FDA Compliance Enforcement Actions: What you need to know for clinical device trials The 3 rd Annual FDA Regulatory and Compliance Symposium Track 3- Pharma

FDA Compliance Enforcement FDA Compliance Enforcement Actions: What you need to know Actions: What you need to know

for clinical device trialsfor clinical device trials

The 3The 3rdrd Annual FDA Regulatory and Compliance Symposium Annual FDA Regulatory and Compliance Symposium Track 3- Pharma Product Development and Clinical TrialsTrack 3- Pharma Product Development and Clinical Trials

August 23, 2007August 23, 2007Cambridge, MACambridge, MA

The 3The 3rdrd Annual FDA Regulatory Annual FDA Regulatory and Compliance Symposiumand Compliance Symposium

PRESENTED BY:PRESENTED BY:Sonali P. Gunawardhana M.P.H., J.D., Sonali P. Gunawardhana M.P.H., J.D., LL.M.LL.M.Regulatory CounselRegulatory CounselFood and Drug AdministrationFood and Drug AdministrationCenter for Devices and Radiological Center for Devices and Radiological HealthHealthOffice of ComplianceOffice of ComplianceDivision of Bioresearch MonitoringDivision of Bioresearch Monitoring

Devices vs. Drugs Devices vs. Drugs

How do studies with investigational How do studies with investigational devices differ from those with drugs and devices differ from those with drugs and biologics?biologics? Nature of industryNature of industry Statutory distinctionsStatutory distinctions Regulatory distinctionsRegulatory distinctions Research distinctionsResearch distinctions

Device FirmsDevice Firms

Entrepreneurial firms commonEntrepreneurial firms common 93% have fewer than 100 employees93% have fewer than 100 employees Venture capitalizedVenture capitalized

Diverse and specialized productsDiverse and specialized products Principles of operation and intended usesPrinciples of operation and intended uses

Device “developer” often involvedDevice “developer” often involved Minimal clinical trial experienceMinimal clinical trial experience Rapid product cycles limiting testing timeRapid product cycles limiting testing time

Statutory DistinctionsStatutory Distinctions

Devices lack market exclusivity provisionsDevices lack market exclusivity provisions Waxman-Hatch (drugs)Waxman-Hatch (drugs) Orphan drug (drugs/biologics)Orphan drug (drugs/biologics)

Differences in standards of approvalDifferences in standards of approval ““Substantial” adequate and well-controlled trials (drug)Substantial” adequate and well-controlled trials (drug) ““Reasonable” valid scientific evidence (device)Reasonable” valid scientific evidence (device)

Devices must down regulate Devices must down regulate FDAMA (1997) “least burdensome” provisionFDAMA (1997) “least burdensome” provision

Well-controlled investigationsWell-controlled investigations Partially controlled studiesPartially controlled studies Studies and objective trials without matched Studies and objective trials without matched

controlscontrols Well-documented case histories by qualified Well-documented case histories by qualified

expertsexperts Reports of significant human experience with a Reports of significant human experience with a

marketed devicemarketed device

Valid Scientific Evidence*Valid Scientific Evidence*

* 21 CFR 860.7

Research ApplicationsResearch Applications

Investigational New Drug (IND) applicationInvestigational New Drug (IND) application Covers all research (drugs and biologics)Covers all research (drugs and biologics) 21 CFR Part 31221 CFR Part 312

Investigational Device Exemption (IDE)Investigational Device Exemption (IDE) Covers significant risk researchCovers significant risk research

Implants, life-threatening, or sight-threatening Implants, life-threatening, or sight-threatening

21 CFR Part 81221 CFR Part 812

Regulatory DistinctionsRegulatory Distinctions

IDE exempt studiesIDE exempt studies In vitro diagnostics (IVDs)In vitro diagnostics (IVDs) In commercial use before May 28, 1976In commercial use before May 28, 1976 Consumer preference testingConsumer preference testing Solely for veterinary useSolely for veterinary use Post Approval StudiesPost Approval Studies

Marketing ApplicationsMarketing Applications

New Drug Application New Drug Application (NDA)(NDA) InnovatorInnovator 21 CFR Part 31421 CFR Part 314

