Case Histories - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 163

CHAPTER 12
Case Histories

12.1 Introduction

Successful freeze-drying, on a commercial scale, of essentially labile
materials depends on a detailed understanding of the complex interplay
between several disciplines: ice physics, chemistry of supersaturated
solutions, pharmacology, materials science of water sensitive materials,
engineering of coupled heat and mass transfer, production economics
and IP law. The case histories discussed in this chapter originate mainly
from projects undertaken by the author and his colleagues at Pafra
Biopreservation during the period 1985-1999 and from various consul-
tancy projects undertaken by the author since that time. w
A logical sequence of activities is recommended for the co-develop-
ment of a specified product and an optimised process cycle. During the
pre-formulation and formulation stages, it is well to carry out a litera-
ture search in order to ensure that the actual formulation arrived at does
not run the danger of excessive IP litigation. Thus, a large international
company was in the process of developing a new product, aiming to use
alanine as the stabilising excipient. The only reason for this choice
turned out to be that a competitor had patented the use of glycine for a
similar product. It was nevertheless intended to use the same dry-
ing cycle as the one described by the competitor, a sure recipe for
disaster.
After a thorough literature search, the suggested sequence to be
followed begins with pharmacokinetics. Assuming that a specified unit
dose of drug is to be delivered, it must be established that none of the
other components in the formulation interferes with the action or the
potency of the drug substance. The formulation is then built up, taking

w Where the results have not been published in the public domain, names of client companies are not
divulged, although the period of confidentiality has expired in every case.

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