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.