Regulatory Considerations for Hemodiafiltration in the United States

Abstract

Online hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10^-6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.

Keywords: Endotoxins; Infertility; Maintenance; Molecular Weight; Online Systems; United States; United States Food and Drug Administration; hemodiafiltration; regulatory approval; renal dialysis; water-electrolyte balance.

Figure 1.

Use of a validation process to aid in ensuring consistent fluid quality. IQ, installation qualification; OQ, operational qualification; PQ, performance qualification. Reproduced from ref. , with permission.