PREPARING FOR MODERN BIOTECH
PRODUCTS IN INDIA
CII New Delhi Lecture, 2009
Prasanta K Ghosh
Managing Director,
KEE GAD Biogen Pvt Ltd., New Delhi
E. mail: gprasanta2008@gmail.com
Introduction
Although the recession has reduced the enthusiasm for investment in new ventures all over the
world, some sectors of the industry like the biotech business have not yet been
pushed to the walls. Hopes prevail in the opportunities emanating from new
discoveries in the management of chronics and life-threatening diseases;
raising the productivities in agriculture; the use of green technologies in
industry to reduce pollution; the utilization of degraded and wastelands by
using modified stress-resistant plants or treating solid and liquid waste using
recombinant microbes and modified plants. Biotechnology applies a set of
techniques developed through basic and applied research, using biological
materials to produce, identify or design substances or to modify living
organisms including human cells. Biotech products meet diverse human needs.
Government
contribution to biotech development
Modern
biotechnology is rather new to India.
The whole sector, conventional and modern, has been promoted mainly through
government departments like the Department of Biotechnology (DBT), Department
of Science &Technology (DST), Department of Scientific & Industrial
Research (DSIR), Ministry of Agriculture, Ministry of Health and a few other
departments. The money has been utilized to promote all aspects of
biotechnology including manpower development, setting up of a basic and
application-oriented research institutions, funding for research, promoting the
development of the technology and technology transfer, providing assistance to
small & medium entrepreneurs, intellectual property protection, setting
rules and procedures for fostering the growth of biotech industries and the
like. Public institutions of the DBT, DST, Council of Scientific and Industrial
Research, Indian Council for Agricultural Research, Indian Council for Medical
Research, the University Grants Commission and the All India Council for
Technical Education had carried out research and development in different
aspects of biotechnology. The combined
expenditure for promoting biotechnology in the country, starting from February
1986 up to December 2008 is estimated to be over rupees 4700 crores from the
Government alone.
Investment
by the Indian modern biotech industry
During
the last 2 decades several industries have made an investment in modern
biotechnology although earlier there had been a sizeable investment in
conventional biotechnology. Conventional biotechnology industries in India are more
than 100 years old; the products include fermentation-based substances
including alcohol, sera & vaccines, antibiotics, certain vitamins,
steroids, industrial enzymes, fermented foods and the like. The investment in
modern biotechnology started from the early ’90s and the first unit went into
production on August 18,
1997 with the basic production of recombinant hepatitis B vaccine
in genetically modified Pichia pastoris. Thereafter, several units have
come up. The modern biotech products include recombinant hepatitis B surface antigen-based vaccines;
granulocyte colony-stimulating factor; erythropoietin in various forms;
interferon-alpha 2B and the pegylated product; epidermal growth factor;
streptokinase; human insulin; and two monoclonal antibodies (MABs). One of MABs
blocks certain receptors of epidermal growth factor and therefore, prevents the
proliferation of certain cancer cells in breast tumor, and the other blocks the
CD20 protein and thereby prevents proliferation and differentiation of cancerous B-cells into plasma cells in diseases like
non-Hodgkin’s lymphoma and rheumatoid arthritis. Several companies are also
producing multivalent vaccines, combining hepatitis- B surface antigen
into them. The total investment in the modern biotech industrial sector including
those in modern vaccines is estimated to be of the order of rupees 900 crores.
Indian Modern Biotech Industry in Global
Context
The Indian Biotech Industry
in the global context is yet small. The Indian contribution in the
manufacture of modern biotech products
was about 0.2% in 2005, which is
expected to rise to 1.3% by 2010,
compared to global production as
could be seen from the following table :
Table:
Estimated global consumption and production of modern biotech products
Global Segment
|
Estimated
Consumption
in
billion US$
2005 2010
|
Estimated
Production
in
billion US$
2005 2010
|
USA & Canada
|
34.0
|
50.0
|
27.0
|
52.0
|
Europe and Japan
|
10.0
|
15.0
|
12.2
|
12.5
|
Rest of the World
|
5.0
|
12.0
|
9.8
|
12.5
|
Total
|
49.0
|
77.0
|
49.0
|
77.0
|
Overlap of the Segments of the Rest
of the World
|
India
|
0.3
|
1.0
|
0.2
|
1.3
|
China
|
1.2
|
3.0
|
2.9
|
3.1
|
South Korea
|
0.5
|
1.3
|
1.1
|
1.4
|
Latin American
countries and the rest of the world
|
3.0
|
6.7
|
5.6
|
6.7
|
Subtotal
|
5.0
|
12.0
|
9.8
|
12.5
|
The
above situation is not surprising, considering the slow development of basic
biology in the country and the weaker affordability of the high-cost medicines.
