Change management and CAPA systems
—Zena G. Kaufman
Within ICH Q10, the phrase "change management" rather than "change control" is used. The new terminology speaks to the fact
that as an industry, we've been reluctant to embrace change. We've been controlling change and where we, both the regulators
and industry, need to move is to managing change using appropriate science and risk-based approaches.
Imagine we're designing a change-management system. The first thing to do is try to understand the purpose of the change-management
system—it's not to control change but rather to improve processes and products, and assure conformance to registration, including
avoidance of unintended consequences. Some of the inputs to a change-management system include innovation, continual improvement,
and the output from analysis of performance indicators and a company's CAPA system.
The output of the change-management system would be a changed process, or a new piece of equipment, or new specifications.
All these would include a documentation of the change. As with any system, there needs to be a defined process owner of the
system. Typically, the quality department has been the system owner for a company's change-management system. As industry
moves forward with Q10, it may become more effective for the technical services group, which is usually charged with innovation
and continuous improvement, to be the system owner.
To execute and improve a current change-management system, there must be defined metrics. There usually are key performance
indicators and metrics against the "logistics" (e.g., cycle time, the number of deviations open over 30 days, trending of
the system). One can always recite the number of open change controls or the time a change control has been open, but moving
into this new paradigm, industry is going to have develop metrics which measure the effectiveness of a given change and evaluate
the return on investment (ROI) of that change.
The ROI of a change transcends beyond dollars and cents to a clear improvement in the quality/control of the product. There
are tangible as well as intangible benefits from implementing change. Sometimes we make a change because there's been a change
in regulatory expectation due to emerging regulations or the "C" in CGMPs or because regulations are being interpreted a little
bit differently globally. We must also look at these perspectives in terms of the ROI of a change.
Companies also need to review how they improve the change-management system. In my experience, change-management systems are
often overloaded with way too many change controls being processed. Rather than managing the change control, industry should
ensure that the system itself supports the business process.
With the change-management system, one of the inputs is the CAPA system, which can include deviations to procedures, nonconformities,
etc. Other inputs come from internal audit reports, inspection observations, and regulatory findings. Also to be considered
are product quality complaints and trending of a company's process monitoring. Most companies understand that a CAPA system
helps them to assess the risk of releasing a deviant batch to market, but a CAPA system also can help prevent the recurrence
of a deviation. A most excellent CAPA system goes beyond addressing the impact to a single batch to develop meaningful corrective
and preventive action to prevent recurrence. The CAPA system is not a tool for facilitating or justifying release of nonconformance
With Q10 in mind, industry needs to move into the quality and effectiveness of a CAPA system. Rather than applying a quick
fix such as retraining the operator, a more robust quality system asks: Is that the most effective CAPA I can think of? This
approach may lead to a more effective corrective and/or preventive action.
Overall, the elements of ICH Q10 and the aspects of a PQS really are at the center of integration, effectiveness, and the
global nature of these systems. And by global, I mean not only global operations but also the life cycle of a product.
Global quality inspections
Although Q10 can be used to create a quality system for an entire manufacturing site or many different sites, GMPs are dedicated
to the manufacture of investigational medicinal products and commercial finished products. Even though certain GMP guidelines
such as those of the EU and the Pharmaceutical Inspection Cooperation Scheme (PIC/S) contain information related to quality
management or quality assurance, it is important to remind industry that GMPs mainly concern systems for finished products,
not the life cycle of these products .
To explain, in a manufacturing site inspection, a quality-management system should be considered a normal part of the GMP-inspection
process. At the EU level, we are not considering the development of a Q10-specific certification scheme inspection. Inspecting
the quality-management system in a manufacturing site will be considered routinely, and will be quoted in the GMP certificate
issued at the end of the inspection (based on GMP compliance evidence). It will be noted that the quality-management system
was inspected and found to be in compliance with GMP. In a development site, inspecting quality-management systems will be
considered on a case-by-case basis, depending, for example, on requests coming from the assessor.
Looking ahead, the IWG for Q10, as well as Q8 and Q9, will address notably the need to train inspectors on the Q10 document.
At the EU level, we will likely develop this summer a work plan for introducing Q10 elements dedicated to GMP into the EU's
GMP guide. In addition, the EU, with the help of PIC/S, may develop a guide for inspection of quality systems in both manufacturing
and development sites.
Overall, ICH Q10 Pharmaceutical Quality System provides a roadmap for product control. And in today's market, with growing supply chains and additional outsourcing, control
is vital to end-product quality. As FDA's Famulare put it, "We've come together with industry that this is a direction and
a way we'd like to see the industry go.... We've become all too accustomed to reacting to problems, issues, and crises...we
hope that Q10, with the other ICH documents, will serve as a basis and a way to prevent some of those incidents and to, in
a global way, have quality medicine products available where and when they're needed."
1. ICH, ICH Q8 Pharmaceutical Development (Geneva, Nov. 10, 2005).
2. ICH, ICH Q9 Quality Risk Management (Geneva, Nov. 9, 2005).
3. ICH, ICH Q10 Pharmaceutical Quality System (Portand, OR, June 2008).
4. S.J. Schniepp, Moderator, Quality Systems in a Global Market webcast, Hosted by Pharmaceutical Technology and Sponsored by SGS (June 12, 2008), available at
For more on this topic, see
Pharma Quality systems