Trastuzumab/Herceptin has been controversy’s child (please read my previous posts on Herceptin here and here.) Initially it was considered for Compulsory license u/s 92 and then last year in a very surprising development Roche decided not to pursue Herceptin patents in India. In a SPICY IP exclusive Prashant had blogged about this development over here.
Shortly thereafter, after regulatory approval a “biosimilar” version developed jointly by Biocon and Mylan was launched in India under the brand names CANMAb™ and Hertraz™ respectively. Swaraj had blogged about the pricing issues of Biocon’s product here. Just when you thought Roche had given up, in a strategic move Roche sued Biocon and its partner Mylan and seeking injunction. The Drug controller general of India was also made party to this suit.
Two specific issues were raised in the suit. Roche alleged that the Defendants (Mylan and Biocon) had not satisfied the requirements for a biosimilar drug in accordance with the guidelines.Please see Shamnad’s article here where he discusses the battleground shift from patents to regulatory.The other issue raised was that of passing off; where Roche contended that the defendants were seeking to pass off their products as being equivalent in quality and class to Herceptin® by referring to their products as “biosimilar version of Trastuzumab/Herceptin®.
Justice Manmohan Singh found merit in the second argument (passing off) and granted an interim injunction restraining US based pharma generic and Bangalore based Biocon from claiming any similarity to Roche’s Herceptin. The Delhi high court order can be accessed here.
Did the defendants satisfy the requirements for biosimilars in accordance with guidelines?
Roche’s counsel argued that Mylan and Biocon’s products were being misrepresented as biosimilar versions of Herceptin/Trastuzumab without following procedures in accordance with Guidelines on similar Biologics.
Biosimilars unlike generic small molecule drugs are produced at the cellular level and are no means identical to the innovator product, but are therapeutically equivalent. In October 2012, Govt of India released guidelines for approval of biosimilars or follow on biologics which provide for a detailed and comprehensive process for comparison of similar biologic with the reference biologic. Our Guest blogger Christopher Ohly had blogged about this over here.
Roche contended that after the issuance of the Guidelines all the applications d marketing authorization of biosimilars in India are required to be evaluated based on Guidelines and only products which have been approved under the guidelines should be allowed to be represented as biosimilar products.
Roche alleged that protocol and study design for CANMAb™ was filed and approved prior to the release of guidelines. Roche also argued that Biocon was already conducting the penultimate phase of Clinical trials for their product CANMAb™ before the guidelines became effective. Roche’s requested that Biocon and Mylan should be restrained from referring to their products as a “biosimilar product” until appropriate tests and studies as prescribed under the said Guidelines have been conducted. Considering the elaborate procedures mentioned in guidelines, Roche also claimed it was impossible to obtain a biosimilar approval within such a short period.
Trademark passing off?
The Counsel for Roche argued that Biocon and Mylan have misrepresented their products by referring to them as biosimilar Trastuzumab/Herceptin®. Such misrepresentations fall within the scope of passing off since the defendants seek to pass off their products as being similar in class and quality as Herceptin®. Roche contended that misrepresentations like these are likely to deceive the patients using Trastuzumab regarding the efficacy and safety of defendant’s products. They also alleged that the defendant’s Biocon and Mylan seek to take unfair advantage of goodwill and reputation enjoyed by innovator Roche’s product.
Delhi High Court Order (available over here)
On the first issue the learned judge opined that no specific interim injunction needs to be passed as the defendants would not be entitled to launch their product without requisite approvals. However it is imperative and necessary for defendants to disclose the nature of the approvals of biosimilar product to the Court on the next hearing.
On the second issue of passing off the Court found merit in Roche’s argument and granted interim injunction restraining defendants from relying on any data related to Roche’s Herceptin® and also preventing the defendants from claiming any similarity to Herceptin. Justice Manmohan Singh opined in the event that the interim order is not passed in this regard, the plaintiffs would suffer prejudice and irreparable injury.
My thoughts
Since biosimilars (unlike conventional small molecules) are never exact copies of innovator biologics regulatory approval standards remain an important area of debate. Read this article for more on regulatory frameworks for biosimilars.
With regard to the issue of passing off, courts have always applied a stricter standard especially in case of medicinal products to safeguard public since any confusion in this respect could have severe repercussions.
In fact in the international platform there is a fierce debate raging on whether biosimilars should be treated as unique products with uniquely distinguishable International Non-proprietary names(INN’s) leave alone trademarks. The bio-pharma industry is divided on this issue and their contention is that “if biosimilars are not same why should INN’s be same?”