Abbreviated New Drug Abbreviated New Drug Application (ANDA)Application (ANDA) Substantial equivalenceSubstantial equivalence 21 CFR Part 31421 CFR Part 314

Biologics Licensing Biologics Licensing Application (BLA)Application (BLA) InnovatorInnovator 21 CFR Part 60121 CFR Part 601

Premarket Approval Application Premarket Approval Application (PMA) (PMA) New Use, Technology, or Class IIINew Use, Technology, or Class III 21 CFR Part 81421 CFR Part 814

Premarket Notification (510(k))Premarket Notification (510(k)) Substantial equivalenceSubstantial equivalence 21 CFR Part 80721 CFR Part 807

Humanitarian Device Exemption Humanitarian Device Exemption (HDE)(HDE) Similar to Orphan ProductSimilar to Orphan Product 21 CFR Part 81421 CFR Part 814

In Vitro Diagnostics (IVDs)In Vitro Diagnostics (IVDs) 21 CFR Part 80921 CFR Part 809

Product DistinctionsProduct Distinctions

vsvs..

Charging for Investigational Charging for Investigational ProductsProducts

Devices: Always have been able to Devices: Always have been able to charge in order to recoup the research charge in order to recoup the research cost. This request for reimbursement is cost. This request for reimbursement is generally submitted in the IDE.generally submitted in the IDE.

Drugs: Special request is made for Drugs: Special request is made for reimbursement – this was not the norm in reimbursement – this was not the norm in the past but now there is a move towards the past but now there is a move towards making it easier for reimbursement.making it easier for reimbursement.

Combination ProductsCombination Products

Types of productsTypes of products Drug/device, biologic/device, drug/biologic, or Drug/device, biologic/device, drug/biologic, or

drug/device/biologicdrug/device/biologic Products are assigned to lead Center based upon Products are assigned to lead Center based upon

primary mode of actionprimary mode of action Other Centers provide consulting reviewsOther Centers provide consulting reviews

Product is required to follow regulation of lead Product is required to follow regulation of lead CenterCenter

Important to seek early consultationImportant to seek early consultation FDA’s Office of CombinationFDA’s Office of Combination ProductsProducts

Enforcement ActionsEnforcement Actions

REASONS WHY SOME OF THESE REASONS WHY SOME OF THESE ACTIONS ARE IMPLEMENTED:ACTIONS ARE IMPLEMENTED:

Untitled Letters/Warning Letters Untitled Letters/Warning Letters Application Integrity Policy/ Integrity Application Integrity Policy/ Integrity

HoldHold Notice of Initiation of Disqualification Notice of Initiation of Disqualification

Proceedings and Opportunity to Explain Proceedings and Opportunity to Explain (NIDPOE)(NIDPOE)

Compliance ToolsCompliance Tools

Untitled/Warning letterUntitled/Warning letter Re-inspectionRe-inspection Informal conferenceInformal conference 3rd party audits3rd party audits Rejection of site dataRejection of site data DisqualificationDisqualification

CI, IRB, or GLPCI, IRB, or GLP

Invoke Application Invoke Application Integrity Policy or Integrity Integrity Policy or Integrity HoldHold

Revoke marketing or Revoke marketing or research permitresearch permit

Civil Money PenaltiesCivil Money Penalties InjunctionInjunction ProsecutionProsecution

Untitled LettersUntitled Letters

■■ Untitled Letters are issued when Untitled Letters are issued when substantial violations are documented substantial violations are documented during inspection and requests voluntary during inspection and requests voluntary corrective action.corrective action.

■■Unlike Warning Letters, Untitled Letters Unlike Warning Letters, Untitled Letters are not posted on the FDA website.are not posted on the FDA website.

Warning LettersWarning Letters

The Warning Letter is the agency’s principal The Warning Letter is the agency’s principal means of notifying regulated industry of means of notifying regulated industry of violations (prior notice) and achieving prompt violations (prior notice) and achieving prompt voluntary correction.voluntary correction.

The Warning Letter clearly states that if there is The Warning Letter clearly states that if there is a failure to promptly achieve correction the a failure to promptly achieve correction the FDA may take enforcement action without any FDA may take enforcement action without any further notice.further notice.

