Developing and Implementing a

Comprehensive Clinical QA Audit

Program
Henry Li1,*, Susan Hawlk2, Kim Hanna1, Gerald Klein1 and Steve Petteway Jr.1
1
Talecris Biotherapeutics, 79 T. W. Alexander Drive, Research Triangle Park, North Carolina, USA
2
QA Consultant, Acworth, Georgia, USA

Summary
The Clinical Quality Assurance (CQA) audit program is a key element of a Good
Clinical Practice (GCP) quality system. The objective of a CQA audit program is to
ensure that trial conduct and data quality meet protocol-specified, GCP, and
applicable regulatory requirements. Due to the increasing complexity of clinical
trials and regulatory scrutiny, the components of a CQA audit program and the
approaches taken towards designing and managing audits are constantly evolving.
In this paper, we will focus on the strategies that are used to develop and implement
a CQA audit program, including types of audits to be conducted and the quality
approaches taken to manage and improve the CQA audit program. Copyright #
2008 John Wiley & Sons, Ltd.

Key Words: audit; inspection; good clinical practice (GCP); quality assurance; clinical trial

Introduction various types of audits. Depending on the size

The fundamental principles of Good Clinical
Practice (GCP) are protection of human subject’s
rights and safety as well as the validity and
accuracy of data generated from clinical trials to
support regulatory submissions. Trial sponsors
are required by the International Conference on
Harmonisation (ICH) guidelines to implement
and maintain quality assurance and quality
control systems to achieve these objectives [1].
Sponsors typically employ a Clinical Quality
Assurance (CQA) unit who oversees the quality
and compliance of clinical studies by conducting
*Correspondence to: Henry Li, Talecris Biotherapeutics,
79 T. W. Alexander Drive, Research Triangle Park, North
Carolina 27709, USA. E-mail: henry.li@talecris.com
and maturity or development and commerciali-
zation stage of pharmaceutical or biotechnology
companies, the CQA audit programs can be
quite different from sponsor to sponsor [2,3]. In
today’s ever evolving regulatory climate, design-
ing and implementing a CQA audit program can
be particularly challenging for a new CQA unit:
where to start and what to audit.
In this paper, we describe a comprehensive
CQA audit program that is based on current
industry practices using a variety of clinical
audits to assess GCP compliance. A risk-based
audit approach is proposed in order to tailor
the program to a given company’s needs.
Preparation of Standard Operating Procedures
(SOPs) and the conduction of training are
critical for successfully implementing a CQA

Qual Assur J 2007; 11, 128–137.

