FDA Updates Inspection Guidance with Minor Additions

The U.S. Food and Drug Administration (FDA) issued an update to its guidance document, “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers,” on January 29, 2021. First issued in August 2020 and intended to remain in effect only for the duration of the COVID-19 public health emergency, the guidance answers ten questions:

• Q1: How are inspections impacted by COVID-19?
• Q2: What types of inspections would be deemed “mission-critical”?
• Q3: Does FDA determine what is “mission-critical” using the same factors for both domestic and foreign inspections?
• Q4: How will FDA ensure the quality of imported products while inspections are limited?
• Q5: How will limited inspection activity affect my application?
• Q6: If my application includes sites that cannot be inspected because of travel restrictions, will my application automatically receive a complete response letter?
• Q7: How do I add or change a facility in my application in response to supply chain disruptions due to the COVID-19 pandemic?
• Q8: What data are required to support manufacturing process or facility changes needed to address disruptions from the COVID-19 pandemic?
• Q9: How can the implementation of manufacturing changes to an ANDA, NDA, or BLA for drugs or biological products needed during the COVID-19 pandemic be accelerated?
• Q10: Can I submit an application if it includes facilities in regions that are impacted by COVID-19-related travel restrictions?

The updated guidance provides new information in response to Question 5 after reiterating that, during the period while inspections are limited, FDA, as part of determining the need for an inspection and to support the application assessment, may request records “in advance of or in lieu of” facility inspections per section 704(a)(4) of the Food, Drug, and Cosmetic Act. The new text in the updated document adds that FDA is working directly with facilities through interim processes to communicate issues identified through a review of requested records. FDA will consider responses from the facility, as feasible, before taking an action on a pending application.

Although the guidance does not describe FDA’s mechanism for requesting records in lieu of an inspection, facilities due for an inspection should expect to receive a Form 4003, “FDA Inspection Records Request,” which includes the notation “Under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 371(a)(4)], FDA requests that you provide the records described below.”

At the completion of normal, routine inspections, FDA investigators meet with the facility’s management to present their observations and a written copy of the observations on a Form 483. However, because FDA’s review of requested records would not qualify as “observations made by the FDA representative(s) during the inspection of your facility,” as noted on each Form 483, it is unlikely that FDA will be sending a Form 483 with issues identified during its record review. FDA’s scant description of its interim process to communicate issues does not identity how FDA will communicates such issues to the facility that supplied the records.