CDRH BIMO INSPECTIONSCDRH BIMO INSPECTIONSFiscal Years 2002 - 2006Fiscal Years 2002 - 2006

357 353 350332 336

100

200

300

400

500

FY02 FY03 FY04 FY05 FY06

CDRH BIMO INSPECTIONSCDRH BIMO INSPECTIONSFiscal Years 2002 - 2006Fiscal Years 2002 - 2006

InspecteInspected Entityd Entity 20022002 20032003 20042004 20052005 20062006

SponsorSponsor 7272 8181 7373 7070 5353

CICI 151151 170170 183183 183183 200200

IRBIRB 128128 8585 7373 4848 5959

GLPGLP 66 99 1919 3131 2424

14

44

3024

9

31

0

5

10

15

20

25

30

35

40

45

50

FY01 FY02 FY03 FY04 FY05 FY06

CDRH BIMO Warning Letters

7

2018

10

6

3

7

3

3

1

24

17

7

2

7

3

0

10

20

30

40

50

FY02 FY03 FY04 FY05 FY06

GLP

IRB

Sponsor

CI

CDRH BIMO Warning Letters

CDRH BIMO Compliance RatesCDRH BIMO Compliance Rates

13% 12%17%

24%

15%11%

0%

10%

20%

30%

40%

50%

60%

70%

10 Years FY02 FY03 FY04 FY05 FY06

NAI

VAI

OAI

CDRH BIMO OAI Rates CDRH BIMO OAI Rates (with & w/o “For Cause” Inspections)(with & w/o “For Cause” Inspections)

13%

16%

9%

5%

10%

17%

24%

15%

11%

7%

0%

10%

20%

30%

10 Years FY03 FY04 FY05 FY06

OAI (NFC) OAI NFC = No “For Cause” inspections included

CDRH Sponsor Compliance RatesCDRH Sponsor Compliance Rates

19%

10%

24%

31%

15%11%

0%

10%

20%

30%

40%

50%

60%

70%


NAIVAIOAI

CDRH Sponsor Compliance RatesCDRH Sponsor Compliance Rates

19%

10%

24%

31%

11% 10%15%

0%

10%

20%

30%

40%

50%

60%

70%

10Years

FY02 FY03 FY04 FY05 FY06 FY06(NFC)

NAIVAIOAI

Sponsor Deficiencies Sponsor Deficiencies Fiscal Years 1999 - 2006Fiscal Years 1999 - 2006

FYFY

19919999

2002000 0

20020011

20020022

20020033

20020044

2002005 5

20020066

Inadequate Inadequate monitoringmonitoring

65%65% 68%68% 65%65% 33%33% 37%37% 40%40% 24%24% 23%23%

Failure to Failure to secure secure investigator investigator compliancecompliance

27%27% 44%44% 27%27% 19%19% 24%24% 21%21% 15%15% 13%13%

Inadequate Inadequate device device accountabilityaccountability

23%23% 28%28% 19%19% 7%7% 19%19% 16%16% 18%18% 15%15%

Obtain FDA/IRB Obtain FDA/IRB approvalapproval

4%4% 18%18% 11%11% 8%8% 5%5%

CDRH Clinical Investigator CDRH Clinical Investigator Compliance RatesCompliance Rates

11%15% 17%

21%

11%

17%

0%

10%

20%

30%

40%

50%

60%

70%


NAI

VAI

OAI

CDRH Clinical Investigator CDRH Clinical Investigator Compliance RatesCompliance Rates

11%15% 17%

21%17%

11%

7%

0%

10%

20%

30%

40%

50%

60%

70%

10Years


NAI

VAI

OAI

Common Investigator Common Investigator DeficienciesDeficiencies

Follow investigational plan, investigator Follow investigational plan, investigator agreement, or protocolagreement, or protocol

Protocol deviationsProtocol deviations Inadequate subject protection or informed Inadequate subject protection or informed

consentconsent Inadequate device accountabilityInadequate device accountability Lack of FDA or IRB approvalLack of FDA or IRB approval Inadequate reporting of UADEs to Sponsor or Inadequate reporting of UADEs to Sponsor or

