The FDA relies on Good Clinical Practice (GCP) inspections to evaluate regulatory compliance and verify data integrity, but unlike the US-based clinical sites, foreign GCP inspections are rare. A recent retrospective analysis provides a comprehensive look at the FDA’s GCP inspections conducted between fiscal years (FY) 2016 and 2018, shedding light on the agency’s operational focus on foreign GCP inspections. Although the data is from almost 10 years ago, it provides a reasonable perspective of regulatory oversight, which is still relevant and should be considered by sponsors of global clinical trials.
FDA inspections to assess clinical trial conduct and verify data integrity in support of marketing applications are critical for due diligence. A retrospective analysis of FDA GCP inspection records for applications submitted during fiscal years (FY) 2016 to 2018, aimed to assess the comprehensiveness and geographic distribution of these inspections. The analysis included 347 marketing applications that required a GCP inspection, resulting in a total of 1,275 inspections during the study period. The majority of the applications were NDAs (72%), and 71% were original submissions.
A critical finding was the overwhelming dominance of US sites in the inspection efforts. While the clinical trials supporting the applications were largely global, 68% were conducted in both the US and non-US countries; the actual inspections heavily favored US sites. Overall, 66% of the 1,275 total inspections were conducted within the US. The remaining non-US inspections primarily occurred in Europe (62%), followed by Asia (17.9%). Focusing on the type of inspection, most were conducted at the Clinical Investigator (CI) sites (86%), followed by sponsors (10%) and Contract Research Organizations (CROs) (4%). For CI sites, 63% of inspections were conducted in the US. For sponsors and CROs, this domestic focus was even starker, with the majority of these inspections conducted in the US (greater than 80%).
The study highlighted a significant imbalance in oversight efforts between US-based and non-US-based clinical sites. Although nearly two-thirds of the enrolled participants were located outside the US, the inspection rate for US CIs (3.7%) was more than double that for non-US CIs (1.5%). This geographic imbalance extended to the data review process. While CI inspections covered about 10% of total enrolled trial participants overall, the proportion was higher for US participants (14%) compared to non-US participants (8%). Similarly, the review of participants’ source records—key to verifying data reliability—was substantially higher for US CI inspections (8.2% of the total US enrolled population) compared to non-US CI inspections (3.3%). This disparity is potentially due to operational limitations, such as language barriers and the fact that inspection duration (averaging about 5.16 business days) remained consistent regardless of location. The findings suggest that while the FDA employs a risk-based approach to select inspection sites, the execution of inspections resulted in higher coverage of US participants and source data.
A few key aspects of the FDA GCP inspection process come to light. First, most FDA GCP inspections were conducted at the clinical sites (9 out of 10), not the sponsor. More than two-thirds of the GCP inspections are conducted at the sites in the US, despite the majority of trial participants being enrolled outside the US. The relatively lower inspection rate of non-US sites and the lower review rate for non-US records likely reflect operational limitations, including a lack of adequate resources, fixed inspection durations, and language barriers.
This study offers valuable insight into the FDA’s GCP oversight practices for clinical trials supporting regulatory applications, underscoring a need for enhanced global coordination. Although the data used for this evaluation is about a decade old, with the pandemic-induced changes about 5 years ago, and the existing resource limitations, the findings are most likely still relevant. This raises questions about the reliability of clinical data from non-US locations.
Although there has been significant internationalization of clinical research in the last 50 years, the US is still the location for more than two-thirds of all clinical trials worldwide. Just like has been done for compliance with the good manufacturing practices, strengthening international regulatory partnerships through information sharing and joint inspection efforts is crucial to ensure the consistent quality and reliability of clinical data, regardless of its geographic origin. Targeted, risk-based oversight strategies, supported by robust global collaborations, will be essential for maintaining the credibility of data used in regulatory decision-making.
