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new study finds that citizens’ petitions can “play a crucial role in delaying” generic drugs from becoming available — and cites Mylan Pharmaceuticals as a prominent example of companies whose reliance on such tactics is questionable.

In particular, the study points to a petition that Mylan filed in early 2015 in an attempt to persuade the US Food and Drug Administration not to approve a rival to its EpiPen device for life-threatening allergic reactions, which was being developed by Teva Pharmaceuticals.

The study arrives amid intense controversy over EpiPen pricing and the extent to which Mylan has exploited its near-monopoly on the market. Since buying EpiPen a decade ago, Mylan has raised the price 548 percent – to $600 – but has faced little competition.

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A rival device from Sanofi was recalled last year due to dosage problems and the FDA rejected Teva’s auto-injector earlier this year. The only competing device, called Adrenaclick, has sold poorly, largely because Mylan has dominated the market and many people are unfamiliar with the way Adrenaclick works. In fact, Mylan has about an 89 percent market share currently, according to Truven Health Data.

What Mylan did is “concerning because they used a petition to delay generic entry,” said Michael Carrier, a Rutgers University School of Law professor and coauthor of the study, which is being published in the American University Law Review.

The analysis found, in fact, that brand-name drug makers filed 92 percent of citizen petitions between 2011 and 2015, although the US Food and Drug Administration denied more than 9 out of every 10 petitions. Last week, the FDA wrote Congress that most petitions do not raise valid scientific concerns and appear to have been filed to delay approval of competing medicines.

The study authors explained that Mylan was aware that Teva would look to sell a generic version of EpiPen by July 2015. That’s because, in 2012, Teva settled a patent infringement lawsuit that was filed by a Pfizer unit that made EpiPen for Mylan. As part of the deal, Teva was allowed to sell a generic by mid-2015, or possibly earlier.

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So Mylan responded by filing a citizen’s petition with the FDA in January 2015, and urged the agency not to approve the Teva product unless it was the same as EpiPen. A key part of the Mylan argument was that anything other than an identical product may make it difficult for patients in an emergency situation to use a generic safely and effectively in keeping with instructions for EpiPen.

The FDA had 150 days to respond to Mylan’s petition, and that deadline coincided with the time when the patent settlement allowed Teva to begin selling a generic. But in May 2015, Mylan supplemented its petition with a report from a consulting firm that gave the generic device to patients and concluded they were not using the Teva product correctly and, therefore, it would not be effective.

However, the analysis “had a lot of problems,” said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank. The analysis lacked a control group; did not study the actual generic but a prototype instead; used a small number of participants; failed to provide them with proper instructions for use; and told participants to watch a video rather than actually use the Teva device.

A Mylan spokeswoman wrote us that the study “applied the fundamentals of human factor engineering and analysis to examine the proposed Teva product against FDA’s standards for approving a generic product like this.  The question FDA asks is whether, in an emergency, a patient or caregiver who is trained on the EpiPen could, without training on the proposed generic, successfully use the generic product in accordance with the EpiPen directions for use. Given the purpose of the study, we believe its design and implementation offered a valid examination of the human factor issues presented by Teva’s distinct design and operating steps.”

We asked Interface Analysis, the consulting firm, for comment and will update you accordingly.

The petition also included a statement from Dr. Eli Meltzer, an allergist in San Diego, who declared that “I do not believe that a user trained on the EpiPen … platform will be able to reliably use a different operational platform in an emergency situation as safely and effectively.” As noted by NBC News, which first reported about the citizen petition and the study, Meltzer was paid roughly $95,000 in fees in 2014 and 2015 by Mylan, according to the OpenPayments federal database.

By filing the supplement, Mylan presumably hoped to further extend the time the FDA would need to review its entire petition. But the FDA denied the petition in June 2015, anyway. Ultimately, the FDA rejected the Teva product last February due to unspecified deficiencies. Carrier speculated that Teva may have been able to fix those problems if the patent lawsuit had not delayed its ability to enter the market.

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  • In my humble opinion any firm caught interfering with a life saving medical device for the purpose of retaining a monopoly on it’s product should immediately loose it’s patent protection.

    • You got it backwards. Patents are obtained in order to create a LEGAL monopoly. That’s fact #1. Fact #2 is that if another company or entity wishes to challenge the validity of a patent it may do so at ANY time during the patent life. Mylan spent millions of dollars to license the patent from Merck. They would not have done so without the expectation of making a profit, your remonstrations notwithstanding.

    • I agree wholeheartedly as would anyone with a conscience. Our society is corrupt, placing financial gain before life itself. Drug patents shouldn’t last 20 years begin with. Once a product is on market the patent duration should be cut down to 5 years. Anyone that cannot compete with a 5 year lead doesn’t deserve to be in business. Human life is more important than profits.

  • This is another story about how the FDA has become captive to special interest groups. Your editorializing would be far more constructive if it focused on the FDA rather than any single company. The FDA should have a specific mandate to actively disempower drug monopolies and oligopolies, to the extent this can be done without commonly accepted interpretations of infringement. At the moment the FDA is as captive to drug companies as the treasury is to large banks on Wall Street.

    • Sorry, Stefan but the FDA is not the Federal Trade Commission. They don’t have the authority to break up monopolies. If you look at the Orange Book about 95% of the generic drugs are multisource products. Monopolies are created whenever a generic competitor can’t get their product approved, but much more commonly these days a monopoly is created for a drug because all the other companies withdrew from the market for economic reasons. The FDA cannot force a drug maker to stay on the market and incur economic loss. In the case of the Epipen I believe that if the potential revenue was significant Teva would have corrected the deficiencies in their ANDA long ago. More likely I believe that the 89% market share that Mylan has in itself creates a huge barrier to entry given their long term exclusive contracts they have built up over the years.

