The uncertainty surrounding the grounds on which compulsory licenses on patented drugs may be granted and lengthy legal proceedings endanger the vitality of the Indian intellectual property (IP) environment. An even greater threat, perhaps the greatest, is the uncertainty surrounding biologic drugs.
On what grounds?
Significant uncertainty surrounds the grounds on which the Indian government might grant compulsory licenses on three patented cancer drugs. Will the ruling cite affordability, access, a public health emergency? This unpredictability around the justification of the potential licenses, makes the decisions appear capricious. Demonstrable predictability is critical if innovation is to be fostered and encouraged.
If decisions are sufficiently unpredictable so as to leave innovative firms unable to recognize when their strategies render them vulnerable to compulsory licenses, innovation will be stifled.
The drawn-out legal process and apparent procrastination of the courts contributes to the uncertainty surrounding IPR protection.
In 2011, Bayer brought patent infringement action against Cipla for the manufacture of an unlicensed version of the patented liver cancer drug Nexavar. Cipla manufactures the unlicensed generic under a marketing authorization from the Drugs Controller General of India since mid-2010. The litigation is still underway. So is Bristol-Myers’ litigation with Natco Pharma over the production of generic Sprycel for leukemia which began over three years ago.
What of biologics?
Biologics are structurally complex drugs, manufactured in living systems such as a microorganism, plant cell or animal cell. Many are produced using recombinant DNA technology and a complex mixture of molecules. Accordingly, even the slightest changes in their manufacture can lead to undetected alterations in the biologic composition of the product, with serious implications for their safety and efficacy.
As an illustration of the challenges surrounding immunogenicity, consider the following incident, relayed by the Biotechnology Industry Organization.
“Unlike chemical drugs, all biologics have the potential to stimulate antibody production in patients and such responses are highly unpredictable . . . One example of immunogenicity occurred a few years ago when, at the request of the European Health Authorities, Johnson & Johnson made a change in the manufacturing process for its EPREX product – a product that had been marketed for a decade with no evidence of immunogenicity problems.
The change caused a serious adverse reaction in a small number of patients. These patients lost their ability to make red blood cells because they produced an antibody (triggered by the EPREX) that inactivated both the administered protein (EPREX) and the body’s natural protein that is essential for red blood cell production . . . The EPREX case shows that one protein can be different from another in ways that cannot be detected in the laboratory, but are seen only by the body’s exquisitely sensitive immune system.
If one change to a well-established complex manufacturing process, made by the manufacturer who has intimate knowledge of the process, can cause a problem with immunogenicity, surely the risk is even greater with an entirely new manufacturer and process – as will be the case with follow-on biologics.” (Biotechnology Industry Organization, 2010)
Importantly, India does not have a clear protocol of how to approve a generic biologic (also known as biosimilars or follow-on-biologics). Due to their size and complexity, in most cases biologics cannot be scientifically characterized in the laboratory. Accordingly, innovative firms ensure product consistency, purity and quality through a consistent manufacturing process. For biologics ‘the product is the process’ and translating such intricate methodology to generic production is a complex challenge.
Of particular significance is the lack of such a protocol in the United States due to its complexity. The US Food and Drug Administration (FDA) has determined that the generic drug approval pathway is not appropriate for complex biologics. Moreover, the US FDA has yet to determine how interchangeability can be established for complex proteins. In February 2012, they began to explore the process (additional information available here) issuing three draft guidance documents on biosimilar product development.
Without established conventions on production, bio-equivalence studies and approval, rushing into generic production through compulsory licensing is strikingly unwise. (Herceptin, one of the three cancer drugs on which the Indian government wants to issue compulsory licences, is a biologic).
The Indian Government made several critical patent decisions over the past year. Their impact on the IP ecosystem is still evolving, and will continue to evolve as pending cases are resolved and new decisions are issued. The benefits to getting it right are tremendous, as are the dangers of getting it wrong.
This is the second in a series of three columns on India’s recent actions on drug patents and their implications.The first column which appeared last week dealt with their possible impact on pharma strategies. The third and final column will examine implications for other emerging economies.
Dr Kristina Lybecker is Associate Professor of Economics at Colorado College in Colorado Springs. Kristina is an economist with a PhD from the University of California at Berkeley. She specialises in innovation and intellectual property rights and has been writing on these issues for 12 years. She is currently employed full-time at Colorado College. In the interests of transparency, the writer states that she has been commissioned to work for the pharmaceutical industry on issues of innovation, corruption, counterfeiting and intellectual property rights. However, she has not been compensated or otherwise rewarded for this piece which stems from her intellectual interest in the topic and closely relates to her academic research.
Pic sourced from http://www.coloradocollege.edu
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