Strategies for Auditors to Prepare Clinical Research Personnel For a Regulatory Inspection: a Presentation by Paul Cobb, MPH, CCRA Clinical Auditor, IMARC Research

1. Strategies for Auditors to Prepare Clinical Research Personnel
For a Regulatory Inspection
Paul Cobb, MPH, CCRA
Clinical Auditor, IMARC Research

2. Agenda
• 2015 BIMO Metrics: Brief Review
• CPGMs and Preparation
• Recent Audit Findings/ Recommendations/ CAPAs
• Q & A

3. Industry Report Card – 2015
Clinical Investigator
Most common Clinical Investigator deficiencies noted during FDA inspections:
• Failure to follow the investigational plan and/or regulations
• Protocol deviations
• Inadequate recordkeeping
• Inadequate accountability for the investigational product
• Inadequate communication with the IRB/EC
• Inadequate subject protection – failure to report AEs and informed
consent issues
36% inspected had voluntary or official action indicated

4. Industry Report Card – 2015
Sponsor/Monitor/CRO
Most common Sponsor/Monitor/CRO deficiencies noted during FDA
inspections:
• Inadequate monitoring
• Failure to bring investigators into compliance
• Inadequate accountability for the investigational product
• Failure to obtain FDA and/or IRB approval prior to study
initiation
39% inspected had voluntary or official action indicated

5. Inspection Preparation: Sites and
Sponsors
• Review documentation, responses, processes through
the lens of the appropriate BIMO Inspectional checklist:
• CPGM 7348.811(Clinical Investigators)
• CPGM 7348.810 (Sponsors/Monitors/CROs)
• Results of BIMO checklist assess strengths, areas of
potential noncompliance, and opportunities for
improvement
• Assessment can inform coaching points and
recommendations for the inspection

6. Recent Audit Findings: Tailored
Preparation
• Results of recent BIMO preparation audits at sites and
sponsors
• Names and details have been altered
• Resulting recommendations used to prepare for
regulatory inspections

7. Failure to Follow the Protocol
(Sponsor)
Finding
• Pre-planned eligibility deviations were not
approved by the FDA and/or IRB
• Sponsor medical-monitor and project manager
granted enrollment “waivers”
• Multiple sites/subjects enrolled via “waivers”
• Not submitted to the FDA and/or IRB until after
subjects were enrolled

8. Failure to Follow the Protocol
(Sponsor)
Inspection Preparation
• Sponsor should review all “waivers” to ensure all have been
submitted to FDA/IRB and to ensure sponsor-team familiarity
in event of inspection
• Sponsor should review “waivers” to determine current clinical
and trial status
• The sponsor should add documentation regarding the
termination of the “waiver” process and re-training of relevant
clinical and quality personnel. Consideration should be given
to developing a new procedure for sponsor review of
potential subject eligibility

9. Inadequate Subject Protection
(Site)
Finding
• Subject’s primary care physicians were not informed of trial
participation:
• Informed consent document contained subject request for
PCP notification
• 75% of subjects enrolled at site indicated that they wanted
PCP notified of trial participation
• None of the subject’s PCPs were notified, enrollment had
been open for 18 months

10. Inadequate Subject Protection
(Site)
Inspection Preparation:
• Investigator should immediately notify PCPs of subjects who
indicated “YES” and documentation of this notification
should be filed
• Site should notify the IRB of the issue in accordance with
reporting guidelines
• The site team should create a procedure for ensuring that
all PCP notification requests are tracked and processed in a
timely fashion. Consider a new ICF CAPA.

11. Inadequate Device
Accountability(Sponsor)
Finding
• Incomplete records of device shipment, receipt, implant,
return, and final disposition.
• Project manager unable to provide current status of 15% of
devices that were shipped to the sites.
• Incomplete tracking of device location within Sponsor facility
(clean room, verification, repack, disposal)
• Sponsor does not maintain records of individual site
accountability; relies on monitors to verify during visits.

12. Inadequate Device
Accountability(Sponsor)
Inspection Preparation
• Sponsor clinical and quality teams should conduct a complete review of
device inventory and should ensure that records are available at the
inspection.
• Device accountability information should be verified with any previous
information provided to FDA (APR, etc.)
• Sponsor should implement procedures to ensure adequate surveillance
and tracking of devices including shipment, receipt, implant, return, and/or
final disposition.
• Sponsor should devise system to ensure site accountability records are
verified and maintained at the sponsor

13. Subject Records/Informed Consent
(Site)
Finding
• Co-Investigator wrote the date on the ICF for the subject:
• Previous instances of investigators dating for subjects
• Previous CAPA “retraining”
• Subject had completed follow-up visit and the consent form
was not corrected

14. Subject Records/Informed Consent
(Site)
Inspection Preparation
• The subjects should correct the errors at the next visits
• Site should review consents for enrolled subjects to ensure
errors have been noted, corrected by subjects if applicable,
submitted to IRB/sponsor if applicable
• Develop a new ICF process in which second staff member
signs off on process prior to subject leaving site

15. Summary
• Review site/sponsor documentation in
context of appropriate BIMO Inspectional
checklist
• 7348.811(Clinical Investigators) and
7348.810 (Sponsors/Monitors/CROs)
• Complete assessment of site/sponsor
including strengths, weaknesses, risk
areas
• Use assessment to design inspectional
strategies

16. References
• FDA’s Compliance Program Guidance Manual. Retrieved from
http://www.fda.gov/downloads/ICECI/EnforcementActions/
BioresearchMonitoring/ucm133773.pdf
• FDA’s Annual BIMO Inspection Metrics (2007-2015). Retrieved
from http://1.usa.gov/HLS1Lt

17. Thank you for your time.