Issue link: https://www.e-digitaleditions.com/i/988595
6 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m • Increased monitoring actually has a negative impact due to increased interventional activity and associated risk of contamination. Instead, patient safety must be maintained through sterility-by-design practices (7). Only validation can provide evidence of control Merely sampling and testing sterile processing environments cannot provide evidence of control. The facility, equipment, and procedures used for the manufacture of sterile medicinal products must be validated to show that their performance in reliable in preventing microbial contamination. The use of closed systems and other technical ad- vances in aseptic processing equipment have made it more reliable and prevented contamination. The solutions that offer the best performance embody the following basic approaches: • The physical separation of personnel from the aseptic environment—initially accomplished by aseptic gowning—evolved into soft and rigid barriers, and eventually into restricted access barrier systems (RABS), isolators, and closed systems. • By limiting direct personnel interaction with sterile materials through clean in place (CIP)/sterilize in place (SIP) and increasingly automation allowing for remote operation. • The elimination of personnel from the aseptic process by the use of robotics— either within a manned cleanroom, and more recently, inside gloveless isolators. These design and engineering features have advanced the state-of-the-art for aseptic pro- cessing dramatically, and further improvements are certain (8). The performance of the newer systems is so superior to the older methods they have replaced, that environmental monitoring no longer serves a meaningful role. In the best of these designs, microbial recovery is non-ex- istent. To some, it might still seem that using additional monitoring or novel microbial methods with ad- vanced aseptic technologies would somehow 'prove' their superiority. That's impossible, and because the "perfect intervention is the one that does not happen," it stands to reason that adding monitoring to asep- tic systems actually increases the potential for mi- crobial contamination and threatens patient safety without adding value (9). In the most advanced aseptic systems now available, monitoring likely has more of a negative impact than a beneficial one. Advances in aseptic processing boost safety Ongoing improvements in aseptic processing have increased patient safety, although it is impossible to measure this improvement using environmen- tal monitoring. The technological changes have largely eliminated the contamination potential associated with personnel. Those same advances have reduced the perceived microbiological pres- ence in aseptic processing well below the limit where it can even be detected. Viable monitoring, which wasn't quantitative in the 1970s, is now more of an encumbrance than Aseptic Processing Viewpoint Viable monitoring ... is now more of an encumbrance than anything else. The steady progress with sterility- by-design concepts ... has rendered [it] largely moot.