Biosimilar Drugs: The Roadblocks and the Road Ahead

Unlike commonly used ‘small molecule’ chemical based drugs, ‘large molecule’ biologic drugs are developed from living cells and using very complex processes. These groups of drugs could range from simpler insulin to therapy for treating complex ailments like, cancer and almost invariably attract a high price tag, which could run even in thousands of dollars.

It is virtually impossible to replicate these protein substances, unlike the ‘small molecule’ drugs. One can at best develop a biologically similar molecule with the application of high degree of biotechnological expertise. These drugs are usually much less expensive than the original ones and called ‘Biosimilar Drugs’. It is expected that ‘biosimilar drugs’ will have lesser market competition than the conventional ‘small molecule’ generic drugs, mainly because of complexity and costs involved in their developmental process.

Future growth potential:

In most of the developed countries, besides regulatory issues, ‘Biosimilar drugs’ are considered to be a threat to the fast growing global biotech industry. At the same time, it is widely believed that in the rapidly evolving global concern for cheaper and more affordable medicines for patients across the world, relatively smaller biotech companies, given the required wherewithal  at their disposal, could emerge as winners in this new ball game as compared to traditional generic pharmaceutical players.

Novartis (Sandoz) – first to launch a ‘Biosimilar drug’ in the US:

In mid-2006, US FDA approved its first ‘Biosimilar drug’- Omnitrope of Sandoz (Novartis) following a court directive. Omnitrope is a copycat version of Pfizer’s human growth hormone, Genotropin. Interestingly, Sandoz had also taken the US FDA to court for keeping its regulatory approval pending for some time in the absence of a well-defined regulatory pathway for ‘Biosimilar drugs’ in the USA. The CEO of Sandoz had then commented, “The FDA’s approval is a breakthrough in our goal of making high-quality and cost-effective follow-on biotechnology medicines like Omnitrope available for healthcare providers and patients worldwide”. Despite this event, none at that time expected the US FDA to put regulatory guidelines in place for approval of ‘Biosimilar drugs’ in the country.

Merck’s entry was through an acquisition:

Merck announced its entry into the ‘Biosimilar drugs’ business on February 12, 2009 with its acquisition of Insmed’s portfolio for US$ 130 million in cash. Rich pipeline of follow-on biologics of Insmed is expected to help Merck to hasten its entry into global ‘Biosimilar drugs’ markets.

Other recent global initiatives:

  • Merck paid US$ 720 million to Hanwha for rights to its copy of Enbrel of Amgen
  • Samsung of South Korea has set up a biosimilars joint venture with Quintiles to create a contract manufacturer for biotech drugs.
  • Celltrion and LG Life Sciences have expressed global ambitions in biosimilar drugs.
  • Dr Reddy’s Laboratories (DRL) has already been marketing a biosimilar version of Rituxan of Roche since 2007.
  • According to Reuter (June 22, 2011), Merck, Novartis (Sandoz), Teva and Pfizer are expected to be strong players in the biosimilar market.
  • Reliance Life Science though has faced a setback in Europe with the regulators asking for more data for its copy of EPO prompting them to withdraw their application for now, is also a potential player in the biosimilar market.

Many other developments are also now taking place in the space of ‘Biosimilar drugs’, the world over. To fetch maximum benefits out of this emerging opportunity, India has started taking steps to tighten its regulatory process for marketing approval of such drugs. This is absolutely necessary to allay general apprehensions on drug safety with inadequate clinical data for similar protein substances.

Current status in the US:

President Barak Obama administration of the US has been expressing for quite some time a strong intent to pave the way for ‘Biosimilar drugs’ in the US. To facilitate this process, a new draft legislation titled, “Promoting Innovation and Access to Life Saving Medicine Act” was introduced by the legislators of the country. This legislation came into force with the announcement by US-FDA the outline of how biopharmaceutical players can submit their application for marketing approval of ‘Biosimilar drugs’ in the country. Many industry players have since then been gearing up, across the world, to have a share of the potentially large ‘biosimilar drugs’ market in the US.

Challenging clinical data requirements in the US:

According to ‘Biologics Price Competition and Innovation Act of 2009 (BPCI Act)’, which was enacted in the US on March 23, 2010, any biological substance to be “biosimilar” will require to be “highly similar to the reference product, notwithstanding minor differences in clinically inactive components”. BPCI also specifies that there should be “no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product”. It is interesting to note that the Act emphasizes on ‘clinical similarity’ rather than ‘biological or structural similarity’ between the original and ‘biosimilar drugs’.