IRBIRB

CDRH IRB Compliance RatesCDRH IRB Compliance Rates

13%9%

14%

8%5%

17%

7%0%

10%

20%

30%

40%

50%

60%

70%

10Years


NAI

VAI

OAI

IRB DeficienciesIRB DeficienciesFiscal Years 1999 - 2006Fiscal Years 1999 - 2006

FYFY

19919999

20020000

20020011

20020022

20020033

20020044

20020055

20020066

Inadequate Inadequate initial &/or initial &/or continuing continuing reviewreview

64%64% 56%56% 39%39% 24%24% 25%25% 50%50% 37%37% 38%38%

Inadequate Inadequate minutesminutes

61%61% 42%42% 35%35% 11%11% 42%42% 28%28% 17%17% 20%20%

Lack of or Lack of or incorrect SR/NSR incorrect SR/NSR determinationdetermination

58%58% 42%42% 57%57% 10%10% 16%16% 34%34% 22%22% 7%7%

Inadequate Inadequate membership membership rosterroster

31%31% 22%22% 30%30% 13%13% 20%20% 21%21% 12%12% 12%12%

Addendum: FY06 – Lack of Quorum & Reporting Non-Compliance 12%

CDRH BIMO OAI CDRH BIMO OAI Follow-up Inspections (as of 9/30/06)Follow-up Inspections (as of 9/30/06)

18%

30%

52%NAIVAIOAI

N = 64

Recidivist OAIs evenly distributed across program areas:

GLP = 17%

IRB = 25%

CI = 33%

S/M = 25%

CDRH BIMO Vulnerable CDRH BIMO Vulnerable Population InspectionsPopulation Inspections

10%

58%

32%

NAIVAIOAI

N = 164

OAI split among Sponsor (44%) and Clinical Investigator (56%) programs

CDRH BIMO COMPLIANCE RATESCDRH BIMO COMPLIANCE RATESFY06: All Inspections vs. ComplaintsFY06: All Inspections vs. Complaints

NAI

VAI

OAI

11%

36%

53%

All Inspections Complaints

17%

35%

48%

333% higher OAI rate in complaint follow-ups

CDRH BIMO COMPLIANCE RATESCDRH BIMO COMPLIANCE RATESFY97-06: All Inspections vs. ComplaintsFY97-06: All Inspections vs. Complaints

NAI

VAI

OAI

14%

31%

55%

All Inspections Complaints

28%

26%

46%

230% higher OAI rate in complaint follow-ups over a 10 year period

What does AIP mean?What does AIP mean?

Application Integrity PolicyApplication Integrity Policy

■■What is “Wrongful Act”?What is “Wrongful Act”?

■■What is an “Untrue Statement of What is an “Untrue Statement of Material Fact”?Material Fact”?

Wrongful ActWrongful Act

“…“…A wrongful act is any act that may subvert A wrongful act is any act that may subvert the integrity of the review process. A wrongful the integrity of the review process. A wrongful act includes but is not limited to, submitting a act includes but is not limited to, submitting a fraudulent application, offering or promising an fraudulent application, offering or promising an illegal gratuity, or making an untrue statement illegal gratuity, or making an untrue statement of material fact. A wrongful act also includes of material fact. A wrongful act also includes submitting data that are otherwise due to, for submitting data that are otherwise due to, for example, a pattern of errors whether caused by example, a pattern of errors whether caused by incompetence, negligence, or a practice such as incompetence, negligence, or a practice such as inadequate standard operating procedures or a inadequate standard operating procedures or a system-wide failure to ensure the integrity of system-wide failure to ensure the integrity of data submissions…”data submissions…”

Untrue Statement of Material Untrue Statement of Material FactFact

“…“…An “untrue statement of material fact” An “untrue statement of material fact” is a false statement, misstatement, or is a false statement, misstatement, or omission of fact. A determination that an omission of fact. A determination that an untrue statement is material is necessary untrue statement is material is necessary for purposes of invoking the AIP…”for purposes of invoking the AIP…”

Materiality- Under DevelopmentMateriality- Under Development Agent- Under DevelopmentAgent- Under Development

Examples of Wrongful ActsExamples of Wrongful Acts

Submit Fraudulent ApplicationSubmit Fraudulent Application Offer Bribe/Illegal GratuityOffer Bribe/Illegal Gratuity Make Untrue Statement of Material FactMake Untrue Statement of Material Fact Submit Data Otherwise UnreliableSubmit Data Otherwise Unreliable Omitted DataOmitted Data Manufactured DataManufactured Data Altered DataAltered Data Other Data Inconsistencies Other Data Inconsistencies

