Figure 6: The basic principles of
the quality by design approach, where more flexibility is obtained by a
characterized space; adapted from (Carta et al., 2010).
Ideally, the full design space is covered by the training, validation
and test data. In this ideal situation interpolation within the design
space will be very good (Figure 6). Rolinger et al. (Rolinger et al.,
2021) five runs in their study. Four runs covered the design space, and
the center point was used as an independent test set. It is not
surprising that the model performed well. Sauer et al and Walch et al.
(Sauer et al., 2019; Walch et al., 2019) on the other hand simulated the
situation of a manufacturing run under clearly defined process
conditions and used eight runs performed under identical process
conditions for model building. The performance was then evaluated on
purification runs performed under identical conditions but with
biological material from a new fermentation and under different process
conditions. It was shown that the model performed well on new biological
material (Sauer et al., 2019) and that model extrapolations are possible
but are limited to modifications in the column load and small changes in
buffer composition (Walch et al., 2019).