session 6: data integrity and inspection of e-clinical computerized systems
Post on 25-Feb-2016
49 Views
Preview:
DESCRIPTION
TRANSCRIPT
Session 6: Data Integrity and Inspection of e-Clinical Computerized Systems
May 15, 2011 | Beijing, China
Kim NitaharaPrincipal Consultant and CEOMETA Solutions, Inc. (USA)
www.diahome.org 2
• To understand data integrity and its relation to computerized systems used in clinical trials
• To review key issues related to the inspection of e-clinical computerized systems
Drug Information Association
Purpose of this session:
www.diahome.org 3
• Data Integrity • Regulatory Requirements for e-Clinical
Computerized Systems• Inspection of e-Clinical Computerized
Systems– Expectations– Results
Drug Information Association
Topics to be discussed:
www.diahome.org 4
• What is Data Integrity?• How is Data Integrity Lost?• How Do We Ensure Data Integrity?• Why is Data Integrity Important?
Drug Information Association
Data Integrity Topics:
www.diahome.org 5
• Data Integrity is the “validity” of the data for its intended purpose and use– Accurate– Complete– Reliable– Accessible– Enduring
Drug Information Association
What is data integrity?
www.diahome.org 6
• Human Errors and Tampering• Storage and Transfer Errors• Software Errors• Software Viruses• Hardware Malfunction• Disasters
Drug Information Association
How is data integrity lost?
Loss of Data Control
Loss of Data Integrity
7
• Personnel Training• Procedural Controls
– SOPs– Quality Assurance and Management
• Computerized Systems Controls– Error Detection and Correction– System Validation
• Information Technology (IT) Controls– Backup and Disaster Recovery Plans– Network Security
www.diahome.orgDrug Information Association
How do we ensure data integrity?
www.diahome.org 8
• Clinical Trials Data May be Used to Make Important Decisions– Industry– Regulatory Agencies– Public
• Data May be Re-Used in the Future– Repeated Analysis– New Purposes
Drug Information Association
Why is data integrity important?
Data Integrity is a Regulatory Requirement
www.diahome.org 9
• How Do Agencies Ensure Data Integrity?• What is Expected During Inspections?• What Are the Requirements?
Drug Information Association
Regulatory requirements topics:
www.diahome.org 10
• Regulations and Guidance• Review of Submitted Data• Independent Analysis of Data• On-Site Inspections
1) They Provide Requirements2) They Confirm Adherence
Drug Information Association
How do agencies ensure data integrity?
www.diahome.org 11
• Effective controls for trustworthy data• Accurate and complete records• Reliable systems and processes• Secure data, systems and facilities• Qualified and trained personnel
Requirements to Ensure Data Integrity
Drug Information Association
What is expected during inspections?
www.diahome.org 12
Provided in:• Regulations• Guidelines and Guidance for Industry• Compliance Policy Guides; Program
Manuals; Advisory Documents• Published Presentations
Drug Information Association
What are the requirements?
www.diahome.org 13
“An investigator is required to prepare and maintain adequate and accurate case histories… and other data…”
Drug Information Association
Example of US FDA Regulation
(FDA 21 CFR 312.62 Investigator Recordkeeping and Record Retention)
www.diahome.org 14
“Systems with procedures that assure the quality of every aspect of the trial should be implemented.”
Drug Information Association
Example of ICH Guidance
(ICH E6 Good Clinical Practice; Consolidated Guidance)
www.diahome.org 15
• (FDA/ICH) E6 “Good Clinical Practice: Consolidated Guidance” (April 1996)
• (FDA) “Computer Systems Used in Clinical Investigations” (May 2007)
• (FDA) “Part 11, Electronic Records; Electronic Signatures – Scope and Application” (August 2003)
These Are Not Regulations
Drug Information Association
Examples of FDA and ICH Guidance
www.diahome.org 16
– “Clinical Investigators” (CP 7348.811)– “Sponsors, CROs and Monitors” (CP
7348.810)
These are used by FDA personnel(and are useful to you!)
Drug Information Association
Examples of US FDA ComplianceProgram Manuals
www.diahome.org 17
• What does FDA ask during inspections?• What records are inspected?• What has FDA observed?• What is FDA’s response to deficiencies?
Drug Information Association
Computerized System Inspection Topics:
www.diahome.org 18
• Were there any problems experienced during the course of the study?
• What is the source of data entered into the computer? Direct (no paper)? Case report form? Office record? Other?
