What Blood Establishments and Biologics Companies Can Expect After an FDA Inspection

From blood supply to vaccines — blood establishments and biologics companies handle complex products that are fundamentally important to human life. It is no wonder that the industry faces some of the toughest regulations and standards today.

The Center for Biologics Evaluation and Research (CBER) is the primary FDA entity that regulates biological products. CBER also regulates medical devices and tests that protect blood and cellular products from infectious agents, as well as machines and software used to collect blood and blood components.

However, when it comes to inspection of blood and biologics companies, the Office of Regulatory Affairs (ORA) takes the lead, while CBER has the option of participating. ORA is the entity responsible for all of the FDA’s field activities. Both CBER and the Center for Drug Evaluation and Research (CDER) may choose to participate in pre-approval inspections of firms with submissions for a new drug/biological product.

For those who just survived an FDA inspection, or those preparing for one, the question is: What happens after inspection?

Patricia Holobaugh, chief of the Bioresearch Monitoring Branch in CBER’s Division of Inspections and Surveillance, outlined the post-inspection process for blood and biologics companies in a presentation at a conference sponsored by the Society of Clinical Research Associates last year. According to Holobaugh, here are some of the things you can expect after an FDA inspection.

End of Inspection
A Form FDA-483, which lists an FDA investigator’s observations, is presented and discussed. The inspection report is written by the investigator and submitted to CBER, which then evaluates the report and determines the appropriate corrective action.

Classification of Inspection
CBER classifies different inspections as NAI (no action indicated), VAI (voluntary action indicated), and OAI (official action indicated).

Possible Actions for OAI
If results of an inspection turn out to be of the OAI variety, the FDA action may focus on the inspected party, or on the application for a new product.

Actions for Inspected Party
Depending on the number and gravity of violations found during an inspection, an action may come in the form of a:

• Warning Letter, which requires a 15-day response
• Clinical investigator disqualification (a notice of Initiation of Disqualification Proceeding and Opportunity to Explain)
• Referral to FDA Office of Criminal Investigations for an injunction, seizure, or prosecution

Actions on Applications

• Clinical Hold: CBER may impose a clinical hold of a drug/biologic study or disapprove a device study
• Reject the Data: The FDA may reject data because they are inaccurate or incomplete. The agency might require additional study; it might delay approval of a BLA/NDA/PMA (biologic license application/new drug application/pre-market approval).
• Terminate IND (investigational drug application)/Withdraw IDE (investigational device exemption): This would end all studies. The sponsor must recall all unused drugs or devices.
• Withdraw approval of an NDA or a PMA, or revoke a BLA.

Read more about FDA inspections:

FDA Links

• Patricia Holobaugh’s Presentation
  Link

• CBER Compliance Program Guidance Manual
  Link

Additional Article

• Preparing for an FDA InspectionFull Article