The next hearing is scheduled for Feb 28, so watch this space for more.
I would like to thank Mr.Yagna Praveen very much for bringing this news to my attention
I shall be grateful if you could clarify 2 points: 1.Is Roches claim that since the phase3trials were in progress even before the new guidelines became effective so the trial output can not meet the requirements of the new guidelines is an inference that Roche conveniently decides to arrive at.
2.If the product by DCGI is evaluated on the base of new guidelines in place how can there be doubt?
there are several biosimilar drugs on market which have been approved under the previous framework. does this imply that they be subjected to similar fate as in the present case?
You say that “there are several bio-similar drugs on market which have been approved ” Can you list a few of them in your response? Are they all by Indian companies ? As I said in my Fierce Pharma comment, “”Mylan has exclusive marketing rights in the U.S…..if they can get approval in any of those countries” It is really a big IF since the API in the bio-similar of Roche’s HERCEPTIN (trastuzumab) does not have DMF number, and consequently, will be unacceptable to United States FDA. Meanwhile, the Korean Company, Celltrion Inc. has announced that the it has received approval for its bio-similar mAb Herzuma (trastuzumab) from the Ministry of Food and Drug Safety (MFDS) from the Korean Ministry. The world market for the cancer treatment with trastuzumab may thus be divided among several nations, each with its own version of “biosimilars”, completely bypassing the DMF requirement of the API, as required by the FDA. It will lead to regulatory mess and lowering of product standards and quality
It is sheer non-sense on the part of Roche to institute a vicious civil proceedings against DCGI and generic manufacturers.
When u have a product undergoing clinical testing under a old valid guidelines, any new guidelines implemented before approval of such product should not be a when the requirement of the old guidelines are fully complied.
Roche itself in its pleadings admitted that drug import licence was obtained by Biocon back in 2002 and the drug was in phase III when new guidelines were effective i.e. in 2012.
Hence how come Biocon/ Mylan would have complied new guidelines when the drug was in the final phase of testing or does Roche intends to say that Biocon/ Mylan should have done clinical trials afresh complying these new guidelines.
Is this not funny
Thanks for your insightful comments.
From the order it appears that Roche’s main contention is the use of the term “biosimilar to Herceptin®
Before the issuance of guidelines for biosimilars , these similar biologics were approved using an abbreviated version of the pathway applicable to small molecule generics on a case by case basis.
A lot of biosimilars in India were approved prior to the effective date of guidelines(reditux etc).
When these companies launched their similar versions ( in their official promotional brochures/press release) they steered clear of the biosimilar tag or referred to their products as being similar to the INN name not the innovators trademark.
This article provides interesting food for thought.
http://pharma.financialexpress.com/editorial/914-testing-the-barometer-for-biosimilars
My comment is in reference to what ZM stated,that “Roche to institute a vicious civil proceedings against DCGI and generic manufacturers.”
The fact that Roche’s Indian market for its Herceptin (original Trastuzumab) is just an insignificant or paltry 0.333% of its global volume ( $ 21 million in India vs. $ 6.4 billion global sales) together with the drastic reduction of the Indian price by 50 % should be convincing proof that the Swiss manufacturer is NOT hell bent on Indian business; but as originators and holders of several patents the Swiss drug maker wants to make sure that the patients are not given short shrift in a country where spurious and substandard drugs are aplenty. This has been the norm since the 60s when mom and pop operations like the family owned Ranbaxy Limited, by imitating Parke, Davis & Co’s CHLOROMYCETIN with its SYNTHOMYCETIN, capsuled out of substandard chloramphenicol made by the Italian outfit Lepitit, grew like “Jack and the Beanstalk”, thanks to the partiality and favoritism bestowed on it by the Indian Government. The statement, “as it was its(Roche’s) duty to ascertain if the drugs were indeed similar to its own innovation” is indeed NO exaggeration and the veracity of its allegation that the arrant paucity of documentation regarding any publicly available data in Clinical Trials Registry in India on the Phase I and Phase II clinical trials, presumably carried out by Biocon-Mylan does not have, a mandatory requirement, while developing the drug. Makes one wonder what kind of R&D efforts were done by these two companies.
