Embed Size (px)
Citation preview
Device Clinical Trials and More…
Michael E. Marcarelli, PharmD
Director, Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health
US Food and Drug Administration
BIMO Program Description
• A comprehensive, Agency-wide program of on-site inspections and data audits designed to monitor all aspects of the conduct and reporting of
FDA-regulated research.
BIMO Program Objectives
• Protect the rights, safety, and welfare of human research subjects
• Assure the quality, reliability, and integrity of data collected
FDA Organization Chart
FDA
CDER CFSAN CVMCDRHNCTR CBER
Office of Compliance
Division of BIMO
ORA
PROGRAM ENFORCEMENT
BRANCH
SPECIAL INVESTIGATIONS
BRANCH
CDRH BIMO Program Responsibilities
• Regulatory Inspections– Develop and issue inspection assignments– Review and assess EIRs– Determine proper compliance action
• Integrity Program - Application Integrity Policy (AIP) - Integrity Hold (IH)
• Promotion and Advertising (P&A)– Investigational Devices
• Educational outreach
Who does CDRH BIMO Inspect?
• Clinical Investigators (CI)• Sponsors/Monitors/CROs• Institutional Review Boards (IRB)• Non-Clinical Labs (aka GLP)
CDRH Inspection Triggers
• Marketing application subject to MDUFMA • Novel Technology• Vulnerable Population• Complaint• Surveillance
• IRBs
What do we look at?
• Compliance programs• 7348.808/9/10/11• http://www.fda.gov/ora/compliance_ref/bimo/
• Intangibles• FDA Perception• Corporate culture• Oversight and control• Patterns of behavior or failures• Attitude
BIMO Inspections
• Section 704 FD&C Act• Generally will call to schedule
– What if they don’t?
• Credentials/NOI (Form FDA 482)• Use FDA Compliance Program
– Inspectional focus• Usually a specific study• Interviews• Document Reviews• Intangibles
BIMO Inspections (cont’d)
• INSPECTIONAL FINDINGS
– CLOSEOUT DISCUSSION w/MANAGEMENT
– SIGNIFICANT OBSERVATIONS (FDA Form 483)
• Prompt and adequate responses may be helpful.
• Help CIs respond to noted observations.
Written 483 Responses
• Assessment of the root cause of the problem
• Any corrective actions to correct the problem
• An evaluation of the extent of the problem
• Any preventative actions to avoid recurrence
• Supporting documentation
• Timelines for implementation
Written 483 Responses Should Include:
Compliance Tools
• Untitled/Warning letter• Re-inspection• Informal conference• 3rd party audits• Rejection of site data• Disqualification
– CI, IRB, or GLP
• Invoke Application Integrity Policy or Integrity Hold
• Revoke marketing or research permit
• Civil Money Penalties• Seizure• Injunction• Prosecution
CDRH BIMO INSPECTIONSFiscal Years 2002 - 2006
357 353 350332 336
100
200
300
400
500
FY02 FY03 FY04 FY05 FY06
CDRH BIMO INSPECTIONSFiscal Years 2002 - 2006
Inspected Entity 2002 2003 2004 2005 2006
Sponsor 72 81 73 70 53
CI 151 170 183 183 200
IRB 128 85 73 48 59
GLP 6 9 19 31 24
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 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 Sponsor Compliance Rates
19%
10%
24%
31%
15%11%
0%
10%
20%
30%
40%
50%
60%
70%
10 Years FY02 FY03 FY04 FY05 FY06
NAIVAIOAI
Most Common CDRHMost Common CDRHSponsor DeficienciesSponsor Deficiencies
• Inadequate monitoring
• Failure to secure investigator compliance
• Inadequate device accountability
• Failure to obtain FDA/IRB approval
CDRH Clinical Investigator Compliance Rates
11%15% 17%
21%
11%
17%
0%
10%
20%
30%
40%
50%
60%
70%
10 Years FY02 FY03 FY04 FY05 FY06
NAI
VAI
OAI
Common Investigator Deficiencies
• Failure to follow investigational plan, investigator agreement, or protocol
• Protocol deviations
• Inadequate subject protection or informed consent
• Inadequate device accountability
• Lack of FDA or IRB approval
What’s new?
• FDA Guidances– Final guidance: Use of Computerized
Systems in Clinical Trials– Draft guidance: AE Reporting to IRBs– Draft guidance: Supervisory Responsibilities
of Investigators
• CDRH– PAS– Pre IDE/PMA
What can be done to modernize clinical trials?
• Build quality into each step of the clinical trials process
• Utilize a risk-based approach to variation; define acceptable levels
• Modify regulatory approaches to enhance continuous improvement
• Develop and implement standardization for each step of process
Web Sites
Device Advicewww.fda.gov/cdrh/devadvice
CDRH BIMO sitewww.fda.gov/cdrh/comp/bimo.html
Good Clinical Practiceswww.fda.gov/oc/gcp/
Contact Information
Michael E. Marcarelli, PharmD
FDA, CDRH, Office of Compliance
9200 Corporate Blvd
HFZ-310
Rockville, MD 20850
(240) 276-0125
