Thanks to the recently reauthorized user fee legislation, the US Food and Drug Administration (FDA) now has to compile an annual report outlining various data points on inspections necessary for the approvals of drugs (but not biologics or biosimilars) and medical devices (but not humanitarian use devices).
At the outset of the report, FDA offers its interpretation of the various provisions in 2017’s Food and Drug Administration Reauthorization Act
(FDARA) that describe what should be included in the report.
On the drug side, the agency said it “interprets the statute as requiring information not only with respect to approval of original new drug applications (NDA) or abbreviated new drug applications (ANDA) but also with respect to approval of supplements to such applications, including both prior approval supplements and changes being effected supplements.”
FDA also said it limited the report to regulatory meetings based on inspections that FDA classified as Official Action Indicated (OAI).
“We note that the FDA sometimes holds Regulatory Meetings with respect to facilities that it classifies as Voluntary Action Indicated (VAI) to discuss the proposed voluntary action, but such meetings are not included in the results reported here,” FDA said.
Median Times and Application Delays
On the pharmaceutical side in calendar year 2017, FDA said the median time between an inspection request from FDA staff to the beginning of an inspection was 102 days, while the median time between the beginning of a pre-approval inspection and the issuance of a Form 483 was seven days.
And the median time between the issuance of a Form FDA 483 and enforcement action was 191 days for warning letters and 169 days for regulatory meetings.
But FDA also said there were no facilities added to its import alert list, meaning the drugs would be blocked from entering the US, that were issued a Form FDA 483 for inspections occurring in 2017, which were classified final OAI and were named in a pending application.
As far as resolving compliance actions for facilities, FDA said there were none in 2017 when a Form FDA 483 was issued in the year and it resulted in a warning letter, import alert or regulatory meeting.
“In CY [calendar year] 2017, 94 applications were denied approval solely due to a facility-related withhold recommendation,” the report added, noting in a footnote: “A total of 2,461 CRs [complete responses] were issued in CY 2017 for Original Applications and CMC [Chemistry, Manufacturing, and Controls] supplements. Of these 2,461 CRs, 288 CR actions were issued only due to a facility deficiency. Of the 288 CR actions that were issued only due to a facility deficiency, 94 CR actions were issued due to an inspection that occurred in CY 2017.”
For devices, the median time between an inspection request from FDA to the beginning of an inspection was 35 days, the median time between the beginning of a pre-market approval (PMA) inspection and the issuance of a Form 483 was five days, and the number of times that a PMA approval was withheld due to the issuance of a Form 483 at the close of a PMA inspection in CY 2017 was five.
On the bright side for device manufacturers, the report noted that in 2017, “there were no regulatory or enforcement actions (i.e. WL, IA, or Regulatory Meeting) at establishments associated with a PMA submission.”
CY 2017 FDARA Section 902 Annual Report on Inspections Facility Inspections Necessary to the Approval of Specified Human Drugs and Medical Devices