Production of biopharmaceutical products using Biosimilars Technique

Biosimilars - Collaterals to the original biopharmaceutical products

Category : General Chemicals
Published by : Data Research Analyst, Worldofchemicals.com

Abstract 

In the year 1980, first generation biopharmaceutical products were manufactured using recombinant technologies and they are on the verge of patent expiration. 

Examples 

Generic name Manufacturer Approval date Expiring date
Ganciclovir Bausch and Lomb March 4, 1996 2012
Eszopiclone Sunovion Pharms Inc December 15, 2004 2012
Leuprolide acetate Abbott Endocrine December 22, 1995 2013

In this context, pharmaceutical firms have commenced the development generic substitutes for original biopharmaceutical products, which are termed as ‘Biosimilars’/‘Biogenerics’/’Follow-on Biologics’/‘Subsequent entry biologics’.  

Biosimilars attempt to copy the original technology, however they are made with a different cell line and different manufacturing and purification processes. But production of biosimilars is a complex process. Biosimilars are considered “similar but not the same” with the first generation biopharmaceutical products. This article will give the various aspects of the biosimilars, other considerations and company strategies for production of biosimilars. 

Introduction 

The factors involved in the introduction of biosimilars are 

  • Expiration of patents 
  • To lower the product costs. 
  • To reduce complexities involved in the drug approval and regulation processes. 

European Agency for the Evaluation of Medicinal Products (EMEA) approved biosimilars which came into focus in 2006. Also multiple biosimilar products are under development for the European market and most of them are expected to be approved in coming years. The pharma market is now open for generic version of biologics, i.e., biosimilars.

Examples

Biosimilars approved with timeline

Biosimilar Reference Approved year
Omnitrope Somatropin 2006
Binocrit Epoetin alpha 2007
Filgrastim Filgrastim 2008
Filgrastim hexal Filgrastim 2009
Nivestim Filgrastim 2010

Chemical drugs are in most cases relatively easy to reproduce as their structure is precisely defined and expressed by the chemical formula. The unique multi-dimensional structures of the proteins and biotechnological medicines, with same molecular weight and produced by same type of cells or microorganisms, can possess different pharmacokinetic and pharmacodynamic properties. Such substances cannot be called biosimilars as they do not meet the regulatory approval standards.

Examples

Biosimilars rejected with timeline

Biosimilar Reference Rejected year
Alpheon Roferon-A 2006
Human insulin Humulin 2007

Other complexities associated with approval of biosimilars include

  • Evidence of integrity and consistency of the manufacturing process
  • Conformance of manufacturing standards to applicable regulations
  • Demonstration of product consistency with appropriate innovator product

Biosimilars are distinct from generics. Generic drug is a much less expensive copy of an innovator drug product. Generics can be produced in two cases, firstly when the patent on a drug has expired and secondly for drugs which never had a patent. Generic drug manufacturers apply for marketing approval of generic drugs under the Abbreviated New Drug Application (ANDA) pathway established by Food and Drug Administration (FDA). The regulations covering market approval of biosimilars is still evolving around the world. US, Australia, Canada, Japan, Turkey and other countries around the world have already designed their regulatory framework for biosimilar medicines.

In last two decades the Indian pharmaceutical industry has emerged as a major supplier of drugs to rest of the world. The reason behind this occurance is the important role played by the Indian Government in encouraging the biosimilar industry. Europe has already cleared the path to biosimilar approval. In June 2007, the US Senate health committee passed a landmark legislation creating an approval pathway for biosimilars. In recent years there has been an increase in the number of major players in the generics industry that are based outside the United States and Europe.

Biosimilars approval status in worldwide

Territory  Drug name Company                               Status                                       Date
US Tev-tropin Teva/Ferring Approved 2005
Australia Omnitrope Sandoz Approved September 2004
EU Valtropin Biopartners Approved April 24, 2006
Japan Somatropin BS Sandoz Approved June 2009

Company strategies on Biosimilars

Following are the few examples of companies and their strategies.