Published online in Wiley InterScience
Copyright r 2008 John Wiley & Sons, Ltd. (www.interscience.wiley.com) DOI: 10.1002/qaj.420
Developing and Implementing a Comprehensive Clinical QA Audit Program
audit program. The execution of audits and
follow-up on corrective action progress and
application of the lessons learned to all company
trials are key steps to ensure that audits
continually add value in improving clinical
development. Furthermore, the CQA audit
program should be periodically reviewed to
assess its effectiveness in ensuring that the
clinical research continues to be conducted to
the highest quality and compliance level.
Regulatory Requirements on the
Sponsor GCP Quality Assurance Audit
Program
The ICH E6 Guideline for Good Clinical
Practice provides specific requirements and
recommendations on developing and maintain-
ing quality assurance and quality control sys-
tems for ensuring quality and compliance of
trials [1]:
* The objective of clinical audits ‘should be to
evaluate trial conduct and compliance with
the protocol, SOPs, GCP, and the applicable
regulatory requirements’.
* ‘The sponsor’s audit plan and procedures for
a trial audit should be guided by the
importance of the trial to submissions to
regulatory authorities, the number of subjects
in the trial, the type and complexity of the
trial, the level of risks to the trial subjects,
and any identified problem(s). The observa-
tions and findings of the auditor(s) should be
documented.’
* ‘The sponsor should ensure that the auditing
of clinical trials/systems is conducted in
accordance with the sponsor’s written proce-
dures on what to audit, how to audit, the
frequency of audits, and the form and content
of audit reports.’
CQA Audit Program
A CQA unit performs many different functions
to ensure that sponsor’s clinical studies are
carried out in compliance with regulatory
Copyright r 2008 John Wiley & Sons, Ltd.
129
requirements, ICH guidelines and company
SOPs [4]. The CQA functions usually include
clinical system-wide training in GCP regulations
and quality practices, review of clinical opera-
tion SOPs, and implementation and manage-
ment of an audit program that is updated at pre-
specified intervals. The CQA unit assesses the
compliance level of clinical trials by conducting
various audits. Issues identified are communi-
cated to the Clinical Study Management group,
who will use the information as a basis for
improvement of the clinical development pro-
cesses including correction/mitigation at in-
vestigators’ sites or wherever else the audit was
conducted [5].
A well-managed CQA audit program has the
following characteristics [6]:
(1) Planning and conducting audits.
(2) Continuously improving its own perfor-
mance.
(3) Producing meaningful audit results.
(4) Verifying compliance.
(5) Promoting continual improvement in con-
duct of clinical studies.
It is important for the CQA unit to develop and
improve its own audit practices and programs
on a continuous basis.
Audit Program Outline
There are several reported benchmarking sur-
veys to gauge the CQA landscape in the
pharmaceutical industry [2,3]. Since clinical
development is a complex process and there
are no regulations or guidelines on the scope of
an audit program, companies utilize different
strategies to target or put different emphasis on
various developmental steps ranging from in-
vestigator site audits to regulatory document
reviews. In general, a CQA audit program
should encompass the following key audit
programs (Figure 1):
* Product-specific/study-specific Audits Pro-
gram: Develop and maintain an audit pro-
gram for clinical studies, including audit
Qual Assur J 2007; 11, 128–137.
DOI: 10.1002/qaj
130 H. Li et al.

CLINICAL QUALITY ASSURANCE AUDIT PROGRAM

TYPE OF AUDITS

Product-specific Audits Supplier Audits Process/System Audits Pharmacovigilance Regulatory Inspection

Program Program Program Audits Program Mngmt Program

Supplier Clinical Safety Safety Data Pre-Inspection Audit

Study 1- Study 2-
Qualification Reporting Management
specific specific
Assist with Audit
Sponsor Data Audit Data Management Communications Response
Protocol, CRF, IC, during the Trial & Reg. Reporting
CSR Clinical Supply
Preferred Vendor List Signal Detection
Supplier after the trials Study Monitoring & Evaluation

Clinical Database Computerized System Risk Management

& PV Planning
Investigator Site
Computerized System
Clinical Site Visit

Study Management Suppliers

SAE Reporting

CRF: case report form; CSR: clinical study report; IC: informed consent; PV: pharmacovigilance;
SAE: serious adverse event.
Figure 1. Types of clinical audits

plans for each drug (and indication) develop-
ment program.
* Supplier Audits Program: Audit Contract
Research Organizations (CRO) and vendors
to ensure that they operate in compliance
with applicable GCP regulations, guidelines
and sponsor quality standards.
* Process/System Audits Program: Perform
internal audits on sponsor’s clinical quality
systems, processes and facilities.
* Pharmacovigilance Audits Program: Conduct
various audits on pharmacovigilance systems
to assess effectiveness and compliance.
* Regulatory Inspection Management Pro-
gram: Host sponsor’s regulatory inspections
and provide assistance to investigators as
necessary for their regulatory inspections.
Development of Quality Audit Plans
Establishment of quality audit plans is the first
step in successfully managing an audit program.
A CQA audit plan defines specific audits that a
CQA unit needs to carry out to assess the
conduct of trials in a given timeframe (i.e.,
a calendar year). Format, content, review,
approval, and revision of the quality audit plans
should be outlined in an approved CQA audit
SOP (discussed in detail later). Development of
an audit plan depends on several factors [1]:
* Trial criticality for regulatory submission.
* The number of clinical trials.
* The type and complexity of the trial.
* The level of risks to the trial subjects.
* The number of centers and subjects in the trial.
* Use of contract suppliers.
* CQA resources (internal and external).
A risk-based approach should be taken to
manage clinical audits (Figure 2). It is crucial
to establish audit plans for all applicable CQA
audit programs. It should be pointed out that the
audits outlined in the following section serve as
a guideline for selecting the types of audits to be
included in a CQA audit plan and should be
used as a supplement to established clinical
auditing SOPs.
Master schedule for clinical audits
The CQA should establish an overall master
schedule for all planned clinical audits in a fiscal

