HELP!HELP!The FDA is Coming! The FDA is Coming!

Margaret M. Groves, JD, CRAMargaret M. Groves, JD, CRADirector, Clinical Trials Quality Assurance (CTQA)Director, Clinical Trials Quality Assurance (CTQA)

School of Medicine (SOM) Compliance OfficeSchool of Medicine (SOM) Compliance Office

AgendaAgenda

What do I do?What do I do?General PreparationGeneral Preparation– Organize FilesOrganize Files

FDA Audit PlanFDA Audit PlanSOM Compliance Office SOM Compliance Office – Advisory RoleAdvisory Role– Organizational ChartOrganizational Chart– Contact InformationContact Information

What to do when the FDA calls to What to do when the FDA calls to schedule a site visit …schedule a site visit …

Obtain the following information: Obtain the following information: – Call date– Starting date/ Expected duration– Name of the person making the call– Telephone number for questions– FDA Investigator contact information/Title– Additional FDA Investigators names?

Ask Questions

Who / what is being inspected? Wait for specific answers. Do not make suggestions.Which clinical trial/studyPrincipal Investigator/Co-Investigator(s)Other details?Why is the inspection being done? Wait for the answer. Do not make suggestions.Routine (i.e. IND)?Directed (for cause)?Follow-up (i.e. 483; warning letter)?

Other Details?Does the FDA want specific personnel available?– If yes, then list

Who/When?Does the FDA want specific documents available?

– If yes, then list

Does the FDA want any of these documents sent prior to their arrival? – How? Send to overnight registered address? Use

certified mail.– Delivery by when?

What should I do first? What should I do first?

Please immediately send notification to the following individuals in the SOM Compliance Office:

• Tina Tyson, JD, Chief Compliance OfficerTina Tyson, JD, Chief Compliance Officer

Tina.tyson@duke.edu / 668-0679

• Margaret Groves, JD, Director CTQA Margaret.clarke@duke.edu / 684-3133 / 684-3133

General PreparationGeneral Preparation

Notify parties involved with your studyNotify parties involved with your study– Sponsor ( if required)Sponsor ( if required)– Study teamStudy team– SBRSBR– IRBIRB– University Counsel’s OfficeUniversity Counsel’s Office– Pharmacy (if applicable)Pharmacy (if applicable)– Laboratories (if applicable)Laboratories (if applicable)– Medical Records (if applicable)Medical Records (if applicable)

General Preparation (cont’d)General Preparation (cont’d)

Respond in an appropriate and timely fashionRespond in an appropriate and timely fashion

Request necessary medical records and/or Request necessary medical records and/or electronic case report form accesselectronic case report form access

Reserve workspace for reviewer/auditorReserve workspace for reviewer/auditor

Arrange for a large table, as well as phone and Arrange for a large table, as well as phone and copier accesscopier access

Organize FilesOrganize Files

Regulatory Regulatory – Protocol (all versions)Protocol (all versions)– Investigator Brochure (all versions)Investigator Brochure (all versions)– Protocol AmendmentsProtocol Amendments– FDA Form 1571/1572 (all versions)FDA Form 1571/1572 (all versions)– Investigator AgreementsInvestigator Agreements– CVs for PI and StaffCVs for PI and Staff– Medical LicensesMedical Licenses– IND/IDE DocumentsIND/IDE Documents– Enrollment/Screening LogsEnrollment/Screening Logs– Delegation of Authority LogDelegation of Authority Log– Drug Package InsertDrug Package Insert

Organize Files (cont’d)Organize Files (cont’d)IRB FilesIRB Files– Approval Letter for Initial Protocol with Original Approval Letter for Initial Protocol with Original

Consent FormConsent Form– All Continuing Review Approval Letters and Original All Continuing Review Approval Letters and Original

Updated Consent Forms Updated Consent Forms – All Amendment Approvals All Amendment Approvals – All Versions of Consent Documents for Screened and All Versions of Consent Documents for Screened and

Enrolled SubjectsEnrolled Subjects– All Status/Progress Reports for:All Status/Progress Reports for:

IRB Approved Renewal(s) IRB Approved Renewal(s) Adverse EventsAdverse EventsDeathsDeathsStudy TerminationStudy TerminationFinal SummaryFinal Summary

Organize Files (cont’d)Organize Files (cont’d)

Correspondence and Phone LogsCorrespondence and Phone Logs– All Sponsor CorrespondenceAll Sponsor Correspondence– All CRO CorrespondenceAll CRO Correspondence– All FDA CorrespondenceAll FDA Correspondence– All IRB CorrespondenceAll IRB Correspondence– Monitoring and Auditing LogsMonitoring and Auditing Logs

Organize Files (cont’d)Organize Files (cont’d)

LaboratoryLaboratory– Laboratory Certification and Normal RangesLaboratory Certification and Normal Ranges– Up to Date CV of Laboratory DirectorUp to Date CV of Laboratory Director

Research Test Article AccountabilityResearch Test Article Accountability– Receipt LogReceipt Log– Dispensing LogDispensing Log– Return and Destruction LogReturn and Destruction Log– Storage Temperature LogStorage Temperature Log

Organize Files (cont’d)Organize Files (cont’d)

Subject DocumentationSubject Documentation– Complete Case Report Forms for Each Subject Complete Case Report Forms for Each Subject

Enrolled Enrolled – Complete Source Documents for Each Subject Complete Source Documents for Each Subject

EnrolledEnrolled– Verification of Inclusion/Exclusion CriteriaVerification of Inclusion/Exclusion Criteria– Contact CRSO to Request Limited Access to Contact CRSO to Request Limited Access to

eBrowser for FDA eBrowser for FDA

On-Site ConductOn-Site ConductResponding to FDA:Responding to FDA:– Be concise, direct, and truthful Be concise, direct, and truthful

– Answer only questions asked, do not volunteer Answer only questions asked, do not volunteer informationinformation

– Ask for clarification if you do not understand a Ask for clarification if you do not understand a questionquestion

– If you don’t know an answer, say so, don’t guessIf you don’t know an answer, say so, don’t guess

– Tell the auditor if you later realize you gave incorrect Tell the auditor if you later realize you gave incorrect informationinformation

Ensure that all staff are educated on proper Ensure that all staff are educated on proper conduct during an FDA Inspection.conduct during an FDA Inspection.