However, the reduction in costs followed by considerable use of some of these
products during the last one and a half-decade or so clearly established the superiority of modern biotech products to prevent or treat certainly dreaded
diseases: vaccination with recombinant HBsAg particles to prevent infection
from viral hepatitis B; use of insulin for treating diabetes; use of
streptokinase and t PA to dissolve the thrombus clot in myocardial infarction;
treatment with erythropoietin to enhance the production of hemoglobulin in
kidney failures; and treating cancer by
using erythropoietin and G-CSF to induce
concurrently the production of red and white blood cells ( thereby
prolonging the life of the patients)had brought in societal demand for more
availability of biotech medicines at affordable prices.The commitment of the government to make a rapid stride in this area
has consequently been strong and vigorous.
Modern Biotech is skill intensive
There are certain skills and instruments
which have contributed greatly to the development of biotechnology around the
world. This includes Microscopy &
Imaging; Air handling, decontamination & sterilization (space,equipment,materials
and air); Recombinant DNA technology, recombinant
products and monoclonal antibodies including the humanized ones; PCR
technology; Proteins & Nucleotide Sequencing techniques and
machines; Chromatography & Electrophoresis; LC-MS & MALDI-TOF
for molecular weight determinations; Protein & DNA Chips and Microarrays; Flow-cytometry
& cell sorting techniques; and Bio-Informatics. Indian scientists,
academia and industry use these skills in different aspects of biotech product
development and management. All these skills were invented and initially
developed outside India.
Use of these skills is linked with the use of highly precise instruments, which
India
had to procure at expensive prices. Nevertheless, a large number of
professionals have emerged within the country that can use these skills. Such
skillful people and the instruments are the strengths on which the Indian biotech
industry has to be developed and expanded. Utilizing a combination of these
skills the Indian industry produces the conventional vaccines, diagnostic
devices, fermentation-based therapeutics including antibiotics, enzymes,
vitamins, steroids, and antilipidemics. As mentioned earlier, certain generic
modern drugs are also being produced, utilizing recombination DNA technology.
Additional production capacities shall be established in off-patent bio-similar
products.
Industrial
environment
There is an acute shortage of skilled leaders to run the
biotech industry to meet the specific needs of commerce. Modern biotech
industries belong to the high tech sector; therefore, the leaders have to have
besides managerial skills adequate expertise in biotechnology including in
research and production. The competitive global environment requires the
leaders to have front line knowledge on the products that are being
manufactured or planned. This responsibility demands knowledge about the
market, the total scenario of existing products, the existing costs and the
means of cost-saving, the information about the new products pipeline, the
ability to appreciate the line of R&D being pursued or to be pursued in the
company (which obviously has to be application-oriented), the capability to
also judge people who would be conducting R&D, the capability to
effectively communicate so that the team is motivated to the pre-set goals for
production, research, and development.
The industry has constraints of abundant infrastructure,
finance, and capabilities. Access to published research literature from
established journals is limited, as the industry does not consider it essential
to subscribe to the state-of-the-art journals on the ground of saving costs.
The leaders have to make a mark within the available facilities or to source
access to these resources to improve their performance. Multi-tasking exposure
and experience are therefore essential.
The industrial environment is yet not strong to maintain
adequate levels of confidentiality and the issues of IPR are more public
friendly; leaders have to take these in to account and try to be ahead of the
existing knowledge.
