Ecosystem of Biosimilars in India & Across the World
Debayan Ghosh
Founder & President
Epygen Biotech Pvt. Ltd.

This article seeks to explain what it takes to establish a thriving biosimilar market terms of accessibility, competition, regulatory strategy, and other facets.

US FDA defines biosimilars as "Biosimilar is a biological product that is highly similar to a USlicensed reference biological product not withstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product".

Over the past few decades, the biosimilar industry has played a significant role in the field of healthcare around the globe. Biosimilars, is the emerging market in India and is considered the future. The Indian biosimilar market has developed rapidly over the last 10 years. Indian Biosimilar Ecosystem is still in rudimentary stage in terms of accessibility, regulatory strategy, and other facets.

Till recent times, most of the Indian drug makers have been small molecule generic manufacturers. However, in the wake of the new potential of Biosimilars in the region, this trend gradually seems to be changing. There are multiple generic companies that have stepped into the biosimilar space, however very few have been able to create a scale and a roadmap for significant market share in this rapidly growing field. There is also indication that large amounts of capital is lined up behind biosimilar drug development, targeting the massive opportunity coming up in the path of biosimilars with the expirations of multiple blockbuster Biologics Patents. Its sales are expected to grow much faster compared to conventional chemical drugs, in years to come.

Unlike traditional small molecule drugs, biologic drugs are much harder to replicate and have allowed originators to maintain market dominance even after their patents have begun to expire. However, generic drug manufacturers are keen to invest in the biosimilar area, eyeing long term revenue opportunities. The ecosystem of the biosimilars seems to be taking shape in India, however it will take some time to assume maturity. A paradign shift in required in the mindset of the Biotech/Pharma companies as well as the drug distribution and access system to match up with the rapidly evolving field of Biosimilars.

As we know that biosimilars are far more complicated than the average competing medicine as they are produced using living cells and have a few caveats, unlike generics which are chemical-based drugs like antibiotics that can be interchangeable with branded versions. Biosimilar products are approved by FDA on the basis of being highly similar to an already approved biological reference product, unlike a generic drug. The original innovator drug itself is highly complicated being in most cases expressed by a recombinant organism, which has undergone genetic manipulation. To add to the misery, most of these protein drugs are subject to molecular modification or proteomic steps including an array of critical purification procedure and handling. It takes much more time, energy, and money to get a biosimilar approved, compared to a generic medicine. For example, where a generic chemical drug has to pass through a few head to head comparisons to be registered as authentic, a recombinant biotech biosimilar drug passes through an battery of around 50 characterization tests followed by some phases of Clinical trials, including 100s of patients. To develop a biosimilar, it could take anywhere from 5 to 10 years and can costs 100s of million dollars. In comparison, a generic drug takes at the most about two years and costs one tenth of the price compared to a biosimilar drug.

While the current global biosimilar market is only to the tune of 2.5 billion dollars, by 2020, it is predicted to jump up 50 billion dollar market across the world and by 2030 it is estimated to go up to around 250 billion dollars. Though Europe had opened its door to biosimilars several years back, allowing upto 40% penetration to its sizeable Biologics market, USA has only opened its flood gates to the biosimilars two years back. Despite, its last entry, the country that will largely contribute to this number will be U.S.A., Europe and Japan would contribute proportionately for another 25% of the huge number and the countries that will closely follow will be Korea, India, Russia, China, and Turkey. USA is the largest market of biologics globally, estimated currently around 42%, and will remain to be the largest contributor for biosimilars in few years time, resulting upto 20 to 30 percent of the global revenue generated.

As far as India is concerned, one needs to understand the critical barriers to the biosimilars for this country. The number one barrier is Technology Barrier. Biosimilars will have to be produced using recombinant organisms using state of the art technology and highest level of care needs to be taken in terms of protein purification and characterization. The process being extremely sensitive to potential contamination, more often thats not over expression of the protein and purification and down streak processing efficiency will be the key parapets to cross this most critical barrier.

