Guest Column | June 11, 2021

The "Resiliency Roadmap" — Next Steps For FDA Inspections

By Kalah Auchincloss, EVP and deputy general counsel, Greenleaf Health, Inc.

Map Keyboard

More than a year into the COVID-19 pandemic and FDA’s abrupt suspension of on-site inspections in March 2020, the agency released the Resiliency Roadmap for FDA Inspectional Oversight in May 2021.[1] The first part of the roadmap provides data on the conduct of inspections during the pandemic and FDA’s use of remote, alternative tools; the second section of the document discusses future plans to address the backlog of routine surveillance inspections. This article summarizes the roadmap and offers several predictions about the future of FDA inspections.

State Of FDA Inspections

In general, FDA was able to conduct only mission-critical and high-priority inspections from March 2020 to March 2021 (see Table 1). FDA determines whether a given inspection is mission critical on a case-by-case basis, weighing “its resources and capabilities for the inspection during the public health emergency against the public health risk or benefit posed by the potential inspection site.”[2] Factors such as breakthrough or regenerative medicine advanced therapy designation; whether the product is for a serious disease or medical condition with no substitute; presence of serious adverse event(s) or recall(s); and whether the product is related to FDA’s COVID-19 response are all part of FDA’s mission critical calculus.

Prioritized domestic inspections include surveillance and for-cause inspections that are not mission critical, but that are high priority based on factors such as whether the inspections is intended to follow up on a previous violative inspection; needed to support a product approval decision; considered high risk under statutory inspection frequency mandates (generally related to food facilities); or “otherwise maximizes the use of limited inspectional resources to achieve the greatest public health impact during the COVID-19 pandemic.”[3] FDA only conducts prioritized inspections if the COVID-19 Advisory Rating Level indicates travel to the region is safe.

Table 1. Data on FDA Inspections During the Pandemic

Type of Inspection

Number of Inspections

Timeframe: March 2020 - March 2021

Mission Critical

821[4] (29 foreign, remainder domestic)

Prioritized

777[5] (all domestic)

PAI/PLI/pre-market

~600 of >13,500 application required inspectional oversight

68 application delays[6]

Timeframe: Fiscal Year 2021

For-cause

90% of planned domestic OAI follow-up activities completed in FY20

164 planned domestic OAI follow-up activities in FY21

  • 49 complete
  • 115 remaining[7]

Surveillance

26,250 planned inspections (includes most, but not all postponed from FY20)[8]

  • 2,953 complete
  • 23,297 remaining[9]
    • Majority are domestic facilities (21,521)
    • Majority are food facilities (19,245)
 

Despite its limited ability to conduct on-site inspections, during the pandemic the agency managed to meet most user fee dates for pending applications and to complete follow-up on domestic facilities classified as “official action indicated” (OAI) during a previous inspection (see Table 1). This was partly due to mission-critical and high-priority on-site inspections, but also a result of FDA’s use of “alternative tools” such as records requests under section 704(a)(4) of the Federal Food, Drug and Cosmetic Act (FD&C Act) to review information about a facility and reliance on foreign inspection reports from trusted foreign partners.

However, the agency was generally not able to conduct lower-priority routine surveillance inspections: a backlog of more than 23,000 routine surveillance inspections remains in FY21 (see Table 1), even after FDA used remote tools to reprioritize relative risk and eliminate the need for some of those inspections. Notably, many of the outstanding inspections are statutorily mandated inspections of lower-risk food facilities. A second sizeable portion is related to annual inspections of mammography facilities, which are also required by statute.

Looking Ahead

After providing data on the current status of FDA inspectional activities, the roadmap turns to the future, outlining a “detailed plan for a more consistent state of operations and [FDA’s] priorities going forward.”10  

The FDA emphasizes that it will continue its prioritized inspectional approach for all commodities through the end of the pandemic and even when travel restrictions and other impediments are lifted. More specifically, FDA will first conduct mission-critical inspections (Tier 1) and will then prioritize pre-approval and for-cause inspections (Tier 2). Lower-priority inspections that do not meet these criteria (Tier 3) may be postponed, which could include some routine surveillance inspections. As such, FDA cautions that there may be a longer interval between inspections of lower-risk facilities as FDA adjusts to the impact of the pandemic. 11

Based on the tiered priority system, FDA then estimates how many routine surveillance inspections it could accomplish in the remainder of FY21 based on certain workload assumptions and possible trajectories of COVID-19. In none of the scenarios will FDA be able to complete all pending routine surveillance inspections. In the base case scenario, FDA expects to be able to complete approximately 26% of remaining domestic surveillance inspections of medical products in FY21. That number drops to zero (no non-mission-critical work) in the worst-case scenario and increases to 50% of remaining domestic medical product inspections in the best-case scenario (see Table 2).

Table 2. Conduct of Routine Surveillance Inspections12

Program Area

Remaining Surveillance Inspections

Human/animal food

12,285*

Human/animal medical products and tobacco**

3,229*

Base Case

  • Gradual transition to standard operations by July 2021
  • 2,123 (14%) remaining inspections conducted
    • Food: 1,272 (10%)
    • Medical products: 851 (26%)

Best Case

  • Standard operations by May 2021
  • 4,192 (27%) remaining inspections conducted
    • Food: 2,579 (21%)
    • Medical products: 1,613 (50%)

Worst Case

  • Continued restrictions through end of FY21
  • Focus on mission critical work; no non-mission critical surveillance work conducted, thus increased reliance on alternative oversight tools.
 

