hepatitis B is also covered in some areas of India. It is, however, not mandatory across all states. At present, India has immunisation coverage of 44%, which indicates that the government has to make substantial efforts to completely eradicate vaccine preventable diseases.
On its part, Shantha Biotechnics has a successful line-up of four (RM1, RM2, RM3 and RM4) fully human monoclonal antibodies against lung cancer, melanoma, pancreatic and breast cancer. It also holds the patent for these antibodies. Going forward, the company plans to launch its typhoid vaccine in the next six months, a rotavirus vaccine in association with National Institutes of Health by 2011, and HPV vaccine for cervical cancer by 2013, besides getting marketing rights for a dengue vaccine.
Globally, vaccine manufacturers are upbeat over India?s achievers. The recent $150-million joint venture between Merck and Wellcome Trust called MSD Wellcome Trust Hilleman Laboratories is to develop and produce new vaccines in India. The joint venture is expected to develop cheap vaccines for neglected diseases that are common in developing countries.
These vaccines, which may be the improved versions of existing ones, will be marketed around the world.
Another example is that of Sanofi Pasteur, the vaccines division of Sanofi-Aventis group, which acquired Shantha Biotechnics, was awarded contracts worth $340 million by a United Nations agency for supplies of pentavalent vaccine SHAN5, which is a combination vaccine of diphtheria, pertussis, tetanus, haemophilus influenza B and Hepatitis B.
Recent years have indeed witnessed an unprecedented progress in immunisation. One hundred years ago, infectious diseases were the main cause of mortality, even in the most developed countries. Today, vaccination has a significant impact on the reduction of mortality and serious diseases. Presently, vaccination can prevent a wide range of infectious diseases, and it holds the promise for more prevention. In fact, several hundred research projects are being carried out worldwide, with the aim of developing new vaccines. Despite the fact that vaccinations save lives of millions throughout the world each year, there is still a lot that needs to be achieved. This will require appropriate immunisation efforts, and financial support, informs Ella.
On a positive note, the domestic vaccine industry has received global recognition as the National Regulatory Authority (NRA) has been approved by the WHO. Predictably, the future lies in niche technologies like needle-free vaccines and cold-chain free vaccines to create impact a global impact.
Moreover, increased market consolidation is expected along with a renewed demand for combination vaccines. DNA vaccines, vaccines against AIDS and cancer are the future R&D focus. Incidents such as H1N1 pandemic only remind us that the battle against infectious diseases is far from being won.