FDA suddenly adds four-letter meaningless suffixes to new biologics’ nonproprietary names

Back in 2015, the FDA implemented a policy which required the addition of suffixes to biosimilars. On June 1 2016, the FDA suggested that sponsors could provide the FDA with up to 10 preferred proposed suffixes for its biosimilars and that the FDA would then choose which preferred suffix met its guidelines. Sounds like a good policy, right? Companies get to suggest their favorite “baby” names and the FDA picks one it likes. Well, the FDA withdrew that plan on June 20, 2016.

However the suffixes for biosimilars have been chosen since June 2016, it was clear that the FDA only applied this requirement for suffixes (which makes sense for biosimilars, so that consumers can tell them apart and doctors can report adverse events) to biosimilars. For example, Sandoz’s Zarxio’s nonproprietary name is “filgrastim-sndz”. Totally logical so far.

On November 16, 2017, the FDA approved Genetech’s hemophilia A biologic Hemlibra (good news for patients!) and assigned it a random suffix of “kxwh” (emicizumab-kxwh).    In the absence of published public comments (which would be published in the Federal Register) and/or the announcement of a policy decision, one has to assume that assigning these suffixes to all new biologics will be the law of the land.

We know the time an effort industry sponsors put into branding their biologics and we imagine that random characters appended to the end of such a carefully-considered name is not the most welcome of surprises. The FDA typically provides sponsors with substantial notice prior to making substantive policy changes (it is a government agency after all!); however, this sort of abrupt implementation of policy may be our new normal.

 

 

 

Sage Therapeutics, Esperion Therapeutics, and Eisai won MAGI Awards for Excellence in Site Payments

The results are in, and our clinical sites have agreed on the list of Industry “power payers” for 2017. From Norm Goldfarb at MAGI:

At MAGI’s recent Clinical Research Conference in San Francisco, Sage Therapeutics, Esperion Therapeutics, and Eisai won MAGI Awards for Excellence in Site Payments, powered by Forte.

MAGI also recognized AbbVie, AstraZeneca, Gilead Sciences, Merck Sharp & Dohme, Novartis and Plexxikon for timely payments.

Clinical research sites want to conduct studies for these companies because they know they will be paid in a timely manner. To learn more, click here.

As of the date of the withdrawal of the UK from the EU, active substances manufactured in the UK will be considered “imported” active substances and other headaches

The European Medicines Agency issued a Q&A to address some Brexit issues that will directly impact US sponsors/manufacturers.

The EMA offers no specific guidance on the transfer and/or handling of clinical trials that are ongoing on the date that the UK leaves the EU, but the guidance does give us an idea of how complicated this is all going to be. Nota bene the issue caused by having one’s Qualified Person in the UK (which is 98% of US manufacturers, followed only by QPs in Ireland). We will continue to follow the EU’s guidance and will craft our EU contracts in such as way as to make the transfer as painless as possible.

Obama’s Department of Justice recovers staggering amount of money from Health Care industry

The 2016 numbers are in, and the health care industry (which includes life sciences companies) had to pay out a total of $2.5 billion (more than half of the total $4.7 billion recovered in 2016) in settlements and judgements from civil cases which involved fraud and false claims against the government. Wyeth and Pfizer, Inc. paid $784.6 million of the $2.5 billion; the payments were made to the federal government and to state Medicaid programs.

What I found most remarkable about the DOJ report was that 60% of all funds recovered by the DOJ in last 30 years under the False Claims Act ($55.17 billion), was recovered between fiscal years 2009 and 2016. This begs the question: Why did the Department of Justice under the Obama administration recover $31.3 billion of the total $55.17 billion recovered by the DOJ between 1986 and 2016? Is it the only administration to actively enforce the law and investigate healthcare fraud, housing and mortgage fraud, and fraudulent activities related to federal contracts and programs? Was there just an unprecedented amount of fraud and abuse during the Obama administration? Was President Obama’s Financial Fraud Enforcement Task Force (established in 2009)just incredibly effective?

The second question is: will the healthcare industry and its pharmaceutical and device companies will continue to pay the proverbial lion’s share of monies recovered by the new adminstration?

In case anyone wondered where the recovered funds are diverted to, according to the DOJ, “…The beneficiaries of these efforts include veterans, the elderly, and low-income families who are insured by federal health care programs; families and students who are able to afford homes and go to college thanks to federally insured loans; and all of us who are protected by the government’s investment in national security and defense. In short, Americans across the country are healthier, enjoy a better quality of life, and are safer because of our continuing success in protecting taxpayer funds from misuse.”.

OIG Issues 2016 Final Rule Expanding Anti-Kickback Statute Safe Harbors; Excludes Pharmaceutical Manufacturers From Most Of Them

Our read of 81 Fed. Reg. 88368 (December 7, 2016), issued by U.S. Department of Health and Human Services’ Office of Inspector General (OIG), does not appear to affect pharmaceutical manufacturers in any substantive way; our obligations are unchanged and no additional “safe harbors” are afforded.

The OIG did make a technical correction to the safe harbor for referral services, which we believe requires an update to the “anti-kickback and fair market value” clauses in our clients’ templates. We’ll be using the italicized text below, from this point on:

Vendor represents and warrants that neither Vendor nor any individual or entity acting on Vendor’s behalf, nor any payee under this Agreement, will, directly or indirectly, offer, pay or accept, or authorize the offering, payment, or acceptance of, any money or anything of value to or from any third party, with the knowledge or intent that the payment, promise or gift, in whole or in part, will be made in order to improperly influence an act or decision that will assist Vendor, the Sponsor or the third party in securing an improper advantage or in improperly obtaining or retaining business or in improperly directing business to any person or entity.

