Freeze Drying and Vial Breakage: Misconceptions, Root Causes and Mitigation Strategies for the Pharmaceutical Industry.

Vial breakage during or following freeze drying (lyophilization) is a well-known and documented phenomenon in the pharmaceutical industry. However, the underlying mechanism and probable root causes are not well characterized. Mostly, the phenomenon is attributed to the presence of crystallizing excipients, such as mannitol in the formulation, while other potential factors are often underestimated or not well studied.

Near Infrared and Frequency Modulated Spectroscopy as Non-Invasive Methods for Moisture Assessment of Freeze-Dried Biologics.

Near-infrared (NIR) and frequency modulated spectroscopy (FMS) were employed, for non-invasive moisture determination of a lyophilized biologic drug product (DP). Development of NIR and FMS provides a rapid non-invasive means of residual moisture measurement, and would be beneficial compared with traditional time consuming, product destructive methods such as Karl Fischer (KF). A model therapeutic enzyme in a sucrose-based formulation was employed for proof of concept studies, and NIR and FMS methods were compared side by side for residual moisture analysis.

Demonstrating the stability of albinterferon alfa-2b in the presence of silicone oil.

Silicone oil is often used to decrease glide forces in prefilled syringes and cartridges, common primary container closures for biopharmaceutical products. Silicone oil has been linked to inducing protein aggregation (Diabet Med 1989;6:278; Diabet Care 1987;10:786-790), leading to patient safety and immunogenicity concerns. Because of the silicone oil application process (Biotech Adv 2007;25:318-324), silicone oil levels tend to vary between individual container closures.

Compound transfer efficiency from polystyrene surfaces: application to microarrayed compound screening.

In microarrayed compound screening (microARCS), compounds are spotted and dried onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay by contacting with agarose gels that contain reagents for the assay. The authors have conducted studies to characterize the compound transfer process using 59 compounds of diverse properties. The amount of compounds remaining on the ChemCard was determined by liquid chromatography/mass spectrometry after incubation with agarose gels for predetermined time periods.

Solutions for library encoding to create collections of discrete compounds.

The ability to design, produce, analyze, and manage high quality combinatorial libraries depends on the encoding strategy applied. Several recent advances in encoding technology have extended the range of library design parameters. Enhancements of established techniques have made them more robust and versatile, while additional new and creative encoding concepts have been introduced.