Influence of particle shedding from silicone tubing on antibody stability

Abstract

Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability.

Effects of Tubing Type, Formulation, and Postpumping Agitation on Nanoparticle and Microparticle Formation in Intravenous Immunoglobulin Solutions Processed With a Peristaltic Filling Pump

“…Arguably, filling pump operation is one of the most important processing steps in terms of impact on quality of therapeutic protein products. As shown in the current and several other earlier studies, [6][7][8][9][10][11] pumping of protein solutions causes formation of relatively high levels of particles. Furthermore, as vials or syringes are filled, there is no filtration of the formulation after it leaves the filling pump.…”

“…Finally, as documented in the current and earlier studies, [6][7][8][9][10][11] "pumpability" studies can provide critically important information about the stability of formulations during the final solution handling step of manufacturing. It is recommended that formulation development studies include testing with the actual filling pump type, brand, and components (e.g., tubing type) that will be use for manufacturing of the drug product.…”

“…The filling process is notorious for causing protein particles. [6][7][8][9][10][11] Importantly, unless a product is delivered to the patient through a filter, particles generated during filling pump operation will be administered to the patient. There are several unpublished studies of product quality problemsdsuch as unexpected appearance of visible particles in product containersdthat have identified filling pump-induced nanoparticles and microparticles as potential underlying causes.…”

“…The pump ranking from high to low particle levels were rotary piston (ceramic) > rotary piston (stainless steel) >> rolling diaphragm > time-pressure > peristaltic pumps. More recently, Saller et al 9,10 found that during peristaltic pumping of placebo solution, the tubing shed microparticles and nanoparticles, but quiescent incubation of unpumped mAb formulations with these particles at temperatures up to 40 C did not result in protein particle formation. Most recently, Kalonia et al 11 documented that microparticle formation in an mAb formulation during rotary piston pump filling operation was due to protein film formation at the stainless steelesolution interface and shearinduced mechanical disruption of the film.…”

Physicochemical Stability of Monoclonal Antibodies: A Review

“…Pumping provokes shearing and cavitation in tubing and has been shown to decrease bioactivity and increase particle count. 178,181,182 Filtration can also be associated to shearing. Shear-thinning behavior (decrease of viscosity under shear strain) has been reported for high concentration mAb solutions, perhaps linked to the dissociation of selfassociating of mAb clusters, 183 but it is unclear if shear forces during by filtration induced other modifications.…”