review and update of internal processes and stan-
dard operating procedures (SOPs).
An effective QM system for clinical research
helps assure that studies are planned, conducted,
analyzed, reported and managed in compliance
with GCP guidelines and ethical principles as
noted in the Declaration of Helsinki, so that
dependable trial results are achieved while ensur-
ing that trial participants are protected.
13.2 Quality management
Surprisingly, ‘quality’ or ‘quality management’ are
not included in the glossary included in the Interna-
tional Conference on Harmonization (ICH) GCP
(1995),although definitions for ‘Quality Assurance’,
‘Quality Control’ and ‘Audit’ are to be found in this
guideline. Useful explanations related to quality are
also included inISO 9000:2005(2005), the ‘generic’
standard that can be applied to any organization
(large or small), including whether its ‘product’ is
actually a service in any sector of activity. Let us
review some of the ISO definitions.
Quality
In ISO 9000:2005 (2005), quality is defined as ‘The
degree to which a set of inherent characteristics
fulfils needs or expectations that are stated, gen-
erally implied or obligatory’.
Hence, the standards for conducting clinical
trials must be known before they can be applied.
Standards are either international (e.g. ICH GCP),
European (e.g. European Union Clinical Trials
Directive (2001) and GCP Directive (2005)),
national (i.e. national drug laws and GCP regula-
tions) or even more local, such as State laws in the
United States (Isidor and Kaltmann, 1999). Apart
from the regulations, the clinical trial protocol,
SOPs and other internal or external instructions
document procedures how the trial should be car-
ried out from start to finish. Compliance with these
standards is expected.
Without clear standards prepared within an orga-
nization, or without adequate knowledge of existing
standards, compliance with GCP requirements,
ethical principles and the trial procedures may be
suffering, up and until the point that regulatory
authorities reject the data because data validity
and adherence to ethical standards cannot be
demonstrated.Quality management
ISO 9000:2005 (2005) defines quality manage-
ment as ‘The coordinated activities to direct and
control an organization with regard to quality’.
ICH GCP does not contain a definition for QM.
QM is not a new concept; it is rooted in medieval
Europe in the late thirteenth century where guilds
were responsible for developing strict rules for
product and service quality. Inspection committees
enforced the rules by marking flawless goods with
a special mark or symbol (Hattemer-Apostel,
2003; ASQ, 2006). This was the start of ‘quality
control’, a process to assess finished products to
evaluate whether they fulfilled pre-established cri-
teria. The statistical evaluation of data paved the
way to focus on improving the manufacturing pro-
cess rather than inspecting the final product by
preventing errors instead of correcting them, that
is ‘assuring quality’ instead of ‘inspecting quality
into a product or service’. The benefits of QA soon
led to the insight that quality is an attribute that can
be managed. On one hand, quality can be influ-
enced in that investments in process quality impact
the outcome of the product or service. On the other
hand, quality has increasingly become a task of
management. ISO 9000:2005 (2005) describes the
role of senior management and emphasizes the
importance of leadership by top management in
implementing quality management.
The absence of the term ‘quality management’
in clinical research regulations and guidelines is
surprising. Neither the US Code of Federal Reg-
ulations nor European documents, such as the most
recent European (EU) Clinical Trials Directive
2001/20/EC (2001) and the EU GCP Directive
2005/28/EC (2005), describe the requirement for
a comprehensive quality management system.
‘quality assurance’ is found in the US Food and
Drug Administration’s (FDA) inspection guide for
sponsors, CROs and monitors (FDA Compliance160 CH13 QUALITY ASSURANCE, QUALITY CONTROL AND AUDIT