Common FDA Observations in a Clinical Trial Audit


December 2017

Common FDA Observations in a Clinical Trial Audit

Bringing your drug to market can be an uphill battle to say the least, and too many trials end in failure for easily avoidable reasons. One of the many facets every sponsor and CRO needs to keep in mind is FDA regulation. FDA clinical trial audits can often decide the success of your drug. So why do so many drugs get flagged in the test phase? Some of the top reasons for this include compliance with protocol, missing source documentation, and, perhaps surprisingly, a lack of informed consent among participants.

When you put your drug in the hands of a CRO, you are accepting and expecting them to possess the knowledge, experience, and ability to move your drug through all of its phases efficiently and without failure. Our InClinica team has witnessed all of these issues and knows what to look for.

Compliance with Protocol

According to the Medicine and Healthcare products Regulatory Agency, MHRA, the reasons most drugs fail in trial are due to deficient pharmaceutical quality systems. These PQS infractions span many facets of your clinical trial and can include anything and everything from quality control, materials management, regulatory compliance, and even personnel.

While these may all seem like disparate issues, it is important to note that they are all interconnected. Perhaps the most crucial element is the very personnel involved at every stage of your trial. It stands to reason that without a properly trained, informed, and committed team that other issues with compliance protocol will inevitably arise.

Missing Source Documentation

Again, it should come as no surprise that clinical trials come with many moving parts and it’s often far too easy to overlook the simplest tasks. This seems especially true when it comes to documentation. For clinical trials, this means case histories. Also called source documentation, case histories are a compilation of every test subject’s case report forms, medical records, hospital data, and even nurses notes. When it doubt, document.

If an FDA investigator discovers missing source documentation, one of two things will ultimately happen. The sponsor and CRO must obtain any and all missing documentation or the study must end for that particular test subject.

Lack of Informed Consent Among Test Subjects

While obtaining source documentation is a necessary step for any successful trial, it is not the ultimate solution. It is crucially important that every test subject fully understands what he or she is signing up for. This may seem like common sense, but it is often overlooked. Many trials often mistake pre-screening activities with actual consent.

In addition, it is important that test subjects are consenting to the appropriate information. This includes an understanding of all elements of the trial, including the knowledge they are participating in a trial in the first place, any and all risks associated with the trial, any alternative treatments, and the overall benefits of the trial.

End Results of FDA Audit

The Food and Drug Administration oversees all clinical trials and oversees multiple audits to ensure all of the preceding areas are addressed and resolved. Through their audits, the FDA will rule on whether or not a trial may proceed or conclude. Ultimately, the FDA will determine one of the following after inspecting your trial:

  • Official Action Indicated (OAI)—Occur when “significant objectionable conditions or practices are discovered.” An OAI will result in regulatory action by the FDA to ensure future compliance with any and all statutes and regulations.
  • Voluntary Action Indicated (VAI)—A VAI classification is the result of the FDA discovering objectionable conditions or variations that are not significant enough to warrant direct action.
  • No Action Indicated (NOI)—Although there was cause for an initial inspection of the grounds of practices deemed objectionable, an NOI means no further action is required on the part of the facility, CRO, or sponsor.
  • No Enforcement Needed—This is ultimately where every trial needs to be. Ideally this finding comes from an initial inspection, but it can also be achieved after any other verdict.

InClinica Knows the FDA

Finding the right CRO to handle your clinical trial is an important step in bringing any drug to market. From ensuring all aspects of a Phase I or Phase II trial function properly, to dealing with FDA and responding to an audit, a CRO needs expertise and experience. At InClinica, we’ve assembled a team of industry-leading professionals with decades of experience covering every aspect of clinical trials.

For quality assurance, one team member you’ll rely on is Vice President and General Manager Danielle Bradbury. A former ICU nurse in the University of Pennsylvania hospital system as well as a member of Penn’s institutional review board, Ms. Bradbury is no stranger to intricacies involved with quality assurance in clinical trials. With nearly 20 years experience in clinical trial quality assurance, Ms. Bradbury has seen FDA audits and failures alike. Contact InClinica today to begin to your next trial.