iQbD: a TRL-indexed Quality-by-Design Paradigm for Medical Device Engineering

Risk assessment is a critical step in the roadmap of medical device development. Failure modes, effects and criticality analysis is a common approach based on declarative prior information that proved beneficial in the risk assessment of well established processes. But at early steps of development when innovative materials or technologies are embedded, the lack of experience on those innovations introduces too much subjectivity in FMECA for a robust risk assessment. Since mid-2000, the Quality-by-Design guideline has been proposed within the pharmaceutical industry as a proactive engineering approach of drug development. This paradigm enables a data-driven risk assessment throughout the development workflow, which completes risk assessment provided by FMECA. Nevertheless, its implementation guide is unclear and not flexible enough to be efficiently applied to the development of medical devices. To address this issue, a new QbD paradigm indexed on the technological readiness level of the innovative product is proposed. It covers the development of medical devices throughout the whole preclinical phase and is composed of at least nine learning cycles. The first part of this medical device QbD layout, composed of three consecutive risk assessment cycles, is evaluated through a real study case with the objective to demonstrate the proof of concept of a photobleaching controller in photodynamic therapy. Beyond this experimental result, this application has confirmed practical ability of the iQbD approach to complete FMECA and to provide an alternative solution to risk assessment when prior knowledge on the technological innovation is not available.