Examples of Data Integrity Examples of Data Integrity ProblemsProblems

Falsification of Specific Data or an Entire Falsification of Specific Data or an Entire SubmissionSubmission

Omission of Relevant and Important Data and Omission of Relevant and Important Data and InformationInformation

Inability to Account for Patient PopulationInability to Account for Patient Population Inability to Account for Investigational DevicesInability to Account for Investigational Devices Failure to Maintain Adequate Investigational Failure to Maintain Adequate Investigational

RecordsRecords Unreported Changes to the Investigational Unreported Changes to the Investigational

DeviceDevice

ProcessProcess: : Pre-Discovery StagePre-Discovery Stage

Tips from Anonymous/Known InformantTips from Anonymous/Known Informant Current/Former EmployeesCurrent/Former Employees Former Business PartnersFormer Business Partners PatientsPatients Other Agencies (SEC, FTC, CMS)Other Agencies (SEC, FTC, CMS) Suspicious Data Found During Suspicious Data Found During

Scientific/Clinical ReviewScientific/Clinical Review Observations During Pre-Approval InspectionObservations During Pre-Approval Inspection

Process: Inspection StageProcess: Inspection Stage

Inspection of Company/ SponsorInspection of Company/ Sponsor Inspection of Clinical SitesInspection of Clinical Sites Inspections of CRO’sInspections of CRO’s Inspection of Clinical SitesInspection of Clinical Sites

• Data AuditData Audit• System AuditSystem Audit• Company Internal DocumentsCompany Internal Documents

Invoking the AIPInvoking the AIP

Pattern or Practice of Wrongful ConductPattern or Practice of Wrongful Conduct Significant Question of Data ReliabilitySignificant Question of Data Reliability System-wide FailuresSystem-wide Failures Decision made by Center Director, The Decision made by Center Director, The

Division of Bioresearch Monitoring and Division of Bioresearch Monitoring and The Office of Device Evaluation Integrity The Office of Device Evaluation Integrity Officer Officer

Agency’s ActionAgency’s Action

Defer Scientific ReviewDefer Scientific Review Issues Letter to ApplicantIssues Letter to Applicant Conducts Validity AssessmentConducts Validity Assessment

Scope, extent of problemScope, extent of problem InspectionInspection Audit ReportAudit Report

Applicant’s ResponsibilitiesApplicant’s Responsibilities

Cooperation with FDACooperation with FDA Internal Review (Audit)Internal Review (Audit) Independent Outside ConsultantIndependent Outside Consultant Identify/Remove IndividualsIdentify/Remove Individuals Submit CAPSubmit CAP

Commit to Safety, Efficacy and QualityCommit to Safety, Efficacy and Quality Describe Ethics/Compliance ProgramsDescribe Ethics/Compliance Programs Standard Operating ProceduresStandard Operating Procedures Steps to Address and Prevent Wrongful ActsSteps to Address and Prevent Wrongful Acts

Application Withdrawal, Patient Notification, Application Withdrawal, Patient Notification, Product Recall etc.Product Recall etc.

Global Industry IssuesGlobal Industry Issues

Systems to identity and/or address Systems to identity and/or address regulatory shortcomingsregulatory shortcomings

Systems to correct/prevent recurring Systems to correct/prevent recurring issuesissues

Accountable company cultureAccountable company culture Environment of conflict of interestEnvironment of conflict of interest

FDA ResponsibilitiesFDA Responsibilities

Review of Corrective Action PlanReview of Corrective Action Plan

Field Onsite Inspection & RecommendationField Onsite Inspection & Recommendation

Headquarters ReviewHeadquarters Review

Letter to ApplicantLetter to Applicant Center Director’s Signature Center Director’s Signature

Application Integrity ProgramApplication Integrity Program

““Fraud, Untrue Statements of Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Material Facts, Bribery, and Illegal Gratuities; Final Policy,”Gratuities; Final Policy,”

