Anatomy GCP Insp TothAllen FDA USA

8/13/2019 Anatomy GCP Insp TothAllen FDA USA

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Anatomy of a GCP Inspection

Jean Toth-Allen, Ph.D.

APEC GCP Inspection Workshop

May 28, 2008

FDA has a Long History ofGCP Inspecting


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GCP Inspectional Activity

FDA conducts approximately 1100 GCP (BIMO)inspections per year

Clinical Investigators (600-700/year)IRBs/Ethics Committees (200-300/year)Sponsors/Monitors/CROs (50-100/year)Bioequivalence facilities (50-100/year)

Approximately 80 of these investigatorinspections (per year) are outside of the U.S.

BIMO Inspections CompletedFY 2007


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FDAs Authority to Inspect

FDA has regulatory authority to inspectstudies conducted under a U.S. IND or IDE

(research permit) Addressed as an element of informed consent

FDAs ability to inspect is a criterion foraccepting non-U.S. non-IND studies insupport of a U.S. IND or NDA and non-U.S.data to support an IDE, PMA, or 510(k)

Bioresearch Monitoring(BIMO) -1-


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Bioresearch Monitoring(BIMO) -2-

Headquarters BIMO staff:Interact with Center reviewers

Issue inspection assignments (GCP & GLP)Interact with FDAs BIMO investigatorsReview and classify inspection reportsIssue post-inspectional correspondenceTake part in regulatory actionsProvide staff for BIMO investigator trainingProvide speakers for outreach activities

Inspection Assignments


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Focus of GCP Inspections

When assigned on receipt of marketingapplications, the main focus is the data audit

BIMO reviewers who issue assignmentsCoordinate with FDAs application reviewers toidentify sties and special issues or concernsSupply FDA investigators with relevant materialcontained in the marketing applicationInclude data line listings for essential data

commonly that supporting primary and secondaryendpoints and documenting adverse events

Site Selection -1-


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Site Selection -2-

Study site selection generally based onSubject enrollmentData concerns

Adverse eventsSite compliance historyStudy specific issues, such as sub-studiesperformed at only a limited number of sites

Timeliness of Inspections


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Support for FDA GCPInspections

BIMO reviewers and application reviewersare available to support FDAs investigators

Either as part of the on-site team or asconsultants

Includes support for primary data auditincluding ECGs, laboratory tests, X-rays, andpathology/ radiology reports

Qualifications/Training ofFDA Field Investigators


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Planning and Preparation -1-

Center BIMO reviewer issues assignment to theDistrict Office closest to the site (or to theinternational coordinator)

An FDA Investigator/Inspector is usually assignedfrom the receiving District Office (or from theinternational cadre)FDA investigator often a GCP/BIMO specialist Investigator assigned conducts assignment alone oras part of an inspection team

Another FDA investigatorBIMO and/or application reviewer



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FDA Investigator/Inspector (continued)May request additional site-specific

information from the investigator or the studysponsorPlans the Inspection

Scientific Preparation Audit Plan

Inventory of RecordsOpening Interview

Conduct of Inspection -1-


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Secondary interviews of key study personnel

Plan for these at the outset of the inspectionConsider additional interviews during theinspection



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Inventory the study records Are essential documents available ? (ICH GCP

Section 8) Are any essential documents missing ?

The Data Audit strongly emphasized by FDA,particularly for inspections triggered bymarketing submission

Both will be discussed in more depth later today



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Research subject protection (ethics)Ethics Committee Review

Identify the IEC name, locationWere required approvals obtained anddocumented by the clinical investigator ?

Were approvals obtained in advance ofstudy initiation and in advance of anychanges to the protocol ?

Were required reports made to the IEC ?



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Supporting laboratories and diagnostictesting facilities

Identify nature and locationIf on-site, consider inspection to:

Verify availability of required equipmentConfirm authenticity of lab/diagnostic data



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Concluding the inspection Verify objectionable findings

Discuss and confirm with the clinicalinvestigator or site staff during theinspection if possible

Develop a written list of objectionablefindings (the Form FDA 483)

Close-out Discussion: more later

Reporting andDocumentation -1-


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Reporting andDocumentation -2-

An abbreviated report can be generatedwhen there are no objectionable findings

But when very serious GCP violations arefound, the enforcement process requireseven further communications andopportunities for the inspected party torespond to FDA

FDA International GCPInspections -1-


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FDA International GCPInspections -2-

Inspections must address the specificquestions and needs of FDAs review team

for that specific application and clinicaltrial as well as assure overall compliancewith GCPThe procedures for inspecting are thesame whether for a U.S. or non-U.S. site

FDA International CI Inspections

Gabon 1 Peru 6Algeria** 1


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CDRH International BIMOInspections (since 1991)

Sponsor inspections:

Australia Austria

CanadaFinlandFranceIsraelItalyNetherlandsSwedenSwitzerlandUnited Kingdom

(2 Sponsor and 9 CI inspections in FY07)

CI inspections:

Austria SwedenBelgium Switzerland

Canada BrazilDenmark ThailandFrance China, TaipeiGermany United KingdomIsraelItalyMexicoNetherlandsSpain

FDA Experience in Asia/Pacificis Still Very Limited


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Center Total

CBER 3

CDER 104

CDRH 11

Totals 118

International GCP InspectionsCompleted: FY 2007


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Disclaimer :

The information within this presentationis based on the presenter's expertise andexperience, and represents the views of the presenter for the purposes of a

training workshop.

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Anatomy GCP Insp TothAllen FDA USA