An important component of QbD is a risk management system that can identify and evaluate potential problems. The ICH Q9 standard,
which has been adopted by Japan and the US (where the guidance was issued in June 2006), but still awaits final implementation
in Europe, describes a range of methods that manufacturers and regulators can use to establish Quality Risk Management (QRM)
systems, which can determine the appropriate level of control for a manufacturing process.
QRM involves identifying risks, analyzing the risks, evaluating the consequences of a high-risk event occurring, and establishing
policies for risk reduction. The aim is to determine the most essential areas to monitor, and to evaluate where such efforts
may be unnecessary or redundant. An annex to the guidance describes more specifically how to apply risk management to documentation,
product defects, inspections, change management, maintaining facilities and equipment, material management, and validation.
For FDA, a risk-based approach is being applied to standards development, regulatory decisions, inspection choices, and setting
enforcement priorities. Joe Famulare, deputy director of CDER's Office of Compliance, explained that FDA is using risk management
in selecting sites for good manufacturing practices (GMP) inspections as well as to audit adverse event reporting and sampling
programs. FDA asks "so what" and "what if" questions in evaluating a system's state of control, Famulare added.
A third ICH document (Q10), which is still under development, will link product development and risk management to assist
manufacturers in establishing pharmaceutical quality systems. These will include process and product monitoring, corrective
actions, and managing change in the postmarket environment. The ultimate quality system begins with the development of active
ingredients and excipients and moves through product formulation, manufacturing process development, design of container closure
and packaging, product release, and distribution, explained Jean-Louis Robert, representing EU authorities at the ISPE–PDA
To implement quality manufacturing and risk-based approaches, industry needs to invest in new technology, including statistical
process controls and continuous processing methods, said Woodcock. There is a growing confidence that "we have the science
and technology to get there," and now "we need to change the system."
Regulatory authorities insist that the ICH documents do not impose new requirements on industry. But they do "strongly encourage"
companies to adopt more advanced quality control approaches, and will increasingly look for such programs in weighing a company's
ability to meet regulatory requirements.
Many of the elements in this science-based, QbD approach are similar to policies and guidances developed under FDA's GMP modernization
program, pointed out Karen Main of AstraZeneca. FDA will examine the status of "GMPs for the 21st Century" further at a workshop
in late February 2007. The aim is to review what this initiative has accomplished so far, what new challenges have emerged
in achieving initial goals, and what remaining issues need to be addressed to continue moving forward.
is BioPharm International's Washington editor, 301.656.4634, firstname.lastname@example.org