qa

Quality Assurance
Why Quality Matter in Clinical Research

Total Quality Management
– Total = Made Up of Whole
– Quality = Degree of excellence a
product/ service provides
– Management = Act / Art (manner of
Handling, controlling, directing, etc
……….)
• TQM is a art of managing the whole to

archive excellence
GCP is an international ethical and scientific Quality standard
for designing, conducting, recording and reporting trials that
involve the participation of human subjects.
Compliance with this standard provides public assurance that

the rights, safety and well being of trial subjects are protected
and that the clinical data are credible.
Introduction to Quality
Assurance
 All those planned and systematic actions
that are established to ensure that the trial
is performed and the data are generated,
documented (recorded), and reported in
compliance with Good Clinical Practice
(GCP) and the applicable regulatory
requirement (s).
How Quality can be
assured
• Standardization
• Quality Control
• Audit & Inspection
Quality Control VS Quality Assurance
QC QA
Role Part of the study Third‐party assurance of
conduct to ensure quality
quality
Responsible •Study team •Independent unit of sponsor /
persons •Monitor Organization
• Auditor
Activities •Monitoring •Audit : systemic &
Timing •Study duration independent examination
•One time point: routine & for-
cause
Summary Procedures that Procedures that verify that QC

ensure that the procedures are effective and
process is in control “the correct things are made”
and
“makes things
correctly”
What is Audit
Systematic and independent examination of trial related
activities and documents to determine whether the
evaluated trial related activities were conducted and
the data were recorded, analysed and accurately
reported according to the
- Protocol,
- Sponsor’s SOP
- Good Clinical Practice and
- Applicable Regulatory requirement
(ICH-GCP Sec 1.6)
What is difference between
Audit and Inspection
Audit Inspection
In Audit, Inspectors are In Inspection, Inspector are
employed of the company employed by government,
who work for a active clinical through the agency of the
quality assurance (CQA) regulatory or competent
function (i.e. Sponsor/CRO) Authority (i.e. FDA/DCGI)
To ensure that a site is

complying with Protocol, To ensure that trial related
SOP, GCP and Applicable obligations and acceptability
regulatory requirements. of resultant clinical data is in
support of a new drug
approval.
What triggers a request for an
Inspection/Audit
• In connection with a clinical study, An
inspection may be undertaken if there are
- Concerns about its safety, data or ethics
- Monitor standards of clinical research
- When there is suspicion of fraud or
scientific misconduct
- When there is serious quality systems
breakdown
Who Conduct Audit
• The following entities have rights to conduct the
Audit/Inspection at site based on regulation
- FDA:
- OHRP: ( Department of health and Human Services)
- The Sponsor of the clinical trial:
- Cooperative Groups/Grant-Funded Research;
(Cancer and leukemia Group B handbook)
- IRBs and Institutions:
What are Audited
• Site
• Investigators and Study Team
• IRB/IEC
• Sponsor
• CRO, if involved
• Laboratories
• Pharmacy (e.g. Investigational Drug
Services)
• Devices (e.g. ECG, Biomedical,
Engineering)
Why are studies Audited:
Routine Audits
(Study-oriented Inspection):
To ensure that a site is complying with Protocol, SOP, GCP and
Applicable regulatory requirements. This is referred as
“ROUTINE AUDIT”
FDA:
• To evaluate data supporting a new drug or device
application
Sponsor:
• To verify site data and conduct
• To verify how the study was monitored
Inhouse (CRO):
• To evaluate quality of research ongoing at the institution.
Cooperative Groups/Grant Funded Research:
• To Justify placing a grant
• Continuous Funding
• To Verify data
For-Cause Audit:
For-Cause:
(Investigator – oriented Inspection)
If the site is out of compliance and the sponsors want to
either verify the problem or be reassured that no problem
exists. This is referred as “FOR-CAUSE AUDIT”
• FDA / Sponsor/Inhouse (CRO)/ IRB:

