Principles and Practice of Pharmaceutical Medicine

2. train employees and colleagues, and implement
   the requirements in the standard processes;
   and


3. follow the rules and provide sufficient docu-
   mentation so that compliance can be verified.

13.3 Implementing quality

assurance

QA’s task to identify noncompliance with regula-
tory requirements, the trial protocol and internal
procedures such as SOPs is not always an easy job.
Communicating deficiencies and highlighting
inadequate procedures is certainly a benefit for
the company as a whole, but the individual may
not appreciate being confronted with audit findings
(Winchell, 2004). In order to be efficient and effec-
tive in QA, the following should be observed.

Organization and independence of QA

According to ICH GCP (1995) and FDA (FDA
Compliance Program Guidance Manual, 2006),
the audit function must be independent of routine
monitoring or quality control functions, so that
auditors are able to provide an unbiased, objective
assessment. Being involved in designing, conduct-
ing, monitoring or analyzing a clinical study would
undermine the requirement of independence.
QA’s independence from operations should be
identifiable in the organizational charts of a com-
pany or CRO. The reporting line of QA should go
directly to senior management and in no case to any
operational function. To preserve the indepen-
dence of the audit function, audits are also often
outsourced to external contractors; however, this is
no GCP requirement.

SOPs for QA

The requirement of having SOPs for all functions
in clinical research also applies to QA and is
emphasized in ICH GCP (1995) in section 5.19.3
(‘The sponsor should ensure that the auditing of

clinical trials/systems is conducted in accordance

with the sponsor’s written procedures on what to

audit, how to audit, the frequency of audits, and the

form and content of audit reports’.) and by FDA

(FDA Compliance Program Guidance Manual,

2006) (‘Obtain a copy of any written procedures

(SOPs and guidelines) for QA audits and operation

of the QAU’.).

The number of SOPs and their topics depend on

the scope of audits performed, the set up and size of

the QA department and whether audits are out-

sourced to external contractors which may

decrease the scope of audits conducted by internal

QA members. The QA department may also be

tasked with activities such as SOP management

and staff training; SOPs would also be needed for

these areas.

Qualification of QA auditors

The need to use qualified and trained employees in

all areas of clinical research also affects the QA

department. As QA auditors are verifying the work

of their colleagues and are evaluating compliance

with regulations, they must have a dependable

knowledge of the clinical trials regulatory frame-

work and practical work experience in clinical

research to be credible in their role (Hattemer-

Apostel, 2000a).

There is no standard professional education for

QA auditors and, therefore, practical experience is

indispensable before embarking on the QA job.

Before joining the QA department, the QA candi-

date may have worked in clinical monitoring,

data management, pharmacovigilance, regulatory

affairs, training and other areas of clinical research.

ISO 19011:2002 (2002) lists the following per-

sonal attributes for auditors (and includes further

information on desired auditor qualifications):

Ethical, that is fair, truthful, sincere, honest and

discreet.

Open-minded, thatis willing to consider alternative

ideas or points of view.

Diplomatic, that is tactful in dealing with people.

162 CH13 QUALITY ASSURANCE, QUALITY CONTROL AND AUDIT