The concepts embedded in Q8 transcend its application solely to drug products. Most of the comments to the docket for the
version posted as FDA guidance suggested expanding the applicability towards drug substances and larger molecules. ICH Q8
is now being revised to clarify its revolutionary concepts. Discussions are under way within ICH about extending the concepts
to active pharmaceutical ingredient (API) development, including both new chemical entities and biotechnology drug substances.
ICH Q9: Quality Risk Management
Q9 is the repository for the risk-management tools to be applied both in Q8 and Q10. John Berridge, who is vice president
for Pfizer Global Research and Development and the rapporteur for the initial stages of Q8 and now its revision, described
Q9 as a collection of tools, drawing the comparison between wrenches, pliers and hammers, which can be used, per the guidance,
to put a car together (development) or to maintain a car (commercial manufacturing). Risk Management tools are commonly used
in many other industries, most notably the insurance industry, to analyze, evaluate, and manage risks. The guidance describes
examples of how to apply the tools to a variety of pharmaceutical systems.
When first faced with implementing Quality Risk Management, one could become paralyzed with indecision about which tool to
use in a given application. Unlike statistical analysis, where it is necessary to understand the data (normality, randomness),
in quality risk management there is no wrong tool to use, since there are no statistical rules to violate. The correct tool
is the one the user feels most comfortable with. In the total absence of experience, one can look at other applications of
Quality Risk Management. For example, a recent FDA white paper, which discusses applying risk management to determining inspectional
priorities, is an excellent example of risk ranking and filtering.4 Quite often, failure mode effect analysis (FMEA) works well in conjunction with a six-sigma approach.
One must be cautious, however, about applying risk management to justify an incorrect decision. For example, Quality Risk
Management does not mean risk can be accepted and used to justify the release of a batch that should be rejected. Bad risk
analyses should not be used as a basis for poor decisions.
Rather, Quality Risk Management can be used to facilitate consistent decisions. The risk-management process encourages a multi-disciplinarian
approach to bringing different experiences to bear on risk analysis. Quality professionals bring unique experiences to their
daily work. By creating a process where collective experiences can be used in a structured approach, the resulting decisions
will be stronger than decisions based on limited experience or knowledge would be.
Since Quality Risk Management is flexible, there will be many applications for its use. As a scientific process, it can be
used in many quality systems both in development and commercial manufacturing. However, there is no reason to create a separate
Quality Risk Management Department; this would probably discourage the wide usage of Quality Risk Management envisioned by
the authors of the guidance document. Instead, Quality Risk Management should be a tool used by many diverse disciplines and
Each firm will need to define the documentation requirements for informal and formal risk management processes. These requirements
will depend on the depth of the risk management process, and its criticality and role in supporting current good manufacturing
practices (GMP) activities. Proper GMP record keeping and documentation will still be a cornerstone in the application of
Quality Risk Management.
ICH Q10: Pharmaceutical Quality Systems
Q10, Pharmaceutical Quality Systems, is currently at step 1 in the ICH process—the initial Expert Working Group is developing and drafting the document.
Within Q10, three elements have been discussed5 :
- Quality management
- Product realization
- Continual improvement
Quality management synthesizes all of the quality indicators that help to uncover systemic issues, determine priorities, and drive improvements.
To comply with GMPs, a given site develops a set of standard operating procedures that define how the site will operate. These
procedures detail requirements for such quality systems, such as deviations, complaint handling, training, internal auditing,
validation, and change management. These concepts are irrespective of technology or national requirements but capture that
intangible asset known as the "quality culture." Quality management synthesizes all of the quality systems to develop a comprehensive
approach to address quality issues, make improvement, and create the quality culture.