(CP 7348.811 Clinical Investigators)
Drug Information Association
What does FDA ask during inspections?
www.diahome.org 19
• What is the source of the hardware and software?
• Who enters data? When?
• How are data changed? By whom?
• Is an audit trail produced?(CP 7348.811 Clinical Investigators)
Drug Information Association
What does FDA ask during inspections?
www.diahome.org 20
• “If a firm is keeping eRecords or using eSignatures determine if they are in compliance with 21 CFR 11.”
• “At a minimum, ensure that:”– Corrective Action Plan is in Progress– Accurate/Complete Copies Available– Employees Are Held Accountable and
Responsible(CP 7348.810 Sponsors, Monitors and CROs)
Drug Information Association
What does FDA Ask during inspections?
www.diahome.org 21
• Software Development Documentation
• Validation Plans and Documentation
• System Description/Configuration Diagram
• System Operations Records
• Configuration and Change Control RecordsDrug Information Association
What records are inspected?
www.diahome.org 22
• Personnel Training Procedures and Records
• Data Collection and Transmission Controls
• IT Security Procedures and Records• Emergency and Back-up Procedures and
Records
Drug Information Association
What records are inspected?
www.diahome.org 23
• Lack of programming standards and conventions
• No documents describing the intended function(s), operation and performance of software
• Failure to test software at its operational limits
• Incomplete test documentationDrug Information Association
What has FDA observed?
www.diahome.org 24
• The firm did not monitor and keep track of changes to hardware, application or operating system software.
• There was no validation data to show that the system gave accurate and reliable results
• There was no written validation plan reviewed or approved by management
Drug Information Association
What has FDA observed?
www.diahome.org 25
• No documentation of training of persons engaged in writing, validating or supporting computer programs
• No written SOPs for user operations, security guidelines, software revision control, virus detection, disaster recovery, and database backup and audit trail archival.
Drug Information Association
What has FDA observed?
www.diahome.org 26
• The audit trail switch was intentionally disabled and prevented the recording of data that was modified or edited
• There is no written procedure to describe the process that is used to assign, maintain passwords and access levels to the system
• There were no restrictions on who could create, rename, or delete data.
Drug Information Association
What has FDA observed?
www.diahome.org 27
• Lack of validation• Validation protocols for upgraded software
do not contain diagrams or lists of hardware configurations and peripheral devices within the system.
• The validation team and individual responsibilities are not specified
Drug Information Association
What has FDA observed?
www.diahome.org 28
• Form FDA 483 Inspectional Observations (“483”)
• Establishment Inspection Report (EIR)• Notification to assigning Center• Regulatory sanctions for violations
Drug Information Association
What is FDA’s response to deficiencies?
www.diahome.org 29
“If initial findings indicate the firm’s electronic records and/or …signatures may not be trustworthy and reliable, or when …systems inhibit meaningful FDA inspection, a more detailed evaluation may be warranted.”
(CP 7348.810 Sponsors, CROs and Monitors)
FDA may perform another inspectionDrug Information Association
What is FDA’s response to deficiencies?
www.diahome.org 30
“In addition to a response to the deficiencies noted earlier in this letter, please outline your firm's global corrective action plan, including timeframes for correction, to address this Part 11 issue…”
FDA Warning Letter
Drug Information Association
What is FDA’s response to deficiencies?
www.diahome.org 31
“When substantial and significant part 11 deviations exist, FDA will not accept use of electronic records and …signatures to meet the requirements of the applicable predicate rule.”
(CP 7348.810 Sponsors, CROs and Monitors)
FDA may not accept the clinical trials data
Drug Information Association
What is FDA’s response to deficiencies?
www.diahome.org 32
• Data Integrity • Regulatory Requirements for e-Clinical
Computerized Systems• Inspection of e-Clinical Computerized
Systems– Expectations– Results
Drug Information Association
Summary of discussed topics:
www.diahome.org 33
• Regulatory agencies establish regulations and guidance to ensure clinical trials data quality and integrity
• Regulatory agencies confirm compliance with regulations to ensure that clinical trials data and reports are accurate and reliable for their purposes
Drug Information Association
Conclusions:
www.diahome.org 34
• Regulatory agencies generally follow their standard procedures when they conduct their inspections of e-clinical systems
• If deficiencies are found during inspections, regulatory agencies have the authority to take actions, including rejection of clinical trials data.
Drug Information Association
Conclusions (continued):
www.diahome.org 35
Questions and discussion
kim.nitahara@metasol.com
Drug Information Association
top related