FDA raises bar for foreign site inspections as China trials surge
In the wake of three deaths reported in separate gene therapy trials conducted in China, U.S. lawmakers called on the FDA to reject clinical data from China unless the trial site has recently undergone an FDA audit. On Wednesday, four agency officials published an op-ed outlining steps the FDA plans to take toward strengthening oversight of foreign trial sites.
The number of clinical trials being conducted in China has risen dramatically over the last 15-plus years. In 2010, fewer than 8% of global clinical trials were run in China, according to an April report from the National Bureau of Economic Research. By 2020, the Asian country had overtaken the U.S. in annual registered trials.
“Accepting Chinese clinical data poses real risks for patients,” Reps. John Moolenaar (R-MI) and Ben Cline (R-VA) wrote in a letter to Acting FDA Commissioner Kyle Diamantas last month.
The FDA will add resources to expand oversight at foreign clinical trial sites, aim to improve communication with drug sponsors and strengthen internal reviewer training to help identify clinical trial sites of possible concern, according to the agency’s editorial, which was published in FDA Voices on Wednesday afternoon. Notably, the article does not refer to any specific geographical region.
“This is not protectionism, and it is not a geopolitical statement about any particular country’s scientific capacity,” the authors wrote. “Many foreign research institutions produce clinical data of the highest quality, and the FDA actively welcomes and relies on such data.”
The piece was penned by Michael Davis, acting director of the Center for Drug Evaluation and Research (CDER); Karim Mikhail, acting director of the Center for Biologics Evaluation and Research (CBER); Michelle Tarver, director of the Center for Devices and Radiological Health; and R. Angelo de Claro, director of the Oncology Center of Excellence.
Three fatalities occurring recently in Chinese clinical trials have spurred two members of U.S. Congress to urge the FDA to enact new policies designed to protect American patients.
Nevertheless, the op-ed comes at a time when the FDA is working to reshore early-stage clinical research. A first step to doing this, a senior FDA representative told BioSpace in a pre-publication interview, is to “modernize and improve the U.S. system”—something the Department of Health and Human Services (HHS) has begun to tackle with the rollout of Operation TrialBlazer. Announced in June, the initiative seeks to reduce the time from drug identification to Phase 1 trials and expedite early clinical development timelines by as much as a year.
Another important step, the FDA representative continued, “is how do we make sure we have a level playing field, so there’s not sort of perception or reality that by moving outside the U.S., you are able to potentially cut corners.” That’s the focus of Wednesday’s editorial, they said, which is the first public step forward to bringing clinical sites in other countries in line with the FDA’s standard in terms of good clinical practice regulations or human subjects protections.
A particular area of concern for the FDA is early feasibility and Phase 1 studies conducted at sites “in countries or regions where geopolitical conditions make informed consent difficult to ensure, or where documented human rights concerns create a heightened risk that consent was not freely and voluntarily given,” the authors wrote.
The senior agency representative pointed to a situation where American biospecimens are sent to China: “Are people informed about that?”
The authors also touched on a key theme of the Department of Health and Human Services (HHS) under Secretary Robert F. Kennedy Jr.: transparency. When the FDA identifies concerns related to human subject protection or data integrity in sites outside the U.S., the agency “will make more information from inspections publicly available, as appropriate, so that sponsors, patients, and the public can understand where deficiencies have been identified and take that into account in development plans,” according to the editorial.
Having started to publish CRLs without consulting the public, the FDA is under pressure to change course amid concerns it failed to openly and fully evaluate a complex issue.
The FDA will also strive for active engagement with sponsors at the pre-submission stage, the authors wrote, including discussing the provenance and investigational new drug (IND) or investigational device exemption (IDE) status of foreign clinical data with sponsors early in development. This “will better position both parties to identify and address data integrity, human subject protection, and related issues prior to application review,” according to the editorial.
The agency is devoting additional resources to help solve these challenges. “We’ve definitely increased the number of BIMO [Bioresearch Monitoring] inspectors both at our China office and . . . throughout some other global offices,” the senior representative said, adding that the FDA is also looking into other tools to expand oversight, including remote assessments and information collection requests.
In parallel to efforts to tighten and reshore clinical research, the Trump administration has been laser-focused on bringing manufacturing back to the U.S. In an executive order in May, President Donald Trump ordered the FDA to cut down the time it takes to approve pharmaceutical manufacturing plants in the U.S., and set the groundwork for the agency to implement surprise inspections on foreign plants, instead of planned visits as is the current process.
Increasing foreign plant inspections has “definitely been an increased area of priority,” the FDA representative said on Wednesday.
The editorial’s tone appeared to be directed at putting drug developers on notice.
“Sponsors should treat the inability to inspect or access all relevant data as a material factor in their regulatory strategy, not an administrative footnote,” the FDA officials wrote.
The authors concluded their editorial with the following message to drug sponsors: “If you are building a regulatory strategy around clinical data from sites where the FDA has been unable to inspect, or from circumstances where the conditions for ethical research are in serious question, think again.”
The U.S. is scrambling to compete with a strategically positioned China on the biotech stage as the Asian country surpasses America in biomedical research and clinical trials. So far, China is winning.