On-line preparation of solutions for dialysis: practical aspects versus safety and regulations.

On-line preparation, i.e., continuous mixing and immediate use, was introduced for dialysis fluid in 1964, and it contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. On-line prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 yr because of regulatory conservatism. On-line preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that contribute a minimum of microorganisms and are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions and dimensioned 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 on-line 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. On-line fluid preparation, when properly performed, is safe, simple, and cost-effective and enhances the efficiency as well as the biocompatibility of dialysis therapy.