• Allegation/Suspicion of non-compliance.
• Safety or efficacy data is inconsistent with other study
sites.
• PI conducting research outside area of specialty.
• Accrual is abnormally high for geographical or
ethnicity/race location.
When is Study Audited:
• At anytime during the study
• After the study is completed prior to regulatory approval

for the product
• At anytime after regulatory approval (15 years) if a safety

concern with the product (rare)
How they select site:
• Study oriented audits: • Investigator oriented audits
• Patient Enrollment: generally occur when the
Highest enrolling sites drug regulatory authority
• Patient Retension: has cause to suspect
Large number of screen particular research’s
failures, unusually high conduct i.e. “For-cause
patient drop-out rates Audit
• Adverse Events: Large
number of severe
adverse events at only
one or two sites
• Trial Importance: Pivotal
studies.
WHAT GETS AUDITED –
5 CATEGORIES
1. Regulatory and protocol compliance
2. Subject Records
3. Investigational Product
4. Adverse events, SAEs or complications
5. Documentation
Pre-Audit Procedures:
 CRC Preparation:
1. Notify all staff involved in study about the audit with date, time &
duration of the audit.
2. Ensure the Investigator’s attendance during the Audit.
3. Reservation/Arrangement for quiet, comfortable place to work
and to assemble the necessary documents for Auditor
4. Defined SOP/Agenda should be present and properly reviewed
by all staff involved in trial before audit about interaction of
auditor with site, from his welcome to exit
5. Assemble all study documents in one place, they should be
complete and well organized
6. Assure accessible photocopier, provide a backup if necessary (to
provide document when requested by them)
7. Confirm / Verify about the CRA’s presence during the Audit and
8. Review all the essential documents or any other problem which
is found during this review so that the situation may be able to be
remedied before audit
 CRA’s Preparation:
1. Review and verification of every essential document
should be complete and properly placed
2. Ensure resolution of unresolved queries before audit
3. Notify confirmation of audit agenda to site for conduct of
audit at selected site
 Auditor’s Preparation:
1. Auditor should have Audit plan/Agenda
2. Auditor may also prepare working documents for use
during audit, sometimes it becomes necessary to
generate Audit-specific working
3. Notify conduct of audit to CRA and Site
Audit Procedure (During):
 Auditors present their credentials (photo ID) & a Notice of
Inspections Form to the Clinical Investigator
 Conduct Introductory Meeting
 Auditor will start auditing by reviewing specific data related to
trial study and regulatory requirements. They will document
all their findings
 Auditor also interview site staff directly involved in trial
activities and process
Audit Procedure (During) cont:
• Auditor’ s common observations for study
1. Protocol Non-adherence
2. Inadequate & inaccurate records
3. Failure to report adverse events
4. Failure to report concomitant therapy
5. Inadequate drug accountability
6. IRB/IEC problems
7. Informed Consent issues
Audit Procedure (During) cont:
 Closing meeting (exit interview):

At site visit completion, Auditor conducts “exit
interview” with all responsible site personnel to:
• Review findings
• Clarify misunderstandings
• Describe any deviations from current regulations
• Suggest corrective action, if appropriate
 Auditor (FDA) may issue a Form FDA 483 (Notice of

Observation) to the Investigator. This form will detail the
findings from the audit that may constitute compliance
violation
After Audit Procedure:
After the Audit is complete, the Auditor prepares an:
• Audit certificate: A declaration of confirmation by the
auditor that an audit has taken place.
• Audit report / Establishment Inspection Report (EIR): A
written evaluation by the sponsor's auditor of the results
of the audit
• EIR Classification:
Classification Type of Letter

NA I (No A ction Indicated) Notice of no significant
deviations
VA I (Voluntary A ction Informational
Indicated)
OA I (Official A ction Warning
Indicated)
Thank You

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Quality Assurance

Why Quality Matter in Clinical Research

• TQM is a art of managing the whole to

Compliance with this standard provides public assurance that

Summary Procedures that Procedures that verify that QC

To ensure that a site is

• FDA / Sponsor/Inhouse (CRO)/ IRB:

• At anytime during the study

• After the study is completed prior to regulatory approval

• At anytime after regulatory approval (15 years) if a safety

4. Adverse events, SAEs or complications

 Closing meeting (exit interview):

 Auditor (FDA) may issue a Form FDA 483 (Notice of

Classification Type of Letter

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