Copyright r 2008 John Wiley & Sons, Ltd. Qual Assur J 2007; 11, 128–137.
DOI: 10.1002/qaj
Developing and Implementing a Comprehensive Clinical QA Audit Program 131

High auditing SOP should provide an algorithm or a

l) methodology to direct establishment of this
na
t er
ex plan. Study management including clinical
d
Regulatory risk

l an monitoring and Serious Adverse Event (SAE)

na
t er
(in reporting functions can be audited as part of an
s
ce investigator site audit. In addition, some CQA
o ur
R es units also conduct audits of key clinical trial
A
CQ documents, such as protocol, Case Report Form
(CRF), Informed Consent (IC) and Clinical
Low
Low Criticality for product registration High
Study Report (CSR) [2]. ICH E6 requires that
adequate quality control (QC) be implemented
Figure 2. A risk-based approach for mana- for each critical process. At least these study-
ging clinical audits specific documents, if not audited by CQA,
should be QC reviewed. Quality reviews (QA
audits or QC checks) should also be applied to
year. The master schedule can be compiled from clinical databases to ensure data integrity. The
individual product-specific, supplier, process/ following is a brief description of audits or
system, and pharmacovigilance audit plans. quality reviews that should be conducted on
Since changes in clinical studies and the avail- pivotal trials. These quality activities may also
ability of CQA resources often affect actual be performed on a sample of non-pivotal phase
execution of an audit, the master schedule I–III studies, post-marketing studies or discon-
should be revised/updated when modifications tinued studies based upon sponsor product
to planned audits occur and when planned development needs or at the discretion of the
audits have been completed. This overall sche- CQA unit.
dule allows the CQA unit to diligently manage
1. Investigator Site Audit
resources to maintain a balance between the
A representative sample of the investigator
compliance oversight obligations and availabil-
sites should be audited within each pivotal
ity of CQA resources [2].
study. Investigator site audits are conducted to
assess an investigator’s regulatory compliance
Product-specific audit plans and clinical data quality (including adherence to
the protocol).
A product-specific audit plan should be gener-
ated for each sponsor’s drug under development. (a) Clinical Site Visit
This schedule should include all planned clinical One of the key components of an investigator
audits for the studies considered as pivotal to site audit is to visit the clinical site where a trial
drug development and registration (Figure 1). is conducted. This audit requires coordination
The information included in this plan can be with the study management and site study
obtained from study-specific audit plans. This personnel. It is critical for key site study
audit plan provides an overall view of a drug personnel such as investigator and study co-
development process and helps maximize the ordinator to be present during the audit. Usually
utilization of CQA resources by minimizing the responsible study monitor such as clinical
overlaps and redundant audits. research monitor should be available to assist
the auditor(s).
(b) Study Management
Study-specific audit plans
Study management including clinical monitoring
A study-specific audit plan should include, at a is critical to the quality and compliance of a
minimum, investigator site audits and audits of clinical trial [7]. It is important to assess how the
suppliers used, if applicable (Figure 1). The trial is managed and check the Trial Master File

