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The bench-to-bedside chasm in the Indian pharmaceutical landscape

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Summary

The purpose of this article is to highlight some of the gaps in the Indian scientific and pharma landscape.

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In India, “Drug discovery” is a term lacking favour from both academicians and industry scientists alike. The academicians believe in the pursuit of science and unraveling the mysteries of nature as a noble calling which cannot be tainted by target driven research. And this is rightfully so, as the scientific mind must be unleashed to its full potential without constraints of forced outcomes. After all, Alexander Fleming was not planning to discover penicillin, but was only a keen observer of bacteria and moulds. Industry is scared of diving too deep into drug discovery due to the risk of investing money, which is often public/ shareholder’s money, into something which may or not succeed commercially. And industry leaders often shy away from deep examination of ‘research’ projects, again, rightfully so, as they are bound to effect the revenue stream.  As a result, nobody really owns the drug discovery process and the Indian scientific and pharma industry are in a place where there are no novel therapeutics that the Indian institutions can claim to be the originator of, and the pharma industry is heavily focused on generic medicines.

 

So, how do we bridge this bench-to-bedside chasm? The purpose of this article is to highlight some of the gaps in the Indian scientific and pharma landscape and hope that the relevant experts can consider the appropriate prescriptive steps towards closing the gaps.

 

The development gap: from R to D

There is a clear distinction between Research (R) and Development (D), which are often clubbed into the single term “R&D”, to indicate the continuity of research into its purpose. It is important to note that the “R&D” in the molecular life sciences -cell biology, biochemistry, molecular biology, biophysics, everything involving understanding of molecular level issues in living things, in Indian academic institutions largely constitutes the “R” part. The “D” or the development portion of R&D is not envisioned at all in the case of most R&D projects. Post the research finding, any idea needs to be developed fully into an actionable concept – which then moves to a “pilot (P)” phase where it is made or used in a limited setting and then it moves into commercialization phase. To take the pharma example, Research would constitute identifying the molecular mechanism of a disorder and potential areas of intervention. Development would be to take this understanding to design a usable intervention – which could be to test various targets and molecules or combinations thereof to arrive at one or more clear leads that are tested in pre-clinical studies. Then in the Pilot phase you produce clinical grade material for testing and this process continues till a suitable candidate for commercialization is arrived at. There are no strict demarcations between the R-D-P phases and the same group of scientists and resources can often cover all the three, provided it is envisioned to take the research to a pilot phase. In academia though, the end goal is often an excellent publication and not a product.

 

Finding new drugs is much easier said than done. However, the scope for invention within the realm of pharmaceutical sector, is much wider than finding new drugs alone. Good diagnostics which could include chemical/ biochemical assays or electronic tools are equally important for tackling the problem of human health. Storage of drugs that are temperature sensitive, delivery mechanism/ route of administration of drugs, combinations of drugs, using a known drug for a different indication, reducing the cost of making drugs, increasing access and reducing cost of  disease diagnosis, early and smart diagnosis – all are areas of innovation to be explored under the pharma sector.

 

It is also not necessary that the level of funding equals the level of innovation in R&D. “Necessity is the mother of invention” – and what better place than India which provides the widest socio-economic population with innumerable health problems as a huge opportunity space. Do our research organisations focus on any ‘necessity”? To begin with, it is not a societal necessity, but the necessities of the research community itself. The funding received by the academic institutions is significantly used for importing equipment and reagents. This results in the researchers not having the necessity to question the ability of the tools they use for their research. The question is if the tools used are not appropriate, would the outcomes of such research be innovative? We must remember that the advancements in X-Ray crystallography techniques allowed for the understanding of the double helix of DNA. Development of new tools often leads to new discoveries.   There may be a lesson to be learnt from the success story of ISRO, the well-known government funded space research organisation. Due to various political and funding reasons, there were probably limitations on a lot of imports, which led to significant indigenous efforts resulting in creating launch vehicle technology at a better competitive price than players in US and Russia. The inventive thought process is important- once a researcher gains the ability to create something that is useful, even if it is only for their own PhD thesis, it does something very important – it takes them from ‘research” to “development’.  The R to D journey is the first step in even considering piloting and commercialization. We need to consider if we are over-enabling our researchers leading to no pressure to be creative. Also, investing in fabricating their own tools or making reagents, helps reduce the overall cost of the research, thereby leaving funds for more exciting avenues. Having said that, it shouldn’t be about re-inventing the wheel, but thinking whether the available wheel is appropriate for the intended purpose or its historical design limits the outcomes of the research.

 

To close the “development gap” we may need to take steps to make us think about D separately, else it gets shadowed by R.  One area could be separation of funding for R and D. It’s important that the government plays a significant role for funding development projects also and incentivises both the institutions and industries participating in these projects. Any funding for ‘translational research’ should be based on clear demonstration and proof -of -concept of ‘translatability’ to be qualified for such funding. We could also enhance the sensitization for bringing in a development mind-set to our researchers.

 

Institutions need to consider an office whose role is to be a patenting and idea-finding centre that will take the available research, assess for patentability and further development.  This office needs to actively liaison with small and large industries to seek projects or to provide ideas coming out of the research labs to suitable industries. Essentially, a match making office that helps both sides find a development idea that can then be either taken up by the institute or by the industry and a joint work and funding model can be established.  Without active and intensive match-making efforts, academia and industry will continue to further go their own ways, each looking outside India. The co-location and collaboration of professionals in medical and institutional research is essential if we desire to foster innovations to cater to human health problems.

