Characterization of a Novel Particle in a Pharmaceutical Drug Product.

A previously unreported particle type was observed during routine visual vial inspection of a liquid drug product and suspected to be the result of vial delamination. Delamination is the corrosive attack on the interior surface of a glass container resulting in the release of thin flake-like glass particles, lamellae, into solution. It is a major concern for pharmaceutical companies, especially for parenteral solutions, and drug programs with a high risk for delamination are typically monitored for lamellae formation through long-term stability studies.

Observation and Mitigation of Lamellar Silica Particles Formed in Pharmaceutical Products Packaged in Glass Vials.

A new type of lamellae-like particles was observed in protein based liquid therapeutic protein drug product (DP) packaged in standard (STD) and delamination controlled (DC) Type IB glass vials stored at 2-8°C as early as two weeks after manufacture. These particles were determined to be remarkably different from lamellae in not only in their chemical composition, but in the mechanism by which these are formed. The lamellae-like particles were an ultra-thin (< 200 nm) film, appeared curled, sheet-like, folded with no defined edges identified as lamellar silica composed of silica and polysorbate 80 (PS 80).