The U.S. Food and Drug Administration (FDA) does not frequently issue Warning Letters to corporate sponsors of FDA-regulated clinical trials, so the June 16, 2015, Warning Letter sent to AB Science, a pharmaceutical company with offices in France and New Jersey, regarding the company’s conduct as a sponsor of several clinical trials is noteworthy. Click here to see the Warning Letter.

The Warning Letter followed a September 2014, FDA inspection of the company that focused on three completed trials. The inspection resulted in a Form FDA 483 to which the company promptly responded. Nevertheless, the FDA concluded that the company did not comply with the statutory requirements governing the conduct of clinical trials and that further action was warranted.

The objectionable conditions observed during the inspection fell under the general description of “[f]ailure to ensure proper monitoring of the investigations and failure to ensure that the investigations are conducted in accordance with the general investigational plan and protocols contained in the IND.” Some of the cited examples of monitoring deficiencies include:

• Failure to identify and correct clinical investigators’ failure to report serious adverse events (SAEs) within protocol-specified timeframes;

• Failure to identify and correct a clinical investigator’s failure to perform protocol-required laboratory tests; and

• Failure to follow the monitoring guidelines that the company had developed for itself.

According to the Warning Letter, the company acknowledged most if not all of the observations that had been made in the FDA Form 483, and proposed corrective action plans in its response to the FDA. The FDA deemed these responses inadequate, however, because the corrective actions made no provisions for assessing the effectiveness of and ensuring sustained compliance with the corrections and monitoring requirements.  

It is not clear what effect, if any, the Warning Letter will have on the company’s use of the results from the clinical trials reviewed during the inspection. When the FDA makes an adverse finding about the way that a clinical trial is conducted by an investigator at a single site, the trial sponsor is often concerned about whether it will be able to use the results from that site to support its application for approval. In this case, three identified protocols and their performance at several sites were the focus of the FDA’s attention. This means that it is possible that one or more previously unanticipated additional clinical trials would have to be performed — an expensive outcome that would also introduce unanticipated delay into the regulatory pathway.  

The number of Bioresearch Monitoring Program (BIMO) inspections by the FDA of sponsors, clinical research organizations (CROs), and monitors has continued to increase (click here for the FDA’s Annual BIMO Inspection Metrics) and will likely remain on an upward trajectory as the FDA continues to be concerned about data integrity, not only for classic clinical trials, but also for an increasing number of expedited trials. As a result, it behooves every sponsor of a clinical trial to actively and carefully audit its clinical trial sites and CROs, implement well-thought-out operating procedures to make these audits routine, and promptly institute corrective and preventive actions if a problem is identified.