Historical Background - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 11

important reason appears to be that freeze-drying of pharmaceutical
products has long been accepted by those national and international
authorities, which regulate the granting of product licences. This alone
would be enough to stifle any development of alternative drying proc-
esses. Even if technically successful, they would have to be submitted for
lengthy and costly examination and validation by the various regulatory
authorities.
Factors in favour of freeze-drying are undoubtedly the ability of
carrying out the process under conditions of absolute sterility and the
rapid reconstitution of the dried product at the point of use. It is also
true that the white solid plugs, so characteristic of properly freeze-dried
solutions, are widely recognised and accepted as a mark of quality by
end users. The most common replies to the question ''Why freeze-dry?''
are ''everybody else does it'' or ''this product has always been success-
fully freeze-dried''. The widespread conservatism of company produc-
tion departments is so well documented that it needs no further
elaboration.
We now come to three doubtful reasons, in particular the view that
low temperatures are beneficial processing conditions. It will be shown
in Chapter 5 that such a statement needs careful qualification; it is
certainly not a universal truth. As to the quality of the freeze-dried
products, here again questions arise. Product catalogues distributed by
manufacturers of biochemicals bear witness to apparent doubts about
quality, because the need for refrigerated storage is usually specified and,
for many biopharmaceutical products, deep frozen storage is apparently
an absolute requirement. If this is indeed the case, then the slow removal
of ice from the frozen solution by sublimation is surely superfluous.
A simple freeze-thaw process would suffice.
The widely accepted, but mistaken, claim that freeze-drying is a simple
process to perform has probably been responsible for its almost com-
plete neglect by chemical engineers as a subject worthy of study.
Although ''drying'' is one of the accepted generic unit operations that
feature in chemical engineering texts, freeze-drying does not even merit a
mention, despite its technical complexity and its undoubted commercial
importance. As it becomes apparent in subsequent chapters, freeze-
drying is anything but simple, if not in concept, then certainly in its
practical operation in pharmaceutical manufacturing technology. 170 Its
neglect by chemical engineers is remarkable, because in this era of
computer simulation, freeze-drying, as usually performed by the phar-
maceutical industry, should provide interesting and unique systems for
study by computer modelling.