The concepts and examples developed reflect some of many optional approaches available to use QbD in pharmaceutical development
and its effect on product realization.
Different activities in the product lifecycle are addressed in the series. Parts 1 and 2 focus on product realization using
QbD. Other parts to be published address activities later in the product lifecycle, such as process performance and product
quality monitoring system, change management, and selected elements of the process-validation lifecycle.
The series uses ICH terminology and the ICH guidelines Q8, Q9, and Q10, as well as Q11 on the development and manufacture
of drug substances as a basis, together with other relevant ICH guidelines, questions and answer documents, and points-to-consider
The need for guidance.
Feedback from many sources indicates that practitioners want clear explanations and examples to demystify the concepts discussed
in ICH Q8, Q9, and Q10, including "criticality" as applied to CQAs and CPPs, and "control strategy." Both terms have been
used in the industry and "critical" has been used in many guidelines globally. "Design space" is a concept introduced and
defined in ICH Q8 (R2).
ICH does not define "critical" even though the word is used extensively in its guidelines. ICH Q8 (R2) does offer definitions
for CQA and CPP. Although the phrase "level of criticality" is not used and "critical" is not defined, there is general agreement
within industry that assigning criticality to an attribute, parameter, or variable can be relatively subjective and dependent
on context. Although a critical attribute or parameter is frequently interpreted as being high risk, what "high risk" means
from a regulatory perspective remains debatable and inconsistent from company to company. Consequently, "criticality" is considered
related to risk; therefore, this topic in the series addresses the application of quality risk management, based on ICH Q9,
to the assignment of criticality.
"Control strategy" is defined in Q8 (R2) and Q10. How to establish a control strategy and its relationship to CGMPs and a
pharmaceutical quality system is not discussed in sufficient detail for practitioners, particularly when some elements of
a control strategy are derived from enhanced, QbD approaches, for example, when introducing real-time release testing (RTRT)
or when PAT tools have been used. Suggestions are given to practitioners in Part 1 of the ISPE Guide and exemplification in
great detail is provided in Part 2 to show how different elements of a control strategy combine to assure compliance with
CQA acceptance criteria. In particular, Part 2 helps readers understand how:
- different control strategy options can be developed
- choices can be made
- RTRT can be introduced
- a control strategy can be implemented into manufacturing
- PAT and RTRT can be applied in development and implemented into manufacturing
- continual improvement options can be considered and progressed.
"Design" space is a relatively new topic and, in response to many questions, guidance is given on the many ways in which design
space can be developed, communicated, and maintained as part of product realization. A number of specific examples are given
to assist the practitioner in understanding and being able to develop design spaces.