In an order that is likely to have wide-ranging ramifications on the biomedicine industry, the Delhi High Court on Monday (25th April) imposed some conditions on the sale of the biosimilar version of Roche’s breast cancer drug, Trastuzumab, by Biocon and Mylan.
The decision, clocking in at 227 pages, discusses a number of profoundly important issues such as data exclusivity, patent linkage, norms to be followed for patient safety and the rights of patentees after the expiry of their patent. We have discussed some of these issues here, here, here and Prashant’s thought-provoking piece about the prohibitive cost of Herceptin can be found here.
In order to constructively analyze the full import of the order, I propose to divide my analysis into two parts.
In this first part, I will set forth the key issues that the court was called upon to grapple with and the main arguments of the parties. In the second part, I will discuss the findings of the court on the main issues and situate the relevance of the decision within a broader context by analyzing what the decision means for data exclusivity, affordable access to medicines and the biomedicine industry.
Plaintiff no. 3 (“Genentech”) developed the biological drug Trastuzumab in 1990 which is used for the treatment of HER 2 positive breast cancer.
Lest our readers think ill of themselves for not knowing the distinction between biological and chemical drugs, I should point out that the key difference between the two is that a biological drug is synthesized by living organisms whereas chemical drugs are produced by chemical synthesis.
This conceptual difference also helps explain the difference between generic drugs and biomedicines. While both possess properties that are identical to a reference/innovator drug, whose data they heavily draw upon after its patent expires, generic drugs are produced through chemical synthesis whereas biomedicines are produced through biological synthesis.
After obtaining the approval of the Drugs Controller General of India in 2002, Trastuzumab is being imported and marketed in India by Roche Products under the brand names HERCEPTIN™, HERCLON™ and BICELTIS™.
Genentech obtained trademark registration for HERCEPTIN in 2005 which will run up to 2018 and for BICELTIS® in 2011 valid up to 2019.
Significantly, Genentech obtained a formulation patent for Trastuzumab on May 3rd, 1993 which expired on May 3rd, 2013.
Defendants no. 2 and 3, Biocon and Mylan, have been selling a purportedly biosimilar version of Trastuzumab under the brand name CANMAB after obtaining the requisite approval on 23rd October, 2013 from defendant no. 1, Drugs Controller General of India.
Mylan Pharmaceuticals, a subsidiary of Mylan Inc. also sells a purportedly biosimilar version of Trastuzumab under the brand name HERTRAZ.
Main questions at issue:
As the court noted in para 21, it was called upon to answer 5 main questions:
- Whether the plaintiffs’ claim challenging the validity of the approval was maintainable directly in the High Court, considering that they had not exhausted other remedies;
- The scope of the court’s power to review the legality of the approvals granted to the defendants to market the biosimilar version of Trastuzumab;
- Determination of the legal importance and binding character of the Biosimilar Guidelines, 2012, especially with reference to its application to the approval granted to the defendants;
- The legal tenability of the Defendant no.1’s decision to grant approval to defendant no. 2 even though the latter did not conduct phase 1 and 2 clinical trials; and
- Ascertaining the legal sustainability of the plaintiffs’ common law claims of misrepresentation and false information against the defendants.
Key arguments of plaintiffs
The kernel of the plaintiff’s arguments was that Biocon and Mylan short-circuited the approval process, outlined in the Biosimilar Guidelines, 2012, for selling the biosimilar version of a drug; this act of riding roughshod over the processes institutionalized for ensuring patient safety, they argued, put into peril the health of cancer patients. The plaintiff’s case broadly rested on 4 fundamental arguments.
First, there is a 3-tier machinery for granting approvals to new drugs in India consisting of the New Drugs Advisory Committee, Technical Committee and finally the Apex Committee. Only after all these 3 agencies give the green signal, the plaintiffs contended, can the defendant no. 1 grant the requisite approval. The defendants filed their application on 15th October, 2013, and the approval was granted on 23rd October – after a short span of 8 days. Therefore, this gave rise to the inexorable conclusion that the defendants application was not evaluated in a rigorous and comprehensive manner by testing it against the touchstone of the 2012 Guidelines so as to assess the robustness of the manufacturing process, structural similarity to the innovator molecule, quality and quantity of the clinical data, etc.
Second, by using the testing and sales material of Herceptin® in the promotional material, package insert and cartons for their product, the plaintiffs argued that the defendants were trying to take undue advantage of the considerable reputation that Herceptin® has attained in the Indian market. In order to substantiate this argument, the plaintiffs gave several examples of the misrepresentations on the package insert of the defendants, such as wrongly stating that the drug could be used for treating early breast cancer and metastatic gastric cancer when the approval was only for metastatic breast cancer; stating that 3 phases of clinical trials were conducted when it was clearly admitted that the defendants only conducted one such trial; and stating that the clinical studies lasted 51 weeks when the same only lasted 24 weeks.
Third, on the issue of the maintainability of the suit, the plaintiffs argued that the High Court did possess the jurisdiction to adjudicate upon the dispute in light of the fact that the defendant’s actions impinged the plaintiffs’ civil rights for which the plaintiffs could not approach any other forum except the High Court.
Finally, the plaintiffs argued that the international nonproprietary name (INN) Trastuzumab was assigned by the WHO to the plaintiffs for the biological drug in question as a global mark of its recognition. Without conducting any comparative tests to assess the properties of the innovator drug and the biosimilar, the plaintiffs argued, the defendants could not use the INN Trastuzumab as it was likely to mislead doctors as well as patients.
Arguments of the defendants
In response, the defendants collectively advanced 4 main arguments.
First, Rule 1(3) of Schedule y of the Drugs and Cosmetics Rules (“the Rules”), the defendants argued, envisages a situation in which the requirement of putting forth toxicological and clinical data in the approval form can be waived if the supply of the drug in question is essential for meeting an exigency. On this basis, they argued that defendant no. 1’s decision to invoke its power to grant an approval in the absence of the requisite data after considering the defendants’ representation in this respect was perfectly legitimate and plausible. They further advanced this line of argumentation by contending that they were entitled to follow an abbreviated pathway for gaining approval, in light of the fact that the safety and efficacy of the reference drug i.e. Herceptin had been clearly established.
Second, contending that the High Court lacked the power to adjudicate upon this dispute, the defendants argued that Rule 122DC of the Rules empowers an aggrieved party to file an appeal against any order of the licensing authority to the central government within 60 days. Therefore, the suit was not maintainable in the High Court, they argued, because the plaintiffs had not exhausted this special remedy.
Third, the fundamental motive underpinning the plaintiffs arguments, the defendants contended, was to stifle competition and thwart any attempts to undercut their monopolistic position with respect to the sale of Trastuzumab. Since the plaintiffs were selling a vitally important drug at an exorbitant price, the defendants argued, the licensing authorities took the right decision of granting an expedited approval for its biosimilar in public interest.
Finally, the approval process started in 2008 and, after going through all the required stages, it finally ended in 2013. Further, the technical committee and apex committee were set up after the defendant no. 2 had commenced its clinical trial and had no role to play in the approval of biological drugs. Therefore, it would be fallacious to assert, contended the defendants, that the approval was vitiated by non-application of mind.