The New England Journal of Medicine dated August 4, 2011 reported that US-FDA is in the process of establishing very challenging clinical requirements from the makers of ‘biosimilar drugs’ for obtaining marketing approval in the country. Such stringent regulatory requirements are expected to push up the cost of development of ‘biosimilar drugs’ significantly, seriously limiting the number of players in the market.

12 years Exclusivity in the US:

In the US, the innovator companies get 12 years exclusivity for their original biologic drugs from the date of respective marketing approvals by the FDA.

The BPCI Act clearly specifies that applications for ‘biosimilar drugs’ to the FDA will not be made effective by the regulator before 12 years from the date of approval of the innovators’ products. In addition, if the original product is for pediatric indications, the 12-years exclusivity may get an extension for another six months.

However, the key point to note here is, if the FDA starts its review process for the ‘biosimilar drugs’ only after the 12 year period, the innovator companies in that case, will effectively get, at least, one more year of exclusivity over and above  the 12 years period, when the applicants for ‘biosimilar drugs’ will keep waiting for marketing approval from the FDA.

The market:

According to Datamonitor the global market for ‘biosimilars drugs’ is expected to grow from US$ 243 million in 2010 to around US $3.7 billion by 2015.

Another report points out that only in the top two largest pharmaceutical markets of the world, the USA and EU, sales of ‘biosimilar drugs’ will record a turnover of US$ 16 billion in the next couple of years when about 60 biotech products will go off-patent.

The Indian biotech players:

Such a lucrative business opportunity in the west is obviously attracting many Indian players, like, Biocon, Dr. Reddy’s Labs, Ranbaxy, Wockhardt, Shantha Biotech, Reliance Life Science etc., who have already acquired expertise in the development of ‘Biosimilar drugs’ like, erythropoietin, insulin, monoclonal antibodies, interferon-Alfa, which are not only being marketed in India but are also exported to other non/less-regulated markets of the world.

Ranbaxy in collaboration with Zenotech Laboratories is engaged in global development of Granulocyte Colony-Stimulating Factor (GCSF) formulations. Wockhardt is expected to enter into the Global ‘Biosimilar drugs’ market shortly. Dr. Reddy’s Laboratories and Biocon are also preparing themselves for global development and marketing of insulin products, GCSF and streptokinase formulations.

Funding by the Government of India:

It has been reported that the Department of Biotechnology (DBT) of the Government of India has proposed funding of US$ 68 million for ‘biosimilar drugs’ through Public Private Partnership (PPP) initiatives, where soft loans will be made available to the Indian biotech companies for the same. Currently DBT spends reportedly around US$200 million annually towards biotechnology related initiatives.

Key success factors for rapid acceptance in the developed markets:

According to a new research finding from ‘The Decision Resources’, one of the key success factors for any such new drugs is how quickly the specialists will accept them. So far as biosimilar drugs are concerned they noted a high level of concern, if such drugs are not supported by robust sets of clinical data on the claimed treatment indications.


With increasing global cost-containment pressures within the healthcare space, the emergence of a lucrative global ‘biosimilar drugs’ market now appears to be inevitable.

In the fast evolving scenario, major research based global bio-pharma and even the pure pharmaceutical companies will have two clear choices. The first choice is the conventional one of competing with ‘biosimilar drugs’ in all important markets of the world. However, the second choice of jumping into the fray, keeping undiluted focus on R&D, appears to be more prudent and perhaps will also make a shrewd horse sense. Only future will tell us, which of these two business senses will prevail, in the run up to success, for the global biotech companies.

With the above background, the report from the ‘Business Wire’ highlighting the fact, ‘the manufacture and development of a biosimilar molecule requires an investment of about US$ 10 to 20 million in India, as compared to US$ 50 to 100 million in developed countries’, vindicates the emergence of another lucrative business opportunity for India.

With around 40% cost arbitrage, as indicated above and  without compromising on the required stringent international regulatory standards, the domestic ‘biosimilar’ players  should be able to establish India as one of the most preferred manufacturing destinations to meet the global requirements for ‘biosimilar drugs’.

Experience in conforming to stringent US FDA manufacturing standards, having largest number of US FDA approved plants outside USA, India has already acquired a clear advantage in manufacturing  high technology chemical based pharmaceutical products in India. Significant improvement in conformance to Good Clinical Practices (GCP) standards will offer additional advantages.

In addition to cost efficiency, available skill sets in developing ‘biosimilar drugs’, will offer another critical advantage to the domestic players in reaching out to the international ‘biosimilar drugs’ markets either by themselves or with appropriate collaborative arrangements, just as we have recently witnessed in case of Biocon’s strategic collaboration with Pfizer in this rapidly evolving sector of the world.

Disclaimer:The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

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