56 F.R. 46191, 9/10/9156 F.R. 46191, 9/10/91http://www.fda.gov/ora/fr/fraud_ill_grat.htmlhttp://www.fda.gov/ora/fr/fraud_ill_grat.html

http://www.fda.gov/ora/fr/fraud_ill_grat.html

Application Integrity ProgramApplication Integrity Program

ApplicationApplication Integrity PolicyIntegrity Policy

RPM Chapter 10RPM Chapter 10http://www.fda.gov/ora/compliance_ref/rpm_new2/rpm10aip.hhttp://www.fda.gov/ora/compliance_ref/rpm_new2/rpm10aip.htmltml

““Points to Consider for Internal Points to Consider for Internal Reviews and Corrective Action Reviews and Corrective Action Operating PlansOperating Plans””

http://www.fda.gov/ora/compliance_ref/aip_points.htmlhttp://www.fda.gov/ora/compliance_ref/aip_points.html

http://www.fda.gov/ora/compliance_ref/rpm_new2/rpm10aip.html

http://www.fda.gov/ora/compliance_ref/rpm_new2/rpm10aip.html

Program Offices/ContactsProgram Offices/Contacts

ODE/OIVD Integrity OfficerODE/OIVD Integrity Officer Carl DeMarco: 240-276-3993Carl DeMarco: 240-276-3993 Division of Bioresearch Monitoring, Division of Bioresearch Monitoring,

Office of ComplianceOffice of Compliance Michael Marcarelli: 240-276-0125Michael Marcarelli: 240-276-0125 Application Integrity Policy CommitteeApplication Integrity Policy Committee FDA Office of Criminal InvestigationsFDA Office of Criminal Investigations

Notice Of Initiation Of Disqualification Notice Of Initiation Of Disqualification Proceedings And Opportunity To ExplainProceedings And Opportunity To Explain

Applies to Clinical InvestigatorsApplies to Clinical Investigators Some clinical investigators may have Some clinical investigators may have

already received a Warning Letter but in already received a Warning Letter but in some cases violations discovered on the some cases violations discovered on the first inspection are serious enough for the first inspection are serious enough for the Center to issue the NIDPOE.Center to issue the NIDPOE.

Disqualification Of Disqualification Of Clinical InvestigatorsClinical Investigators

Disqualification Of Disqualification Of Clinical InvestigatorsClinical Investigators

A NIDPOE letter informs the recipient clinical investigator that A NIDPOE letter informs the recipient clinical investigator that FDA is initiating an administrative proceeding to determine FDA is initiating an administrative proceeding to determine whether the clinical investigator should be disqualified from whether the clinical investigator should be disqualified from receiving investigational products pursuant to the Food and Drug receiving investigational products pursuant to the Food and Drug Administration's regulations. Generally, FDA issues a NIDPOE Administration's regulations. Generally, FDA issues a NIDPOE letter when it believes it has evidence that the clinical investigator letter when it believes it has evidence that the clinical investigator repeatedly or deliberately violated FDA's regulations governing the repeatedly or deliberately violated FDA's regulations governing the proper conduct of clinical studies involving investigational proper conduct of clinical studies involving investigational products or submitted false information to the sponsorproducts or submitted false information to the sponsor. .


Definition under CFR 812.119Definition under CFR 812.119

If FDA has information indicating that an investigator If FDA has information indicating that an investigator has repeatedly or deliberately failed to comply with the has repeatedly or deliberately failed to comply with the requirements of part 812, part 50, or part 56 of this requirements of part 812, part 50, or part 56 of this chapter, or has repeatedly or deliberately submitted chapter, or has repeatedly or deliberately submitted false information either to the sponsor of the false information either to the sponsor of the investigation or in any required report, the Center for investigation or in any required report, the Center for Devices and Radiological Health will furnish the Devices and Radiological Health will furnish the investigator written notice of the matter under investigator written notice of the matter under complaint and offer the investigator an opportunity to complaint and offer the investigator an opportunity to explain the matter in writing, or, at the option of the explain the matter in writing, or, at the option of the investigator, in an informal conferenceinvestigator, in an informal conference. .


If an explanation is offered and accepted by the If an explanation is offered and accepted by the Center for Devices and Radiological Health, the Center for Devices and Radiological Health, the disqualification process will be terminated. If disqualification process will be terminated. If an explanation is offered but not accepted by an explanation is offered but not accepted by the Center for Devices and Radiological Health, the Center for Devices and Radiological Health, the investigator will be given an opportunity for the investigator will be given an opportunity for a regulatory hearing under part 16 of this a regulatory hearing under part 16 of this chapter on the question of whether the chapter on the question of whether the investigator is entitled to receive investigational investigator is entitled to receive investigational devices.devices.