The production and the research infrastructure in the industry
are often not adequately evaluated either by the owners or by the regulatory
authorities to ascertain if the facilities and the people are adequate for the
tasks that are being handled by it. The list of expensive equipment in place or
the number of ‘qualified people” people recruited is not the end of evaluation
about whether the facility is reliable for quality production or whether the R&D team is capable of delivering. Objective judgments must be applied.
Another shortcoming is that the industry is not adequately
linked with R&D institutions and therefore, the basic knowledge flow is
slow. The statutory requirements are
often more demanding and the conformation criteria for the approval process
under the statute are some times hazy for new products to be first time
introduced. The opinion-makers are often biased and stick to borrowed opinion
from outside the country.
These situations need to be examined and better solutions
should emerge to improve the industrial environment and to benefit the country.
Priority
and choice in the Biotech sector
Of
all the areas of biotechnology, health care are presently receiving the highest
attention for technology development and product use around the globe. The main
products are r-DNA based therapeutic substances, vaccines, diagnostic devices, and humanized monoclonal antibodies.
Stem cell research is also progressing with rapt attention. Tissues
specific deliveries through nanotechnology are other areas of considerable
interest.
In
the development of r-DNA products it is important to develop expertise in the
cloning of certain cell types. Most of the presently used products deploy E.coli,
S.cerevisae, P.pastoris, H.polymorpha, and CHO cell lines. In a
few cases, BHK and VERO cell lines have been used. Only one
product has been produced in baculovirus mediated insect cell lines. Indian The industry will do well if it narrows down its choice to E.coli, P.pastoris
and CHO cell line-based products.
More than 60% of the modern biotech products are presently made in CHO
cell lines. Operations are another important area where the right choice of
processes must be made. Since the
volumes are small, the use of glass reactors or the SS reactors for cell
multiplication can be alternate choice options. If CHO cell lines are the main
workhorses, it is beneficial to look for disposable bioreactors to cut down the
cost of sterilization, which is sizable. Chromatography is a downstream
processing operation where standardization is required to minimize the use of
columns; rugged columns must be used that can be resorted to cleaning in place
(CIP). Formulation development is another area where success would depend upon
simplification and the use of simple, easily sterilizable substances.
Stem
cell research has picked speed and products are on the horizon. One aspect of the
activities is to isolate and preserve the embryonic stem cells. This work has
made considerable progress with the hope that methods shall soon be in place to
multiply them in the desired direction for differentiation. However, the meat
is in the abilities to develop the re-programming techniques to induce
pluripotency in aged genomes. Such work requires the development of retro and
non-retroviral means of overexpression of certain oncogenes into engineered
cell types. Non-retroviral means would be preferred as the retroviral means
change the chromosomes considerably through the insertion of viral DNA, which
is not preferred.
Tissue
target specific deliveries requiring the use of biodegradable polymers and nano
particles are other areas where high technologies can be developed and the
industry can be set up.
The pace of global development in health care areas is diverse. The present
skills of proficiency at different levels of materials handling and product
development can be summarized below:
Skills in India
at the industry, the level is yet up to the mammalian cell stage although there are
some pockets where research is being conducted in the other areas. Indian
industry shall have to go a long way to catch up with the global proficiency level.
The reasons are not difficult to find. Biotech product
development is highly capital intensive. The following figure depicts the time
and efforts that are required to be spent to develop a jackpot pharmaceutical
product.
Development of a bio-pharmaceutical product is
highly capital intensive. Studies have been made for the development of small
drug molecules and the cost from concept to marketing has been estimated
through several publications; the gist is presented above. Presently, it is
estimated that US $ 1.2 to 1.4 billion are being spent to have a jackpot
pharmaceutical product. Such is also the scenario for the development of
jackpot biotech products. Several
effective biotech substances are in the pipeline that holds the aspirations of
treating some life-threatening ailments more effectively. But for India to be
into such ventures, wherefrom the money shall come? The question, therefore, is
how can India
survive in the biotech sector?
India
must prioritize
The health of the people decides how the economy
of a country shall be. Good community health determines social development;
it is the indicator of the earning power or the poverty- status of people.
