Program Guidance Manual, 2006), stating: ‘Clin-
ical trial quality assurance units (QAUs) are not
required by regulation. However, many sponsors
have clinical QAUs that perform independent
audits/data verifications to determine compliance
with clinical trial SOPs and FDA regulations’.
Regulatory agencies have not yet made it man-
datory to implement a comprehensive quality man-
agement system in clinical research; however, they
expect that a QA function be established.
Quality assurance
ICH GCP (1995) defines QA as ‘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 GCP and the applic-
able regulatory requirement(s)’.In clinical devel-
opment of pharmaceuticals, QA usually describes
the audit function within a company; however, QA
should not be limited to auditing.
According to ISO 9000:2005 (2005), QA activ-
ities are not confined to auditing, but comprise all
activities suitable to ensure that company proce-
dures are designed so that the product or service
will comply with pre-established quality require-
ments: ‘The part of quality management focused on
providing confidence that quality requirements will
be fulfilled’.This definition emphasizes that QA
activities are future-oriented and should focus on
improving systems and procedures to be followed
to ensure that these are set up in such a way that
produces a quality result or service.
The conduct of audits is not a mandatory
requirement in GCP. ICH GCP (1995) mentions in
section 5.19: ‘If and when sponsors perform audits,
as part of implementing quality assurance’ – this is
not interpreted as an obligation to establish an audit
program. Similarly, FDA does not mandate the con-
duct of audits (FDA Compliance Program Guidance
Manual, 2006).
Quality control
The ICH GCP (1995) definition for QC is
‘The 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’. ISO
9000:2005 (2005) uses a more precise definition
which nicely contrasts the above definition
for QA. Quality control is ‘The part of quality
management focused on fulfilling quality
requirements’.
QC activities in clinical research are manifold
and comprise all activities undertaken by opera-
tional departments (such as clinical monitoring,
project management, data management, etc.) to
ensure that activities are performed in compliance
with the trial protocol, SOPs and other procedure
guides. These in-process quality controls are vital
to the quality of the documents prepared (e.g. trial
protocols, study reports) and the integrity of the
trial conduct.Compliance
‘Adherence to all the trial-related requirements,
Good Clinical Practice (GCP) requirements and
the applicable regulatory requirements’ – this is
how ICH GCP (1995) defines compliance.
A myriad of laws, regulations and guidelines
specify the requirements to be adhered to when
conducting clinical trials. Responsibilities of clin-
ical investigators, sponsors, CROs, independent
ethics committees (IECs), monitors and auditors
are described, including also activities such as
pharmacovigilance/safety reporting, data manage-
ment/statistics, notification of trials at regulatory
authorities and so on.
It is important to be aware of the enforce-
ability of requirements laid down in documents
(e.g. legal requirements vs. industry best prac-
tice) and the geographic coverage of guidance
documents (e.g. FDA regulations vs. EU Direc-
tives) (Hattemer-Apostel, 2004). Without depend-
able knowledge on the applicable regulatory
requirements it is unlikely that GCP compliance
can be achieved. Key steps toward compliance
are- know the regulatory framework and keep
abreast of changes;
13.2 QUALITY MANAGEMENT 161