In one my earlier comments elsewhere on the website I had stated: ‘India’s pharmaceutical and biological s market and the manner in which some Indian companies do their business need to be considered from the international regulatory points of view. Biocon CEO’s claim, “”We have completed the Phase III trials and are awaiting the result, We are sure the product will be launched this financial year” , while quite impressive, makes one wonder how a Company that came into business less than 25 years ago could have the capability to produce a chemical or molecule (biosimilar trastuzumab) of such structural complexity. These API s are produced in bulk by several companies in China and S. Korea etc. The singular fact the MYLAN-BIOCON business partnership allows BIOCON exclusive marketing rights ONLY IN INDIA, whereas the US based MYLAN has rights to almost the rest of world suggests that the API (trastuzumab), perhaps, is not manufactured by BIOCON but bought from an India based vendor such as Pune-based Manus Atteva Biopharma LLP; moreover, the API trastuzumab by Atteva Biopharma LLP is not listed in FDA’s DMF, thus making it unsuitable to the FDA regulated US market.’
It remains to be seen how far the small Biocon can go in this battle against the Swiss giant Roche in selling its duplicate drug which is just AS EXPENSIVE as as the authentic or original Herceptin.
Would like to just remind you that as of date Roche do not have any IP protecting trastuzumab in India.
Secondly multinational like Roche would first look into their own business interest rather than patients interest.
It is on the part of DCGI/ FDA to see and approve the drugs and not multinational like Roche to institute a legal proceedings and justify that said suits are filed to check that the generic version is not spurious and substandard.
May I attempt to put things in perspective for Joseph.
India is a large country with abt 10,000 pharma companies. While none of us are proud of Ranbaxy;s dubious achievements but wd it be fair to club the rest 9999 companies with Ranbaxy. If the same erroneous comparison were taken forward USA has companies both like Enron and Apple does one Enron make thug and thieves of entire corporate America obviously not it wd be a biased extrapolation & one that I do not wish to make. Extrapolating the manufacturing lapses of Ranbaxy to the entire Indian pharma industry and in this particular case to Biocons Canmab is as erroneous and maybe even biased.
In the last year 120 warning letters were issued by USFDA only six of them were to Indian companies so your imagination that the hapless Indian patient is subjected to spurious & substandard drugs is just that your imagination. However it shall also be pertinent to point out even among the rest Biocon has a remarkable record with the regulators and as such has till date not received any warning letter from regulators of any country.
Why is it so incredulous to you that Biocon has the ability to manufacture Herceptin it has been manufacturing a mab called Biomab for years with no complaint & thousands of patients have been treated with it. I also assume that Biocon shall manufacture the api for it in house but that can always be clarified from the company before arriving at need less conclusions.
Mr. Sunil Mehrotra:
When you are trying to quibble with Enron and Apple while discussing pharmaceuticals you are talking apples and oranges. Please learn to stay on the same topic. All I want you to do is read today’s NYT article, “Medicines Made in India Set off Safety Worries”
http://www.nytimes.com/2014/02/15/world/asia/medicines-made-in-india-set-off-safety-worries.html?nl=todaysheadlines&emc=edit_th_20140215&_r=0
I will reproduce below some excerpts for other’s benefit:
“But Heather Bresch, chief executive of Mylan, which has plants in the United States and India, said regulatory scrutiny outside of the United States was long overdue. “If there were no cops around, would everyone drive the speed limit?” Ms. Bresch asked. “You get careless, start taking risks. Our government has enabled this.”
“…..from India in 2011 because it had received shipments of drugs that turned out to be counterfeit and inactive, with Cipla labels that Mr. Mwesige believed were forged.
He became suspicious when doctors began seeing chemotherapy patients whose cancer showed none of the expected responses to the drugs — and who also had none of the usual side effects. The drugs that had been prescribed were among the mainstays of cancer treatment — methotrexate, docetaxel and vincristine. Laboratory tests confirmed that the drugs were bogus, and Mr. Mwesige estimated that in 2011 ABOUT 20 PERCENT OF THE DRUGS THAT THE INSTITUTE BOUGHT WERE COUNTERFEIT”.
As an American I want FDA to make absolutely sure that the imported drugs from wherever they come pass the rigorous stringent protocols laid down by the FDA, and NOT some flyblown dirty product as mentioned in the NYT article:
“when a top executive at Ranbaxy — which has repeatedly been caught lying to the F.D.A. AND FOUND TO HAVE CONDITIONS SUCH AS FLIES “too numerous to count” in critical plant areas — pleaded with Dr. Hamburg at a private meeting with other drug executives to allow his products into the United States so that the company could more easily pay for fixes. She politely declined.”
