Biosimilars are biological drugs that can be generated via a microorganism, for example, a bacteria or yeast. They are almost the same when compared to other biological drugs that have existed in the market. Their makeup can range from molecules that are small in size, e.g. human insulin to larger ones, e.g. antibodies that are monoclonal in nature. As soon as a company or an institution loses the intellectual property rights over the first biological drug, then and there, the biosimilars are brought into the market for consumption [1].

Basis of Biosimilarity:

This can be explained by an example-

Erythropoietin is a hormone that controls the production of red blood cells in the body. One of the reasons for anemia is that the body stops producing this hormone, resulting in the decrease of red blood cells. Hence, one has to take this hormone through an external source to maintain the production of red blood cells at the required levels. Erythropoietin (biological medicine) is modified using recombinant DNA technology to epoetin alfa (an erythropoietin stimulating factor). Epoetin alfa is then inserted into a gene that is injected into a cell which, starts showing the effects of erythropoietin. The medium for this injection is a liquid, Abseamed that contains the required amounts of epoetin alfa [2].

Factors Affecting Biosimilarity:

1. Structural Analysis: Biosimilars & biological medicine can differ in only small amounts in their clinical constituents that are inactive.

2. Functional Assays: Threshold level and biologic activity of the biosimilars have to be almost the same as that of the biological medicine.

3. Studies in animals: Animal Toxicity, taking into account the pharmacokinetic (PK) and pharmacodynamic measures (PD) in animals, animal studies for immunogenicity.

4. Clinical studies: Human pharmacology, Clinical Immunogenicity, safety and effectiveness, issues in designing the study, extrapolating data for different outcomes.

5. Post-marketing surveillance [3].

Advantages of Biosimilars:

1. The margins of profit can be slightly greater than the generic drugs.

2. The safety, efficacy and other data that are generated for biosimilars is much less when compared to its original biological medicine. Hence, the cost of treatment using biosimilars also reduces.

3. The treatment processes using these drugs are growing by leaps and bounds [4]. The market share of biologics worldwide is expected to be $200-$210 billion by 2016 [5].

4. As the patent of biopharmaceuticals expires, the opportunity for the growth (use) of biosimilars increases [4].

Disadvantages of Biosimilars:

1. Sensitivity of biosimilars is high i.e. the temperature plays a big role in their maintenance. Hence, they have to be distributed through a cold chain network.

2. Their development costs are much more as compared to the generic drugs.

3. The difference in the manufacturing costs & the necessary capital amount put in for equipment, plant and property between biosimilars and generics is huge.

4. As pharmacopeia monographs do not exist for biosimilars anywhere, hence such medicines brought into the market and thereby sold, need not abide by the appropriate monograph [4], [6].

State of Biosimilars in Various Countries:

In India, the guidelines for regulating the development of biosimilars are looked after by Department of Biotechnology (DBT), Central Drugs Standard Control Organization (CDSCO), Indian Council of Medical Research (ICMR), Institutional Biosafety Committee (IBSC), National Control Laboratory for Biologicals and National Centre for Biological Sciences [7], [9].

The various Acts and Guidelines that the biosimilars come under:
• Drugs and Cosmetics Act (1940)
• Drugs and Cosmetics Rules (1945)
• Environment Protection Act (1986)
• Recombinant DNA Safety Guidelines (1990)
• Guidelines for preclinical and clinical data for rDNA vaccines, diagnostics and other biologicals (1999)
• CDSCO guidance for industry (2008)
• Guidelines and Handbook for Institutional Biosafety Committees (2011) [8]

In India, due to the lack of relevant resources and the required experience, the authorities are seeing to apply the rules and regulations without many changes (as it is in the developed world) [9].

Some of the companies producing biosimilars in India:

Biocon, Zenotech, Dr. Reddy’s Laboratories, Reliance Life Sciences, Ranbaxy Shantha Biotechnics, Intas Pharma, Lupin Pharma, Zydus Cadilla [10], Bharat Biotech [12], Kemwell Biopharma [11], Panacea Biotec [7], Wockhardt, Strides Arcolab, Cipla and Avesthagen [13]

In the US, the guidelines for regulating the development of biosimilars are looked after by the FDA.
The various Acts and Guidelines that the biosimilars come under:
• Public Health Service Act (1944) - this Act governs the Biologic License Application (BLA). Most of the biologics get approved through this method (e.g. epoetins). There are no official laws currently to approve biosimilars.
• Federal Food, Drug and Cosmetic Act (1938) - this Act governs the New Drug Application (NDA). Products made of insulin and the human growth hormone gets approved by this method. The official laws that exist to get the NDAs approved are the Hatch-Waxman provisions [4].

Till February 2013, the FDA did not get any applications for biosimilars. The biosimilars market is still to develop in the US, despite many regulatory happenings [14].

Some of the companies producing biosimilars in the US:
Amgen, Momenta Pharmaceuticals, Actavis [15], Teva Pharmaceuticals USA, Hospira [16], Lonza , Baxter International and Merck & Co. [17]

The European Union:
The earliest to generate regulatory guidelines to get the approval of biosimilars was the EU [18]. Biosimilars were brought into the European market successfully in 2006. Till now, 14 biosimilars have been approved for use. The biosimilars and their biological medicines have the exact International Nonproprietary Name (INN). The EU requires that the companies submit a Risk Management Plan (RMP) to ensure a smooth Pharmacovigilance process [19]. In the EU, the guidelines for regulating the development of biosimilars are looked after by the European Medicines Agency (EMA).

The various Acts and Guidelines that the biosimilars come under: European Commission (EC) [1]

Some of the companies producing biosimilars in the EU:

Curaxys [20], Sandoz [21], Hospira [16], Roche [22] and Novartis [23]

The Future:

- In making policy decisions for biosimilars, patient safety would be the utmost factor [24].
- The patient should be given the right to choose between a biological medicine and the new biosimilar entrant.
- There should be standard regulatory guidelines for global players [25].




3. Food and Drug Administration. Guidance for Industry: Scientific considerations in demonstrating biosimilarity to a reference product. Biosimilarity. 2012; 1-22.

4. Veeda Clinical Research. Biosimilars. 2012. Website:



7. Pruthviraj U. Biosimilars: Emerging market in India.

8. DBT and CDSCO, Government of India. Guidelines on Similar Biologics: Regulatory requirements for marketing authorization in India. 2012.

9. Dr Nellore R. Regulatory considerations for Biosimilars. Perspect Clin Res. 2010; 1[1]: 11-14.



12. India Brand Equity Foundation. Formula of Success: Emerging trends in Biosimilars in India. 1-17.


14. Bourgoin A F, Nuskey B. An outlook on US Biosimilar Competition- White Paper. Thomson Reuters. 2013; 1-16.




18. Bogaert P, Lietzan E, et al. Biosimilar regulation: important considerations and global developments. Cross-border Life Sciences Handbook. 2011.







25. Sharma A. Biosimilars. 2012.

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