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DOI: 10.1002/qaj
132
(TMF) of the clinical trial at the sponsor/CRO
to assure that the project/study files being
maintained by or on behalf of the sponsor are
complete and up-to-date.
(c) Safety Reporting
Collection and reporting of Serious Adverse
Events (SAEs) and Adverse Events (AEs) gener-
ated during the course of a clinical study is a key
compliance component for study subject safety.
SAEs recorded by the clinical operations group
should be consistent with those archived and
retained in the global drug safety database. This
aspect of the clinical trial requires timely
submission of SAE reports as required by the
regulatory agencies. Investigators are obligated
to report SAEs promptly to the trial sponsors
and the Institutional Review Boards/Indepen-
dent Ethics Committees. It is critical to examine
the effectiveness and compliance of the prac-
tices.
2. Supplier Audits
Suppliers used in clinical trials should ideally
be audited or assessed prior to use. Periodical
re-assessments of the suppliers should be
performed as long as the suppliers are in
use. This can be managed on an individual
study basis. For a large clinical development
program, a supplier audit management program
should be established to enhance efficiency and
effectiveness. This will be discussed later in
detail.
3. Clinical Database Audit or QC Check
The QA audit or QC check of a clinical
database consists of a comparison of the data
entered on the CRF or source document and any
data clarifications/corrections with the clinical
database. The CQA unit in consultation with
Clinical Study Management and Data Manage-
ment develops a written directive that describes
the extent of the quality review and acceptable
error rates. The audit should be performed once
the database has been finalized (preferably
frozen or soft-locked). The quality check pro-
vides a mechanism to assure that the clinical
study database accurately reflects the data
collected and clarified during the study. Various
electronic data capture systems are increasingly
Copyright r 2008 John Wiley & Sons, Ltd.
H. Li et al.
used in conducting clinical trials. Robust, real-
time data quality checks should be developed
and implemented upfront.
4. Quality Review of Protocol, CRF, IC, and
CSR
Each clinical study protocol, especially those
for pivotal clinical trials should be reviewed for
quality prior to implementation. The CRFs will
be evaluated to ensure all protocol-required
elements are being captured. The content of
the subject IC form may also be assessed at this
time to assure that all required elements per the
applicable regulations and guidelines are pre-
sent. The quality review activities of the CSR are
performed to verify completeness and internal
consistency. A comparison of the in-text tables/
figures to the corresponding statistical tables and
associated data listings are usually performed as
necessary. The quality review should confirm (1)
whether conclusions made in the report accu-
rately reflect the data generated during the
study; (2) that internal consistency within each
section of the report has been maintained; (3)
that the formatting and content of the final
CSR meets ICH guidelines and country-specific
regulations.
Supplier audit plan
It is common for a sponsor to outsource parts or
even all clinical study activities to suppliers such
as CROs and various vendors. Although the
suppliers carry out trial-related activities, the
sponsor retains ultimate responsibility for the
conduct of suppliers with respect to regulatory
compliance. It is in the sponsor’s best business
interest to ensure that suppliers comply with
applicable regulatory requirements and spon-
sor’s quality standards.
Prior to use for any process of trial conduct,
suppliers including Phase I facilities should be
assessed for their capability to provide the
quality services that a sponsor requires. During
a trial, they may be further audited to evaluate
the quality of the data being generated. Depend-
ing on the performance of suppliers, a preferred
vendor list can be established to guide the future
Qual Assur J 2007; 11, 128–137.
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Developing and Implementing a Comprehensive Clinical QA Audit Program
selection of suppliers. In general, the suppliers in
use should be re-audited/assessed periodically
(e.g., every two years) based on risk assessment.
In the event that a previously used supplier/
vendor is to provide contractual services in
another area of its expertise, a separate audit
may be necessary to assess that functionality.
The sponsor’s experience with particular suppli-
ers should be considered when planning audits.
A variety of clinical functions may be out-