Medicines from modern biotechnology shall ensure prevention and recovery much
quicker. But they must be available for use. The disease burden must, therefore, be addressed in the national context. Several neglected diseases of the
poor including tuberculosis, malaria, diarrhea, trypanosomiasis, dengue,
leishmaniasis and lymphatic filariasis are responsible for many man-day losses
in productivity. HIV is also becoming a
major threat. Indian biotech has to address these problems and come out with
robust solutions. In other major areas that contribute to significant loss of man-days
such as diabetes, cardiovascular diseases, cancer and mental health disorders,
efforts have to be made to have access to current biotech drugs to treat these
disorders. The innovation platform can be drawn up professionally on a national
drawing board. The plan needs to be piloted by the government, which has to
generously shell out the resources through a mechanism involving the industry,
the specialists who would invent & discover, the money providers and the
vocal public.
With
the rise of the growing middle class, there will be the creation of demand for
the latest biotech drugs. It is anticipated that basic production of these
would not be possible locally due to technology protection and technology
non-availability. Newer approaches for registration shall emerge for such
products in the country.
One
of the elements of success lies in the conduct of basic research. But India has to
prioritize its need-based areas, where basic research has to be
intensified. It would not be beneficial
to pursue the same areas of basic research that skilled scientists learn
elsewhere, which has little relevance to Indian needs. The question is how can
this be done and how can this be made attractive to the young scientists.
There
is a great need to develop innovative processes for biogenerics and bio-similar
products. A large number of these have
become off-patent and many others are going out of IPR. How to attract young
scientists to developmental work in this area? Why such innovations scarcely
attract the best talent?
Mass
production of multivalent vaccines and diagnostic agents at affordable prices
shall enable the improvement of the health of Indian children as well as the aged.
This will make a great impact on the country.
Products can also be exported. India has developed great skills in
these areas. More can be done to meet global needs.
Novel
drug delivery and nanotechnology require relatively less investment. The industry can concentrate to develop products in these areas for diverse applications.
“Innovation”
has to be the backbone for survival
Innovation, which is the backbone for
acquiring proficiency and an edge, has to take a quantum jump to enable India, to make
significant contributions in the global context. In- house technologies for
deployment shall not be many; imported technologies shall be very expensive.
Cutting edge technologies shall not be available for purchase. India realizes this and of late has
started paying considerable attention towards developing its own technologies.
Several strategies are being opted for, which include strengthening own R&D
capabilities, teaming up with institutions and technology companies, buying /
acquiring biotech companies that have core competence and the like. It is
necessary to examine if these strategies adequately cover the vulnerability of
the Indian biotech companies and the people to receiving an abundant supply of
modern biotech medicines at affordable prices for treatment and cure. In India,
innovation generally includes covering any or all aspects that provide more
competitive advantage in value addition; besides innovation in products or
process improvements, the functional areas such as finance management,
materials procurement and use, sales & marketing operations including
products push-channel management and the likes are areas where more
concentrations are insight. Efficient organizations review on a daily basis the
top lines (sales), bottom lines (profit) and collection. While innovating in
these functions the organizations stand to gain, success in R&D as sources
of innovations provide a quantum jump to the creation of surpluses and greater
wealth. Innovation has to be in all areas that have relevance to the reduction in
product cost and maximization of product use.
Concluding
Remarks
The scenario of the biotechnology industry in India is going to be complex and
multifarious. While there shall be a considerable increase in the production of conventional biotech products
including sera and vaccines, diagnostic devices and fermentation-based therapeutic substances,
the modern biotech products deploying recombinant DNA technology shall hover
around patent expired therapeutics and diagnostics. Government support
especially in the form of providing seed capital shall encourage the expansion
of new industries in the small and medium scale sector in these areas. Societal demand shall encourage the
registration of high-tech new products, the technologies of which are developed
outside India.
Such products shall be expensive and it would not be easy for a common man to
afford them. Therefore, cheaper substitutes have to be in place even though
they might not be as effective. As the reimbursement of medical treatment costs
is not liberal and adequate for a common man, the situation is likely to
contribute to societal turbulence. A difference can be made only through
appropriate planning, prioritization, action, and implementation. Time is
running out.
