eBook: Analytical Method and QC Testing Strategies for Biologics Production - 5

management and control is a systemic approach for the
assessment of risk to the quality of the reportable value
generated from the analytical procedure.
For the purposes of this article the focus will
be how to utilize design of experiments (DoE)
principles for developing robust analytical methods
for quality control (QC) environments by initially
understanding the method as a process and secondly
by demonstrating robustness.
How Design of Experiments
(DoE) Principles Can Be Utilized
in Developing Robust Analytical
Methods for QC Environments
In current practice, analytical procedures are typically
developed utilizing a one factor at a time approach
(OFAT), in which one parameter is optimized in isolation
with the others remaining constant. By following this
approach for method development no information is
obtained around how method parameters interact with
each other and therefore impact the results obtained.
This can lead to analytical procedures with very narrow
robust ranges of operation. Hence this strategy has
the potential for an increase in risk of method failure
after the analytical procedure is transferred from the
development environment into an internal or external
QC laboratory.
The Design of Experiments (DoE) methodology is a
test or series of tests in which purposeful changes
are made to the input variables (factors) of a process
so that we may observe and identify corresponding
changes in the output response. In short, DoE is an
approach that can be used to determine cause and
effect relationships in a stepwise manner (Figure 1). In
the context of developing robust methods for the QC
Figure 1. The stepwise manner in which the design of
experiments (DoE) methodology can be utilized to develop
and implement robust analytical procedures in a quality
control (QC) laboratory environment.
environment, DoE can be utilized in a variety of ways.
For example; determining, identifying and evaluating
the effect of the most influential method parameters
and any interactions between method parameters
within the design space so that the method can be
developed and then validated in accordance to the
guidance provided by the International Conference on
Harmonization (ICH) quality guideline Q2: Validation of
Analytical Procedures.7
Or secondly, for the purposes
of demonstrating robustness of the analytical
procedure by assessing the capacity of the method to
remain unaffected by small variations in the method
parameters, so that it can perform to the requirements
stated in the ATP and can be successfully transferred to
QC laboratories with a reduction in the risk involved.
One challenge to analytical development is that
the timelines can often be compressed for various
reasons. For novel molecules, the sooner methods are
optimized, the lower the risk will be to overall product
development. By utilizing the DoE methodology for
method development, optimization and assessing
robustness we can increase our scientific understanding
of the method in the same and often shorter time frames
than if the OFAT approach is used. Therefore, reducing
the risk associated with the results obtained from the
analytical procedure in a highly cost-effective manner.
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eBook: Analytical Method and QC Testing Strategies for Biologics Production

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