Biosimilar Drugs -A raging scientific debate with mounting global commercial interest

On December 11, 2008, Reuters reported that two days after Merck & Co. announced a major push into generic versions of biotechnology medicines, Eli Lilly & Co. signaled similar aspirations. This report raised many eyebrows in the global pharmaceutical industry, in the midst of a raging scientific debate on this issue. Be that as it may, many felt that this announcement ushered in the beginning of a new era. An era of intense future competition with Biosimilar drugs in the world market with immense commercial interest.Globally, the scenario for generic versions of biotechnology medicines, which are called Biosimilars, Biogenerics or follow-on Biologics, started heating up when Merck announced that the company expects to have atleast 5 follow-on biologics in the late stage development by 2012. The announcement of both Merck and Eli Lilly surprised many, as the largest pharmaceutical market of the world – the U.S.A is yet to approve the regulatory pathway for generic biologic medicines. In the developed world, European Union (EU) has taken a lead towards this direction by already having a system in place for regulatory approval of Biosimilar drugs in 2003.What then prompts the research based global pharmaceutical companies like Merck and Eli Lilly to step into the arena of Biosimilar medicines? Is it gradual drying up research pipeline together with skyrocketing cost of global R&D initiatives?

The future business potential of Biosimilar medicines:

Currently, over 150 different biologic medicines are available in the Global Pharmaceutical market. However, the low cost Biosimilar drugs are available in just around 11 countries of the world, India being one of them. Supporters of Biosimilar medicines are indeed swelling as time passes by. At present, the key global players are Sandoz (Novartis), Teva, BioPartners, BioGenerix (Ratiopharm) and Bioceuticals (Stada). This market is expected to develop slowly because of regulatory hurdles in the major countries of the world.

Very recently, the EU has approved Sandoz’s (Novartis) Filgrastim (Neupogen brand of Amgen), which is prescribed for the treatment of Neutropenia. With Filgrastim, Sandoz will now have 3 Biosimilar products in its portfolio.

Raging debate on Biosimilar Drugs still continues:

The debate is centered on the argument that like small chemical molecules is it possible to replicate large biological molecule of the innovator? It is widely believed that a protein cannot be absolutely replicated. How could possibly then Biosimilar drugs be considered equivalent to the original product by a regulator and marketing approval be granted to them without full scale clinical trials ignoring safety concerns of the patients? In favor of this argument some refer to the problem of red cell aplasia that affected many patients administering Johnson & Johnson’s Exprex (Epoetin) after only a minor change made in its manufacturing procedure.

Hurdles to cross for future Market entry of Biosimilar Drugs:

Emergence of second generation branded biosimilar products such as PEGylated products Pegasys and PegIntron (peginterferon alpha) and Neulasta (pegfilgrastim), and insulin analogs etc. have the potential to reduce the market size for first generation Biosimilar drugs creating significant entry barrier.

Even otherwise, the barriers to market entry of Biosimilar drugs are much higher than any small molecule generic drug. In the markets within EU, many companies face the challenge of higher development costs for biosimilar drugs because of stringent regulatory requirements and greater lead time for product development. Navigating through such a tough regulatory environment will demand a different type of skill sets from the generic companies not only in areas of clinical trials and pharmacovigilance, but also in areas of manufacturing and marketing. Consequently, the investment needed to take Biosimilar drugs from clinical trials to launch in the developed markets, will indeed be quite significant.

Current Scenario in the U.S:

Recently in the U.S.A, the new, widely reported, biotechnology policy of President Barak Obama has become one of the most closely watched healthcare policy initiatives of the country. It is expected that such a policy will help facilitate regulatory approval process of Biosimilar drugs in the USA by end 2009. This new policy initiative could have a major impact on many biotech companies who will face new generic competition, rather quickly. On the other hand, it will prove to be a boon to the new entrants in this market like, Merck and Eli Lilly, besides the existing ones.

