Orientation Guide

1
Orientation Guide
Research and Development VAMC- Houston
Modified Dated 07-12-2007
2
Audit Process

• Audits from the RD office are to ensure
  compliance with requirements of the RD
  Committees.
• The following items are reviewed
• Essential documents and organization of these
  documents.
• 10 of current study subject charts are reviewed.
  This includes consents, amendments adverse
  events, and research notes.

3
FDA Audit

• FDA audit is designed to monitor all aspects of
  regulated research through
• Evidence of regulatory obligations
• Evidence that subject rights and welfare are
  protected
• Evidence that data filed by the sponsor are real.
• Evidence that sponsor and site regulatory
  obligations were met
• Consents are review for accuracy usually 100
• Who did what, when and why

4
FDA Audit

• Purpose is quality assurance, not quality
  control/monitoring
• Inspections must serve both a compliance
  function as well as a review function
• ANDREA BRANCHE
• INVESTIGATOR US FDA
• Houston Resident Post
• Dallas District

5
FDA Audit

• The clinical investigator is expected to
• Conduct the study according to protocol
• Personally conduct/supervise the study
• Ensure proper consent IRB review
• Report adverse events
• Read and understand investigators brochure
• Maintain adequate and accurate records
• Ensures IRB complies with CFR 50/56, (code of
  federal regulations) does initial and continuing
  review
• Promptly report to IRB all changes in research
  activity.

6
FDA Audit

• Audits issued by FDA centers will be
• Routine- QA on a percentage of all new trials,
  especially high patient enrollment, usually last
  3-7 days or
• Directed- or for cause, triggered by an event or
  circumstance, usually last for 7 days or longer
  due to
• a. Protocol violations
• b. falsifications
• c. non-compliance of informed consent.
• d. non-compliance of AE reporting
• e. non-compliance of drug accountability
• f. IRB problems

7
FDA Audit

• FDA inspector follows Compliance program, through
  the code of federal regulations (CFR)
• You should have available
• a. All Study documents
• b. Person knowledgeable about the study
• c. A place to review records
• d. Access to a copier
• The inspection is conducted in two parts
• a. process-reviewed (who,what, when and why)
• b. procedure for data obtained ( the
  management, storage and QA of records)

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FDA Audit
FDA Classification of Inspection 1. NAI- No
Action Indicated 2. VAI- Voluntary Action
Indicated 3. OAI- Official Action
Indicated Advisory Actions- Warning letters-
are sent only when violations are of regulatory
significance. Warning letters are issued by
district directors to inspected sites when
compliance with the laws enforced by the agency
has not been forthcoming.
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FDA Audit

• Before the Audit
• Notify all involved parties including RD office
  and consider a pre-inspection internal audit.
• During the Audit
• Cooperative and answer questions directly.
• Periodically attend to FDA investigator.
• Review and discuss deviations during the visit.

10
FDA Audit

• After the Audit
• Corrective actions should be addressed and
  implement.
• Provide, although not required, a written
  response to be submitted to the FDA within 10
  days of receiving the FDA 483, a verbal response
  maybe given during the exit visit.
• Identify with the individuals who may have been
  associated with or involved in wrongful acts.
• Discuss findings with all site personal.
• (Are You Audit Ready? , Robin Newman RN,
  MedTrials, Inc)

11
Audit by Sponsors

• Audits from sponsors focus on Guidelines
• All files are audited
• The focus remains on the guidelines and follow
  up
• Regulatory Documents
• Protocol Compliance
• Drug Accountability

12
Audit by Sponsors

• Verify that the rights and well being of the
  subjects are being protected.
• Verify that trial data are accurate and
  verifiable.
• Verify that the trial is being conducted in
  accordance with
• The Protocol
• Regulatory requirements
• GCP
• Monica Acree, CCRP
• Encysive Pharmaceuticals

13
Study Close out

• All subjects have completed the study.
• CRF collected, corrections made.
• Investigator obligations are met and ongoing
• All study procedures completed
• Monica Acree, CCRP
• Encysive Pharmaceuticals

14
Study Close out

• All data collected.
• Proper accounting/disposition of study product
  supplies.
• AE documentation
• Notification to the IRB
• Monica Acree, CCRP
• Encysive Pharmaceuticals