- Humanized Monoclonal Antibodies of diverse kinds
- Molecular Diagnostics and Point of Care devices
- Vaccines especially to treat tropical and poverty-linked diseases, some viral and bacterial infections
- Vaccines to treat systemic disorders, e.g. prostate ailments, hormonal disorders, certain cancers etc.
Tuesday, June 3, 2014
The Indian Biotechnology sector is expected to emerge as a global key player as India has its strong pool of engineers and scientists, profound institutional network and cost-competitive manufacturing outfits. In addition the national research laboratories with their scientists can develop innovative R&D and application-oriented materials. The biotech industry turnover is considered to be over USD 5 billion in FY 2013-14 and is poised to grow at 15-18% per year.
Biopharmaceutical sector holds the major chunk of the biotech industry. While a wide range of products are manufactured, in the global context there is a great gap between what is available globally and what is available in Indian market in the following sub-sectors:
Humanized Monoclonal Antibodies
These products are entering into the market with rapid speed from different parts of the world. India is making progress but at a much slower pace. Biologics or Biopharmaceuticals or Similar Biologics or Biosimilars are terms coined by different countries for biological substances produced by living organisms. Such products are generally produced by recombinant DNA technology utilizing microorganisms or eukaryotic cell lines, depending upon the complexity of the biologics. The products are also purified by complex processes. Because of these inherent complexities, no two biologics produced by two organizations are exactly similar, although there exist substantial resemblance. Since the biologics are complex biopolymers, existence of all the molecules in specific orientation is also another issue as the bio-activities are linked with ligand-receptor interactions where the intact structures of molecules in right orientation are extremely important. Even though a large number of biologics is getting patent-expired every year and therefore, other manufacturers would try to encash the opportunity for business gain, worldwide there are debates among the regulators, the manufacturers, the users and the vocal public on issues relating to efficacy and safety of similar biologics supplied by other manufacturers who are not the inventors. The following issues in this context require to be addressed and resolved:
Ø There is a strong contention from some countries that non-inventor suppliers of similar biologics should compare the efficacy of their products against one reference product only and that the reference product should be the product manufactured and marketed by the inventor. The issues among others are how to get the authentic bulk materials of the inventors; at best the formulated materials could be available from the market. Here also, issues of restricted availability or non-marketing of products in Indian market could create hindrance. The debate is therefore whether there could be exceptions to such assumptions and if so, what alternate solutions could be put forward that are doable and acceptable by the regulators in India and abroad.
Ø There is good agreement among different stakeholders that the similar biologics should conform to the general physico-chemical properties of the inventors’ product. There is however disagreement about how much variation on the “residues” be allowed. There is also disagreement about how much purity, measured by which method is acceptable for a similar biological to be accepted as equivalent to the inventors’ product. There is a need to develop standards to resolve this issue for each biosimilar products and that such standards should be acceptable to the regulatory authorities all over the world. The debate is who is going to develop such a standard and wherefrom the basic inputs of information be obtained.
Ø While a similar biologic can be produced by use of different recombinant hosts/cell lines, which are different from those utilized by the inventor, there can be disagreement about the product equivalence of the manufactured similar biologic as there could be minor difference in the content of impurities in such similar biologics from the inventor’s biologic. Here also an agreement is to be arrived at on the extent of the presence of the impurities and their safety as well as efficacy issues. The debate is, how could an unanimity be arrived at which is also acceptable to the regulators.
Ø While biosimilar products or similar biologics are supposed to be therapeutically interchangeable for different approved applications, there are issues and argument for agreeing to “interchangeability concept” based on different kinds of factors such as change in the cell line, change in the downstream processing operations etc. although the similar biologics may conform to the general physico-chemical properties of the invented biologic product. We need to come out with solutions that are acceptable to the regulators.
Ø For generating efficacy and safety information on similar biologics, the trials that are required to be conducted following establishment of safety of the formulated similar biologics in approved animal models, the number of human subjects are to be limited and also the sites of trials are to be in smaller in numbers, as enough efficacy and safety information had already been generated by the inventors. The numbers of human subjects to be considered and also the testing sites are also a subject matter on which there is no unanimity as yet.
There is a need to prepare and announce a policy paper in consultation with the industry to promote the introduction of Similar Biologicals faster into the Indian market.
Molecular Diagnostics and Point of Care devices
India is yet much behind in the actual use of techniques of Diagnosis at molecular level as the nucleic acid extraction kits are expensive, not easily made in India and that the DNA amplifying machines are also expensive. This is also true for all other kinds of Point of Care devices. While there is an urgent need to set up target oriented R&D projects, efforts are also to be made to pinpoint which equipment, devices and consumables must be made locally to compete with the world. The industry can team up with the National R&D laboratories and draw a White Paper to cover these aspects.
Vaccines of diverse kinds
India has made strong contribution to the health of the people in the world by producing cheapest vaccines for containing childhood diseases commonly occurring from bacterial and viral infections such as DPT, Polio, MMR, Hepatitis B etc.
