Thompson: I believe that in the next 5 years, Process Control
and PAT will be the major considerations for freeze dryers.
Currently, the freeze drying process is an open loop control
with very little monitoring in-situ, meaning that the processing
company may not know there is a faulty run until it is completed. Most of the measuring instruments, such as TDLAS,
NIR, and Mass Specs are expensive, intrusive, provide marginal
process improvement, and are not economically feasible for
process control. New technologies will enable complete control
of the freeze drying process including controlled nucleation,
controlled crystal growth during freezing, product temperature
control instead of shelf temperature control, the ability to determine the end of freezing, the end of primary drying, the end of
secondary drying, and the ability to verify that the process has
executed properly. ■
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with an automated vial-filling line and the vials are made out
of break-resistant material, which helps reduce the risk of vial
breakage during shipping. The biggest drawback to using a
non-glass vial is that additional material compatibility studies
are required and there is a risk of extractables and leachables
with certain product formulations. Additionally, because the
vials arrive pre-sterilized, the handling procedures can vary.
Have new control systems been developed in recent years
to ensure quality and reduce waste?
Palus: Some new control systems have emerged over the
last 5 years but I think that we are going to see an increased
number of them over the next decade along with more implementation of them at CMOs. Control systems can be helpful to ensure that CMOs can deliver the safest and most effective products into the clinic or to the commercial market.
Thompson: There are several recent improvements in the
control of freeze drying that will likely have a significant impact on future processing. The freezing process is considered
the foundation of the freeze drying process, yet it has never
been properly controlled. Simply placing vials on a shelf and
lowering the shelf temperature leads to heterogeneous nucleation and non-uniform crystal growth, which impede primary
drying. We have developed new technology that controls
nucleation enabling all the vials to nucleate at the same time,
temperature, and rate to produce a consistent starting point
for freezing control across the entire batch. It is a common
misconception that controlled nucleation results in up to a
40% reduction in primary drying times. Since controlled nucleation results in less than 15% of the available water being
crystalized, a method for controlling crystal growth post-nucleation is required. The combination of controlled nucleation
and proper post-nucleation crystal growth can result in <50%
reductions in primary drying times.
What do you see as the future for freeze drying/lyophiliza-tion technologies in the next five years?
Palus: We have seen significant growth in the need for
lyophilization over the last decade and we anticipate that
this growth will continue over the next 5 years. Without lyophilization, many drugs would either not make it to market or
they would require cold chain logistics, which are not always
desirable. It is currently estimated that over half of biopharmaceuticals must be lyophilized and this number is continuing to grow due to the increased demand for lyophilization
against a backdrop of some capacity being removed.
Zimmerman: The demand for solutions involving
freeze-drying will continue to grow as an increasing number
of biotechnologically-produced drugs and candidate substances appear on the market. This will require more innovations in the machines, leading to greater efficiency and
safety. We expect to see greater demand for user-friendly injection systems and I believe these systems will gain market
shares over lyophilization in the vial, since they can be used
safely and simply by the patients themselves.