Ensuring the Biologic Safety of Plasma-Derived Therapeutic Proteins

Abstract

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. Fortunately, between 1970 and 1990, the molecular biology of each of the major viruses was elucidated. These advances led to the development and implementation of effective donor screening tests, mainly based on immunoassays and nucleic acid testing, which resulted in a significant reduction of disease transmission risk. In addition, viral inactivation and removal steps were implemented and validated by manufacturers, further reducing the risk associated with known, as well as unidentified, viruses. Since the late 1990s, a different class of transmissible agent, referred to as prions, has been identified as a new risk for disease transmission. However, prion diseases are very rare, and prion transmission through plasma-derived proteins has not been reported to date. The prion-related risk is minimized by deferring donors with certain key risk factors, and by the manufacturing processes that are capable of removing prions. Advances in science and pathogen safety-related technology, compliance with good manufacturing practices by manufacturers, and increasingly stringent regulatory oversight, has meant that plasma-derived proteins have been developed into today's highly effective therapeutics with very low risk of disease transmission.

Human Recombinant Butyrylcholinesterase Purified from the Milk of Transgenic Goats Interacts with Beta-Amyloid Fibrils and Suppresses Their Formation in vitro

“…In the transgenic platform, rBChE is expressed in high concentrations in the milk of transgenic goats [16] , overcoming supply limitations and health risks associated with the use of human-derived proteins [17] . Milk containing rBChE was clarified using a tangential flow filtration system to remove fat and casein.…”

Engineering of protein thermodynamic, kinetic, and colloidal stability: Chemical Glycosylation with monofunctionally activated glycans

“…This has been reported for different glycosylated isoforms of insulin (Baudys et al, 1995). Yet at high temperatures (near or above the T m ) like those used routinely during biocatalysis and bioprocessing (Cai et al, 2005;Illanes, 1999;) one would expect protein-protein interactions and the low solubility of the unfolded state to dominate the aggregation process. In this context our accelerated aggregation studies with the different sized glycans reveal that while small glycans might slow the aggregation process at low temperatures they are inadequate at preventing protein-protein contacts and thus aggregation once unfolding occurs.…”

Recent Advances in the Research and Development of Alpha-1 Proteinase Inhibitor for Therapeutic Use

“…Moreover, despite effective viral inactivation/removal steps in the manufacturing of plasma proteins (Cai et al, 2005;Hotta et al, 2010), the risk of contamination with new and unknown pathogens may still exist. Therefore, recombinant technology has been widely explored as an alternative approach for the production of human 1 -PI since the pioneering works of the early 1980s (Bollen et al, 1983;Cabezon et al, 1984;Rosenberg et al, 1984).…”