CCI orders Investigation against Roche

The Competition Commission of India (CCI), based on a prima facie determination on contravention of Section 4(2)(c) of the Competition Act, ordered investigation against Roche with respect to the cancer drug, Trastuzumab. The complaint was filed by Biocon and Mylan Pharmaceuticals.

Facts of the case: –

  • Genentech developed a monoclonal antibody, which is used in the targeted therapy to treat breast cancer that over expresses the HER-2 (human epidermal growth factor receptor 2) protein. The International Non-Proprietary Name (hereinafter ‘INN’) for this monoclonal antibody is Trastuzumab
  • Genentech signed an agreement with Roche in July, 1998, whereby Roche was given the exclusive marketing rights to sell Trastuzumab, under the brand name HERCEPTIN, outside the USA. HERCEPTIN was introduced in India in 2002 by Roche. The drug was imported and marketed in India initially through a distributor, Taksal Pharmaceuticals, under a marketing arrangement. This arrangement was subsequently terminated, and the marketing was thereafter done by Roche Produces, India.
  • Roche was granted following approvals:
11th October, 2002, import of HERCEPTIN for treatment of patients suffering from ‘metastatic breast cancer’. HERCEPTIN in 440 mg.
25th January, 2008, import and market HERCEPTIN in 150 mg vials
07th August, 2006 HERCEPTIN for treatment of patients suffering from HER-2 positive early breast cancer (adjuvant and neo adjuvant)
03rd April, 2010 HERCEPTIN for treatment of patients suffering from HER-2 positive metastatic gastric cancer
  • Glenmark Pharmaceuticals Limited Challenged the drugs patent in a post-grant opposition on 12th December, 2008. Before a decision could be reached on this opposition, the Roche Group stopped paying annuities in May, 2013 and consequently, the patent lapsed.
  • Roche withdrew HERCEPTIN from the Indian market and rather introduced a lower cost version of Trastuzumab, known as BICELTIS, which was distributed and marketed by Emcure Pharmaceuticals as per an agreement.
  • The Informants have claimed that BICELTIS, which was priced at USD 1270 (Rs.75,000) per 440 mg vial, was primarily introduced in India due to the threat of compulsory licensing and development of biosimilar Trastuzumab. The Roche Group also launched another low cost version of Trastuzumab under the brand name HERCLON in India at a price of USD 1270 (Rs. 75,000) per 440 mg vial
  • On 18th January, 2014, the launch of biosimilar Trastuzumab was announced by Boicon and Mulan under the brand names, CANMAb and HERTRAZ, respectively.
  • It has been stated that the drug was proposed to be launched in vials of 150 mg priced at Rs. 19,500/-per vial and 440 mg priced at Rs. 57,500/- per vial. The price of the 440 mg vial of Trastuzumab manufactured by the Informants is claimed to be 25% lower than HERCLON and BICELTIS and 50% lower than HERCEPTIN.

It was alleged by the Informants that Roche Group, with the intention of preventing the entry of new players in its market of ‘Trastuzumab’, started indulging into frivolous litigations against the Informants: –

  • Writing frivolous communications to various authorities thereby attempting to impede the entry of the Informants.
  • Roche Group has also resorted to vexatious litigation against the Informants and other competitors/potential entrants in the relevant markets, with the sole intention of preventing launch and/or market penetration of approved biosimilars of Trastuzumab.
  • Misinforming doctors and hospitals about the pending Civil Suit and warning them of severe consequences as a result of prescribing HERTRAZ while the suit is pending.

Findings in the order:-

Before analysing the aforesaid allegations within the realm of the Act, the order deals with the preliminary objection raised by the Roche Group on maintainability of the present case. During the hearing, Roche Group has argued that the issues raised in the present information are squarely covered by the Civil Suit pending before the Hon’ble Delhi High Court and thus, the Informants should not be permitted to raise similar issues before the Commission.

