Biohazards in pharmaceutical freeze drying.

Among freeze-dried drugs there are many which may imperil manufacturing personnel, e.g. cytostatic drugs possessing carcinogenic effects. Production zones must be specially adapted for handling such drugs. There are many risks endangering a freeze-drying operation--power or water supply failure, but also improperly established freeze-drying cycle. A production batch of a rare, expensive and sensitive product represents a big value; modern equipment therefore features sophisticated automation, overriding possible human error. Problem of particulate contamination is less severe with vials stoppered inside the vacuum chamber, but rubber closures still may become a source of haze. Back-migration of oil from vacuum pumps may be another source. Economy of industrial freeze-drying may be much improved if freezing sequence, drying rate, adjustment of vacuum by "bleeding" nitrogen are tailored specially for each particular product.