Accumulation of organic compounds leached from plastic materials used in biopharmaceutical process containers.

Plastic materials are widely used in medical items, such as solution containers, transfusion sets, transfer tubing, and devices. An emerging trend in the biotechnology industry is the utilization of plastic containers to prepare, transport, and store an assortment of solutions including buffers, media, and in-process and finished product. The direct contact of such containers with the product at one or more points in its lifetime raises the possibility that container leachables may accumulate in the finished product. The interaction between several commercially available container materials and numerous model test solutions (representative of buffers and media used in biopharmaceutical applications) was investigated. This paper summarizes the identification of leachables associated with the container materials and documents the levels to which targeted leachables accumulate in the test solutions under defined storage conditions.

Development and validation of chromatographic methods for the identification and quantitation of organic compounds leached from a laminated polyolefin material.

Chromatographic methods for the identification of organic compounds leached from a plastic material used in solution containers in the pharmaceutical industry are described. Based on a set of compounds identified in extracts of a multilayered polyolefin film, targeted leachables are delineated for accumulation assessments, and methods to perform target quantitation are developed and validated.

Leaching of organic acids from irradiated EVA plastic as a function of solution pH and polarity.

The leaching of several target organic acids from an irradiated ethylene vinyl acetate material, such as those used as a solution product container, is examined as a function of solution pH and polarity. The targeted compounds included highly soluble weak acids such as acetic and formic acids, and larger, more lipophillic acids such as myristic, palmitic, and stearic acids. The leaching of these compounds was examined over a pH range of 3 to 11 and in various ethanol/water proportions. While pH and solution polarity had only a modest impact on the accumulation of the acetic and formic acids, the accumulation of the fatty acids was greatly affected by both factors. It is suggested that the accumulation of these leachables at high pH is influenced by two processes. The first process, partitioning, the speciation of the acidic leachables (protonated versus dissociated form) contributes to the pH trends observed. In this case, entities that already exist in the plastic partition themselves between the plastic and solution via migration. A second, more important, contributor to the leaching of these acids is a pH-dependent increase in their availability arising from an unspecified reactive process.