A Scientific Approach to Mitigating Particulate Risks in Vial Containment Systems

The development of combination products starts with deriving specific Design Input requirements, for the device constituent part, which are based on international standards, guidance documents, formative human factors studies and risk assessments of the combination product’s performance. Once the combination product is developed, laboratory-based Design Verification Testing (DVT) must be performed to demonstrate that the device constituent part of that combination product meets the performance requirements that were set in the Design Inputs stage. The analytical methods used to perform Design Verification require analytical method validation. For physical test methods, validation requires assessments of method accuracy (through calibration) and method precision (with a Gauge Repeatability and Reproducibility study). This validation can be performed using actual devices, but for destructive test methods that approach cannot distinguish between poor method precision and part-to-part variation, resulting in high estimates of measurement uncertainty. However, by designing surrogate devices that look and perform like the devices being tested, but that can be used in a non-destructive fashion, one can perform method validation using those surrogates to demonstrate better method precision and lower measurement uncertainty. Case study examples will be presented.