Biomedical Engineering Reference
In-Depth Information
validmeasurement of product temperature during primary drying even at temperatures as
low as
45
C.
Mass balance determination using a tunable diode laser absorption spectroscopy
(TDLAS) has recently been introduced as an analytical tool capable of obtaining
real-time water vapor concentration and gas flow velocity measurements in the duct
connecting the dryer chamber and condenser without process interruption [49, 51]. The
device is used to determine the duration of the drying cycle to determine the total amount
of water removed during the drying process. Pikal et al. [48] demonstrated that
gravimetric and TDLAS flow sensor mass flux determinations showed a deviation of
5%, on average, during lyophilization cycles. With this flow senor, detection of primary
and secondary drying end points was possible in real time, thus making the system
amenable to end point analysis as a critical process parameter, rather than a time-based
parameter.
12.5 PAT TOOLS FOR BIOPROCESS STARTING MATERIALS,
DEFINED MEDIA, AND COMPLEX RAW MATERIALS
One of the most difficult, but the most fruitful, areas of controlling bioprocess variability
pertains to incoming raw materials analysis for components used in bioprocesses. Too
frequently, bioprocess manufacturers rely on vendor Certificates of Analysis to ensure
the quality of the raw material they are using to manufacture their product. While many
biopharmaceutical companies have QC raw material testing laboratories, the off-line
analyses have to deal with many of the same issues as off-line product quality analysis.
The analyses occur at a stage of the material manufacturing where it is too late to react to
raw material quality changes that occur between the time of testing and the time of use.
Often, the methods used are compendial, and while they faithfully detect the quality of
the desired raw material, they are often not adequate enough to detect impurities and
adulterants. Consequently, the finished product may result in rework, scrap, or even
product safety issues.
Raw material stability may play a role in process variability for materials that are
heat, moisture, or photosensitive, which may not be properly controlled. Analysis, just
prior to use, is often a desired control point for most process scientists and engineers.
Several spectroscopic techniques are suitable for in-line, “prior to use” raw material
monitoring such as optical density, NIR, and fluorescence, which may allow process
decisions to be made prior to the initiation of the manufacturing process. In addition, a
host of off-line methods are being used to better understand how individual components
of complex raw materials affect process outcomes.
One of the most abundant raw materials used in bioprocess unit operations is water.
One in-line PAT tool to help with water monitoring is for total organic content (TOC).
Online TOC is becoming a more commonplace tool for determining effects of carbon
source fromwater on the process. Several commercial systems already available have the
potential to reduce the sample load of QC labs to test for TOC.
For defined media, the components going into the defined media are measured and/
or controlled independently prior to mixing, but little attention is paid to interactions