The Court agreed with Biocon and Mylan , that while the issues before the Hon’ble Delhi High Court pertain to the validity of approvals granted by DCGI to Informants, the primary issue before the Commission is whether the Roche Group’s conduct in the market is abusive or not. The two are therefore different, and CCI has jurisdiction to decide the present case.

The order also first defines the relevant product market of the drug in question. Biological drugs as well as its biosimilars form part of the same relevant product market. In the present case, the relevant product market, thus, would be the “market for biological drugs based on Trastuzumab, including its biosimilars”. The court held that drugs based on Trastuzumab,i.e., the reference biological drug as well as its bio-similars, would be considered part of the same relevant product market. A relevant product market, within the meaning of Section 2(t) of the Act, need not comprise of products which exhibit ‘identical’ properties; it may also include products which are ‘similar’ in terms of their intended use. In this regard, the Commission finds force in the submission made by the Informants that a biosimilar drug obtains an approval from the regulatory authority only after proving itself to be similar to the reference biological drug in terms of ‘safety’ ‘efficacy’ and ‘quality’. Despite not being identical to the reference biological product, a biosimilaris highly analogous to an already approved biological product and may not have any meaningful differences from the reference product

With regard to the relevant geographic market, the Commission held that the conditions of competition are homogenous across India for pharmaceutical products. Therefore, the relevant geographic market in the present case would be ‘India’.

The Commission observes that undoubtedly, after the introduction of biosimilars, the market share of Roche Group has gone down in the relevant market during 2014 and 2015. However, the allegations in the present case pertain to abusive conduct by Roche Group during the period starting from year 2013 till date. Till 2014, Roche Group had 100% market share. Although its market share fell in the year 2014; it still held a considerable market share in 2014 (83.9% in terms of value and 77% in terms of volume of sales) and 2015 (70.9% in terms of value and 61% in terms of volume of sales).

Considering the long drawn legal battle between the parties before the Hon’ble Delhi High Court, the Commission held that they are reluctant to hold that the litigations filed by Roche Group are baseless. Recourse to legal proceedings, being a right of every party, cannot be concluded to be tainted with ulterior motives as a general principle. Such determination has to come sparingly in exceptional circumstances and the Commission held that it is not convinced that any such circumstance has arisen in this case. Thus, for the foregoing reasons, the allegations of the Informants with regard to vexatious litigation were, prima facie, found to be without merit.

It was however held by the commission that Roche group has approached doctors, hospitals, tender authorities, etc., to influence their perception about the efficacy and safety of the Informants’ products. The Commission is conscious that competitors, in normal business parlance, indulge in tactics to belittle competitors’ products. However, the commission observed that there is difference between puffery aimed at promoting one’s own product and adopting practices which disparage or malign the image of competitors, thereby causing competitive disadvantages to them. This is even more harmful in the pharmaceutical sector, where such disparagement is made to the doctors who are treating the patients of cancer. The line of difference between these two business strategies is very thin, however, when crossed by a dominant enterprise to its own illegal advantage, it warrants intervention by the competition authority.

The Commission also held that creating any iota of doubt in the minds of doctors can adversely affect the market for biosimilars, which is prescription induced, beyond repair. Such disparagement may also have ripple effects within the medical community. In this scenario, those biosimilar manufacturers who do not have strong marketing channels amongst doctors may be forced out of the market because of abusive denigration by a dominant player.

Based on the foregoing analysis, the Commission held that prima facie, the contravention with regard to Section 4(2)(c) of the Act is made out against Roche Group, which warrants detailed investigation into the matter.


Trastuzumab “can” be sold as a bio similar to Roche’s Trastuzumab

The division bench of the Delhi High Court, of Badar Durrez Ahmed and Sanjiv Sachdeva, has permitted Biocon and Mylan to use Roche’s product data for Trastuzumab. Roche had challenged the approval mechanism adopted by the central drug standards controller (CDSCO) in giving Biocon and Mylan approval for its biosimilar drug and their product inserts containing product data before the single judge.