 

Medical schools do medical research and often physicians work with pharma industry on trials that the pharma industry is keen to conduct, again probably with a large percentage with only generic medicines. There are physician led trials but again in a limited space wherein new molecules are rarely tried. In fact, it is surprising that in India, we don’t have a good regulatory framework that allows new molecule studies or trials, while the generics (small molecules or /and biosimilars) all have well-defined regulatory approval pathways. There is a lot to be done in how we curate and handle medical data, which could be an entirely separate topic. Here, the suggestion is to just bring together medical and molecule level researchers so that the science between them is connected and brings about a place where development of innovative therapies can take This initiative may need to be taken by research institutions by reaching out to medical schools and understanding the unmet needs of the medical community. Further, a review of clinical trial literature in various therapeutic areas would be helpful in assessing where their research can be directed. It may be useful to assess how universities in the US foster such collaborations between research and medical school, by inviting such professionals to be participate in establishing the vision for the research institutes.

 

The vision gap

Who should think about how to solve human health issues – science institutions or medical institutions or pharma industry or government? The right answer has to be: all of them together. However, where and why would they all come together? Institutional boards or steering committees have distinguished scientists from all over the world, but rarely do they include reputed medical professionals or industrialists. Similarly, hospitals lack any outreach into high end research laboratories or scientists.  Pharma industry steering committees will often have scientists, medical professionals and industry leaders all together, but these committees work at a high level to enable the pharma company’s business objectives since it is an industry led committee, i.e. appointed by the industry. Government or institution led platforms may serve better to allow more collaborative, exploratory and innovative discussions.  It is safe to say that currently there is no vision in the country to work towards novel therapies. Innovation will only come about in a highly collaborative ground including scientific, medical, technology and industry specialists.  No one can force innovation, but it can be facilitated through creation of the right ecosystem and collaborative environment.

 

Policy makers are pushing institutions to collaborate with industry, with grant incentives. This is enabling some conversations between the two, but the real meeting of minds has not yet happened. In these conversations, both academicians and industry are risk averse. The academicians do not want to be rushed on timelines and be tied to milestones and industry doesn’t want to spend resources on academic research projects. There are no common goals or necessities that would drive the appropriate collaboration. Government agencies have significant influence over industry, academic institutions and medical institutions and can hence play a pivotal role in establishing governance bodies that can ensure that the funding provided for development is used for truly collaborative endeavors resulting in development of products.  Innovative forums or workshops with experts from academic institutions, medical institutions and pharma industry need to be brought together by government to co-create actionable development ideas could work towards short and long term plans that envision mechanisms that lead to development of indigenous solutions to medical problems.

 

In summary, India has a significant opportunity space to explore unmet medical needs that can result in innovations that benefit the world. There are a significant number of research institutions with infrastructure and people capable of exploring this opportunity. The generic pharma industry is mature enough to plunge into novel pharmaceutical development if the research and medical community reach out with developed/ pilot stage ideas.  A strong push from the government to ensure that the capability meets opportunity is needed to build the platform for innovation in pharmaceutical development.

 

 

Dr. Sridevi Khambhampaty is Vice President, Biosimilar Product Development at Intas Pharmaceuticals, Ahmedabad. She has been in the Indian pharma industry for the past 12 years after completing postdoctoral studies at the Stanford University School of Medicine, California, and holds a PhD degree from NCBS-TIFR. The views expressed are her personal views.

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1

This excellent article makes several points that are worthy of contemplation. Here are my takes on a few of them:

a) Co-location of institutes: Although the article makes this point specifically in the context of hospitals and research institutes, I feel that this is part of a bigger issue in terms of choosing the places to set up new institutes wisely. Research institutes function best when they are part of an ecosystem comprising of other research institutes, colleges, hospitals, administrative bodies etc. Therefore, whenever a new institute is proposed, it is imperative to look at what else exists around it, a consideration that seems to be generally lacking in India.

b) On fabricating own tools and making own reagents: This is a more tricky point. On one hand, making one's own reagents/ instruments and not depending on the exorbitantly priced kits / equipment, is definitely a good idea, both in terms of the control it gives one in terms of experiments as well as the cost factor. However, this way of functioning typically requires more time, something that is often in short supply in the publish-or-perish world of Academia. In fact, as far as I understand, scientists and technologists in ISRO do not have to publish papers, and I do not think that they would ever have been able to send a Mangalyan if they were needed to justify their existence through publications.
Thus, that comparison is an unfair one. If the Indian academia wants its scientists to deal with knotty problems in health, then it needs to revise the reward structure, at least for those scientists who are working in such areas.

c) I feel that the biggest missing component in industry-academia collaborations is mutual trust and respect. The Government can perhaps act as an enabler to a certain extent, but there is only so much that it can do. People from the two sectors must come together and start talking to each other about their problems and core strengths without necessarily expecting immediate and magical returns. It will take time for the trust to develop, but when it comes, hopefully it will be a more mature and long-lasting affair! The suggestions by the author in this direction are nice food for thought.

2

Much needed discussion of an important topic. In general, in India, if we consider bio-medical sciences, even much of the "R" component is not really great research, which is why scientists try to sell it as "D", which it isn't. The molecular biology/biomedical research community needs to do some serious soul searching about how much real good "R"and "D" they have delivered, and at what cost.