The second important aspect is the regulatory barrier. Biosimilar guidelines in India were laid down in 2012 and further amended in August 2016. The regulatory bodies made responsible for approval of 'similar biologics' in India were Department of Biotechnology (DBT), Review Committee on Genetic Manipulation (RCGM), and the Central Drugs Standard Control Organization (CDSCO). India has approved more than 70 biosimilars till now with a robust pre-clinical and clinical data requirement to establish similarity with the reference drug. To further strengthen regulatory framework, post marketing phase IV studies were introduced, which includes a pre-defined single arm study of more than 200 evaluable patients and compared to historical data of the reference product. The study has been advised to be completed within two years of the marketing permission/manufacturing license unless otherwise justified. This matches with the highest requirement standards of proof of Biosimilarity worldwide and further prepares Indian companies to be able to face international regularity needs.

The third important barrier to the Biosimilars in India is its affordability and market access feature. Affordability of biosimilars will be the most important factor for growth in India and other ROW markets. However price erosion in these markets is not expected to be greater than that of Europe. To use as a reference, examples from Europe will continue to set price erosion patterns across global markets.

There is no doubt that the Indian market for biosimilars is getting competitive and busy and will continue to be so. While the number of Indian companies to make it to the developed markets could only be few, the Indian market itself will continue to see multiple players including several international companies marketing products in India through collaborations and further contributing the emerging Eco-system for biologics in the country.

Considering the current scenario in India, the Ecosystem for Biosimilars development and manufacturing seems to be quite polarized in the south, namely Bangalore and Hyderabad. Setting examples, these cities are at the forefront and doing a great job of utilizing the facilities provided to them by the Government. However, Maharashtra is also trying to get into the league and establish a well structured eco-system for biosimilars, to once again play a key role in catapulting the countries' economy to the next level.

There is a tremendous need of biosimilars in countries like India because of its financial advantage over innovator drugs for critical ailments like oncology and immune disorders. The plan to launch cheaper biosimilar drugs is in congruence with the government's affordable healthcare policy and makes India's biotech industry globally competitive.

Serving twin purposes of providing affordable drugs to critical patients and making Indian biotech industry globally competitive, the department of biotechnology has led the opportunity for the existing biotech companies and the new-comers to progress in this sector.

The factors and driving points that are applied& carried out in India can be applied in other nations in the region as well. The biologics in the developed countries are very expensive, with annual treatment costs reaching up to $100,000 per patient for rehematoid artheritis. This is practically impossible for the patient population in developing countries to afford such costs, and thereby creates an opportunity to harness the local industry and operating environment to develop biosimilars. There seems to be a great potential for biosimilar products in the emerging markets as they allow for early entry and launch, with more affordable pricing, greater access to patients and the medical community. Markets like Russia, Turkey, South Korea, and Argentina have sustained strong biosimilar sales for many years. Nations such as Vietnam and Taiwan are also moving in the same direction. Citing examples of regional co-operation, India and Malaysia are forging an alliance for biosimilars, both in the government and the private sector.

Steering through the teething issues, R & D expenditure for biosimilar development in India increased substantially to $ 1.4 Bn during the year ended March, 2015, a 28.8% increase from $ 1 Bn in the previous year. [Source: OPPI November 2015-Assocham]. This increased R & D expenditure is results from the engagement of life science companies from large biopharma, major generic companies, young biotech JV ventures and start-ups developing skills for biosimilars manufacturing. It is reported that there are more than 10 companies in India, genuinely developing biosimilars for the highest selling monoclonal antibodies of the world.
Even globally, the technology development landscape for biosimilars reflects deeper engagement. The current vibrant landscape includes companies across the spectrum of large, mid-sized and smaller ventures. With several active global programs on biosimilar opportunities, there is a good possibility today to partner for technology access. While technology still remains key to competitive biosimilar business, its threat as a barrier is diminishing given the expanded global partnership possibilities.

In the coming years, it is very critical that the biosimilar aspirants in India streamline their regulatory compliance with new stipulations while not only producing and processing of molecules, but also in generating clinical trial data. This will open the gates to a larger global biosimilar market, potentially changing the game for the Indian biosimilar developers. Biosimilar drugs will definitely reshape the global pharmaceutical market as they grab market share in the years to come. The speed with which this happens will depend only on how the biosimilar manufacturers choose to use their capital to position themselves in the global market, keeping their focus squarely on affordability without compromising quality.