FDA’s Bioresearch Monitoring (BIMO) Inspections

FDA BIMO inspections, Form 483 and Warning Letter

BIMO, the Bioresearch Monitoring Program, is a Food and Drug Administration (FDA) program of on-site inspections to ensure the quality and integrity of the data submitted to the agency from regulated clinical trials of investigational drugs, devices, and biologics. Inspections are made both in the U.S. and internationally at clinical investigator sites, institutional review boards (IRBs), and sponsors (e.g., pharmaceutical, medical device, and biologic companies, including monitors and contract research organizations or CR0s working under the sponsor).

Inspections are conducted by the following FDA Centers under the BIMO program:

  • CDRH – FDA Center for Devices and Radiologic Health
  • CDER – FDA’s Center for Drug Evaluation and Research
  • CBER – Center for Biologics Evaluation and Research
  • CVM – FDA’s Center for Veterinary Medicine

Following each BIMO inspection, FDA classifies the overall findings under one of three possible categories:

  • NAI (No Action Indicated) means that no objectionable conditions were noted during the inspection.
  • VAI (Voluntary Action Indicated) means that objectionable conditions or practices were found that depart from the regulations. The FDA will generally send a Warning Letter following a VAI inspection-finding.
  • OAI (Official Action Indicated) means that objectionable conditions or practices representing significant departures from the regulations were observed. An OAI finding on an inspection will generally result in a Warning Letter and/or administrative and regulatory sanctions.

 

FDA Bioresearch Monitoring (BIMO) Program Activity in 2007

FDA conducted 1024 total BIMO inspections in 2007, about the same as the prior year’s 1100 inspections. Half of all inspections in 2007 were classified NAI.

Of this total number of inspections in 2007:

636 were of clinical investigators (52% were NAI, 40% were VAI, 8% were OAI)

  • 367 by CDER
  • 183 by CDRH
  • 77 by CBER
  • 9 by CVM

221 were of IRBs (51% were NAI, 47% were VAI, 2% were OAI):

  • 101 by CDER
  • 92 by CDRH
  • 28 by CBER

88 were of Sponsors (54% were NAI, 24% were VAI, 22% were OAI):

  • 23 by CDER
  • 53 by CDRH [usually higher due to larger number of small device companies doing 1st clinical trial]
  • 12 by CBER

CDRH’s routine inspections focused on pediatric devices and drug-eluting stents in 2007 and, in 2008, on implantable orthopedic products and cardiovascular devices.

Between 2000 and 2005, FDA inspected only 1% of all clinical trial sites and 75% of the inspections were reviews of already-completed trials for data verification purposes pursuant to a marketing clearance application. Less than 40% of IRBs were inspected during that period.

More recently, FDA has intensified its commitment to this area and the number of inspections will undoubtedly rise. Areas of focus:

  • Informed Consent – content, timing, documentation
  • Protocol Compliance – inclusion/exclusion deviations, patient schedule
  • IRB reporting – notifications for protocol violations, Serious Adverse Events (SAEs), maintenance of ongoing approval
  • Disclosure and proper documentation of adverse events at the clinical trial site
  • Drug/Device accountability
  • Delegation of investigator responsibility to sub-investigators and other staff
  • Foreign clinical trial sites

Agency Initiatives:

  • Reducing  the time required to disqualify an investigator
  • Intensifying follow-up actions taken in response to VAI or OAI Warning Letters
  • Registration of IRBs
  • Improved tracking of current clinical trials
  • Better uniformity in the inspection reports