Validatibility of a capillary isoelectric focusing method for impurity quantitation.

A strategy is presented for examining the validatability of a capillary isoelectric focusing (cIEF) method, intended for quantitation of product-related impurities in a protein drug substance, according to guidelines published by the International Conference on Harmonization (ICH). The results of this study demonstrate the suitability of cIEF as an analytical method for the quantitation of two product-related impurities in a protein drug substance: a monodeamidated degradation product and an aggregated form of the parent molecule. A range of impurity levels was generated by spiking the isolated impurity species, into a representative production lot of the drug substance.

Rational scale-up of a baculovirus-insect cell batch process based on medium nutritional depth.

We have developed a serum-free cell culture process utilizing a recombinant baculovirus (AcNPV) expression vector to infect Trichoplusia ni insect cells for the production of the human lysosomal enzyme, glucocerebrosidase. The enzyme, which is harvested as a secreted protein in this process, can serve as a replacement therapy for the genetic deficiency Gaucher disease. In the course of pilot scale-up of a batch glucocerebrosidase process from 25-mL working volume shaker flask units to 25-L working volume stirred bioreactor units, a semi-empirical model was developed for the rational determination of scaleable process parameters, including host cell density at infection, multiplicity of infection (MOI), and harvest time.

Endopeptidase-24.15 in rat hypothalamic/pituitary/gonadal axis.

Endopeptidase-24.15 (E.C.

Inhibition of endopeptidase 24.15 greatly increases the release of luteinizing hormone and follicle stimulating hormone in response to luteinizing hormone/releasing hormone.

Inhibitors of endopeptidase (EP) 24.15, an enzyme cleaving the Tyr5-Gly6 bond of LHRH, greatly increase the half-life of i.v.