[The concept of ultrapure solution online production]

Online preparation of dialysis fluid, i.e., continuous mixing and immediate use, was introduced in 1964 and has contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. Online prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 years because of regulatory conservatism. Online preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions to remove bacteria and endotoxins, which gives a sterility assurance level of at least six magnitudes, as required by the pharmacopoeia for sterile products. Microbiologic testing of the fluid should be applied when designing, validating, and troubleshooting online systems but not for routine quality control, because it only gives retrospective information. Quality assurance has to be built into a system and the way it is operated. The use of ultrapure dialysate must be considered as a suitable option for all hemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultra-purity and/or sterility of the final solution relies on the weakest or worst component of the chain. Online fluid preparation, when properly performed, is safe, simple, and cost-effective and enhances the efficiency as well as the biocompatibility of dialysis therapy.