QUALITY CONTROL AND QUALITY ASSURANCE
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WHY QA & QC To ensure clinical data accuracy and
integrity, it is necessary to thoroughly review these data, to assess the validity of data and to carefully document query identification and resolution throughout a study's duration.
Maintaining accuracy and quality throughout a clinical study is a continual, dynamic process
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Understanding “Quality”
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DEFINITIONS Conformance to the standards.
Achieving excellence in a product/service by meeting/exceeding the requirements of the customer.
A refined process in which products are assessed, improved, ensured, and confirmed.
Quality means producing a defect free product from both manufacturer and customer’s viewpoint.
"Quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skillful execution; it represents the wise choice of many alternatives."
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Good quality product
Identify the needs/
requirements/
expectations of the
customer
Keep the PROACTIVE
PLAN in place
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PROACTIVE PLAN
QCQA
Make the QUALITY happen 6
Understanding “Quality Control”
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QC(ICH sec 1.47) : Operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial related activities have been fulfilled.
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Understanding “Quality Assurance”
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QA(ICH sec 1.46) all those planned and systemic actions that are established to ensure that the trial is performed and data are generated, recorded and reported in compliance with GCP and regulatory requirements .
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QC vs QA
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QC QA
helps to identify
abnormalities/inconsistencies
helps to prevent
abnormalities/inconsistencies
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QC QA
verification process
preventive process
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QC QA
it is the responsibility of a scientist
it is the responsibility
of management
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QC QA
will not perform QA
activity.
will perform QC activities to validate
the system.
so also called “QA over QC”
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QUALITY
Tries to find out the defects
QC QA
Tries to prevent the
defects 16
BENEFITS OF QUALITY SYSTEMS
Quality improvement
Work culture improvement
Teamwork Improved
Less waste and reworks Increased productivity
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QUALITY AND STANDARDS
Quality can be defined as:1. A standard of excellence2. Having or showing excellence3. Superiority in performance4. Suitability of intended purpose
A more tangible definition would be ADHERENCE TO STANDARDS
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THE QUALITY PLAN
The quality plan describes how the quality control and quality assurance processes will be applied throughout the clinical trial
Operational QC QC plan for each key operational stage of the
study that defines standards against which QC will be conducted
E.g. acceptable quality levels E.g. appropriate methods to report and
distribute results.
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THE QUALITY PLAN
PROTOCOL REVIEW During the study design phase, QC personnel
provide an independent review of the approved proposed protocol.
CRF The QC plan includes comparison of the
study's CRF to the objectives set forth in the protocol to ensure that it is designed to collect all necessary data
CRF FILLING GUIDELINES A requirement to review CRF completion
guidelines is also an element of the QC plan.20
FOR OVERALL SITE MANAGEMENT, A COMPLETE QC PLAN ADDRESSES
FOLLOWING
Investigator selection and qualifications – experience in conducting clinical trials
– experience with the specific indication– not on the FDA's restricted or debarred lists– adequate staff and facilities– personal involvement
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STUDY CONDUCT (MONITORING)
– subject informed (signed informed consent form)– subject's eligibility (inclusion/exclusion)– protocol compliance– adverse events (AEs) and concomitant medication– drug accountability and storage
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SOURCE DOCUMENT VERIFICATION
– medical records– lab data– progress notes– diagnostic tests
query resolution completed data clarification forms compliance with regulations
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FIVE BASIC VARIABLES
1. Man2. Materials3. Methods4. Equipment5. Environment
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THE ROLE OF QA FUNCTION Confirm GCP compliance Act as a catalyst for quality
improvement Provide advice on GCP matters Provide help with training clinical
research staff To help establish a quality and
compliance based culture
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CLINICAL TRIALS – GCP ASPECTS
Design Conduct Performance
Good Clinical PracticeGood Clinical PracticeGCP StandardsGCP Standards
Reporting
Monitoring Analysis Recording Audits26
ASSURANCE BY GCP
Credibilityof data
Accuracyof data
ASSURANCEASSURANCE
Protection of Rights,Integrity & Confidentiality
of Trial Subjects27
CLINICAL TRIALS – GLP ASPECTS
LaboratoryRecords
BioanalyticalMethods
Controls
Assurance of Compliance to Assurance of Compliance to Regulations (GLP aspects)Regulations (GLP aspects)
Facilities(Laboratory)
Equipment &Instruments
Personnel(Analysts)
WorkPractices
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ROLE OF QUALITY ASSURANCE
COMPLIANCETO GCP
COMPLIANCETO GLP
COMPLIANCE TOSTUDY PROTOCOL
COMPLIANCE TOSOPs / WGs
COMPLIANCE TO OTHERAPPLICABLE REGULATORY
REQUIREMENT(S)
QUALITY ASSURANCE (QA)QUALITY ASSURANCE (QA)
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HOW IS IT ENSURED ?
Screening ofVolunteers
ClinicalChemistry
ClinicalResearch
Implementation ofImplementation ofQUALITY SYSTEMSQUALITY SYSTEMS
Bioanalytical
ProjectManagement
TechnologyServices
Pharmacokinetics& Biostatistics
QualityAssurance
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HOW IS IT MEASURED / ENSURED ?
