UPDATED JANUARY 22, 2018: Implementation of the Common Rule is Delayed for Six Months

Updated January 22, 2018: HHS and fifteen other federal departments and agencies have delayed implementation of the revised Common Rule for six months. Originally set to take effect on January 19, 2018, the effective date and compliance deadline have been deferred until July 19, 2018.

The delay will provide institutions with at least six months to prepare for eventual implementation and compliance with the 2018 requirements—which might come as welcome news to those who were unprepared to meet the original deadline.

Currently, HHS and the fifteen other agencies are working toward a proposal to even further delay implementation of the revised Common Rule and will be seeking feedback and public comment via the rulemaking process.

Contracts Associates will continue to monitor the status of the revised Common Rule very carefully and will update this blog with any important new insights. If you have any questions about the changes, we encourage you to contact our office at 781-598-8000 or email our CEO, Colleen Sproul, at cms@contractsassociates.com so that we can provide you with the most current information regarding changes and compliance.

[Originally Published on January 4, 2018] The U.S. Department of Health and Human Services (HHS) has proposed a one-year delay in implementation of the revisions to the Common Rule. The updated rule was set to take effect on January 19, 2018 with compliance expected on the same date. But, as of this writing, the effective date and the applicability of the revised Common Rule is uncertain.

During the waning days of the Obama administration, the final text of the updated Common Rule was released by HHS. Upon entering office, the Trump administration immediately froze all new or pending regulations left over from the previous administration to allow them to be reviewed by the new President’s appointees. Implementation of the Common Rule changes was accordingly placed on hold.

What are the Revisions to the Common Rule?

The Common Rule, or the Federal Policy for the Protection of Human Subjects, is a set of regulations governing federally-funded research involving human participants, their data and biospecimens. First promulgated in 1991 and not updated since 2005, HHS proposed updating the Common Rule to reflect the rapidly-changing research landscape, especially in terms of human subject data and advancing digital technologies.

The revision process began in 2011 with the goal of enhancing protections of participants (relative to informed consent and data) and reducing administrative burdens. The Common Rule underwent significant revision with informed consent provisions requiring “a concise and focused presentation of the key information” in contracts. The updated rule also requires informed consent provisions to explain, among other things, the purposes of the research, risks and benefits of participation, and any appropriate alternatives so that a “reasonable person” can more easily decide whether or not to participate in the research.

In addition, the new rule requires that a version of the consent form that was used for enrollment purposes for each clinical trial be posted to a federal website. It also allows for gaining broad consent for secondary research use of identifiable data and biospecimens of participants.

So What Happens Next?

The Office of Management and Budget (OMB) is currently reviewing the proposal by HHS to delay implementation and compliance by one year. Along with the one-year delay, HHS is considering allowing three burden-reducing provisions to be implemented during the delay to ease administration. Precisely which three provisions remains unclear as they have not been specifically enumerated and the proposal currently exists as a title with no accompanying text.

It is unclear whether both the effective and compliance date would be pushed back, or only the compliance date, or whether there will be no changes at all and the new rule will be fully implemented on January 19, 2018. The possibility of delay in compliance might be seen as good news to some institutions who are unprepared to comply with the new rule and need time to make necessary changes. But as of now, the future of the revised Common Rule is unknown.

Contracts Associates will continue to monitor the status of the revised Common Rule very carefully and will update this blog with any important new insights. If you have any questions about the changes, we encourage you to contact our office at 781-598-8000 or email our CEO, Colleen Sproul, at cms@contractsassociates.com so that we can provide you with the most current information regarding changes and compliance.


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.




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.