"The Biopharmaceuticals Doyen Speaks…"

Dr Gautam Daftary
Vice Chairman and Managing Director, Bharat Serums and Vaccine
The fact that most of our products continue to be the preferred product in crowded market is a testimony to our success.
In this Biopharmaceutical special issue of Pharma Bio World, Dr Gautam Daftary, Vice Chairman and Managing Director, Bharat Serums and Vaccine in an interview with Ananya Sen discusses product differentiation of biologics, their affordability, BSV's product pipeline and more.

How important according to you is product differentiation of Biopharmaceuticals and in what way?
Not so long back, the area of Biopharmaceuticals had high barriers to entry - mainly being technology, scale and regulations. However, over the period of time, these traditional barriers to entry have been dismantled allowing more entrants to enter the area of Biopharmaceuticals. With more entrants in the markets, it is important to have some product differentiation which means that the customers perceive more value in our product and hence given a choice they opt for our product.

Under the new competitive scenario where we have many players offering the same product, product differentiation is the only way to provide more value to the end customer, allowing the company to maintain the market share.

The most simple, but unsustainable way, of product differentiation would be offering the product at a low price - however in the long run such strategy is neither good for the customers nor for the industry as it kills innovation and deprives customers with improved product.

The way to look at product differentiation is to look at it from a strategic perspective and include product differentiation in each value chain business process - starting from drug development process and right up to marketing and sales of the product. I will cite a typical case of one of BSV's successes.

One of our earliest Biopharmaceutical drug developments was a novel monoclonal antibody product. There were other Biopharmaceutical products in the markets for the same indication - however, there were certain factors like threat of viruses, limited and disruptive supplies due to difficulties associated with the active ingredient were some of the perceived risks with the products. Our approach of taking the monoclonal route addressed both the issues and translated into a long term competitive advantage to BSV. The product continues to be a market leader even after a decade of launch.

What would be the approaches to enable product differentiation ?
There could be various approaches to product differentiation - however in Pharma, we need to understand that given the high number of regulations, it is important to integrate such product differentiation approaches with the entire drug development process.

Broadly, there could two categories of product differentiation - one from the front end perspective and second would be the back end perspective. From the front end perspective, product differentiation can be achieved through the right message and education of the medical fraternity on the product attributes. However longevity of such measures can be short lived if such messages are not backed with sound technical attributes (back end product differentiation), such measures are only good for mid term.

The key to long term product differentiation is to incorporate such attributes as a part of drug development process. It is therefore important for the person, at the helm of the drug development, to always have the patient/unmet medical need in mind rather than the particular target molecule - this helps in envisaging all parameters and desirable product attributes to be listed out. I also think that Quality by design is one of the ways to achieve this. Again speaking from one of our successful drug development projects which is now being considered by the Government of India for the eradication of a vector borne disease, we had a product which is considered as a gold standard in a particular therapeutic area - however its use was limited severely by the side effects.

We looked at the problem and practically redesigned the product to address the safety aspects of the product while maintaining the efficacy- the resultant product, patented globally, is proving to be game changer in this treatment regimen as it not only benefits the patients but also curtails the requirement of health care delivery for administration of such product. A well thought out and well planned drug development process ensures that your product stands out from competition. At BSV, we have always believed in this process and the fact that most of our products continue to be the preferred product in crowded market is a testimony to our success.

Do you feel the need to have risk management plans worked out before launching a product in the market especially biologics? Can you elaborate ?
To put simplistically, a risk management plan articulates the potential risk , and mitigation of such risks, that a patient may have on administration of the product. It is a well established fact that all biologics products go through extensive drug development as no two biologics can be termed as generics. Hence specifically in terms of Biologics, one cannot only rely on the reported risks with other similar products which may be in the market .

Hence it is important to monitor all developmental data to highlight and note potential risks and have these put in the risk management plan. BSV has developed several biologics drugs - from equine sources (Anti Snake Venom, Anti Rabies Serum and Anti Thymocyte Globulin), from natural sources like urine ( fertility hormones, Ulinastatin) and recombinant products (from CHO cells). We have a very wide and diverse experience in developing such drugs and putting such risk management plans prior to the launch of the drugs.

With the boom of Biosimilars, Biosuperiors and Personalised Medicines today, how close are the common Indian masses from gaining affordable access to these highly specific drugs?
It's a good question, a question which many in the industry, government and medical fraternity are asking. The way I would look at it is from two different perspectives - the technical capabilities of the industry at large and the evolution of regulation to establish guidelines to pave a smooth path for approval of such medicines. From an industry perspective and looking at the work that we do at BSV, I think the industry is now in a position to provide such drugs.