The world is making phenomenal progress in containing several disease conditions through immunological interventions, ligand-receptor interactions and signal modulation methods. Vaccines are making great progress in containing not only certain microbial diseases but also several kinds of cancer, auto-immune disorders etc. The emphasis in research and development in this country has also to keep pace with such advancements. Specific programs can be drawn up by the industry to suggest application oriented research in national institutes for doable product development in specific areas. India is yet quite behind in knowledge and applications in this important emerging area.
Certain systemic disorders leading to diseases related to post-industrialization syndrome such as diabetes, hypertension and stress among the working class including laborers are fast increasing. These are resulting in cardio-vascular diseases, stroke and kidney disorders. Different kinds of cancer are also rapidly increasing. Diagnosis, treatment and cure are the areas where new products can be developed and introduced by the industry. There is a need for encouragement and facilitation from the government in terms of policy support to promote diagnosis and therapy in these areas. There is a need to identify specific industry-related problems and prepare a white paper for a roadmap for future development.
Among the other areas in biopharmaceuticals requiring government and industry intervention are to treat cost effectively malnutrition, tuberculosis and certain viral diseases like HIV, HBV, HCV and HPV. Biotech inputs for the promotion of cost-effective products and services can be identified and specific government interventions for promoting such products in people-friendly programs can be thought about.
In bio-agricultural sector including animal husbandry is another important area which needs promotion. Use of Bt-cotton technology in Indian agriculture made a sea change in increasing the production of better quality of cotton lint in the country and in promoting Indian textile industry in the global context. However, the GM technology for developing better seeds has been put to debate. This situation needs to be reversed. The industry should plead with the government to allow the development of GM seeds for a wide range of cereals, pulses, fruits and vegetables. The development in the Indian public sector institutions in GM research is inadequate compared to what such institutions have done in the development of quality hybrid seeds and varieties. Research needs to be intensified and extensive collaboration should be encouraged to develop GM technology in seed sector in the country. This is an area requiring extensive financial resources and the Indian government may like to take the lead. Industry can be active partners.
Even though India produces largest quantities of milk in the world, the per-animal milk yield is yet very poor. Our dependence on buffalos for milk is very high and yet much needs to be done to improve the health of the animal. Moreover, the country also has a very large number of non-productive animals in all categories of mulching life forms. This situation can be tackled by using genetically modified bovine somatotropin to improve milk yield in mulching animals. The technology is doable and such products are already approved elsewhere in many countries. Milk yield can be substantially raised by use of bovine somatotropin.
Increase in the fish production is constrained by several factors, one among them is the non-availability of adequate numbers of fingerlings. Different kinds of highly purified GnRH can be produced by recombinant DNA technology and these can be used to raise different kinds of fingerlings in proper seasons. Use of such fingerlings shall certainly contribute to increased production of fish.
Genetically Modified Enzymes
The consumption of enzymes in industry is rising at a galloping speed. In food, feed and fodder industry, a wide range of enzymes are being utilized. Proteases of various kinds, phytase, amylase, cellulose and lipase of a wide spectrum are being used for obtaining better quality of products. The dairy industry also is in need of various enzymes, especially for producing better quality of cheese. Rennet of different qualities is required for the industry. In detergent industry, the use of alkaline protease, lipases, amylases, cellulases and pectinases have also increased sizably. In leather, paper and textiles, the use of enzymes in various operations have also increased considerably. In order to meet the rising demand of enzymes, many countries have resorted to the use of genetically modified organisms for boosting production. In India the production is yet from non-recombinant organisms and therefore the yields are low. There is a need to relook at the whole operation and introduce genetically modified enzymes utilizing a wide range of GM organisms. This will not only boost the local industry but would also increase the availability of the enzymes considerably.
It is therefore suggested that the following factors and issues be considered in preference for preparing position papers by the country to promote the Indian Biotech sector during the coming years:
1. All efforts should be made by the industry and the government jointly to ease the production of Similar Biologicals within the ambit of national and international laws.
2. New and effective vaccines utilizing recombinant DNA technology should be promoted to develop newer therapies to treat a wide range of life-threatening conditions.
3. Cheaper and cost-effective diagnostics based on nucleic acids need to be developed to diagnose and treat certain communicable diseases like tuberculosis, HIV, HBV, HCV and HPV. Besides, emphasis should be made to diagnose early systemic diseases such as diabetes, cardio-vascular ailments, diseases of kidney, arthritis and various types of cancer of different organs.
4. Emphasis should be made promote the use of GM seeds in Indian agriculture.
5. For increasing milk production, use of bovine somatotropin of various types need to be produced and utilized.
6. For increasing fish production, the use of different kinds of purified GnRH should be intensified.
7. Enzymes of various qualities required for the industry need to be produced by utilizing genetically modified organisms including E.coli, yeast and other microbial life forms.
8. Industry and Government should work in close collaboration and utilize the public funded institutions to the maximum extent for generating new products and services in modern biotech sector. Where necessary, collaborations with knowledge intensive companies including the multinational corporations should also be promoted and intensified. Policy statements towards achieving such goals should be made on a faster mode.