Research endeavors to discover and develop new chemical entities, followed
by developmental work and integration with business to enable
candidate drug enter the market as a new commercially viable therapeutic agent,
is a difficult terrain.
Before I deal with the subject in this inaugural post of the blog,
allow me some interruption.
First and the foremost, let me explain, why this blog?
I have worked for over thirty years in a drug research
organization, and writing has been central to the most of my
functions. Thus the compulsion of writing has narrowed
down to the choicest field of drug research. Though, the other three blogs
I run are in different domains; the one on biodiversity is out of
my deeper interests in biology and evolution, the next on new found
interest in advocacy in prevention and control of non-communicable diseases (NCDs), and the fourth one
on career.
Research and development of new
drugs, diagnostics, and preventive therapies, together constitute a domain
which assumes a special place due to its direct relevance and impact on human
health. Undoubtedly, the advent of vaccines, antibiotics and other new drugs
and health interventions, made possible as a result of scientific advances in biology
and biomedicine, are singularly responsible for the increase in life expectancy
over the last century.
A peep into a pharmacy offers an intriguing view: so many drugs
lined up on shelf, each preparation different from the other in their constituents,
mechanism of action, therapeutic use, dosage, delivery, for use in adults,
women, men, and children.......and in side effects(?). Interestingly most of
them are novel innovative products. Physicians prescribe those
medications confidently, patients use them with ready acceptance, and
pharmacists sell them with smile. There is a win-win situation for all
stakeholders in this innovation chain of new drug research and development.
How all this has been made possible? Great men of science,
entrepreneurs, men of industry collectively have invested their time and money
to make it possible. They were not hollow scientists grandising their
achievements but proved the worth of their research investment
for development of ultimate products which now sit on pharmacy shelves,
and are written in doctors prescriptions. Drug research earlier considered
a field marred by chance findings (serendipitous discovery of novel
molecules), has of late become a more organised knowledge-based endeavour, and
is evolving further.
With each passing day, drug research and development evolves
along with the growing body of knowledge of the basic understanding
of the functioning of a healthy or diseased body parts, the tissues and
cells. Thanks to rapid advances in tools, techniques, and the competence of
trained scientists, and emerging disciplines of translational research,
the era of tailor-made medicine are adding new opportunities as well as posing
new challenges.
Scientists engaged in drug research are now deploying emerging
tools and techniques made possible due to advances in genomics, proteomics,
structural biology and other emerging disciplines which offer new opportunities
for discovery of better drugs. Claims are made for discovery of new genes,
proteins, markers, novel biological targets, etc. and these are associated with
a big finding (in future). Institutions are spending all their focused
efforts on discovery of new targets as aid to develop new drugs.
The domain of drug discovery is now like a large sea, and
the organizations and industries engaged in drug discovery are fishing in
the sea of those resources of unfathomable dimensions, leading to
emerging new knowledge, for new starting points or leads; following
those emerging trails, rough weather, waves and currents, in hope and
desperation, to catch a big fish, a blockbuster drug, they travel far and wide.
For, once they have the catch all costs will be recovered, huge profits
made, and ailing humanity served, with a new drug. Then, there will
be time to celebrate the big catch!
However, linking every new development to discovery of a
new drug is however a far cry, as the outcome from drug discovery
and development research is possible only if an integrated effort is
pursued in a multi-disciplinary and multi-institutional
framework right from the beginning, and is part of overall planning. No
piecemeal approach is expected to lead to a drug. In any case, the
ultimate success in drug discovery is not achieved unless the
candidate drug passes through the vigilant eyes of dedicated preclinical
and clinical scrutiny, and it stays in the market without unwarranted adverse
reactions.
High quality basic research ranking high on
'high impact factor' publications may not always transform into new drugs.
Though it does create a wealth of knowledge so important in drug discovery
and development; more directly though it leads to research papers and
patents fuelling scientists' journey to a better career, prestige,
position, and pride of achievement! No doubt the need for basic research,
opening new vistas of opportunities, is fundamental to advancements and
is the most necessary aspect to begin with.
A recent
study does throw light on this aspect. It has been found that in spite
of growing investment in pharmaceutical R&D the new drugs are not emerging.
