The Pharmaceutical Inspection Co-operation Scheme (PIC/S) has finalized a risk-based inspection planning tool for inspectorates
to use in applying science- and risk-based principles to planning GMP inspections. The tool is contained within a PIC/S document
titled, "A Recommended Model for Risk-Based Inspection Planning in the GMP Environment," which was published in Dec. 2011
and became effective on Jan. 1, 2012 (1). This article describes the history behind the new methodology.
PIC/S' work to develop a quality risk management (QRM) tool designed to facilitate risk-based GMP inspection planning began
in 2007 through an Expert Circle. The International Conference on Harmonization's (ICH) Q9 QRM guideline, which had been finalized
in 2005, provided a firm regulatory basis for developing such a tool as well as other risk-based initiatives.
The Expert Circle first met in Paris in July 2007 to create a QRM work program for inspectorates, which involved developing
a QRM training program and related guidance for inspectors that would enable them to inspect QRM-related activities at manufacturers
in a harmonized manner. Another task was the development of QRM models for inspectorates that would address the planning and
conduct of inspections, as well as their follow-up, and the management of quality defects.
In Jan. 2008, a working group (part of the Expert Circle) comprising inspectors from various drug regulatory agencies assembled.
Over the next three years, the group developed an approach to risk-based inspection planning that was relatively novel, simple
to use, science-based, and highly flexible in design. It became apparent early on, however, that the remit of this working
group was very broad in scope. Hence, it was decided during the third meeting of the Expert Circle, in Malta in Sept. 2008,
that the working group would focus only on the GMP and GDP risk-based inspection planning aspects of the mandate. This shortened
goal proved a wise decision because it allowed efforts and resources to be dedicated to, what was proving to be, quite a difficult
task. The aim was to develop a tool that would allow the frequency and scope of GMP and GDP inspections to be determined using
a formalized risk-based approach, a concept directly based on ICH Q9. Several different types of risk scoring models were
developed and assessed, but each was found to be problematic, for one reason or another.
For example, a key development at the Maltese meeting was the identification of a set of nine risk-indicating factors that
could form the basis for risk assessment of GMP and GDP sites. These factors related to:
- The known effectiveness of the site quality management system
- The complexity of the site, its products and processes
- The major changes at the site since the last inspection
- The criticality of the products manufactured/wholesaled by the site, and the criticality of the analytical tests used by the
- The profile of quality defects and recalls relating to the site
- The overall compliance history of the site
- The financial situation and resources in place at the site
- The level of competence demonstrated by staff at the site
- The culture that is in place at the site.
Coming up with an effective and practical scoring system for these various factors, however, proved to be a challenge. The
group had to always bear in mind that any risk-scoring approach developed for the tool had to be one that could be easily
used by a large and diverse group of inspectorates, ranging from those in European, African, and Asian countries, to the inspectorates
of certain parts of North and South America, as well as Australia and New Zealand.
By the fourth meeting, in Paris in April 2009, the group saw some breakthroughs. Key concepts underpinning the tool were crystallized
into a risk-scoring model and a tool design that were, while not yet optimized, capable of meeting the broad requirements
set out for the tool. These requirements included that the tool should represent a simple and science-based QRM methodology
that may be used by inspectorates when planning the frequency and scope of inspections. The tool also had to be based on the
principles of ICH Q9 and the concept of ranking sites on the basis of an estimated risk that they may pose to patients, consumers,
animals, and users of the drug products. The model also had to take into account the risk to product quality, such as the
risk of producing non-compliant batches as a result of high levels of process complexity.