A practical and scalable manufacturing process for an anti-fungal agent, Nikkomycin Z.

A scalable and reliable manufacturing process for Nikkomycin Z HCl on a 170 g scale has been developed and optimized. The process is characterized by a 2.3 g/L fermentation yield, 79% purification yield, and >98% relative purity of the final product.

Ensuring the biologic safety of plasma-derived therapeutic proteins: detection, inactivation, and removal of pathogens.

Human plasma-derived proteins, such as immunoglobulins, coagulation factors, alpha1-antitrypsin, fibrin sealants, and albumin, are widely used as therapeutics for many serious and life-threatening medical conditions. The human origin of these proteins ensures excellent efficacy and compatibility but may also introduce the risk of unintentional disease transmission. Historically, only viruses, particularly hepatitis and HIV, have posed serious threats to the safety of these therapeutics.

An improved Western blot assay to assess the clearance of prion protein from plasma-derived therapeutic proteins.

Specific detection of the pathogenic prion protein, PrP(Sc), is essential for determining the prion clearance capacity of purification processes for therapeutic proteins. Use of a previously described indirect (two-antibody) Western blot assay sometimes resulted in the appearance of non-specific protein bands that interfered with the detection of small amounts of PrP(Sc)-specific signal, limiting the amount of clearance that could be determined for steps so affected. It is shown that these non-specific signals are due to the interaction between immunoglobulin fragments in the sample and the secondary antibody used in the assay.

Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process.

Background And Objectives: Minimizing the transmission risk of infectious diseases is of primary importance in the manufacture of products derived from human plasma. A novel chromatography-based intravenous immunoglobulin (IGIV) manufacturing process was developed and the reduction of virus and transmissible spongiform encephalopathies (TSE) during the manufacturing process was assessed. Mechanistically distinct steps that could affect virus reduction were identified, and the robustness of virus reduction over the range of process conditions was determined.

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

Background: Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies.