Vaporized Hydrogen Peroxide Sterilization in the Production of Protein Therapeutics: Uptake and Effects on Product Quality.

The aseptic filling of drug products is carried out in pharmaceutical isolators that have been sterilized. A commonly used method for achieving a high level of sterility assurance is vaporized hydrogen peroxide (VHP) sterilization, which is favorable to other methods, such as ethylene oxide sterilization, due to its low cycle times and nontoxic residuals. While VHP cycles are often employed to create a sterile environment within an isolator, they can leave residual levels of hydrogen peroxide behind that can enter the product during fill-finish operations.

Water loss from silicone tubing and effect on protein concentration during drug product manufacturing.

Silicone tubing is used in various unit operations during drug product (DP) manufacturing. Hold of protein formulations in silicone tubing over time may have an impact on product quality, particularly protein concentration. This study evaluated the change in protein concentration of a test monoclonal antibody (mAb) formulation over various hold times in silicone tubing as a function of tubing internal diameter (ID) and wall thickness.

Container Closure and Delivery Considerations for Intravitreal Drug Administration.

Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life.

Mechanistic studies of an autonomously pulsing hydrogel/enzyme system for rhythmic hormone delivery.

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion.

Solution pH that minimizes self-association of three monoclonal antibodies is strongly dependent on ionic strength.

Monoclonal antibodies display highly variable solution properties such as solubility and viscosity at elevated concentrations (>50 mg/mL), which complicates antibody formulation and delivery. To understand this complex behavior, it is critical to measure the underlying protein self-interactions that govern the solution properties of antibody suspensions. We have evaluated the pH-dependent self-association behavior of three monoclonal antibodies using self-interaction chromatography for a range of pH values commonly used in antibody formulations (pH 4.