A Mechanistic Understanding of Monoclonal Antibody Interfacial Protection by Hydrolytically Degraded Polysorbate 20 and 80 under IV Bag Conditions.

Purpose: Polysorbates (PS) contain polyoxyethylene (POE) sorbitan/isosorbide fatty acid esters that can partially hydrolyze over time in liquid drug products to generate degradants and a remaining intact PS fraction with a modified ester distribution. The degradants are composed of free fatty acids (FFAs) --primarily lauric acid for PS20 and oleic acid for PS80-- and POE head groups. We previously demonstrated that under IV bag agitation conditions, mAb1 (a surface-active IgG4) aggregation increased with increasing amounts of degradants for PS20 but not for PS80.

Evaluating a Modified High Purity Polysorbate 20 Designed to Reduce the Risk of Free Fatty Acid Particle Formation.

Purpose: To evaluate a modified high purity polysorbate 20 (RO HP PS20)-with lower levels of stearate, palmitate and myristate esters than the non-modified HP PS20-as a surfactant in biopharmaceutical drug products (DP). RO HP PS20 was designed to provide functional equivalence as a surfactant while delaying the onset of free fatty acid (FFA) particle formation upon hydrolytic degradation relative to HP PS20.

Methods: Analytical characterization of RO HP PS20 raw material included fatty acid ester (FAE) distribution, higher order ester (HOE) fraction, FFA levels and trace metals.

A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation.

Purpose: Enzymatic polysorbate (PS) degradation and resulting free fatty acid (FFA) particles are detrimental to biopharmaceutical drug product (DP) stability. Different types and grades of polysorbate have varying propensity to form FFA particles. This work evaluates the homogenous all-oleate (AO) PS80 alongside heterogeneous PS20 and PS80 grades in terms its propensity to form FFA particles and other important attributes like interfacial protection and oxidation susceptibility.

Dissolution of Polysorbate 20 Degradation Related Free Fatty Acid Particles in Intravenous Bag Solutions.

Degradation of Polysorbate 20 (PS20), a commonly used surfactant in drug product (DP) formulations, is a phenomenon of increasing concern to the biopharmaceutical industry. One of the most prevalent modes of PS20 degradation is enzymatic hydrolysis resulting from co-purified hydrolases that make their way into biologic DP formulations at trace levels. Enzymatic PS20 degradation results in generation of free fatty acids (FFAs) that have limited solubility in aqueous formulations and can form visible and/or sub-visible particles which is undesirable for parenteral DP stability and administration.

Impact of Silicone Oil on Free Fatty Acid Particle Formation due to Polysorbate 20 Degradation.

Purpose: Polysorbate 20 (PS20), a commonly used surfactant in biopharmaceutical formulations, can undergo hydrolytic degradation resulting in free fatty acids (FFAs) that precipitate to form particles. This work investigates the ability for silicone oil (si-oil) coated on the interior walls of prefilled syringes (PFSs) to act as a sink for FFAs and potentially delay FFA particle formation.

Methods: Myristic acid distribution coefficient was measured in a two-phase system containing si-oil and formulation buffer at a range of aqueous conditions.

Improving Prediction of Free Fatty Acid Particle Formation in Biopharmaceutical Drug Products: Incorporating Ester Distribution during Polysorbate 20 Degradation.

Polysorbate 20 (PS20) is a commonly used surfactant in biopharmaceutical formulations. It is a heterogeneous surfactant containing a distribution of fatty acid esters, which are subject to hydrolytic degradation, generating free fatty acids (FFAs). The FFAs can form visible or subvisible particles in drug product on stability.

Evaluation of Super Refined™ Polysorbate 20 With Respect to Polysorbate Degradation, Particle Formation and Protein Stability.

Super Refined™ and Tween™ 20 HP polysorbate 20 (PS20) are two commercially available compendial grades of PS20 frequently used in biopharmaceutical formulations as protein stabilizing surfactants. PS20 degradation has been a major concern recently for potentially limiting drug product shelf life due to free fatty acid particle formation. This work is a side-by-side comparison of SR and HP PS20 in terms of PS20 degradation, particle formation and protein stability.

A Case of Intestinal Microsporidiosis in a Renal Transplant Recipient.

Post-renal transplant diarrhea is a common clinical presentation. An extensive list of potential etiology adds to the diagnostic dilemma. In cases of prolonged or intractable diarrhea, invasive tests are often performed.

Understanding Particle Formation: Solubility of Free Fatty Acids as Polysorbate 20 Degradation Byproducts in Therapeutic Monoclonal Antibody Formulations.

The purpose of this work was to determine the aqueous solubilities at 2-8 °C of the major free fatty acids (FFAs) formed by polysorbate 20 (PS20) degradation and identify possible ways to predict, delay, or mitigate subsequent particle formation in monoclonal antibody (mAb) formulations. The FFA solubility limits at 2-8 °C were determined by titrating known amounts of FFA in monoclonal antibody formulations and identifying the FFA concentration leading to visible and subvisible particle formation. The solubility limits of lauric, myristic, and palmitic acids at 2-8 °C were 17 ± 1 μg/mL, 3 ± 1 μg/mL, and 1.

Visual diagnosis: newborn with absence of skin.

ACC is a rare condition that has to be approached by a multidisciplinary team, including a pediatrician, dermatologist, and plastic surgeon. Associated malformations should be ruled out in a patient with ACC, and conservative management is usually the mainstay of treatment. Antibiotic therapy is not used routinely unless lesions are infected.