Assessing the risk posed by leachables from single-use assemblies can be challenging. Disposable assemblies are often constructed of a mix of functional components, containers, tubing, valves, and filters, each made from several materials by complex manufacturing processes. Additionally, the gamma sterilization pretreatments of such assemblies potentially can create trace-level leachables that are nearly impossible to completely identify and quantify. Regardless of these challenges, it is necessary to assess the risk posed by leachables for the following reasons:
BUILDING QUALITY INQuality by design (QbD) is defined as the systematic process to build quality into a product from its inception. This principle can be leveraged during the design and engineering of components of single-use systems to minimize the risk of leachables. Component materials should be nonreactive, 21 CFR-cleared material and pass USP Class VI specifications.
PureFlex polyethylene film (EMD Millipore) is an example of a material that can be designed into single-use systems to minimize generation of leachables. PureFlex film is a high-purity, medical-grade coextruded film designed to provide strength, flexibility with maximum resistance to flex-crack, excellent gas-barrier performance, and inert contact. The fluid-contact material is ultra-low-density polyethylene (ULDPE), which was chosen because of its inertness.
PureFlex film is produced using additive compounds that either help process the film or help protect the film. Typical processing additives include slip agents that reduce the film-to-film friction, thereby allowing faster processing speed. A common slip agent is composed of fatty acid amides (e.g. erucamide). Slip agents are added at a concentration from a few parts per million (PPM) to a few thousand PPM (2). Though these agents may be present at high concentrations, aqueous solubilities are very low (e.g., erucamide has an aqueous solubility of 0.00045 mg/L ). Antioxidants comprise another common type of additive. These compounds are added to the polymers to protect the film from ultraviolet radiation, and are typically large molecules (hundreds of Daltons in size) with very low aqueous solubility. Commonly used antioxidants include Irganox 1010 (Ciba Specialty Chemicals, 2-[3,5-di-tert-butyl-4-hydroxyphenyl] propionate), with an aqueous solubility of 2.3 × 10-16 mg/L and Irgafos 168 (Ciba Specialy Chemicals, tris[2,4-di-tert-butylphenyl] phosphite), with an aqueous solubility of <0.09 mg/L.