Joseph you have remarkable sight for catching the tiniest flies in the Indian pharma industry but even then your are rather selective with your vision just as you have misread my name for Sunil while I am Sunit OK but let that be let us stick to the point .What has flies or any other animal at Ranbaxys plant have to do with Biocon & its Canmab the topic under discussion.Can u sight one manufacturing lapse or anything wrong with Biocons products.Selective vision is usually a result of biased view
As u mentioned above “Please learn to stay on the same topic” please u too try to be on the same topic.
U were arguing on the vicious litigation started by Roche, form where does america comes into picture.
Second u say the drug made by Mylan/ Biocon in India might be bogus and on the contrary u site some lines spoken by the CEO of the same organization on which u are pointing your finger that it might be spurious.
Third I advice u do a homework and see the FDA violators list/ notices and compare viz-a-viz which country has got more no. of violators including your own american companies.
Don’t forget to see billions paid by american companies/ sister concerns to settle the class action law suits for drugs side effects which were held back by these companies when the drug were in clinical trials.
In US it is very simple violate a rule earn billions and then settle if any class action law suit is filed and again start the same cycle.
This is in continuation to my earlier post. Regarding Clinical trials of Biocons canmab.
We must realize that a global phase 3 trial of canmab of 440 patients is underway for European markets and as such at this stage Biocon has to be reticent with data dissemination .A global phase 1 trial was done and on the base of which the EU regulators gave permission for phase 3 trials
I must also congratulate Roche for the amazing concern and care that it is now showing for the Indian patients and which rightly Joseph so admires.But what does seem ironical to me is that Roche can only get into the caring act one there is competition for their product shd they not have show the same concern for the hapless Indian patient with their pricing also .Their initial price tag of 22ls for the course was affordable by less than 5% of the patients.So while Joseph seems an ardent fan of Roches altruistic nature it wd do well to see the picture in its entirety
LEARN TO CONFINE YOUR COMMENTS TO THE TOPIC UNDER DISCUSSION. Don’t be asinine and uncivil in making uncalled for personal remarks. I can’t emphasize this point anymore. If I had you in my lecture room, I would certainly have shown you the door.
Joseph if there is anybody who is being uncivil & rash it is you.By the way regarding being in your lecture class & u showing the door I never intend to subject myself to ranting of a bigot so sorry you shall never have the pleasure of showing me the door
ZM@Feb 13, 4:43 PM: FYI: Don’t forget IP encompasses Trademark as well AND Roche has their trademark Herceptin registered in the Indian Trademark registry.
So what the big deal in having a TM.
In India even any pharma company may have its own TM for its brand.
If u mean to say that by the sale of Mylan/ Biocon product Roche TM is infringed then U need a medical attention.
@ TM Crusader:
Since you bothered to highlight ‘Herceptin’, please also note remember another thing.
HERCEPTIN in NOT SOLD in India since around Sep 2012.
Roche only sells Herclon and its partner markets Biceltis in India.
I think today’s Economic Times’ article by Soma Das gives more information and without getting confused:
http://economictimes.indiatimes.com/news/news-by-industry/healthcare/biotech/pharmaceuticals/biocon-mylan-challenge-ban-on-using-roche-data/articleshow/30536488.cms
This litigation history is surprising.
First an injunction,
Second a variation that makes it worse for defendants.
Next in line will be contempt actions against defendants – particularly since the regulatory bodies do not give separate approvals for pack inserts and labels. Wonder what strategy is being followed by Defendants – whcih results in their clients being laid open to the risk of contempt.
Mylan did a good job in getting the three divisionals refused by bringing errors in prosecution to the Controller’s table – but seem to have lost the plot after that.
Dear Sayantan, you seem to have an interesting piece of information – the issue of contempt has not been discussed yet at all in any news article.
Dear Sayantan cd u pl explain the contempt angle more for people like me who r not legal experts.I mean how does it result in contempt and all
Dear XYZ – is there already a contempt petition filed? I was assuming that this would take place since the order and its variation would lead to not other option but total injunction. It is not possible to sell without using the pack insert material and labels – and removing them and replacing them will delay launch and sales at least by few months – till the Drug Controller approves the changed label and insert.
Sayantan:
I do not know whether any contempt petition has been filed.
I was intrigued by the point itself since contempt has not been a focus yet in the earlier pharmaceutical litigations.