sourced. In some instances, applicable regula-
tions or guidelines may not be readily available
for the work being outsourced, for example,
central laboratories and speciality laboratories
that perform clinical sample testing. Besides
evaluating the supplier’s capability to meet
contractual obligations, the supplier audit may
be conducted using a quality systems approach
to assess the level of quality and compliance of
the supplier for conducting the specified out-
sourced services. For instance, the audit can
focus on quality elements such as personnel/
organization, training, SOPs, equipment, com-
puterized systems, QA/QC, and ancillary aspects
of each system evaluated with respect to how
they interrelate to overall contractual service.
Systems to be evaluated and the depth of
evaluation will be planned prior to each audit
and documented.
Process/system audit plan
Internal system audits should include a cross-
section review of one or more of the clinical
processes. It is suggested that an initial clinical
system-wide audit be conducted on all critical
processes, which would then establish a baseline
for the level of compliance. After this quality
system audit, selection of processes for evalua-
tion should be based on risks and changes/
updates made in a process that could potentially
impact drug development and regulatory sub-
mission. To efficiently utilize CQA resources,
process/system audits should be carefully
planned to avoid overlapping with the pro-
duct-specific audits. Critical processes to be
audited include, but may not be limited to those
listed in Figure 1.
Copyright r 2008 John Wiley & Sons, Ltd.
133
* Clinical Safety Reporting Audit: The prac-
tices and processes of collection and reporting
of SAEs should be consistent across all
clinical trials. A process-based audit, a
cross-section review of SAE reporting, can
achieve this objective. Clinical safety report-
ing is a critical component of an overall
pharmacovigilance program.
* Data Management Audit: This is also per-
formed to assess data management
at the process level. This is done particularly
to ensure that data management practices/
activities are consistent across multiple
trials.
* Clinical Supply Audit: Drug accountability is
crucial for clinical studies that test unproven
drugs, and is usually examined during study-
specific audits. However, during the process
audit, drug distribution, accountability, re-
conciliation and destruction across multiple
studies would be reviewed as part of this
audit as well as the ability to retrieve drug
from study sites if necessary. However, it is
critical to examine periodically the whole
process to ensure that drug accountability is
managed consistently and quality is not
compromised as a company.
* Study Monitoring Audit: A company may use
multiple strategies for managing clinical
monitoring – utilization of in-house or con-
tract monitors for global trials or single
country trials. An audit can be designed to
focus on the monitoring processes across
multiple trials.
* Computerized System Audit: Computerized
systems are increasingly used in clinical trials.
Validation and security measures are exam-
ples of critical factors for ensuring data
integrity [8].
Pharmacovigilance audit plan
Pharmacovigilance means ‘all scientific data
gathering activities relating to the detection,
assessment, and understanding of adverse
events’ and ‘principally involves the identifica-
tion and evaluation of safety signals’ [9]. Due to
the increased regulatory scrutiny of post-mar-
Qual Assur J 2007; 11, 128–137.
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134
keting drug safety, a pharmacovigilance pro-
gram has become a necessary element for
enhancing the safe use of approved drugs. Often
CQA is responsible for monitoring the effective-
ness and compliance of the pharmacovigilance
program through the conduct of process audits.
A pharmacovigilance audit may focus on, but
not limited to, a review of the areas discussed
below (Figure 1):
* Safety Data Management: Effective manage-
ment of drug safety data including collection,
integration, and reporting of safety informa-
tion critical in meeting global adverse event
reporting regulations. It is critical to verify
the quality and compliance of the data
collected to facilitate effective assessment
and analysis.
* Communications and Regulatory Reporting:
The reporting procedures and practices in
place should meet the requirements of the
regulations which incur tight timelines for
drug-related SAEs. Responsibilities for addi-
tional safety reporting, such as Periodic
Safety Update Reports (PSURs) and Annual
Safety Reports (ASRs) should be fulfilled as
well. An auditor can sample different pro-
