Historical Background - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 3

storage properties of a freeze-dried, stable potato product, which was
first described by chroniclers who accompanied the Spanish invaders of
the Inca Kingdom. 2
1.2 Advent of Industrial Freeze-Drying
In reality, the consequences of freezing and thawing are usually more
complex than those described by de Veer, or as performed by the South
American Indians. For example, the removal of water from complex
solid substrates, such as fish or meat, is accompanied by an irreversible
aggregation of muscle tissue, which is then unable to reintegrate enough
water into the muscle tissues after thawing, giving rise to what is known
as ''drip loss''. Other deleterious processes that may occur during drying
include the rupture of cell membranes (e.g. soft fruit) or enhanced lipid
oxidation, leading to off-flavour and rancidity (e.g. fish). Nevertheless,
the controlled drying of food, leading either to the so-called intermedi-
ate- or low-moisture products or to ''instantisable'' products has made
great strides and has established itself as an important branch of food
process development. Although frozen distribution and storage of food
is still widely practised, freeze-drying, i.e. the sublimation of ice from a
previously frozen product, has been largely superseded by other, more
economical drying methods. Its current use is limited mainly to the
production of high-value products, e.g. Japanese fish specialities, or
products where losses of volatiles would seriously impair quality. The
place of freezing and freeze-drying in food process technology, as it
existed in the 1970s and how it was predicted to change during the 1980s,
is well summarised by the contributions presented at a Royal Society
Discussion in 1974. 3 With the benefit of hindsight, the reader is left to
decide to what extent the predictions actually came true.
The situation is totally different in the pharmaceutical industry, where
freeze-drying has gradually established itself as the standard method for
rendering aqueous (or even some non-aqueous) solutions of bioactive
substances into solid, stable states. An important difference between
food and drug processing lies in the contribution of processing towards
the total cost. In the case of food production, the various processing
stages account for an appreciable contribution towards the total cost,
whereas in the pharmaceutical industry the cost of downstream process-
ing, although appreciable, is usually only a minor factor, compared to
the cost of the purified bioactive raw material, the drug substance.
Another reason is that the regulatory requirements in the food industry
are less stringent than those which govern purity, sterility and stability