Characterization of Subvisible Particle Formation During the Filling Pump Operation of a Monoclonal Antibody Solution

An Interlaboratory Comparison of Sizing and Counting of Subvisible Particles Mimicking Protein Aggregates

“…Protein particles, consisting of aggregated protein and possibly a nonprotein nucleating core, can form in biopharmaceutical drugs . Stresses that can lead to the formation of protein particles include changes in chemical environment, exposure to interfaces, agitation, elevation of temperature, or the introduction of nonprotein particles . Counting and characterizing these particles is necessary to assure the quality of these drugs.…”

Particle Shedding from Peristaltic Pump Tubing in Biopharmaceutical Drug Product Manufacturing

“…For fill and finish processes, several types of pumps are generally employed, including rotary piston pumps, rolling diaphragm pumps, peristaltic pumps, and time‐pressure fillers. Given the fact that pumping to dispense into units occurs after the sterile filter in order to avoid backpressure peaks and to ensure adequate dispensing accuracy, generated particles may directly end up in the final DP units . The European and United States Pharmacopeia require parenteral DPs to be essentially/practically free from visible particles.…”

“…Moreover, stainless steel particles can be shed from the pump head . In contrast, stress on the proteins exercised upon filling with peristaltic pumps has been shown to be minimal and the use of peristaltic pumps has not led to a significant increase in particle counts and turbidity . Another main benefit of filling with a peristaltic pump is the fact that the DP solution only comes into contact with the inner surface of the disposable tubing.…”

Reduced Subvisible Particle Formation in Lyophilized Intravenous Immunoglobulin Formulations Containing Polysorbate 20

“…Subvisible particle characterization is particularly valuable in detecting trace amount of protein aggregates. [23][24][25] Particle counting methods provide a much more sensitive means by which to detect and quantify protein aggregation than traditional methods such as size exclusion chromatography (SEC). In 2 recent examples, particle formation was observed after monoclonal antibodies were subjected to freezethawing 23 or pumping, 24 but no loss of monomer or formation of soluble aggregates could be detected with SEC.…”