ducts and examine the process effectiveness.
* Signal Detection and Evaluation: The safety
signals are analyzed using appropriate med-
ical and epidemiological methods to confirm
whether there is a possibility of a safety issue.
The auditor can focus on whether the
procedure and process in place ensure that
safety signals are timely analyzed and eval-
uated.
* Risk Management and Pharmacovigilance
Planning: The regulatory bodies have increas-
ingly focused on the role of formal risk
management approaches in drug safety. These
proactive actions go beyond routine post-
approval surveillance. During an audit, the
auditor can assess whether these plans are in
place.
* Computerized Systems: Often computerized
systems are used to manage safety data. These
systems should be validated and have the
necessary security, back-up, and disaster
Copyright r 2008 John Wiley & Sons, Ltd.
H. Li et al.
recovery procedures in place to ensure
regulatory compliance and operation
continuity.
* Suppliers, if applicable: Companies may use
suppliers to perform some or all pharmacov-
igilance related functions. These suppliers
should be assessed to ensure they have the
necessary quality systems in place.
Regulatory inspection management
The CQA unit assists in preparing the sponsor
for regulatory inspections. It usually hosts the
sponsor’s regulatory inspections and oversees
the development of responses and corrective and
preventive action plan (CAPA) to deficiencies
identified (Figure 1). The sponsor’s auditors may
also assist the investigators in preparing for
pending inspections of the investigator sites by a
regulatory agency and provide other support as
necessary.
Implementation of the CQA audit
program
The audit plan is a blueprint for implementation
of a CQA audit program. Each individual CQA
unit can tailor its audit program based on the
company’s compliance and business needs. For
example, there may be no need for a small
biotech company with only one drug candidate
in the clinical development stage to establish a
pharmacovigilance audit program. A company
that outsources all its clinical development
activities to suppliers may want to focus on the
supplier management component of the audit
program.
The next key step is development and adop-
tion of CQA SOPs and the conduct of training
for CQA auditors. Administrative aspects of the
CQA audit program such as selection and
employment of qualified auditors have been
eloquently discussed elsewhere [4,10–13]. Ex-
ecution of the audit plans requires extensive
interactions between auditors and Clinical Study
Management, investigator sites, and suppliers.
The CQA unit usually develops an audit
tracking system to track the audits planned
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Developing and Implementing a Comprehensive Clinical QA Audit Program
and actually conducted. This could be accom-
plished by using a simple excel spreadsheet for a
small audit program or a more sophisticated
database to electronically generate audit reports,
maintain essential supporting documents, verify
audit responses and completion of corrective
actions. For an audit to be effective, it is critical
to communicate audit results to the auditees
including Clinical Study Management to ensure
that issues or deficiencies are clearly discussed
and agreed upon to facilitate implementation of
corrective action plan.
CQA SOPs and Training of Auditors
The CQA unit should develop necessary SOPs or
operation manuals and perform training to
support implementation of the CQA audit
program and to ensure all auditors are qualified.
All appropriate personnel should receive train-
ing on these SOPs prior to the implementation of
the CQA audit program. If consultants and/or
subcontractors are used, they also need to be
included in the training. Training is an integral
part of the CQA audit program to ensure that
all auditors conduct audits in compliance with
the SOPs or operation manuals to achieve audit
objectives and consistency despite the different
audit styles that each auditor may have.
Typical SOPs for a CQA audit program
should include but not be limited to the
following:
* Clinical audit planning.
* Clinical audit coordination between the CQA
group and the Clinical Study Management
department.
* Clinical investigator site audit.
* Quality review of clinical documents (Proto-
col, IC, CRF, CSR).
* Database audit, TMF audit, and other spe-
cific audits as necessary.
* Clinical system audit conduct and manage-
ment.
* Supplier audits.
* Pharmacovigilance audits.
* Regulatory inspections.
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135
CQA Collaborative Expectations
The CQA unit coordinates and schedules audit
activities using information regularly commu-
