Proteins plasma-derived therapeutic

Plasma-derived therapeutic proteins are parenteral biologies that are purified on an industrial scale. All biologies derived from human sources, such as plasma, carry the risk of viral contamination. Thus, in order to market a medicinal product derived from human plasma, manufacturers must assure the absence of specific viral contamination. Virus validation studies are performed to evaluate the capacity of a manufacturing process to remove viral contaminants. Virus clearance across three different terminal inactivation steps, low pH incubation of immunoglobulins (IgG), pasteurization of albumin, and freeze dry/dry heat treatment of plasma-derived products (Factor VIII and Protein G), is discussed in this article. The data show that, like all other upstream virus reduction steps, the methods used for terminal inactivation are process and product dependent, and that the reduction factors for an individual step may be overestimated or underestimated due to inherent limitations or inadequate designs of viral validation studies. 

Plasma-derived therapeutic proteins are parenteral biologies that are purified on an industrial scale. Most biologies are highly complex, heat-sensitive, protein... 

The starting source materials used for the production of therapeutic proteins were heterogeneous mixtures obtained from several humans or animals, requiring the pooling of somce material from a large number of individuals to eliminate individual and batch to batch variation of post-translational modifications in the final product. Thus, starting plasma lots used in fractionation are made from pools of plasma derived from 10,000 to 12,000 individuals (Snape, 1991). 

Blood Plasma Processing. Purified therapeutic proteins are derived from human blood plasma via cryoprecipitation followed by sequential precipitations effected through increasing ethanol concentrations at controlled temperature, pH and ion composition ("Cohn precipitation"). As discussed in the section on fractionation of solutes, UF cannot be used to fractionate the various plasma... 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the... 

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