Further, the parties acknowledge and agree that the amounts payable by Sponsor or Sponsor’s designee under this Agreement represent the fair market value of the covered costs associated with the Services and no part of any consideration paid hereunder is a prohibited payment for the recommending or arranging for the referral of business otherwise generated by either party for the other party or the ordering of items or services; nor are the payments intended to induce illegal referrals of business.

Phase III Clinical Trial Agreements: Ex-US Clinical Sites and FDA Inspections

With increasing frequency, an ex-US clinical site, in Poland or Hungary, for example, will delete all trial agreement references to compliance with FDA inspections (see sample text below), on the grounds that it is not required to comply with FDA inspections and/or is not subject to inspection by the FDA at all. In such cases, the site will seek to replace references to “FDA” with local, country-specific regulatory authorities.  However, foreign sites participating in clinical studies conducted under a FDA IND are subject to FDA inspections, and best practice dictates that the trial agreement should obtain the site’s agreement to notify sponsor’s in the event such an inspection takes place.

Sample ex-US trial agreement clause:

The Institution and Investigator agree that personnel from regulatory authorities including but not limited to the United States Food and Drug Administration Food and Drug Administration (“FDA”) (“FDA”) may visit the Institution to inspect Study records (including portions of other pertinent records for all Research Subjects in the Study) and those procedures, facilities or Study records of any employee, contractor or agent that the Investigator or the Institution uses in conducting the Study. Investigator will notify Sponsor, promptly of any regulatory inquiries, investigations, site visits (whether announced or unannounced), correspondence or communication that relates to the Study and will consult and cooperate with Sponsor in responding to any such event, including providing documents, information and access as properly requested.Institution and Investigator will make all reasonable efforts to coordinate any scheduling of agency inspections to permit Sponsor and its designees to attend such inspections. Institution and Investigator will make reasonable efforts to segregate, and not disclose, any Records or other materials, correspondence and documents that are not required to be disclosed during such an inspection, including financial data and pricing information.  If the EC or any Regulatory Agency issues any notice, warning, demand, report or request related to the Study, Institution or Investigator, as applicable, shall send a copy of such document promptly to Sponsor, along with any proposed response to such document, before the same is submitted to the EC or any Regulatory Agency.”

By was of example, one can click here to view a 2015 Warning Letter, issued to a principle investigator, following a site inspection in France.

Of course, a sponsor may agree to a site request to omit reference to compliance with notification of an FDA inspection (remember, sponsors “audit” but the FDA “inspects”; the FDA does not “audit”, even though many in the industry use the terms interchangeably) in an effort to finalize the agreement in a timely manner. Our role at CA is to advise that the FDA can inspect any foreign site on a clinical study and we strongly urge sponsors to obtain a site’s agreement to be given immediate notice of any regulatory inspection during the study.

 

 

 

 

Journal of Commercial Biotechnology

Contracts Associates is proud to announce that Joanna Brougher has been named Editor-in-Chief of The Journal of Commercial Biotechnology .  We at CA will be submitting several articles over the next year or so, in an effort to continue to highlight changes and industry trends that will affect clinical trial contracting best practices.

Please feel free to submit ideas or queries directly to Joanna by emailing her directly at jbrougher@contractsassociates.com.

And I cannot end this post without wishing Joanna well at the USTA 2015 National Championship Adult 18 & Over Championships in Palm Springs on October 9th!

 

 

Random notes from ACI’s Women Leaders in Life Sciences Law Annual Meeting

I had the pleasure of attending the 2nd Annual ACI’s Women Leaders in Life Sciences Law meeting in Boston last week. While I originally registered to ensure that stay on top of the latest developments in the law that affect our Life Science community, I ended up getting a lot more out of the, for lack of a better word, “personal” disclosures, shared by the women leaders who spoke.

There were a lot of interesting exchanges and factoids, among them:

  1. PhRMA has only 30 member companies.
  2. Little-known effect of the ACA: Insurance companies have created “access tiers” for certain health plans so that, while the Affordable Care Act prevents them from denying one insurance for a pre-existing condition, only certain “tiers” will cover high-cost disease states. Consequently, the plan sold to a person who would have otherwise been denied, could cost more. I thought that the whole point of the “non-discrimination” clause was to to ensure :non-discrimination”?
  3. 22 US States have enacted their own, “Right to Try” (Abigail Alliance) laws. These laws allow patients to try unapproved drugs, after a successful Phase 1. There may be conflict with the FDA regs in some states but these conflicts are addressed on a case-by-case basis.
  4. Five countries have enacted or updated new Global Transparency Laws in the  past year. France, Denmark, Slovenia, Romania and Estonia have updated guidelines for paying any health care provider in those countries.
  5. “No. But being the only woman in the room makes people remember you, for a long time”  – Response to the following question, posed to a US District Court Judge, “Have there been any circumstances where being the only woman in the room, in a high-stakes meeting, actually contributed to a resolution or in some way helped further your cause?

There was just not enough time to get into detail regarding those states that have passed “tissue property laws”, which restrict use of research tissue and bestow ownership of the tissues upon, in most cases, the patient, but those have to considered. We at CA will be doing a deep-dive into these new states laws and will provide an analysis here.

Thanks to the speakers who took the time to come to Boston for such a great conference; I am looking forward to next year’s meeting in Paris.