Global Market Potential of Biosimilar Drugs:

The biosimilar drug market in the world is estimated to be around U.S. $ 16 billion by 2011. Currently, off-patent biologic blockbusters including Erythropoietin offer an excellent commercial opportunity in this category of drugs. By 2013, about 10 branded biologics with a total turnover of around U.S. $ 15 billion will go off-patent.

Biosimilar Drugs in India:

Sales of biosimilar drugs in India are estimated to be around U.S. $ 4 billion by 2011.

Biosimilar drugs fall under high growth segment within Indian pharmaceutical Industry. Recombinant vaccines, erythropoietin, recombinant insulin, monoclonal antibody, interferon alpha, granulocyte cell stimulating factor like products are manufactured by a number of domestic biotech companies like Biocon, Panacea Biotech, Wockhardt, Emcure, Shantha Biotech, Bharat Biotech, Serum Institute of India, Dr. Reddy’s, Ranbaxy, etc. The ultimate objective of all these Indian companies, I am sure, will be to get regulatory approval of such products in the EU and then in the U.S. when the time comes.

It is worth mentioning here that to give a fillip to the Biotech Industry in India, the National Biotechnology Board was set up by the Government of India under the Ministry of Science and Technology in 1982 and the Department of Biotechnology (DBT) came into existence in 1986. The DBT now spends around US$ 200 million annually to develop biotech resources in the country and have been making reasonably good progress. The DBT is reported to have undertaken an initiative to prepare regulatory guidelines for Biosimilar Drugs, which is expected to conform to international quality and patients’ safety requirements.

The points to ponder with the Biosimilar Drugs in India:

It is, indeed, quite surprising that in India there is still no separate transparent and published guidelines for regulatory approval of Biosimilar drugs, although the Drug Controller General of India (DCGI) seems to have a different view in this matter. The Drugs and Cosmetics Acts of India have no separate provisions either, for Biosimilar Drugs. In a situation like this, we find that many Biosimilar Drugs are still getting regulatory approval in India.

Currently India supplies 30% by volume of the global requirements of generic drugs both in regulated and non-regulated markets. In the regulated markets like North America and EU, for small molecule generic products, Indian manufacturers conform to the global safety and efficacy standards by getting these products approved by the most stringent regulators of the world like, U.S. FDA, MHRA (Medicines and Healthcare products Regulatory Agency) etc. The very fact that none of the Biosimilar drugs developed in India could get approval in the EU as yet, may well suggest that the stringent regulatory requirements for both efficacy and patients’ safety followed in the EU for Biosimilar drugs, could not be met by the Indian manufacturers, as yet. The question, therefore, comes to my mind whether the Biosimilar drugs manufactured in India conform to international quality and safety standards? If not, who will address the safety concerns of the patients who are or will be administering these medicines?

Such a concern gets vindicated by widely reported serious quality problems, detected by the drug regulatory authorities, at some large and well known Biosimilar drugs manufacturing units in India and also from the condition of some vaccine manufacturing units in our country.

India needs to manufacture the world class Biosimilar drugs conforming to the highest efficacy and patients’ safety standards, just the way Indian pharmaceutical manufacturers have demonstrated with ‘made in India’ generic drugs, the world over. The Indian drug regulatory authority should now take some important initiative with the publication of world class Biosimilar drugs regulatory approval guidelines, may be following the similar process as what we see in the EU.

Currently, experts from India are participating towards preparation of ‘WHO Guidelines’ for Biosimilar Drugs. The progress made towards this direction is yet to be ascertained. Simultaneously, the DBT is reported to have under taken an independent initiative to prepare similar guidelines, the progress of which is also yet to be known.

Before other developed markets open up for Biosimilar drugs, if India can align itself with its own world class regulatory standards for the same, yet another significant export opportunity could be created for the country, competing with the best performers of the world in this category.

Meanwhile, it will only be good to know that like many other initiatives, India has taken one more important initiative to address this important issue, for the sake of humanity. As the existing process of granting regulatory approval for Biosimilar drugs continues in India, the lurking fear towards patients’ safety with such drugs will remain unabated with a large majority of experts in this field.

By Tapan Ray

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.

Leave a Reply