    • Hi Stefan,
      Thanks for the note, although I did not write an editorial. The reporting focused on a specific example in which one company attempted to exploit the system for citizen’s petitions, specifically. As for the FDA, its role is not to create or dismember monopolies. Whether its role should include such authority is another matter, but that was not the point of this post.
      Regards
      ed

    • Ed, Farmvet, thank you for the responses and valid clarifications. My frustration with many of the articles on this topic is that I feel it is not constructive to demonize a company for doing what it’s actually supposed to do. I think a more constructive focus would be to address aspects of the protection and registration process, which seem to reveal elements of institutionalized corruption.

    • Drug monopolies exists because of patents, it’s not the FDA’s fault. Regardless, the solution is to cut patents down to 5 years after the product is on market. That gives drug companies a chance to make it through the approval process, while denying them the ability to hold an indefinate monopoly.

      Please sign my petition: https://petitions.whitehouse.gov//petition/stop-epipen-and-aids-drug-price-gouging-cutting-down-drug-patent-duration-5-years-after-market-availability

    • Hi Stefan,
      There was no attempt to demonize Mylan. And what it did was perfectly legal, but as the FDA and the referenced study pointed out, these petitions can be misused or manipulated, which does not serve the greater good. That is why I chose to write about this particular instance.
      Regards
      ed

  • This is an excellent summary of how a manufacturer could theoretically use citizen’s petitions and flawed clinical studies as an underhanded generic defense strategy.

    However, let’s not forget the tangible, documented reason Teva’s product wasn’t on the market: Unspecified deficiencies!
    To me this article is more of an interesting summary of how Mylan would’ve kept Teva from entering the market, if not for Teva’s own ineptitude (i.e. Zecuity).

  • Dear Stat team:

    While I commend on your generally very high reporting standards, I would have also appreciated if you would have mentioned how many citizen petitions Teva filed for protecting its Copaxone franchise.

    The important part of FDA rejecting Mylan’s petition is hidden in a middle para and not discussed in detail. So, at the end, if FDA made a decision and did not grant approval to Teva, then how does Mylan’s filing the original petition make any difference?

    Finally, let us face the facts – both Copaxone and Epipen are big products for the respective companies and each of them is using strategies that they think will protect the product’ sales.

    • Dear Z11,

      Thanks for your note. You raise a fair point – I could have mentioned that Teva has also attempted to exploit the citizen’s petition process. I didn’t so in this instance, however, because the focus of attention recently has been on Epipen, which made it a legitimate choice.

      And yes, as noted, the FDA ultimately rejected the petition. The point, however, was to illustrate how companies – in this case, Mylan – attempt to use the process to delay competition, and I mentioned the issue more broadly in the context of the results of the new study being published.

      I agree that companies should be permitted to use these tactics if they are legal. On the other hand, the FDA may have a point by complaining that many petitions are nothing more than a ruse to thwart competition and do not raise any legitimate public health concerns.

      Perhaps it is time to revisit the petitions and find a way to minimize the detrimental effect they may have genuine competition and, more important, the public health.

      Regards
      ed

    • Dear Ed:

      First, a thank you note for acknowledging the comment and then for acknowledging that Teva too had (in my view- much more than fair) its share of using this procedure.

      I acknowledge your point that Epipen has been the focus in last few days, but I have generally noted in other articles – for instance on FDA inspections – you generally include relevant/ recent examples of other companies.

      It could be argued that the (mis)use of the process is an art that Teva taught Mylan!

      If the FDA believe that the process is a ruse to delay approvals – well, nobody stops them from making this simpler – ultimately it is FDA’s discretion on rule making and they don’t the approvals from Senate to change process’ rules.

      And yes, I would still like to see if the Teva’ petitions are mentioned at least in passing as an after-edit – your site is read by a very large number of folks and they should know that who has used the process many more times. Presently, in my subjective view, it comes across as very harsh to only one side.

      Have a nice weekend.

  • You don’t need a doctorate in engineering to figure out how to use these devices yet there have been two rejections recently for “human factors” issues. Maybe FDA is requiring studies in people with limb prostheses, like the villain in “The Fugitive” just to covert their tracks.

  • Well, if I was a shareholder in Mylan, I would certainly hope they explore any and all avenues to protect their products’ market share. Don’t forget, that is a legally enforcable fiduciary duty.

    • Hi SM,

      I agree that companies have fiduciary responsibilities to shareholders, as I noted the other day (please see this: https://www.statnews.com/2016/08/29/epipen-open-letter-bresch/ )

      Although it might be worth considering the extent to which certain practices reach a tipping point in which society does not benefit. Consider the FDA concerns about citizen’s petitions and the delay of generics into the marketplace.

      This can be an interesting debate, and so for the sake of conversation, I’ll ask you this – should all avenues be pursued to maximize shareholder value if, in the process, one or more are detrimental to society?

      Regards
      ed

    • Ed-
      That is not a question that can be answered and there will be numerous opinions. However, I don’t see how paying $600 for a potentially life saving medication for your child is detrimental to society. Many of the people that complain here will be paying $1200/year for cable TV, $700 for their phones, $2000/year for phone service, and thousands for brand name shirts. I would ask this: what is the reasonable value for possibly saving your kid’s life? What should be a priority? I guess everyone has a different opinion about that as well.

    • I agree with Ed but for a different reason. I can state from experience that these CP’s usually require hundreds of thousands of dollars for outside legal counsel to research and draft the petitions with only a 10% chance of success. So I think there is also a responsibility to spend the shareholder’s money wisely and on projects that have a decent chance of success.

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