 Earlier, the Delhi High Court, in a single bench order, had allowed Biocon and Mylan to market their product without any reference to Roche’s product or biosimilarity.

 Stay tuned for a fuller report!

Guidelines on Similar Biologics

The “Guidelines on Similar Biologics” prepared by Central Drugs Standard Control Organization (CDSCO) and the Department of Biotechnology (DBT) laying down the regulatory pathway for a biologic claiming to be Similar to an already authorized Reference Biologic have been published.

The objective of the guidelines is to provide guidance to the applicants to enable them to understand and comply with the regulatory requirements for market authorization of Similar Biologics in India.

Stay glued for more updates on this!

Trastuzumab cannot be sold as a bio similar to Roche’s Trastuzumab

In a recent decision, Justice Manmohan Singh of the Delhi High Court has restrained Biocon and Mylan to sell, manufacture, market and advertise their Trastuzumab as a bio similar to Roche’s Trastuzumab which is sold under the brand names of HERCEPTIN®, HERCLON™ and BICELTIS®.

Trastuzumab enjoys a global reputation for being an accepted biological treatment for HER 2 positive breast cancer worldwide. The facts of the case are as follows:

Roche Products is the importer and marketer of this innovator molecule in India. Biocon Limited co-developed and purported biosimilar version of Trastuzumab, along with Mylan Inc. and obtained an approval to market and sell the biosimilar version of Trastuzumab. Roche filed a suit for injunction against Biocon, Mylan Inc., and Mylan Pharmaceuticals Private Ltd. The Drug Controller General of India (DGCI) who granted the approval to Biocon and Mylan was also made a party to the suit.

Roche contended that the defendants’ drugs are, inter alia, being misrepresented as “Trastuzumab”, “biosimilar Trastuzumab” and a biosimilar version of HERCEPTIN® without following due process for obtaining appropriate approvals in accordance with the Guidelines on Similar Biologics. Roche also argued that Biocon has not conducted various tests required under the law for drug approval including  Phase I and Phase II trials. The defendant has also not independently generated requisite data in order to demonstrate similarity between the drug and the plaintiffs’ Trastuzumab, both in terms of the stages and the sample size of the tests conducted by defendant No.2.

It was also averred that as per the procedure for the approval of new drugs in India, after New Drugs Advisory Committee (NDAC) has reviewed an application for a new drug and given its recommendation, it refers such application to a Technical Committee (the “TC”), for consideration along with its recommendation. After the TC has endorsed the recommendation made by NDAC, it refers the application to the Apex Committee, and only after both TC and the Apex Committee have endorsed the recommendation of the NDAC, should defendant No.1 consider granting its approval to such an application.

This is usually a time consuming process and the consideration by the NDAC, the TC and the Apex Committee , but however this was done in a short span of five days i.e. between 18th October to 23rd October, 2013. The undue haste with which the approval was granted suggests that all factors relevant to the approval of a biosimilar drug under the Guidelines on Similar Biologies and under other internationally recognised standards were not taken into consideration at the time of granting such an approval.

The defendants argued that the application for manufacture of its drug was in conformance with the statutory requirements as contained in the relevant rules read with schedule Y of the Drugs & Cosmetics Act. under the said Act and corresponding Rules,  the term “Similar Biologics” has not been defined. However, the DCGI along with the Department of Bio -Technology had prepared “Guidelines on Similar Biologics: Regulatory Requirement for Marketing Authorization in India” in the year 2012. These guidelines are not statutory under the Drugs and Cosmetics Act and the Rules made thereunder. It was averred by the defendants that though the clinical trials of Phase I and Phase II have not been registered with the defendant No.1 but it did not skip Phase I trial as the main the objective of a Phase I trial is to establish comparative pharmacokinetics (pK) and this pK data was generated as the initial part of the Phase III trial. Defendant No.2 tried to give its justification for not doing the Phase II study as dose finding and POC studies are not required for follow-on products (biosimilars or generics).

