Case Study 3
Intensive BIMO Preparation is Key to Successful Inspection Results for Sponsors and Sites
A medical device manufacturer conducted a successful randomized IDE clinical trial, but at the time of study closure they decided not to file the Premarket Approval (PMA) application for business reasons. However, five years later, the business climate had improved and the company proceeded with its PMA application. The sponsor knew this unique situation would present significant challenges readying the long-closed study sites for the expected FDA BIMO inspections.
The Client’s Challenge
Many of the 30+ clinical study sites had study team turnover, archived study documents, or in some cases, actually ceased to exist. Additionally, RCRI had also archived the sponsor documents. The sponsor needed to ensure all study documents at all locations were accessible to FDA and in excellent order and that study sites were well-prepared to participate in successful BIMO inspections.
The RCRI Integrated Approach
Senior clinical staff at RCRI worked with the sponsor to develop a multi-tiered plan to prepare both sites and RCRI for the BIMO inspections. First, RCRI contacted all the sites, updated their contact information, documented the location of the study files and the process required to retrieve them from archives. A list of all sites and the status of their documents was provided to FDA as part of the PMA application to help FDA with its BIMO plans. Next, RCRI retrieved its archived study documents, which included most sponsor-required files and the paper case report forms and subject questionnaires, and meticulously cataloged and filed them. RCRI developed detailed electronic tracking documents to record all items and to allow for rapid retrieval during the inspection. At the time of the PMA submission, RCRI spoke with all of the sites to notify them of the submission and pending BIMO inspections. Each site was offered customized, proactive training via webinar to ensure that current site personnel were refreshed on the specifics of the study and the site’s participation in it. Training also included proper inspection conduct, how to interact collaboratively and effectively with FDA, and to ensure personnel were comfortable with the inspection process and could answer FDA’s questions honestly and confidently. RCRI trained the principal investigator specifically on what to expect during the inspection and refreshed his memory about the study and his site’s results, adverse events and protocol deviations. RCRI also offered to come to the site in advance of an announced inspection to facilitate document organization and to be present during the inspection as support to the PI and site staff.
As expected, the FDA conducted intensive BIMO inspections at RCRI and two study sites. All inspections went very smoothly with no issuance of a Form 483 for any entity, and the inspectors were highly complementary to all involved. FDA noted the level of organization of the documents, quick responses to their questions and document requests, and the professionalism and collaborativeness of the inspections. One of the two sites requested RCRI’s presence before and during the inspection and the FDA inspector expressed her sincere appreciation the support RCRI provided. She acknowledged the challenges for a site to be inspected by FDA under more typical circumstances, such as during a study or immediately after closure, but also commented on the unique burden placed upon the site during the inspection of a long-closed study. She stated that FDA recognized that sponsor/CRO support is very helpful to both the site and FDA in reducing that burden. Well-planned and well-executed preparation for any BIMO inspection is key to a successful outcome for sponsors and sites, and the on-site support of the sponsor or CRO can ensure a successful result especially under unique circumstances, such as this long-closed trial.