eBook: Analytical Method and QC Testing Strategies for Biologics Production - 9

of the method development process the ranges
selected were characteristically, the ranges should
be two to three times the level of process control. For
assessing the robustness of the analytical procedure,
the ranges of the factors under investigation should
now be tightened to be representative of the level
of acceptable process control. For example, if the
factor under investigation is temperature then for
the optimization DoE the range for this factor could
be 65°C ± 5°C and where if 65°C is the determined
optimum, for the robustness DoE the range could
be 65°C ± 2°C. The aim of the robustness DoE is that
for all conditions investigated the reportable results
obtained are within the acceptable level of variation
stated in the ATP and that additionally all criteria of
the ATP be met. To mitigate the risk further the final
analytical procedure conditions can be performed by
additional scientists on different instrumentation to
gain an additional understanding of the performance
of the analytical procedure before implementation.
Summary
A DoE approach for how to optimize and demonstrate
robustness of the analytical unit operation for sample
preparation of novel molecular formats for a platform
analytical procedure has been presented in this article.
This sequential process built on objective data and
not personal intuition guides the decision making
and affords the mitigation of risk
of data generated from utilizing DoE methodologies
can be an important aspect of an AQbD approach
with regards implementing an appropriate ACS for the
analytical procedure.
Acknowledgements
The author would like to acknowledge the following
people for their on-going support and assistance
Guillermo Miro-Quesada, Christopher Larkin, Douglas
Johnson, Kristin Schultz-Kuszak, Derek Schildt, Eric
Meinke and Xiangyang Wang
References
1. ICH, Q8(R2): Pharmaceutical Development (ICH, August 2009)
2. ICH, Q11: Development and Manufacture of Drug Substances
(Chemical Entities and Biotechnological/Biological Entities) (ICH,
May 2012)
3. P. Borman, P. Nethercote, M. Chatfield, D. Thompson, K. Truman, The
application of quality by design to analytical methods, Pharm. Tech.
31 (2007) 142-152
4.
in comparison
to utilizing a OFAT methodology and additionally
allows for investigating factor interactions which is
also not possible from the OFAT approach leading to
the generation of more robust analytical procedures
suitable for the QC environment. A supplementary
benefit of utilizing DoE software is that graphical
data representation allows for easy analysis of the
reportable results obtained and that the large amount
J. Kochling, W. Wu, Y. Hua, Q. Guan, J. Castaneda-Merced, A platform
analytical quality by design (AQbD) approach for multiple UHPLCUV
and UHPLC-MS methods development for protein analysis,
Journal of Pharmaceutical and Biomedical Analysis. 125 (2016)
130-139
5. Y. Li, G.J. Terfloth, A.S. Kord, A systematic approach to RP-HPLC
method development in a pharmaceutical QbD environment, Am.
Pharm. Rev. 12 (2009) 87-95.
6. E. Kovacs, J. Ermer, P. L. McGregor, P. Nethercote, R. LoBrutto, G. P.
Martin, H. Pappa, Stimuli to the Revision Process: Analytical Control
Strategy, 42 (5) (2016)
7.
ICH, Q2(R1): Validation of Analytical Procedures: Text and
Methodology (ICH, November 2005).
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