Biocon

Biocon’s biosimilar insulin is an outcome of incremental innovation and is one of the world’s most affordable therapies for insulin dependent diabetes. Biocon has also invested significantly in development of other biosimilars such as Granulocyte Colony Stimulating Factor (GCSF), Streptokinase, Reteplase, Human Growth Hormone, etc. using bacterial (E. coli) and yeast fermentations.

In October 2010, Pfizer formed a strategic global agreement for worldwide commercialization with the Indian biotechnology company Biocon for biosimilar versions of insulin and insulin analog products.

Hospira, Inc

Hospira is a global specialty pharmaceutical and medication delivery company. It is the world leader in specialty generic injectable pharmaceuticals.  Hospira offers one of the broadest portfolios of generic acute-care and oncology injectables.

Hospira, Inc has announced enrollment of the first patient in a Phase III U.S. clinical program for its biosimilar erythropoietin (EPO) on January 09, 2012. Hospira's Phase III program, which follows a successful Phase I trial that concluded last year, will compare safety and efficacy of Hospira's EPO and the reference product, Amgen's Epogen® in patients with renal (kidney) dysfunction who have anemia. Erythropoietin is a treatment for anemia associated with chronic renal failure.

Teva Pharmaceutical Industries Ltd.

Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the leading generic pharmaceutical company. The company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients. Over 80 percent of Teva's sales are in North America and Europe.

Teva announced that the EMEA has granted a Marketing Authorization for its Human Granulocyte Colony Stimulating Factor (G-CSF) product, a generic form of Amgen’s Neupogen. Teva's product is the first biosimilar G-CSF to receive a Marketing Authorization in the European Union and will be marketed under the brand name TevaGrastim.

Conclusion

Increasing demand for biologics for new and improved disease treatments alongside the demand for more cost effective treatment has created a growing market for biosimilars in both developed and developing countries. This article reviewed the highlights the favourable position for suppliers that aim to provide biosimilars for markets regulated by authorities other than the FDA.

A 2010 report by BioPortfolio estimated that the global biosimilars market would be worth $19.4 billion by 2014, growing at an expected compound annual growth rate of 89.1% from 2009 to 2014 (Ariyanchira, 2010). This report was superseded by a more conservative estimate in 2011 of a worldwide market valued at $3.7 billion by 2015, up from about $250 million last year (Datamonitor, 2011 cited by Wechsler, 2011; Sutton, 2011).

A number of companies are entering into strategic partnerships with biotechnology companies in order to acquire capabilities in biosimilar production.

Although biosimilars have begun to enter the global market, the biosimilar manufacturers’ long-term capability to manufacture a consistent product still remains to be proven. At present, even though European legislation is in place to assess and grant marketing approval for biosimilars, the EMEA guidelines only provide a road map and leave challenging areas still to be explored and monitored. Moreover, approvals of biosimilar products should be dealt on a case-by-case basis. In the end, with a suitable regulatory process in place, biosimilars have the potential to provide considerable cost savings to all concerned people. Only after addressing the concerns and designing proper policies the future of biosimilars can becomes a reality.

Reference

[1] thinkBiotech LLC, website - http://drugpatentwatch.com/ultimate/preview/patent/index.php?year=2012

[2] Bhupinder Singh Sekhon, Vikrant Saluja, March 2011 Volume 2011:1 , Pages 1 – 11, Biosimilars: an overview, Available from -http://www.dovepress.com/biosimilars-an-overview-peer-reviewed-article-BS

[3] John Hodgson, WHO guidelines presage US biosimilars legislation? , Biotechnology 27, 963 - 965 (2009) , Available from - http://www.nature.com/nbt/journal/v27/n11/fig_tab/nbt1109-963a_T1.html

[4] Hospira, Inc, website - http://phx.corporate-ir.net/phoenix.zhtml?c=175550&p=irol-newsArticle&ID=1646177&highlight=

[5] Teva Pharmaceutical Industries Ltd., website - http://www.tevapharm.com/en-US/Media/News/Pages/2008/1554758.aspx

To contact the author email: articles@worldofchemicals.com

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