FDA Sets ‘Good Clinical Practice’ Bar for Clinical Data Generated Outside U.S.

Posted February 20, 2018

Reflecting the increasing globalization of clinical trials and the evolution of standards protecting trial participants, the Food and Drug Administration (FDA) has issued a final rule updating how the agency will evaluate clinical data submitted to the agency from medical device investigations conducted outside of the United States. Beginning next year, such investigations will need to conform to good clinical practice (GCP) standards, a bar typically set for studies based in the U.S.

“FDA will accept data from well-designed, well-conducted clinical investigations conducted [outside the United States] as support for an investigational device exemption (IDE) or device marketing application or submission if the investigations were conducted in accordance with GCP, supporting information is provided as applicable, and FDA is able to validate the data from the investigation through an onsite inspection, if necessary,” the FDA wrote in the final rule.

The FDA defines GCP as “a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical investigations in a way that provides assurance that the data and results are credible and accurate and that the rights, safety, and well-being of subjects are protected.” That means including review by an independent ethics committee before and during the study and documenting informed consent by study participants.

The final rule is intended to “ensure the quality and integrity of clinical data and the protection of human subjects,” according an FDA guidance document published alongside the final rule, as well as “predictability, consistency, and transparency of the review process to sponsors and applicants while allowing some flexibility to meet GCP requirements.”

“The intent of the rule is not to disallow the use of data from certain investigations but rather to ensure FDA’s decisions are based on scientifically valid, ethically derived data. Conformance with GCP is one way to help ensure clinical data are credible, accurate, and ethically procured,” the FDA wrote.

Under the new rule, study sponsors seeking a device marketing application or IDE will need to submit a statement attesting that the study meets GCP guidelines, along with supporting information, or provide an explanation as to why GCP standards weren’t followed. If GCP standards can’t be met for an investigation, then study sponsors can apply to the FDA for a waiver on a case-by-case basis.

Comments submitted for the FDA’s 2013 proposed rule supported efforts to protect human subjects and the quality of data but cited a lack of international agreement for what constitutes GCP and the need to work with global regulators. However, in its guidance document, the FDA said that it does not intend to regulate clinical investigations conducted outside of the United States.

“We expect that foreign clinical investigations will be conducted in accordance with local laws and regulations. The requirements outlined in the rule allow the flexibility needed to accommodate those laws and regulations,” the FDA wrote. “The application of a GCP standard would be in addition to the local laws and regulations to the extent that the local laws and regulations do not incorporate such a standard. If needed, the rule allows sponsors and applicants to explain why GCP was not followed and to describe the steps taken to ensure that the data and results are credible and accurate and that the rights, safety, and well-being of human subjects have been adequately protected.”

The final rule also contains changes for studies conducted within the United States, requiring a statement regarding compliance with FDA regulations for human subject protection, institutional review boards, and IDEs. This change is intended to promote consistency across different application types, according to the FDA.

The final rule will go into effect for studies enrolling their first subject on or after Feb. 21, 2019.