FDA Inspections and Whistleblowing: Inspection Numbers Will Continue to Rise

FDA has resumed inspections at prepandemic levels, and the number of inspections continues to rise because the agency is seeking to clear a major backlog of inspections that developed from 2020 to 2022. In doing so FDA is continuing to make use of tools it pioneered or increased the use of during travel lockdowns, such as remote regulatory assessments (RRAs). This will likely lead to increased enforcement in connection with GMP compliance. Unfortunately, inspection readiness at some manufacturing sites has declined due to a lack of experience and practice in managing inspections, likely from the extensive delay between inspections resulting from the pandemic. In many cases this has been compounded by the loss of key personnel or subject matter experts at sites.

In addition to managing RRAs, FDA has also begun conducting unannounced inspections of foreign manufacturers, particularly in India, a major source of pharmaceuticals for the U.S. market. Unannounced inspections in China are also likely to materialize once travel restrictions in the country are lifted. Companies whose pharmaceutical supply chains rely on manufacturing sites located in India or China should therefore take steps to assess and ensure that these sites are GMP compliant and to shore up their operations or consider alternative manufacturing sites for key materials.

We also predict more public regulatory actions by the FDA, including the increased use of warning letters and import alerts. Many of these are likely to focus on the product quality issues that are being reviewed now during inspections and RRAs but originally occurred during the pandemic; in many cases, these issues actually manifested themselves due to COVID-related staffing and supply chain restrictions. Data integrity (DI) also remains an inspectional priority for the FDA in its enforcement activities. Both prior to and following the agency’s issuance in 2018 of guidance on DI, the agency has shown a willingness to refer DI issues found during inspections to the DOJ for possible enforcement action.   

The decline in inspections in recent years may have also created a lack of urgency at some sites, and in some places this is manifesting itself in backlogs in closing quality investigations or implementing Corrective and Preventative Actions (CAPAs). Sites should be on alert for such backlogs developing because a failure to execute on such matters in a timely fashion can lead to repeat problems, closer FDA scrutiny during inspections or RRAs, and whistleblower risks.

In 2023, we will likely see the wider economic slowdown start to affect manufacturers and companies and in turn reduce workforces. As a result, we expect there to be an increase in the number of whistleblowers. We already saw a number of large government investigations stemming from whistleblower complaints in the second half of 2022, and we expect this trend to continue. Indeed, in recent years, whistleblowers have attempted to expand the playing field of potential FCA cases by making the following allegations:

1. violations of GMP or Quality Systems Regulations (QSR), leading to the shipment of adulterated products
2. the FDA’s postmarketing oversight being hindered by material violations of GMP/QSR in the complaints handling and investigation process
3. “fraud on the FDA,” an allegation that the FDA would not have approved a product if it had been aware of undisclosed GMP/QSR violations

We also anticipate an increase in inspections related to clinical trials. Due to the pandemic, bioresearch monitoring (BIMO) inspections declined significantly in 2020 and 2021. However, the DOJ has said in its public statements that clinical trial fraud is an enforcement priority, and we expect this intention to be put into practice in 2023. In both December 2020 and December 2021, the Deputy Attorney General for the Consumer Protection Branch noted that clinical trial fraud was an area where enforcement would be “aggressive,” with a focus on “liability for submitting false information and failing to submit required reports.” The DOJ brought a number of cases involving fabricated or falsified clinical trial data in 2020 and 2021. The smaller number of inspections during the pandemic may also have created increased risks in this area, and we believe these risks will persist into 2023.

Tips

• Assess the inspection readiness of your key sites, and take steps to shore up the supply chains for critical products. Companies should consider creating or updating policies relating to FDA record requests and remote interactive evaluations by FDA.
• Consider additional steps to ensure inspection readiness at manufacturing and clinical sites, including third-party audits with a focus on issues such as data integrity. Prepare for disclosure of challenging manufacturing deviations discovered and addressed over the past few years; this includes demonstrating the effectiveness of corrective and preventative actions that were implemented.  
• Practice how to handle, manage, and respond to an unannounced inspection, and conduct regular “mock audits” and document reviews to stay in a state of inspection readiness, including identifying the best subject matter experts for potential interactions with an investigator.
• Conduct thorough investigations of any compliance concerns raised by employees in the manufacturing and clinical trial spaces, with the help of outside counsel where needed, to document the identification and resolution of issues.