Phase 1 clinical trial unit

At some point or another, every Phase 1 clinical trial unit has or will receive a 483 from the FDA. Before we delve into what this means for a site, we’ll provide a bit of background. When are 483s issued? From the FDA website:

“An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.”  

The purpose of the 483 is to notify the Phase 1 site and its management of “objectionable” conditions. Following this, the company is expected to submit in writing a plan for correcting the issue and implement that plan in an expedited fashion.

When a Phase 1 clinical trial unit that you are using or have used in the past receives a 483, should you still consider using that site in the future? Ultimately, it depends on the severity of the issue; sometimes, a 483 can be issued for a reason that is actually quite benign. What matters is how the site responds to the 483, and whether the site was able to successfully resolve the issue and learn from the experience. If the issue was very detrimental and the Phase 1 unit was unable to easily improve upon the issue, then the site is still at risk for issues and deviations in the future.

While a site receiving a 483 can be an opportunity for improvement, thus resulting in a better Phase 1 unit all-around, a single 483 is by no means an all-inclusive assessment of the site’s performance and conditions. The 483 will only include observations of significance during the time of inspection, and thus, there may be other conditions that are not cited on the report. This means that the could be other issues which the site needs to improve upon which are not observed in the report, so Sponsors and CROs must understand that no matter what the issue is on the 483, it does carry some bit of complexity.

Ultimately, Sponsor companies should conduct their own thorough review of their Phase 1 clinical trial units and determine if they are up to their standards of performance, as well as request a full regulatory history of their current and prospective sites, to ensure that the success of their early clinical development programs.