developing and implementing a comprehensive clinical qa audit program

Developing and Implementing aComprehensive Clinical QA AuditProgram

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, USA2 QA Consultant, Acworth, Georgia, USA

Summary

The Clinical Quality Assurance (CQA) audit program is a key element of a GoodClinical Practice (GCP) quality system. The objective of a CQA audit program is toensure that trial conduct and data quality meet protocol-specified, GCP, andapplicable regulatory requirements. Due to the increasing complexity of clinicaltrials and regulatory scrutiny, the components of a CQA audit program and theapproaches taken towards designing and managing audits are constantly evolving.In this paper, we will focus on the strategies that are used to develop and implementa CQA audit program, including types of audits to be conducted and the qualityapproaches 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

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

various types of audits. Depending on the size

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

*Correspondence to: Henry Li, Talecris Biotherapeutics,79 T. W. Alexander Drive, Research Triangle Park, NorthCarolina 27709, USA. E-mail: [email protected]

Qual Assur J 2007; 11, 128–137.Published online in Wiley InterScience

(www.interscience.wiley.com) DOI: 10.1002/qaj.420Copyright r 2008 John Wiley & Sons, Ltd.

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 theSponsor GCP Quality Assurance AuditProgram

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

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

Developing and Implementing a Comprehensive Clinical QA Audit Program 129

Copyright r 2008 John Wiley & Sons, Ltd. Qual Assur J 2007; 11, 128–137.DOI: 10.1002/qaj

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

CLINICAL QUALITY ASSURANCE AUDIT PROGRAMTYPE OF AUDITS

Study Monitoring

Data Management

Computerized System

Clinical Supply

Clinical SafetyReporting

Process/System AuditsProgram

Assist with AuditResponse

Pre-Inspection Audit

Regulatory InspectionMngmt Program

Signal Detection& Evaluation

Communications& Reg. Reporting

Risk Management& PV Planning

Safety DataManagement

PharmacovigilanceAudits Program

Suppliers

Computerized System

Protocol, CRF, IC,CSR

Study 1-specific

Study 2-specific

Product-specific AuditsProgram

Supplier

Clinical Database

Investigator Site

Clinical Site Visit

Study Management

SAE Reporting

SupplierQualification

Sponsor Data Auditduring the Trial

Preferred Vendor Listafter the trials

Supplier AuditsProgram

CRF: case report form; CSR: clinical study report; IC: informed consent; PV: pharmacovigilance;SAE: serious adverse event.

Figure 1. Types of clinical audits

130 H. Li et al.


year. The master schedule can be compiled from

individual product-specific, supplier, process/

system, and pharmacovigilance audit plans.

Since changes in clinical studies and the avail-

ability of CQA resources often affect actual

execution of an audit, the master schedule

should be revised/updated when modifications

to planned audits occur and when planned

audits have been completed. This overall sche-

dule allows the CQA unit to diligently manage

resources to maintain a balance between the

compliance oversight obligations and availabil-

ity of CQA resources [2].

Product-specific audit plans

A product-specific audit plan should be gener-

ated for each sponsor’s drug under development.

This schedule should include all planned clinical

audits for the studies considered as pivotal to

drug development and registration (Figure 1).

The information included in this plan can be

obtained from study-specific audit plans. This

audit plan provides an overall view of a drug

development process and helps maximize the

utilization of CQA resources by minimizing

overlaps and redundant audits.

Study-specific audit plans

A study-specific audit plan should include, at a

minimum, investigator site audits and audits of

suppliers used, if applicable (Figure 1). The

auditing SOP should provide an algorithm or a

methodology to direct establishment of this

plan. Study management including clinical

monitoring and Serious Adverse Event (SAE)

reporting functions can be audited as part of an

investigator site audit. In addition, some CQA

units also conduct audits of key clinical trial

documents, such as protocol, Case Report Form

(CRF), Informed Consent (IC) and Clinical

Study Report (CSR) [2]. ICH E6 requires that

adequate quality control (QC) be implemented

for each critical process. At least these study-

specific documents, if not audited by CQA,

should be QC reviewed. Quality reviews (QA

audits or QC checks) should also be applied to

clinical databases to ensure data integrity. The

following is a brief description of audits or

quality reviews that should be conducted on

pivotal trials. These quality activities may also

be performed on a sample of non-pivotal phase

I–III studies, post-marketing studies or discon-

tinued studies based upon sponsor product

development needs or at the discretion of the

CQA unit.

1. Investigator Site Audit

A representative sample of the investigator

sites should be audited within each pivotal

study. Investigator site audits are conducted to

assess an investigator’s regulatory compliance

and clinical data quality (including adherence to

the protocol).

(a) Clinical Site Visit

One of the key components of an investigator

site audit is to visit the clinical site where a trial

is conducted. This audit requires coordination

with the study management and site study

personnel. It is critical for key site study

personnel such as investigator and study co-

ordinator to be present during the audit. Usually

the responsible study monitor such as clinical

research monitor should be available to assist

the auditor(s).

(b) Study Management

Study management including clinical monitoring

is critical to the quality and compliance of a

clinical trial [7]. It is important to assess how the

trial is managed and check the Trial Master File

High

LowLow HighCriticality for product registration

Reg

ulat

ory

risk

CQAReso

urces (in

ternal and exte

rnal)

Figure 2. A risk-based approach for mana-ging clinical audits



(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

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

132 H. Li et al.


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.

* 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-



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

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 auditprogram

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

134 H. Li et al.


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.

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



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 CQAAudit 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

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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