The leaching of chemicals by materials has been integrated into risk management procedures of many sectors where hygiene and safety are important, including food, medical, pharmaceutical, and biotechnological applications. The approaches focus on direct contact and do not usually address the risk of cross-mass transfer of chemicals from one item or object to another and finally to the contacting phase (e.g., culture medium, biological fluids). Overpackaging systems, as well as secondary or ternary containers, are potentially large reservoirs of non-intentionally added substances (NIAS), which can affect the final risk of contamination. This study provides a comprehensive description of the cross-mass transfer phenomena for single-use bags along the chain of value and the methodology to evaluate them numerically on laminated and assembled systems. The methodology is validated on the risk of migration i) of ϵ-caprolactam originating from the polyamide 6 internal layer of the overpackaging and ii) of nine surrogate migrants with various volatilities and polarities. The effects of imperfect contacts between items and of an air gap between them are particularly discussed and interpreted as a cutoff distance depending on the considered substance. A probabilistic description is suggested to define conservative safety-margins required to manage cross-contamination and NIAS in routine.
Keywords: cross-mass transfer; extractables; laminates; migration; modeling; non-intentionally added substances (NIAS); risk assessment; single-use.