In-processAudits
RetrospectiveAudits
Compliance to the RequirementsCompliance to the Requirements(GCP, GLP, SOPs, Protocol and others)(GCP, GLP, SOPs, Protocol and others)
System Audits &Other Internal
Audits
ManagementReview Meetings
Quality ControlExternal Auditsby Sponsors /
Regulatory Bodies31
CLINICAL AUDIT POLICY QA is independent to systems and
persons Agreement and commitment of all QA
persons. Applied on clinical trial process as well
as data Audits are done during as well as after
trial Applied to each part of clinical
development process 32
SYSTEMS AUDITS
Adverse event handling and reporting Staff training records Standard Operating Procedures Equipment records Facilities Procedural inspections Archiving
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ADVERSE EVENT HANDLING
All staff aware of reporting AE procedure
SOPs available for reporting AEs Documentation to demonstrate timely
and satisfactory handling of AEs Regulatory reporting requirements
fulfilled
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STAFF TRAINING Job description must be created for
each member of staff A CV Training records Organizational chart of the company Procedures and SOPs
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STANDARD OPERATING PROCEDURES
Ensure that they are consistent with:
Relevant international regulations Local requirements eg Thai FDA Guidelines such as ICH-GCP Company policies and procedures
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EQUIPMENT RECORDS An SOP describing the use of the
equipment The service and maintenance
requirements of the equipment Records to illustrate that the use,
service and maintenance of the equipment occurred in accordance with requirements
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FACILITIES
Certain in-house facilities, for example , for human volunteer studies, may need to comply with specific standards. QA need to verify for compliance.
Eg. ABPI guidelines on standards for the facilities in which studies on non-patient volunteers are conducted.
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ARCHIVING A dedicated facility An individual responsible An index of the archive contents Records of entry and data examined Data should be logged into the archive within
a resonable period of time Appropriate data protection measures SOPs
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MASTER SCHEDULE
Aware of planned studies and must have a copy
Plans audits necessary to support the study Maintains its own audit plans study by study
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RESPONSIBILITIES OF QA PERSONNEL Maintain all approved protocol and
SOP’s and have access to up-to-date master schedule
Verify Protocol Conduct audits – Study based, facility,
processed (record to be retained) Audit records and final reports Training organizational personnel in
regulatory requirements41
RESPONSIBILITIES OF QA PERSONNEL Report inspection report to
management/study director/ principal investigator
Prepare and sign a QA statement Acting as the laboratory contact point
for regulatory and other inspections Maintaining record of quality assurance
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REQUIREMENTS FOR FUNCTIONING Written SOPsRepresentative list Quality assurance units aims, scope and
organization Selection and training of QAU SOPs Conducting study phase inspection Conducting study data inspection Conducting process inspection Final report audit Preparing QA statement
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REQUIREMENTS FOR FUNCTIONING
Documented training program Encompassing all aspects of QA work Where ever possible include on-the-job
experience Training in communication techniques
and conflict handling(advisable) Training documented and evaluated
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QUALIFICATION OF QA PERSONNEL
Training, expertise and experience Familiar with test procedures, standards and
systems Understand the basic concepts underlying the
activities being monitored
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QUALITY SYSTEMS
Organizational Structure
– Well defined functional departments and organograms
– Clearly identified and written job responsibilities of employees
– Continuous training to the employees
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QUALITY SYSTEMS
Operational Procedures
– Quality manual of the Organization
– Study specific Protocols
– Department wise SOPs and Working Instructions for conduct of study related activities
– Review of SOPs & Working Instructions periodically
– Design of study specific Protocols
– Evaluation of technical changes through Change Control system
– SOPs / Protocol deviations handling procedure47
NEED FOR QA IN CHANGING CLINICAL TRIALLANDSCAPE
More studies, more sites, greater volume New players in the role (CROs)
New technologies (Electronic Records, Electronic CTD ofdossiers)
Stringent regulatory requirements(EC Directives – 2001/20/EC)
Increasing inspections by Regulatory Authorities(WHO, USFDA, MHRA-UK etc.)
More participation by vulnerable subjects
Global expansion48
Internal audits by Quality Assurance
– In-process Audits– Retrospective Audits of raw data generated during
study / reports / documents– System Audits– Pre-inspection audit– Follow up audit– For cause (Investigational)
QUALITY SYSTEMS
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WHAT DOES QA DO ?
QA Assures:
Readiness of site for any external audit
Internal processes are effectively implemented
Data generated is valid & verified
Study personnel are compliant
Avoid reworks !!50
QA POLICIES AND PROCEDURESQA SOPS Review of clinical study protocols Audit of clinical study reports Audit of clinical study data bases Investigator site audit Filing and archiving of QA records Training of QA staff Review of SOPs Inspection of clinical study files Review of data handling procedures Inspection of CROs Review of computer systems Handling of fraud Systems inspection
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THE ROLE OF QA IN COMPUTER SYSTEMSCHECK FOR MINIMUM DOCUMENTATION TO DEMONSTRATE:
System is clearly defined including objectives A formal validation policy and master plan
exists Systems and its functions are adequately
tested (test protocols, records of testing, lists of tests performed)
Procedures for making any changes Security of the system Electronic archiving of the data and related
SOPs Necessary documentation and SOPs exists in
the production area52
EFFECTIVE QUALITY MANAGEMENT1. Anticipate errors
- Look for all the ways a process could fail and then make improvements to ensure that it doesn’t
2. Procedures- Develop clear systems and procedures
3. Train- Ensure that staff are trained for the tasks they perform
4. ValidateAll operations must be validated
5 Avoid short-cuts- Follow SOPs
6. Control change- Uncontrolled change can cause non-compliance
7. Challenge what you do-Regularly check that systems meet applicable standards53
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