FDA Inspections Face Continued Overhaul and Changes

Jill Wechsler, Washington Correspondent

As part of agency initiatives to strengthen its oversight of human food and food products, FDA is revising inspection and compliance programs for all regulated products, at home and abroad. While an overriding aim is to improve FDA’s capability for monitoring and curbing contamination issues involving foods, the changes also involve revised oversight and inspection programs for medicines and other regulated products. Some of these actions arise from FDA’s greater reliance on remote oversight activities advanced during the global COVID-19 pandemic, which encouraged more cooperation with foreign inspection programs. Others have been advanced by FDA for years, such as encouraging modern manufacturing processes and attention to quality issues to ensure reliable supplies to prevent drug shortages.

For these purposes, FDA is in the process of restructuring its Office of Regulatory Affairs (ORA) to better monitor food safety issues and to schedule field inspections more efficiently. A prime aim is to prevent delayed responses to serious food contamination issues, as occurred with the baby-formula recall in 2022, which created a national crisis in formula shortages. FDA Commissioner Robert Califf announced in June a revised model for ORA to better align with a new unified Human Foods Program and to coordinate and respond expeditiously to public health issues. Califf further implemented these changes with the appointment of the first Deputy Commissioner for Human Foods on Aug. 23. This high-level official will oversee all human foods programs and work closely with a new associate commissioner for regulatory affairs who will head up revamped ORA operations.

As part of these changes, FDA said in its June announcement that it will shift certain enforcement functions currently managed within ORA to compliance offices in FDA centers. This move aims to “streamline operations and expedite decision-making” so that the agency can determine more quickly what sites to inspect and what compliance actions to take. ORA will focus more on conducting investigations, inspections, and oversight of imports, still operating through offices for medical devices, human and animal drugs, biologics, and bioresearch monitoring inspections (BIMO). More details on the plan are emerging and will involve Congressional review and more formal rulemaking, as well as agreement from FDA unions and staff.

More foreign inspections

Furthermore, ORA is taking steps to strengthen its oversight of domestic and foreign drug manufacturing activities. Alonza Cruse, director of ORA’s Office of Pharmaceutical Quality Program Operations, reported at the PDA/FDA joint regulatory conference in September that the agency has resumed foreign inspections, including those in China, and is implementing pilot programs for unannounced inspections of manufacturing facilities in China and India. Cruse also noted an expansion in cooperative inspection activities with European and other regulatory authorities under enhanced mutual recognition agreements (MRAs).

These initiatives reflect recent Congressional directives. Under the Food and Drug Omnibus Reform Act (FDORA) enacted in late 2022, the legislators encouraged more unannounced FDA inspections of foreign drug establishments, shifting away from FDA’s usual practice of scheduling foreign site visits in advance to ensure access to the facility. At the same time, FDORA aimed to reduce unneeded foreign site visits by supporting expanded FDA use of MRAs with trusted foreign regulatory counterparts to obtain reports and information related to pre-approval inspections, as well as more routine manufacturing site visits.

Similarly, the Center for Drug Evaluation and Research (CDER) is ramping up its compliance and inspection efforts to further encourage quality production operations and prevent drug shortages. CDER Director Patrizia Cavazzoni emphasized at the PDA/FDA conference the importance of manufacturers maintaining proactive and prevention-focused quality systems to ensure “sustainable compliance” with current good manufacturing practice. This involves ongoing oversight of facilities by senior management, effective systems for detecting emerging quality issues, and a structured approach to determine the root cause of such problems.

Quality clinical trial operations

FDA’s emphasis on considering risk factors in planning for product oversight also applies to BIMO investigations, an effort also encouraged by a provision in FDORA that clarifies FDA’s authority to conduct BIMO inspections and which sites and facilities are subject to this oversight and required to provide records and other information. FDA issued a guidance in April that makes recommendations to industry on implementing a risk-based approach to monitor investigational studies on human drugs, biologics, medical devices, and combination products. 

Jill Wechsler is ACT's Washington Correspondent