QUALITY BY DESIGN - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 94

2

Friability

1.8

1.6

1.4

1.2

Design
space

1

0.8

0.6

Dissolution

0.4

0.2

0

40 42 44 46 48 50 52 54 56 58 60

Parameter 1

Figure 5.7 To show an example of design space (proposed design space, comprising
the overlap region of ranges for friability and or dissolution) Ref ICH Q8R2 [1].

variety of controls, such as automated process controls, manual controls, standard
operating procedures (SOPs), etc., to assure product quality. Some product
controls may be highly product specific. For example, it may be necessary to
control particle size distribution of an aerosol product to assure patient efficacy
and this, in turn, may highlight the need to control CPPs at micronizing and
blending unit operations. The control strategy should provide a clear rationale
as to how the product CQAs are assured at all stages of manufacture.
Hand in hand with the product control strategy is the need to consider the
requirements of ICH Q10, [3] the PQS. The PQS is defined in ICH Q10 [3]
as, “ a management system to direct and control a pharmaceutical company with
regard to quality .” The product-specific controls and broader GMP controls that
apply to more than one product (such as the adequacy of changing facilities
for operators to dress into pharmaceutical clothing) should be integrated with
the PQS and at the same time permit business requirements, such as operational
efficiency, general safety, health and environmental considerations, financial, etc.,
to be met.
Finally, in regard to the QbD flow diagram in Figure 5.1, there is Continual
Improvement . This is to ensure that as knowledge is gained over the life cycle of
the product, such knowledge can be used to seek improvements to both products
and processes. For example, it may be that practical manufacturing experience