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
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 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.
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.
BIO-AGRICULTURE SEGMENT
GM seeds
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.
Bovine Somatotropin
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.
GnRH
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.
BIOINDUSTRIAL SECTOR
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.