However the challenges that industry is facing is the lag in the regulations to approve such drugs. There is an urgent need for a greater co-operation and discussions between the regulatory agencies and the industry to discuss and put in place such guidelines in a time bound manner.

How would you visualise the Indian Biologics market of the future ?
I foresee an interesting and challenging time ahead for the Indian biologics market. We are most likely to see pharma companies moving up the value chains. While we are going to see more entrants into this segment mostly into the biosimilar space, some of the existing companies will move on to the next challenge of Biosuperiors and novel Biologics.

At the same time, evolving regulations are going to raise the bar for entering the market - in terms of extent of studies which will have an impact on the resources required to come into the market. I can also talk from our experience in BSV. Our driving force for all development programmes has been providing a cost effective quality product for an unmet medical need. BSV has been unique in it approach as we saw the opportunity in Biologics more than a decade ago.

Looking back, I can proudly say that we have been the only Indian company to initiate work on novel Biotech molecules and biosimilars -in late 1990's and early 2000's.

We were amongst the first companies in India to commercialise and market a novel biotech compound in India more than decade ago. I should also mention here that this product continues to be a market leader in its segment. We expanded our Biotech research programme in early 2000's to two Biosimilars and two novel Biotech molecules. While we already commercialised one biosimilar drug 5 years back, we are in the late stage development on two novel biotech molecules which would be for the first time in world.

Our competencies in Biologics, therapeutic proteins isolated from natural sources, have also enabled us to provide path breaking therapies for unmet medical need. While we have been successful in bringing to market a novel biological compound for an unmet medical need of Sepsis and very shortly, we will be able to bring to the market another novel biological for treatment of stroke for the first time in India.

What are the challenges involved in the clinical trials for biosimilars in your opinion?
We see a lot of different clinical development requirements across countries which necessitate more than one clinical development programme if one aims for global market. In India itself, we have seen regulations evolve over a period of last few years with more extensive data requirements. The stricter requirements on the manufacturing scale of clinical supplies are also indirectly increasing the cost of such trials. The need to demonstrate the immunogenicity has made designing of such trial challenging and intricate .

What was your vision when you started SIRO Clinpharm way back in the mid 90's?
As I always say, the starting of SIRO was more by default than by design. The actual start up was only for helping one of our German partners to generate some clinical data for their product.

However, the way we executed the project led to more such trials being awarded to us, and before we knew, there were flood of offers from various global companies. It is at that time that we realised the need for a good quality clinical research organisation and I think what also helped was the fact that India was just emerging as a clinical trial destination.

Which are the areas that BSV is currently working on? Could you update us on BSV's product pipeline?
Over the years, we have consciously built our competencies in three broad technology platforms - novel drug delivery systems, Biotechnology and Biologicals. Within BSV, we differentiate Biotech from Biologicals - we consider Biotech products to be the product which are made from recombinant Cell lines - whether bacterial or mammalian or any other cell lines, while we term Biologicals as therapeutic proteins which are isolated from natural sources.

In terms of novel drug delivery molecules, BSV would be one of those very few companies which at global scale has global drug development programmes based on various technology platforms: liposomes, microsphere, implants, emulsions, etc. We have been very successful in development and commercialisation of such products and we will continue to focus in introducing more products in the Indian market on such platforms but also take a majority of these products to global scale. Our ability to patent such products on global scale and the immense interest shown by global companies are proof enough on the quality of work that we do.

In Biotechnology, these are more long term projects with each product requiring at least 6 years to come in the Indian market. As I had mentioned earlier, probably we were amongst the earliest to realise the potential of Biotechnology in India and commercialised novel Biotech entity in India more than a decade ago. In Biotechnology, we have been focused on limited Biotech molecules - 2 each in Biosimilar and Novel Biotech molecules - however the entire drug development right including cell line development, process development & scale up and clinical trials have been conducted in- house. We are in late stage clinical development of two novel Biotech molecules, which would be for the first time globally. In the near mid term, we should be able to provide these products to the Indian patients.

On the Biological segment, we have a very successful product range of fertility hormones which have been entirely developed in house. We are amongst the very few companies in India to have a backward integration right up to the API stages for this class of products. While we recently launched a novel biological entity for Sepsis in the Indian market, we are in the late stage development of another novel biological entity for the Indication of stroke.

The other major area of research for us is equine antitoxins and equine immunoglobulin - our cutting edge technology has enabled BSV to be amongst the largest producers of equine antitoxins globally.