nicated from a variety of sponsor sources,
including sponsor study management represen-
tatives (Clinical Study Management, Data Man-
agement, and Drug Safety) for each study, for
instance, clinical project schedules and updates
for the proposed and ongoing drug development
programs. Inputs from the Study Management
such as Clinical Research Associates (CRAs) will
be useful in planning and designing specific
audits such as a targeted or for cause audit.
Information on clinical study activities to be
outsourced (monitoring, data management, and
safety reviews, etc.) and suppliers expected to
participate in clinical drug development pro-
grams should be forwarded in a timely manner
(i.e., prior to signing contractual agreements) to
the CQA unit. As necessary, a CQA unit
representative should be assigned to attend key
drug development meetings (i.e., clinical project
team meetings) to gain appreciation of nuances
of a given program. An assigned CQA unit
representative meets with the appropriate spon-
sor departments to discuss the scope of a
planned clinical audit, the audit timeline, and
expected deliverables necessary in order for the
CQA unit to initiate and complete the planned
audit.
At the program level, the CQA unit should
communicate all planned clinical audits and
audit management updates to these parties
especially Clinical Study Management on a
regular basis. This process helps ensure that
the CQA unit gets buy-in from the Clinical
Study Management, so the CQA focuses on
clinical studies that are considered pivotal or
critical to drug development and registration.
Depending on the type of audit being conducted,
the auditor will need in advance some essential
trial–related documents to help plan and execute
each specific audit, for example, protocol and
protocol amendments, annotated CRF, informed
consent templates, data management guidelines/
conventions, monitoring guidelines, study-spe-
cific patient recruitment advertisements, and
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136
investigator’s brochure or package insert to
name a few. Different essential trial-related
documentation will be required for each given
type of audit and should be outlined in detail in
CQA SOPs. The CQA unit will need the support
from various departments such as Clinical Study
Management, Global Drug Safety, and Regula-
tory Affairs to provide these documents.
Continuous Improvement of the CQA
Audit Program
For a well-managed CQA audit program, con-
tinuous improvement is vital to remain effective
in the evolving regulatory climate [6]. It is a good
practice to summarize audits conducted and
provide key findings and deficiencies identified
in each fiscal quarter in an overall compliance
audit report to senior management. Critical
issues and new quality initiatives, however,
should be discussed in a timely manner with
senior management to obtain feedback and
approval. The CQA audit program should be
reviewed annually and evaluated for its contin-
ued effectiveness and updated based on new
regulatory development, which is critical to the
quality of clinical studies. As the CQA audit
program improvement is designed as a colla-
borative effort amongst departments, feedback
from other departments should be actively
sought. Continued improvement in a CQA audit
program will ensure compliance objectives are
achieved in support of clinical development.
Conclusion
ICH guidelines require sponsors to establish a
clinical quality assurance and quality control
program to ensure the compliance of clinical
studies with regulatory requirements. It is very
challenging for a new CQA unit to map out
audit strategies. A comprehensive CQA audit
program should encompass various types of
audits to assess and verify that ‘trials are
conducted and data are generated, documented
(recorded), and reported in compliance with the
protocol, GCP, and the applicable regulatory
Copyright r 2008 John Wiley & Sons, Ltd.
H. Li et al.
requirements’ [1]. Besides investigator site audits
and supplier audits, the CQA units increasingly
conduct audits at the process and system levels
to achieve cross-section review and assessment
of the clinical quality system. Due to recent
regulatory scrutiny of drug safety post-market
approval, the CQA units often take on the
responsibility of auditing pharmacovigilance
systems. Management of regulatory inspections
is highly visible within the organization and the
outcome of a regulatory inspection can have
significant impact on the clinical development
programs. Like any other successful audit
program, the CQA audit program should be
periodically reviewed and improved with new
initiatives implemented to meet ever increasing
regulatory challenges.
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