Across the world, biologic drugs, in general, have a successful record in treating many life threatening and other complicated ailments. Expiration of product patents of the first major group of originators’ biologic molecules has led to the development of products that are designed to be ‘similar’ to the originators’ products, as it is virtually impossible to replicate any protein substances, unlike the ‘small molecule’ drugs.
These are known as ‘Follow-on Biologics’ or more commonly ‘Biosimilar Drugs’, which rely in part, on prior information obtained from the innovators’ products and demonstration of similarity with the originator’s molecule based on detailed and comprehensive product characterization, for their marketing approval.
The bedrock:
India seems to have a good potential to become one of the key players in the development and manufacture of biosimilar drugs, not only to serve the needs of the local population, but also for exports to large developed and other developing markets. However, for this dream to materialize science-driven ‘Biosimilar Guidelines’ are absolutely necessary and should form the bedrock in the development process of all such drugs.
Paving the way:
These guidelines will provide a regulatory framework or pathway to ensure that biosimilar Drugs approved in India are of good quality and demonstrably similar in efficacy, safety and immunogenicity to the original reference products.
Paving the way for such regulatory framework in the country with comprehensive sets of guidelines is of utmost importance, especially in the light of prevailing sub-optimal pharmacovigilance system in India.
Setting ground rules:
Considerable developments have occurred across the globe in the scientific and regulatory understanding of biosimilar drugs. Nearly all developed nations and many developing countries have now defined or in the process of defining appropriate regulatory framework for the same.
However, due to lack of such guidelines in India, until recently, there have been instances of so called ‘biosimilar drugs’ being approved for marketing, reportedly with sub-optimal testing and dossiers, thereby putting into question the product quality, comparability and patient safety.
With the above backdrop, the Ministries of Health & Family Welfare and the Science and Technology have now set the ground rules and released India’s first “Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in India”. These Guidelines are already in place effective September 15, 2012.
A step in the right direction:
Long awaited new ‘Biosimilar Guidelines’ of India, demonstrating an overall similarity in the philosophy and approach with the those in the U.S and Europe, though a belated move by the Government, but certainly a step in the right direction.
The global potential:
In most of the developed countries, besides regulatory issues, biosimilar drugs are considered to be a threat to fast growing high value innovative global biotech industry.
At the same time, there is an urgent need to effectively address the global concern for cheaper and more affordable biologic medicines for patients across the world. To achieve this objective, 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.
Biosimilar drugs will, therefore, have immense global potential to improve access to life saving biologic medicines for the ailing population across the continents.
First ‘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 a while in the absence of a well-defined regulatory pathway for ‘Biosimilar drugs’ in the USA at that time.
Having received the US-FDA approval, 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, very few people at that time expected the US FDA to put regulatory guidelines in place for approval of ‘Biosimilar drugs’ in the largest pharmaceutical market of the world.
Global initiatives:
Internationally most known companies in the biosimilar drugs space are Teva, Stada, Hospira and Sandoz. Other large research based global innovator pharmaceutical companies, which so far have expressed interest in the field of biosimilar drugs are Pfizer, Astra Zeneca, Merck and Eli Lilly.
Following are the examples of some relatively recent biosimilar drug related initiatives of the global players:
- 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. The company also 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.
According to Reuter (June 22, 2011), Merck, Sandoz, Teva and Pfizer are expected to emerge stronger in the global biosimilar market, as we move on.
In India:
- Dr Reddy’s Laboratories (DRL) has already been marketing a biosimilar version of Rituxan of Roche since 2007.
- Reliance Life Science is also a potential player in the biosimilar market, though it has reportedly faced a setback in Europe with the regulators asking for more data for its version of EPO prompting them to withdraw their application for now.
Many other developments are also taking place in tandem in the space of biosimilar drugs, the world over. To fetch maximum benefits out of this emerging opportunity, as mentioned above, India has already 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.
The global 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.
Major Indian players:
Such a lucrative business opportunity in the western world 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-alpha, 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.
The domestic market:
According to IMS Health March 2012, the biosimilar drugs market in India is around US$ 700 million with the main categories being as follows:
| Therapy Area | US $ Million |
| Insulin | 250 |
| Hepatitis-B Vaccine | 200 |
| Heparin | 70 |
| Human Chorionic Gonadotropin | 50 |
Moreover, as per available reports, till March 2012 about 91 clinical trials have been lined-up in India for 20 recombinant therapeutics, as approved by the Genetic Engineering Approval Committee.
Brand proliferation offering wider choices:
Currently there has been huge brand proliferation for biosimilar products in India with around 250 brands in 20 therapeutic areas. Some examples are as follows:
| Therapy Area | No. of Brands |
| Insulin | 40 |
| Erythropoietin | 55 |
| Human Chorionic Gonadotropin | 48 |
| Streptokinase | 33 |
| Interferon | 10 |
| Heparin | 10 |
Increasing demand:
The demand of such drugs even in India is increasing at a rapid pace. The focus of the government on various immunization programs is also getting sharper simultaneously. For example, during 2011-12, the government spent around US$ 115 million for routine immunization covering reportedly about 25 million pregnant women and children and nearly US$ 140 million towards pulse polio vaccination initiatives. This trend, though may not still be enough for the size and scale of a country like India, but praiseworthy nonetheless.
The focus on Oncology:
Within bio-pharmaceuticals many companies are targeting Oncology disease area, which is estimated to be the largest emerging segment with a value turnover of over US$ 55 billion in 2010 growing over 17%.
As per recent reports about 8 million deaths take place all over the world every year only due to cancer. May be for this reason, the research pipeline for NMEs is dominated by oncology with global pharmaceutical majors’ sharp R&D focus and research spend being on this particular disease area.
About 50 NMEs for the treatment of cancer are expected to be launched in the global markets by 2015.
Indian market for oncology products:
Current size of the Indian oncology market is reportedly around US$ 75 million.
Biocon has launched its monoclonal antibody based drug BIOMAb-EGFR for treating solid tumors with intent to introduce this product in the western markets as soon as they can get necessary regulatory approvals. Similarly, Ranbaxy with its strategic collaboration with Zenotech Laboratories is planning to market oncology products in various markets of the world like, Brazil, Mexico, CIS and Russia.
Government support:
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 projects.
Areas of concern:
According to a research report from ‘The Decision Resources’, one of the key success factors for any such new biosimilar drugs, especially from India, will be how quickly the specialists accept them.
The report also noted a high level of concerns, if such drugs are not supported by robust sets of clinical data on the claimed treatment indications. To allay this concern robust implementation of the recent biosimilar guidelines in India will play a very critical role.
Conclusion:
As the R&D based global innovator companies are expanding into the biosimilar space, many Indian domestic pharmaceutical companies are also poised to invest on biosimilars drugs development to fully encash the emerging global opportunities in this area. It is quite prudent for the Indian players to focus on the oncology therapy area, as it has now emerged as the fastest growing segment in the global pharmaceutical industry.
With around 40 percent cost arbitrage and without compromising on the required stringent national and 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 conformance to stringent US FDA manufacturing standards having largest number of US FDA approved plants outside U.S, India has already acquired a clear advantage in manufacturing high technology chemical based pharmaceutical products in India.
Having progressed thus far, with adequate additional investments for similar biologics and ensuring robust implementation of new ‘Biosimilar Guidelines’, India has the potential to earn the leadership status even in the global biosimilar segment, just as it did in the generic pharmaceutical space of the world.
By: Tapan J 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.