The challenges of riskbased environmental monitoring in sterile product filling
Completing risk assessments is an inherent part of good manufacturing practice (GMP) and risk-based environmental control and monitoring (EM) in sterile product filling within isolators and restricted access barrier systems (RABS). This article considers the challenges the pharmaceutical industry faces in characterising conventional risk assessments like failure modes and effects analysis (FMEA) for determination of risk-based EM programs, considering aspects of the filling machine, barrier separation technology, surrounding cleanroom environment, monitoring methods/systems and process operations. The requirement for process monitoring for the manufacture of sterile medicinal products is starting to be discussed in the revision of EU GMP Annex 1, so as to bring together all EM data and hence consider the process holistically.
Overview of the challenges Risk assessment models like FMEA and those that use risk priority numbers to set scores are generic and need characterisation to set rationale for outcomes. In filling sterile products, this requires the pharmaceutical/biopharmaceutical company, filling machine vendor, isolator/RABS vendor and EM equipment vendor to collaborate to set the rationale, apply risk assessments and develop risk-based EM technical and program solutions. Each party may have a very different understanding of EM risk assessments and responses to outcomes.
In filling lines, EM sampling tools and systems require a comprehensive technical integration into the process machine bed plate and barrier system. Therefore, if the exercise is not completed at the appropriate project stage (i.e., before mock-up study), the sampling may be compromised, since setting sampling locations later on site is technically challenging, impacting qualification and the overall project timeline together with generating additional costs.
Risk assessment methodology In principle, environmental classification does not need to be riskassessed since there are requirements to meet specified environmental conditions set out in EU GMP Annex 1 and the US Food and Drug Administration’s guide to industry for sterile products produced by aseptic processing. However, in practice, we classify with sampling at risk-based locations so risk assessments are required to define these locations ahead of any classification studies.