24 Pharmaceutical Technology
®
|
BioPharm International
®
Bio/Pharma Outsourcing Innovation February 2025
alytical development, MSAT, manufacturing, and
quality teams and the client. In our case, the client
can be involved as much as they want to be," says
Schrock. "What we end up with as the deliverable
is a big table that addresses each unit operation, as
well as the analytical methods and the associated
failure modes or risks that go with those different
steps. We then identify the worthy parameters to be
addressed in the [process characterization] studies
based on these risks and the cell culture parameters
[i.e., cell passage, number, cell densit y, perf usion,
rate, pH, dissolved oxygen]. All these can be varied
in either design of experiment (DoE) or one factor at
a time (OFAT) [methods]."
Process validation
is a necessity to be sure
the manufacturing process
produces the desired,
safe product.
CPPs are a part of a control strategy and should be
monitored or controlled to ensure product quality
(1). A combination of approaches to obtain CPPs may
be used, including risk assessments and experimen-
tal investigation. Selecting CPPs include identifying
critical quality attributes (CQAs), selecting materi-
als, excipients, and APIs, defining unit operations,
process f low, process specification limits, exploring
the design space, and achieving acceptable method
validation results (2).
"CPP selec t ion ha s t rad it iona l ly been d i f f ic u lt
because of a lack of a systematic approach to t he
problem ," accord i ng to T hom a s L it t le (2). "CPPs
can be found in media, upstream and downstream
unit operations, and drug-product processing. Due
to the large number of unit operations and media
complex it y, it i s ea s y to overlook processi ng pa-
rameters and materials that may impact drug-sub-
stance and drug-product variation and CQAs. Fail-
u re to ident i f y cr it ica l pa ra meters ca n resu lt i n
unexplainable variation during batch processing
and lot acceptance" (2).
References
1. Vukovinsky, K.; Watson, T. J. Statistical Tools to
Aid in the Assessment of Critical Process Parame-
ters. Pharmaceutical Technology. 2016 40 (3).
2. Little, T. A. Using a Systematic Approach to Select
Critical Process Parameters. Supplement to Phar-
maceutical Technology. November 2012. ht t ps://
www.pharmtech.com/view/using-systematic-ap-
proach-select-critical-process-parameters Q
PROCESS
DE
VELOPMENT
Cell Culture Optimization
Optimization of process development for cell
culture is dependent on the type of product
being produced, according to Bob Schrock ,
PhD, senior director, global head of Process
Development, at Lonza, who talked about cell
culture optimization in an two-part interview
with BioPharm International®.
In Part One of the interview, Schrock provides
insight on how cell culture processes may be
optimized and what kind of process studies are
performed for cell culture.
Watch Now!
https://www.biopharminternational.com/view/
cell-culture-optimization-part-one
In Part Two of the interview, Schrock provides
insight on how process controls change during
development through commercialization, how cell
harvesting can be optimized, and which validation
and/or qualification studies are performed for cell
culture.
Watch Now!
https://www.biopharminternational.com/view/
cell-culture-optimization-part-two
