Introducing the Alba^® Primary Packaging Platform. Part 1: Particle Release Evaluation

The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failures as worst-case scenarios. This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, silicone oil droplets, or other particles. The Alba primary packaging platform was designed in order to have the same interface between the drug and the glass container surface on the different primary packaging containers to minimize the emergence of instabilities at later stages during the formulation development. The Alba containers are internally treated with an innovative cross-linked coating based on silicone oil lubricant, and the additional rubber components have been selected to minimize the possible differences between the container typologies. This paper shows in deep detail the subvisible particle release reduction and the comparability of the performances of different containers, obtained using such technology. To demonstrate this improvement, different analytical methods for particle measurement were used on bulk containers, Alba-treated ones and containers from a standard production (spray-on siliconization). Considering that Alba containers are conform to the standard compendial testing and the amount of particles released from Alba-coated syringes was comparable to the bulk syringes for the first two mildly stressful methods, it was decided to develop and apply a more challenging method, such as an autoclave treatment for 1 h at 121°C, to better highlight the performances of this innovative technology. The data obtained, under the most stressful conditions, show a substantial reduction in the released particle concentrations compared to a spray-on siliconized container, with comparable performances for all the containers included in the Alba platform. The latter could heavily reduce drug formulation development timing, facilitating the transition from one container to another.LAY ABSTRACT: The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failures as worst-case scenarios. This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, or substances coming from the production process, silicone oil droplets, or other particles. The Alba primary packaging platform was designed to solve these problems associated with the interaction between the drug and its primary packaging. This paper shows in deep detail and with robust data the subvisible particle release reduction obtained using such technology.