Protein loss during membrane processes in biopharmaceutical manufacturing.

Maximizing product yield in biopharmaceutical manufacturing processes is a critical factor in determining the overall cost of goods, especially given the high value of these biological products. However, there has been relatively limited research on the quantitative analysis of protein losses due to adsorption and fouling during the different membrane filtration processes employed in typical downstream operations. This study aims to provide a comprehensive analysis of protein loss in the range of membrane systems used in downstream processing including clarification, virus removal filtration, ultrafiltration/diafiltration for formulation, and final sterile filtration, all using commercially available membranes with three model proteins (bovine serum albumin, human serum albumin, and immunoglobulin G). The correlation between protein loss and various parameters (i.e., protein type, protein concentration, throughput, membrane morphology, and protein removal mechanism) was also investigated. This study provides important insights into the nature of protein loss during membrane processes as well as a methodology for quantifying protein yield loss in bioprocesses.

Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins.

Recent studies have demonstrated that one can control the packing density, and in turn the filterability, of protein precipitates by changing the pH and buffer composition of the precipitating solution to increase the structure/order within the precipitate. The objective of this study was to examine the effect of sodium malonate, which is known to enhance protein crystallizability, on the morphology of immunoglobulin precipitates formed using a combination of ZnCl2 and polyethylene glycol. The addition of sodium malonate significantly stabilized the precipitate particles as shown by an increase in melting temperature, as determined by differential scanning calorimetry, and an increase in the enthalpy of interaction, as determined by isothermal titration calorimetry. The sodium malonate also increased the selectivity of the precipitation, significantly reducing the coprecipitation of DNA from a clarified cell culture fluid. The resulting precipitate had a greater packing density and improved filterability, enabling continuous tangential flow filtration with minimal membrane fouling relative to precipitates formed under otherwise identical conditions but in the absence of sodium malonate. These results provide important insights into strategies for controlling precipitate morphology to enhance the performance of precipitation-filtration processes for the purification of therapeutic proteins.

Metal-based nanoparticles for bone tissue engineering.

Tissue is vital to the organization of multicellular organisms, because it creates the different organs and provides the main scaffold for body shape. The quest for effective methods to allow tissue regeneration and create scaffolds for new tissue growth has intensified in recent years. Tissue engineering has recently used some promising alternatives to existing conventional scaffold materials, many of which have been derived from nanotechnology. One important example of these is metal nanoparticles. The purpose of this review is to cover novel tissue engineering methods, paying special attention to those based on the use of metal-based nanoparticles. The unique physiochemical properties of metal nanoparticles, such as antibacterial effects, shape memory phenomenon, low cytotoxicity, stimulation of the proliferation process, good mechanical and tensile strength, acceptable biocompatibility, significant osteogenic potential, and ability to regulate cell growth pathways, suggest that they can perform as novel types of scaffolds for bone tissue engineering. The basic principles of various nanoparticle-based composites and scaffolds are discussed in this review. The merits and demerits of these particles are critically discussed, and their importance in bone tissue engineering is highlighted.