* Total inspections remaining does not add up to the total in Table 1, because FDA assumes state and local partners will conduct 35% of remaining food facility inspections, and foreign partners will conduct 25% of remaining medical product facility inspections. FDA also focuses on domestic rather than foreign inspections.

** Note that Table 7 in the Roadmap refers to “Human and Animal Medical Products and Tobacco.” Tables 8 and 9 refer only to “Human and Animal Medical Products.” All three tables, however, cite 3,229 as the number of remaining inspections in that category, thus we believe there is an error: either Table 7 should not include tobacco, or Tables 8 and 9 should include tobacco. Our best guess is that tobacco was accidentally deleted from Tables 8 and 9, as these are routine domestic surveillance inspections, thus there is no reason not to include tobacco (particularly as other tables in the Roadmap also refer to tobacco).

4 Predictions On The Future Of Inspections

Even in FDA’s best-case scenario, the agency will need to address a growing backlog of surveillance inspections in future years. Delayed surveillance inspections may worsen drug shortages, bleed over into missed user fee goal dates or postponed for-cause follow-up, and put patients at risk of adverse events from sub-quality products. FDA clearly recognizes the need to adjust to this new reality; thus, we can expect certain pandemic practices to become permanent and new changes to be implemented. Below, I make four predictions on the future of FDA inspections:

  1. The agency will conduct lower-risk surveillance inspections only as workloads and the pandemic permit. Surveillance work is likely to increase over time as the agency returns to more normal operations, but not in the immediate future; thus, the backlog may grow unless FDA is able to contain it through means other than on-site inspections.
     
  2. The COVID-19 focus on domestic facilities may signal a reverse in the recent trend toward greater numbers of foreign inspections, particularly if FDA continues to rely on inspection reports from trusted foreign authorities. It almost certainly will accelerate FDA’s shift in focus to conducting inspections in China and India, which are not party to information sharing agreements with FDA, rather than Europe.
     
  3. Given the limited ability to conduct on-site inspections, FDA will continue to rely heavily on alternative tools, including new Remote Interactive Inspections (RIE)13 and Remote Regulatory Assessments (RRA). FDA is likely to continue to rely on these tools even as pandemic restrictions subside, to eliminate the need for on-site inspections in certain cases and lower the relative risk of facilities in other instances.
     
  4. Over time, FDA will both refine and expand its arsenal of oversight tools. For example, it may extend mutual reliance or other information sharing agreements to additional trusted regulatory partners and new commodities and/or refine the process for RIEs and RRAs. The agency may also expand its remote capabilities with new technology as part of the Data Modernization Action Plan (Editor’s Note: covered here) and use data analytics to better estimate risk and adapt its risk-based inspection model. As relative risk is adjusted, FDA may be able to reduce the inspection backlog.

Perhaps one silver lining in the black cloud of COVID-19 is that the pandemic has forced FDA to rethink its inspectional oversight and modernize its approach. The FDA announced the creation of an agency-wide Inspectional Affairs Council at the same time as the release of the roadmap, which may help guide the new inspectional approach.

References & Notes

  1. Resiliency Roadmap for FDA Inspectional Oversight, May 2021, https://www.fda.gov/media/148197/download.
  2. Roadmap, p. 2.
  3. Roadmap, p. 4.
  4. Table 1 in the roadmap breaks down these inspections by commodity. More than half (475) were medical product inspections, excluding tobacco products, which FDA does not consider “mission critical” work.  Interestingly, 408 of those 475 medical product inspections were bioresearch monitoring (BIMO) site inspections. Roadmap Table 1, p. 3.
  5. Table 2 in the roadmap breaks down these inspections by commodity. FDA conducted 266 prioritized medical product inspections, again excluding tobacco products. Roadmap Table 2, p. 4.
  6. Table 3 in the roadmap breaks down these inspections by commodity. 48 human drug applications were delayed solely as a result of FDA’s inability to conduct an on-site inspection. Six of those applications were mission critical; FDA has scheduled those inspection to take place in FY21. Roadmap Table 3, p. 8.
  7. Table 4 in the roadmap breaks down these inspections by commodity. 108 of the remaining 115 inspections are medical product inspections. Roadmap Table 3, p. 8.
  8. Most, but not all inspections postponed in FY20 are included in FDA’s FY21 planned surveillance inspections. However, FDA was able to use remote tools to provide oversight that lowered the relative risk for some facilities, bumping them out of the risk-based site selection model in favor of higher risk facilities. Roadmap, p. 11.
  9. Table 5 in the roadmap breaks down these inspections by commodity. FDA estimates that there are 857 human drug, 110 biologic, and 279 BIMO surveillance inspections remaining. Roadmap Table 5, p. 12.
  10. Forward to the Roadmap by Dr. Janet Woodcock, acting FDA commissioner.
  11. Roadmap Table 6, p. 14; roadmap, p. 15.
  12. Roadmap Tables 8 and 9 and p. 20
  13. Guidance for Industry, Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency, April 2021, https://www.fda.gov/media/147582/download.

About The Author:

KalahKalah Auchincloss, J.D., M.P.H., is executive vice president of regulatory compliance and deputy general counsel for Greenleaf Health. She has more than a decade of food and drug legal, policy, and regulatory experience at the FDA, on Capitol Hill, and in the private sector. At Greenleaf, Auchincloss advises pharmaceutical and medical device companies on compliance, policy, and other issues. Before moving to Greenleaf, Auchincloss spent six years at the FDA, most recently as deputy chief of staff, but also serving in CDER’s Office of Compliance and Office of Regulatory Policy. You can contact her at kalah.auchincloss@greenleafhealth.com.