FDA defends its oversight of foreign drugs amid Senate, GAO criticism
During a Senate Committee on Finance hearing Tuesday, officials from the FDA responded to criticism from senators and a new report from the Government Accountability Office (GAO) on its oversight of foreign drug manufacturers.
The hearing follows FDA’s move to halt most foreign inspections in March as a result of the coronavirus disease (COVID-19) pandemic.
Much of the criticism centered on the agency’s practice of giving foreign facilities advanced notice of inspections while most domestic surveillance inspections are unannounced, as well as US reliance on foreign drug manufacturing.
Opening the hearing, Chairman Chuck Grassley (R-IA) pointed out that most manufacturing sites for finished drugs and active pharmaceutical ingredients (API) are located outside the US. Other senators raised concerns about the security of the US pharmaceutical supply chain, including Sens. John Cornyn (R-TX) and Mark Warner (D-VA).
Doug Throckmorton, deputy director for regulatory programs at FDA’s Center for Drug Evaluation and Research, told senators that FDA is looking for ways to leverage advanced manufacturing to both improve drug quality and promote the onshoring of drug manufacturing.
“CDER’s vision is to spur the industry to modernize so that quality can be consistently and reliably built into each tablet and vial they produce,” he said.
However, Throckmorton also acknowledged that FDA lacks some of the information to have a thorough understanding of the earlier stages of the pharmaceutical supply chain, such as the sources of chemicals used to produce API and the API themselves.
“We know substantially less about the sources of those products than we do about API and … we know less about API and its manufacturing and distribution than we do about finished dosage forms,” Throckmorton said.
In response to criticisms over FDA’s practice of notifying foreign facilities in advance of inspections, Judith McMeekin, associate commissioner for regulatory affairs at FDA’s Office of Regulatory Affairs (ORA) said that preannouncing inspections helps to avoid potential refusals and conserve FDA resources.
McMeekin also pointed out that both foreign and domestic manufacturers are held to the same standards and that FDA must deal with jurisdictional differences in conducting foreign inspections. Because FDA does not have the same authorities that it does in the US when operating in other countries, the preannouncement process gives the agency a chance to document a firm’s agreement to allow an inspection, McMeekin said. When a foreign firm refuses an inspection, FDA may take other actions to address the safety of the US drug supply, such as placing the firm on Import Alert.
“The FDA does not draw upon the same enforcement mechanisms or have a comparable level of infrastructure,” McMeekin said, noting that in the US the agency can seek a warrant if a firm refuses inspection.
McMeekin also later clarified that FDA does conduct some unannounced inspections in other countries, but they are typically for-cause inspections. She said she does not know how many unannounced inspections the agency conducted in India and China in 2019.
However, GAO’s Mary Denigan-Macauley told senators that GAO feels “that unannounced inspections are very important … but they are very few and it does raise questions about the equivalency to what we do here in the United States.” In 2018, GAO found that only a small percentage of inspections carried out by FDA’s China and India office investigators were unannounced or conducted on short notice, while most of FDA’s foreign inspections were carried out by US-based investigators and were typically preannounced 12 weeks in advance.
When asked by Sen. Maggie Hassan (D-NH) about FDA’s decision to halt foreign inspections amid the COVID-19 pandemic, Denigan-Macauley said that, “The fact that [foreign inspections have] stopped – I understand the need for being able to protect their own people – but it is concerning and I would want to ensure that the other steps that they have in place are rigorous.”
Hassan responded by saying she believes “FDA’s decision to curtail inspections is inappropriate.”
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.