FDA Audit PlanFDA Audit Plan

Review of Each Subject Enrolled or Possibly Review of Each Subject Enrolled or Possibly Only Those Chosen for ReviewOnly Those Chosen for Review– Are case report forms complete for each subject?Are case report forms complete for each subject?– Are data collection forms complete?Are data collection forms complete?– Is inclusion/ exclusion criteria documented?Is inclusion/ exclusion criteria documented?

FDA Audit Plan (cont’d)FDA Audit Plan (cont’d)

Review of Source Documentation for Each Review of Source Documentation for Each Subject Enrolled that Documents the Following:Subject Enrolled that Documents the Following:– Condition of the Subject at the Time of Entry (Inclusion/ Condition of the Subject at the Time of Entry (Inclusion/

Exclusion Criteria)Exclusion Criteria)– Exposure to Research ArticleExposure to Research Article– Concomitant MedicationsConcomitant Medications– Clinical Assessments of the Subject During the StudyClinical Assessments of the Subject During the Study– Laboratory ReportsLaboratory Reports– Diagnostic TestsDiagnostic Tests– Dose ModificationDose Modification– Adverse Events/DeathsAdverse Events/Deaths– Protocol ExemptionsProtocol Exemptions– Early TerminationEarly Termination

FDA Audit Plan (cont’d)FDA Audit Plan (cont’d)

Review of Files/LogsReview of Files/Logs– RegulatoryRegulatory– IRBIRB– Correspondence and Phone LogsCorrespondence and Phone Logs– LaboratoryLaboratory– Research Test ArticleResearch Test Article

FDA Audit Plan (cont’d)FDA Audit Plan (cont’d)

At the conclusion of the on–site review, there will At the conclusion of the on–site review, there will be an Exit Meeting:be an Exit Meeting:– Typical FindingsTypical Findings

No Actions IndicatedNo Actions Indicated

Voluntary Actions IndicatedVoluntary Actions Indicated

FDA 483 Inspectional ObservationsFDA 483 Inspectional Observations

If you receive a 483, please call SOM If you receive a 483, please call SOM Compliance Office immediately so that we can Compliance Office immediately so that we can assist you with your responses!assist you with your responses!

SOM Compliance OfficeSOM Compliance OfficeAdvisory RoleAdvisory Role

Not Just about Human Subject/Billing Reviews Not Just about Human Subject/Billing Reviews or Other Risk Areasor Other Risk Areas– A Source of Information and Guidance on Compliance A Source of Information and Guidance on Compliance

AreasAreas– Prevention of Future Compliance Problems through Prevention of Future Compliance Problems through

EducationEducation– Educational Compliance ReviewsEducational Compliance Reviews

Contact the SOM Compliance Office:Contact the SOM Compliance Office:

The IntegrityLine: 1-800-826-8109.The IntegrityLine: 1-800-826-8109. - Compliance concerns can be reported- Compliance concerns can be reported anonymously. anonymously.

Non-retaliation and non-retribution policy Non-retaliation and non-retribution policy

Reporting Compliance Concerns

Compliance Office Organizational ChartCompliance Office Organizational Chart

Compliance Office Contact Information

Tina R. Tyson, Chief Compliance Officer, Tina R. Tyson, Chief Compliance Officer, tina.tyson@duke.edu tina.tyson@duke.edu

CTQA and Billing Compliance,CTQA and Billing Compliance, ctqa@mc.duke.edu ctqa@mc.duke.eduMargaret Groves, Director, Margaret Groves, Director, margaret.clarke@duke.edumargaret.clarke@duke.eduAliki Martin, Senior Compliance Auditor, Aliki Martin, Senior Compliance Auditor, ahm@notes.duke.eduahm@notes.duke.eduNancy Szczech, Senior Compliance Auditor, Nancy Szczech, Senior Compliance Auditor, nancy.szczech@duke.edu nancy.szczech@duke.edu Natasha Tapp, Compliance Auditor, Natasha Tapp, Compliance Auditor, natasha.tapp@duke.edunatasha.tapp@duke.edu

Compliance Review ServicesCompliance Review ServicesRenée deGuehery, Director, Renée deGuehery, Director, degue001@mc.duke.edudegue001@mc.duke.eduTara Clayton, Senior Compliance Auditor, Tara Clayton, Senior Compliance Auditor, tara.clayton@duke.edu tara.clayton@duke.edu Mike Petrichko, Senior Compliance Auditor, Mike Petrichko, Senior Compliance Auditor, petri006@mc.duke.edupetri006@mc.duke.eduMichele Ragland, Compliance Auditor, Michele Ragland, Compliance Auditor, ragla009@duke.eduragla009@duke.edu

Compliance Integrity Line 1-800-826-8109

Questions?Questions?