A Proof-of-Concept Study on a Universal Standard Kit to Evaluate the Risks of Inspectors for Their Foundational Ability of Visual Inspection of Injectable Drug Products

Abstract

Visual inspectors’ ability to detect foreign matter in injections must be qualified for each product type or bracketing group, as stated in the USP <1790>. The common defect criterion is “visible”. However, this qualitative lower rejection limit is based on the premise that the nature of human inspection at one site is globally comparable to that at all other sites. If not, the “visible” foreign matter can vary among inspector groups for each product, leading to quality differences between sites. Inspectors are trained and qualified using “visible” foreign matter samples from their site; therefore, inspectors’ ability to detect foreign matter can differ due to different standards. Japanese pharmaceutical companies import injections and perform secondary visual inspections because variations in “visible” ability arise due to individual differences among regions. Currently, there is no universal method for comparing “visible” rejection zones among manufacturing sites for different products because product-specific standard samples for qualifications cannot be universalized. Therefore, instead of comparing the product-specific “visible” standard sample, this study proposes a novel universal particle standard challenge kit to compare sites' or inspectors' inner “visible” detection ability. Our results suggest that the proposed kit could be used to evaluate the comparability of “visible” at each site and for each inspector but not on sites’ “visible” standard samples. The primary challenge in implementing a universal standard lies in the inherent bias of inspectors already acclimated to specific products. This study found that an inspector’s foundational ability can be evaluated by canceling the bias via rapid and effective training in cases of simple standard samples. Our results suggest that using a universal standard kit to assess an inspector’s fundamental ability to detect “visible” foreign matter is feasible. The study does not aim to replace the inspectors’ product qualifications but to compare their inner transferable foundational ability for risk assessment.