Table 1.

Major common concerns raised by the Food and Drug Administration during review of submissions for investigational device exemption and marketing applications for hemodiafiltration systems

Category and Issues Raised in ReviewReference for Deficiency
Clinical study design
 Study outcomes: The study should consider the effect of the following on outcomesGuidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems, section X (hemodiafiltration, section D) (8)
  Adverse events
  Water sterility
 Data collection should include (as for all hemodialysis systems)
  UF rate
  General system (e.g., blood flow rate, arterial and venous pressure, and transmembrane pressure) information
Sterility
 Data showing that the replacement fluid meets standard for USP sterile water for injectionGuidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems, section X (hemodiafiltration, section B) (8); standards: ANSI/AAMI/ISO11663:2009: Bacteria: Sterile and Endotoxin nonpyrogenic (<5 EU/kg per hour); references: Ledebo (20)
 Sterility testing by challenging system with water-borne organisms and endotoxin
 Biofilm testing
 The types and sizes of filters and the schedule of filter changes affect sterility
 Method(s) for sterilization should be verified and validated
Performance testing
 Biocompatibility: information required includes
  Patient- and fluid-contacting materials
  Comparison of materials with other legally marketed devices
  Leachables
Labeling
 Instructions about how to conduct microbiologic testing and quality controlGuidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems, section X (hemodiafiltration, section C) (8)
 Disinfection procedures
 Requirement for AAMI quality water
 Instructions on when to change the filters
Software
 The following information is recommendedFDA Guidance Document: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (21)
  Flow chart showing architecture
  Development procedures
  System specifications and software requirements
  System test–level results
  Validation and verification tests
  • FDA, Food and Drug Administration; UF, ultrafiltration; USP, United States Pharmacopeia; ISO, International Organization for Standardization; ANSI, American National Standards Institute; AAMI, Association for the Advancement of Medical Instrumentation.