The reasons are that investments are concentrated in areas where failure risks
are higher, and in use of tools and technologies not known to lead to new
drugs.
Searching a target, its validation, its actual deployment in drug
discovery will not necessarily lead to new drugs. Organisations having the
objective to develop new drugs may know it better, but scientists out of
their compulsion to build their CV and fuel their career advancements by
decorating them with awards and honors, recognitions, etc, adopt a
publication strategy, instead of a product oriented research approach.
Basic research remains only a pleasure trip unless the
journey concludes to a logical end and a new, safer and
efficacious drugs emerge from the rigorous, expensive and time consuming
enterprise of drug R&D, for the benefit of ailing men unattended by
existing therapies, and for the service of humanity, and the society. And,
there are always huge profits to reap from a novel blockbuster drug for
the investment made on R&D.
Investment of now over US $ one billion mark is prohibitive
for new drug discovery, and few can afford the innovative R&D workload
unless it is shared through strategic alliances. New drug discovery
R&D works well with both the ends open: through upward and backward
integration. Integration is pursued all through the innovation change, that is
discovery of molecule, its evaluation for activity through in vitro and in
vivo systems, physiology, pharmacology, dosage evaluation, delivery
systems, toxicity studies and rigorous clinical evaluations.
Drug R&D
follows business strategies adopted by the leading pharmaceutical companies.
What are those aspects which can ensure better drugs' outcome: planning,
business strategy formulation, infrastructure, networking with concerned
groups, integration and filling of knowledge gaps. A business plan needs to be
prepared beforehand a project is launched.
The strategies include partnering on promising compounds for
development of pipeline of products, outsourcing of different R&D stages in
product development, extending life of an aging brand, expanding
into emerging markets, as well as focusing on internal packaging and delivery
mechanisms, etc.
In India where there is a large livestock we seldom hear of any
R&D organization working for development of drugs for farm animals,
or pets. (If I am ignorant I will like to be corrected). Most new veterinary
products we have are the result of R&D abroad. Though there are companies
in India making and distributing drugs for livestock and pets.
My association with a drug research institute has left me
amused as to the total apathy towards the urgent need to develop drugs for
diseases of the livestock, poultry, pets. Even if as spin off, there
ought to be some projects to attend to livestock diseases. We can not leave
guessing if research and development of drugs for farm animals is left out
from the agenda for reasons that drug research for human needs is more
fashionable or respectable, than drugs for farm animals? Veterinary medicines
are indeed a bigger R&D challenge? Healthy livestock is related to health
of humans!
Drug research is a hard-core scientific endeavour, and
successes depend upon passion for research, knowledge, hard work,
availability of funds, infrastructure, ability to network and establish
linkages with organisations and industry which share the collaborator's
vision. Work ethics, business processes used, issues of the availability
of quality systems, and trust are of no less concern.
Slogans, big and false claims do not help in science-driven drug
research. The bogey of MNCs versus indigenous R&D, and industrial
productivity, often raised, make no sense if we continue with our dependence
for new drugs discovered and developed by them. Our pride however
rests mainly in our ability to produce quality generics at cheaper
cost.
Non-communicable
diseases (NCDs) are assuming greater importance internationally, so
much so that they now endanger the developing world economy by their increasing
hold on their populations; pharmaceutical companies are constructing
healthy pipelines in areas of heart disease, cancer, and diabetes, besides
other diseases. Industry experts agree that the costs to develop new drugs
are rising rapidly. The rapidly increasing costs that go into the R&D of
promising new medicines make it a great challenge to develop new drugs that are
affordable to the patients who need them!
As this blog develops and takes shape over time, I shall welcome
any advise on the contents of this blog. Errors, omissions, and contradictions,
if inadvertently appear, and are pointed out to me will be
readily corrected. My efforts shall be to constantly upgrade the blog to serve
the drug research community!
As I conclude, I invite the industry and organizations engaged in
drug research to forward their latest achievements and discoveries to me
(zakaimam@gmail.com) for inclusion in this blog. Developments that merit
coverage will find speediest place as a post.
