FDA Resumes Medical Device Inspections
It is much more likely that you noticed changes to what the FDA has been doing during the COVID-19 pandemic rather than changes to what it has not been doing. One example of what they have been doing is the review and issuance of Emergency Use Authorizations. As discussed in a previous blog post, FDA panel meetings have gone virtual, as have routine meetings with the agency such as pre-submission meetings. However, you may not have noticed that during the pandemic, the FDA has significantly limited the number of medical device inspections, halting all inspections between March 2020 and June 2020 and then only resuming critical inspections in June 2020.
In a May 2021 report entitled, “Resiliency Roadmap for FDA Inspectional Oversight” (https://www.fda.gov/media/148197/download) the FDA reports on its management of inspections during the first year of the COVID-19 pandemic, reporting on activities from March 2020-2021. At the start of the pandemic in March 2020, the FDA stopped all but the most critical of inspections before working to resume some inspection activities in June 2020. Since that time, they have focused on Mission Critical inspections (8 device inspections) and Prioritized Domestic inspections (72 device inspections). This means many medical device, electronic product, and MQSA inspections were delayed as a result of the pandemic including 2,002 domestic surveillance and 424 foreign surveillance inspections.
Although little information has been communicated publicly about the resumption of normal inspection activities, all indications are that FDA resumed conducting at least some of its routine medical device inspections starting this July. While FDA has not provided specific information about its plans to resume medical device inspections, the agency is consistent about prioritizing work based on risk. This may include factors such as:
- a facility’s past inspection history including any open Warning or Untitled Letters,
- a lack of inspectional history for new manufacturers or a new manufacturing facility for well-established manufacturers; or
- the classification of the devices manufactured at the facility (e.g., Class III devices which are higher risk).
While it is important to review your Quality System periodically, as well as a requirement under 21 CFR 820.22, to ensure it is performing as intended and meets the regulatory requirements, it is especially important for facilities with a history of regulatory problems, recurring observations, or no inspectional history, to take this opportunity to review their Quality System and assess any gaps which may exist. Taking action now can help ensure an inspection goes well.
If an FDA investigator does issue an FDA Form 483 for any observations noted during the inspection, this is done at the conclusion of the inspection and is the investigator’s documentation and notice of observational findings. As a part of this process, you can request that the investigator annotate the 483 to indicate one of the following regarding each of the listed observations:
- Reported corrected, not verified
- Corrected and verified
- Promised to correct
- Under consideration
Upon issuance of the 483, the investigator should explain that FDA policy allows for a written response to be submitted within 15 business days. Responses can be submitted via e-mail to a mailbox specifically for firm responses based on the geographical medical device division where the inspection occurs. Responses are reviewed by the division’s Compliance Branch as a part of their review of the Establishment Inspection Report (EIR) and the 483 when determining the final inspection classification. Depending on the specific observations on the 483, 15 days may not be sufficient to fully remediate some or all, of the observations. FDA understands that 15 business days is a limited period and some corrective actions require extensive work. When it is not possible to fully correct the observation(s), FDA is looking for a plan with steps and a timeline by which the observations will be addressed. It can also be helpful to indicate when updates or progress reports on remedial actions will be submitted. Updates should be submitted to provide updates on key milestones, but you should not flood the FDA with minor updates or updates that are repetitive.
Once the Compliance Branch has reviewed the EIR, 483, and the company’s initial response, they will classify the inspection into one of three classifications:
- No Action Indicated (NAI): No objectional conditions or practices were found during the inspection (or the significance of the documented objectionable conditions found does not justify further FDA action.)
- Voluntary Action Indicated (VAI): Objectionable conditions were found and documented but the District and/or Center is not prepared to take or recommend any of the regulatory (advisory, administrative, or judicial) actions since the objectionable conditions do not meet the threshold for regulatory action.
- Official Action Indicated (OAI): Objectionable conditions were found and regulatory (advisory, administrative, or judicial) action is recommended.
Inspections with either no observations or minor observations are typically classified as either NAI or VAI. In these cases, the inspection will be closed and the FDA will issue a letter to the company indicating that the inspection is closed along with a copy of the EIR. Inspections that are classified as OAI result in additional regulatory action. This usually results in the issuance of a Warning Letter or Untitled Letter as long as the recent inspection history does not include additional OAI inspections for the same facility, in which case FDA would consider escalating the official action to a seizure or injunction. As an alternative, the FDA may hold a Regulatory Meeting to discuss the observations with the company and discuss the agency’s concerns. While Untitled Letters and Regulatory Meetings are not publicly disclosed, Warning Letters are posted on the FDA’s webpage. Warning Letters are generally issued within 4 months of the close of the inspection and Untitled Letters are generally issued within 6 months of the close of the inspection. Both types of letters are issued to the “most responsible person” at the company, typically the CEO, and request a written response within 15 days for a Warning Letter and within 30 days for an Untitled Letter. Responses to a Warning Letter or Untitled Letter should be submitted within the required response time and should include a description of any actions taken to date to address the observations as well as a timeline for any planned corrective actions, similar to what should have been done when responding to the 483. When developing a timeline, it is important to understand that the FDA believes you are manufacturing and marketing devices in violation of the Federal Food, Drug, and Cosmetic Act, so it is their expectation that planned corrective actions are being aggressively pursued so that they are mitigated and resolved as quickly as possible. Timelines should reflect this urgency while remaining realistic and achievable. Warning and Untitled Letter responses should address three key aspects of each observation:
- Correction: This directly addresses the observed problem which may include correcting documentation, re-working, or scrapping manufactured devices.
- Corrective Action: This is aimed at not just fixing the observed problem, but identifying the root cause of the problem and taking action to fix the root cause to ensure that the problem does not occur again.
- Systemic Corrective Action: This is intended to be your assessment and actions in regards to other devices which have or may have the same problem, or could be affected by the same deficiency.
It is important to consider systemic corrections since the observations are based on an audit of the facility. This means that certain devices or manufacturing operations could have been selected to review for conformance to the regulatory requirements, but similar issues may exist elsewhere that were not specifically audited. FDA will expect that you evaluate the entire system and not just treat the 483 observations as a checklist of specific items to correct.
Updates should be provided to FDA on a regular basis to demonstrate that both corrections based on the observation as well as systemic corrections, are being implemented according to your plan and timeline. Responses should include a narrative explaining what steps have been taken and objective evidence of the correction or corrective action. The FDA will review the submitted responses and inform the company regarding the adequacy of the response. Once FDA believes all responses are adequate, they will conduct a follow-up inspection to confirm that all corrections have been made and ensure that the facility is in compliance.
Food and Drug Administration (FDA). (May 2021). Resiliency Roadmap for FDA Inspectional Oversight. Retrieved from source.