After evaluating all available information, including After evaluating all available information, including any explanation presented by the investigator, if the any explanation presented by the investigator, if the Commissioner determines that the investigator has Commissioner determines that the investigator has repeatedly or deliberately failed to comply with the repeatedly or deliberately failed to comply with the requirements of this part, part 50, or part 56 of this requirements of this part, part 50, or part 56 of this chapter, or has deliberately or repeatedly submitted chapter, or has deliberately or repeatedly submitted false information either to the sponsor of the false information either to the sponsor of the investigation or in any required report, the investigation or in any required report, the Commissioner will notify the investigator, the sponsor Commissioner will notify the investigator, the sponsor of any investigation in which the investigator has been of any investigation in which the investigator has been named as a participant, and the reviewing IRB that the named as a participant, and the reviewing IRB that the investigator is not entitled to receive investigational investigator is not entitled to receive investigational devices. The notification will provide a statement of devices. The notification will provide a statement of basis for such determination. basis for such determination.


Each investigational device exemption (IDE) Each investigational device exemption (IDE) and each cleared or approved application and each cleared or approved application submitted under this part, subpart E of part 807 submitted under this part, subpart E of part 807 of this chapter, or part 814 of this chapter of this chapter, or part 814 of this chapter containing data reported by an investigator who containing data reported by an investigator who has been determined to be ineligible to receive has been determined to be ineligible to receive investigational devices will be examined to investigational devices will be examined to determine whether the investigator has determine whether the investigator has submitted unreliable data that are essential to submitted unreliable data that are essential to the continuation of the investigation or essential the continuation of the investigation or essential to the approval or clearance of any marketing to the approval or clearance of any marketing application.application.


Consent AgreementsConsent Agreements List specific responsibilities of the Clinical List specific responsibilities of the Clinical

Investigator in terms of coming into Investigator in terms of coming into compliance.compliance.

Can last for a specific amount of time or can be Can last for a specific amount of time or can be an agreement the disqualification is permanent.an agreement the disqualification is permanent.

Can be viewed as a tool to bring the Clinical Can be viewed as a tool to bring the Clinical Investigator into compliance which in turn Investigator into compliance which in turn serves as a way to educate the Clinical serves as a way to educate the Clinical Investigator as to their regulatory responsibility Investigator as to their regulatory responsibility for the current and future clinical trials.for the current and future clinical trials.


What does disqualification mean for the What does disqualification mean for the Sponsor?Sponsor? The data from the disqualified clinical site The data from the disqualified clinical site

can not be used in their submission. can not be used in their submission. (Monetary and Ethical considerations)(Monetary and Ethical considerations)

Sponsor is responsible for oversight of all Sponsor is responsible for oversight of all clinical investigators so there might be some clinical investigators so there might be some serious issues in terms of monitoring which serious issues in terms of monitoring which can lead to further regulatory action.can lead to further regulatory action.


What does disqualification mean for the What does disqualification mean for the clinical investigator?clinical investigator? Their name is added to a list on the FDA Their name is added to a list on the FDA

website that indicates that they are website that indicates that they are disqualified from participation in any type of disqualified from participation in any type of clinical trial.clinical trial.

Generally it means that they have incurred Generally it means that they have incurred legal fees and it can open them up to more legal fees and it can open them up to more eminent liability.eminent liability.

Some might feel that it has had a negative Some might feel that it has had a negative impact on their reputations.impact on their reputations.

Web SitesWeb Sites

Device Advice

www.fda.gov/cdrh/devadvice

CDRH BIMO sitewww.fda.gov/cdrh/comp/bimo.html

Contact InformationContact Information

Sonali P. GunawardhanaSonali P. Gunawardhana

FDA, CDRH, Office of ComplianceFDA, CDRH, Office of Compliance

9200 Corporate Blvd9200 Corporate Blvd

HFZ-310HFZ-310

Rockville, MD 20850Rockville, MD 20850

(240)276-0246(240)276-0246

[email protected]@fda.hhs.gov