Considering the overall facts and circumstances, Justice Manmohan Singh made the following prima-facie observations:-

–       the approvals as per existing protocol of biosimilar drug are contrary to the Rules, Guidelines of Biosimilar 2012 as well as directions issued by the Supreme Court.

–       the approvals which are in the hands of defendants are not in accordance with the protocol of biosimilar drug and guidelines, so far the defendant has not been able to satisfy before the Regulatory Authority as to whether the drug manufactured and marketed by the defendants is biosimilar.

As the final finding in this respect is yet to be arrived, the Court has given the following interim directions:

  1. a) The defendants may continue to manufacture, market and advertise their product under the name CANMAb or Bmab-200 or Hertraz on the basis of the approvals already granted without calling their product as “bio similar” and/ or “bio similar to HERCEPTIN, HERCLON, BICELTIS” or in any way ascribing any bio-similarity with that of the plaintiffs products HERCEPTIN, HERCLON, BICELTIS in any press releases, public announcements, promotional or other in printed form and from relying upon or referring the plaintiffs’ names.
  1. b) The defendants may also manufacture and market the drug by qualifying the INN name Trastuzumab but not to use the said name stand alone on the carton or package insert as a brand name. The defendants No.2 to 4 can use the INN name as Biocon’s Trastuzumab or Mylan’s Trastuzumab wherever applicable to describe the composition of molecule on the product as well as in its insert and not in a prominent manner. The said expression shall be used at the bottom part of the carton and should be in small size letters than their respective brand names.
  1. c) In view of prima facie findings that the use of the data by the defendants in the product insert without undergoing the entire process of the trials is misleading, the defendants are also restrained from using the data relating to manufacturing process, safety, efficacy and tests conducted for the safety of the drugs as complained of by the plaintiffs till the time the final decision on the issue of the bio similarity is made in the present suit.
  1. d) In the event, the defendant No.2 intends to claim bio similar as a description of its product or part of its promotional campaign or otherwise in any other form, the defendant No.2, if so advised, can re-apply the said license before the relevant authorities including defendant no. 1 and in which case, the defendant No.1, the authorities and committees framed therein shall decide the said approval application in accordance with the Rules and Guidelines of 2012 and also the observations made by this court in the present order. In the alternative, the defendant No.2 may await the outcome of the present suit and can continue with the present arrangement as an interim measure.
  1. e) This interim measure is made only in view of the peculiar facts in the present case wherein the defendant No.2 is already in possession of approvals granted rightly or wrongly validity of which is questioned in this suit. All the decisions made by the DCGI and authorities and committees made therein in connection with future approvals shall take into consideration the guidelines of 2012 and also the findings arrived at in the present order by this court.

Reliance Life Sciences restrained from launching their Biosimilar version of Herceptin

Roche has been successful in obtaining a temporary injunction from the Delhi High Court to block the expected launch of a biosimilar of breast cancer drug Herceptin (trastuzumab) by Reliance Life Sciences.

The order dated 2nd November 2015 of Justice Manmohan Singh of Delhi High Court restrains Reliance from launching the drug in the market till the next date of hearing.

Reliance Life Sciences has recently obtained approval for its biosimilar version of Herceptin named TrastuRel. According to Roche, Reliance Life Sciences has incorrectly been granted an approval by the Drug Controller General Office for TrastuRel. Roche argued that Reliance was supposed to conduct the clinical trials of all phases (I, II and III) to obtain an approval, however the approval has been granted without the clinical trials of Phase I and Phase II.

 The Counsel’s for Roche argued that the result of clinical trial of Phase III is dependent upon the results of trials of Phase I and Phase II. Thus, on the basis of clinical trial of Phase III even if valid the product of Reliance Life Sciences cannot be treated as “biosimilar product of Roche”.

 Justice Manmohan Singh held that serious issues are raised in the matter which would be decided after considering the explanation and reply of the defendants and till the next hearing Reliance has been restrained from launching the product.