On June 14, 2023, FDA issued a guidance titled Content of Premarket Submissions for Device 
Software Functions.1 This final guidance supersedes the Guidance for the Content of Premarket 
Submissions for Software Contained in Medical Devices, issued on May 11, 2005. The final 
guidance issued on June 14, 2023, provides information regarding the recommended 
documentation sponsors should include in premarket submissions for FDAs evaluation of the 
safety and effectiveness of device software functions. In particular, the final guidance includes 
information to help determine a devices Documentation Level (formerly known as Level of 
Concern). The purpose of the Documentation Level is to help identify the minimum amount of 
information that would support a premarket submission that includes device software functions. 
Within the framework of the superseded guidance, nocturnal home hemodialysis systems were 
considered a device with a Major Level of Concern. Based on the devices risk in the context of 
the devices intended use, as discussed in the final guidance Content of Premarket Submissions 
for Device Software Functions, nocturnal home hemodialysis systems should generally address 
the recommendations for an Enhanced Documentation Level. The actual Documentation Level 
for your device may vary based on the specifics of your device. For more information about the 
Documentation Level and recommended documentation for a premarket submission, sponsors 
are encouraged to review the guidance Content of Premarket Submissions for Device Software 
Functions. 
 
1 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-device-software-functions.   
Guidance for Industry and FDA 
Staff 
 
Investigational Device Exemptions 
(IDEs) for Devices Indicated for 
Nocturnal Home Hemodialysis   
 
Document issued on: April 15, 2008 
 
 
 
For questions regarding this document, contact Gema Gonzalez at 240-276-4151 or by email at 
gema.gonzalez@fda.hhs.gov 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
 
Gastroenterology and Renal Devices Branch 
Division of Reproductive, Abdominal, and Radiological Devices 
Office of Device Evaluation 
 
  Contains Nonbinding Recommendations 
 
Preface 
 
Public Comment 
Written comments and suggestions may be submitted at any time for Agency consideration to the 
Division of Dockets Management, Food and Drug Administration, 5630 Fisher Lane, Room 1061, 
(HFA-305), Rockville, MD, 29852.  When submitting comments, please refer to the exact title of 
this guidance document.  Comments may not be acted upon by the Agency until the document is 
next revised or updated. 
Additional Copies 
 
Additional copies are available from the Internet at 
http://www.fda.gov/cdrh/ode/guidance/1650.html.  You may also send an e-mail request to 
dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request to 240-
276-3151 to receive a hard copy.  Please use the document number (1650) to identify the 
guidance you are requesting.  
 
  Contains Nonbinding Recommendations 
 
Table of Contents 
 
1.  INTRODUCTION.................................................................................................................1 
The Least Burdensome Approach............................................................................................1 
2.  SCOPE...................................................................................................................................2 
3.  DEVICE DESCRIPTION....................................................................................................3 
PHYSICAL AND/OR ELECTRONIC DESCRIPTION...............................................................................3 
SYSTEM FEATURES AND FUNCTIONS..............................................................................................5 
SOFTWARE......................................................................................................................................6 
4.  REPORTS OF PRIOR INVESTIGATIONS.....................................................................7 
BENCH TESTING.............................................................................................................................7 
BIOCOMPATIBILITY TESTING..........................................................................................................8 
Sterility.......................................................................................................................................8 
Disinfection................................................................................................................................8 
Expiration Date Testing............................................................................................................8 
HUMAN FACTORS RECOMMENDATIONS..........................................................................................9 
PREVIOUS CLINICAL DATA.............................................................................................................9 
BIBLIOGRAPHY...............................................................................................................................9 
5.  INVESTIGATIONAL PLAN..............................................................................................9 
STUDY DESIGN.............................................................................................................................10 
SUBJECT SELECTION.....................................................................................................................10 
ENDPOINTS...................................................................................................................................10 
STATISTICAL PLAN.......................................................................................................................10 
SUBJECT MONITORING AND MONITORING BY THE CARE PARTNER..............................................11 
MONITORING OF DIALYSATE CHEMISTRIES AND WATER QUALITY..............................................11 
TRAINING.....................................................................................................................................11 
LABELING.....................................................................................................................................12 
Therapy Background...............................................................................................................12 
Device Description...................................................................................................................12 
Device Operation.....................................................................................................................12 
Alarms and Troubleshooting..................................................................................................13 
Cleaning, Disinfection, and Preventative Maintenance........................................................13 
  Contains Nonbinding Recommendations 
 
 
Guidance for Industry and FDA Staff 
 
Investigational Device Exemptions (IDEs) for 
Devices Indicated for Nocturnal Home 
Hemodialysis  
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on 
this topic.  It does not create or confer any rights for or on any person and does not operate to 
bind FDA or the public.  You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations.  If you want to discuss an alternative 
approach, contact the FDA staff responsible for implementing this guidance.  If you cannot 
identify the appropriate FDA staff, call the appropriate number listed on the title page of this 
guidance.  
 
1.  Introduction 
FDA has developed this guidance document to assist industry in preparing Investigational Device 
Exemption (IDE) applications for nocturnal home hemodialysis (NHHD) systems.  These dialysis 
devices are intended to administer dialysis therapy in the home setting, while the patient is 
expected to be asleep.   
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
The Least Burdensome Approach 
The issues identified in this guidance document represent those that we believe need to be 
addressed before your device can be marketed.  In developing the guidance, we carefully 
considered the relevant statutory criteria for Agency decision-making.  We also considered the 
burden that may be incurred in your attempt to follow the guidance and address the issues we 
have identified.  We believe that we have considered the least burdensome approach to resolving 
the issues presented in the guidance document.  If, however, you believe that there is a less 
burdensome way to address the issues, you should follow the procedures outlined in the A 
Suggested Approach to Resolving Least Burdensome Issues document.  It is available on our 
Center web page at:  http://www.fda.gov/cdrh/modact/leastburdensome.html. 
 
 
  1 Contains Nonbinding Recommendations 
 
2.  Scope 
This guidance document addresses IDE applications only for the clinical investigation of a 
hemodialysis delivery system for NHHD.  Manufacturers of delivery systems for conventional 
hemodialysis should refer to the Guidance for the Content of Premarket Notifications for 
Hemodialysis Delivery Systems.1  For the purposes of this guidance, FDA defines conventional 
hemodialysis and NHHD systems as shown below.   
 
Conventional Hemodialysis 
Conventional hemodialysis is a type of chronic hemodialysis that takes place in a clinical 
environment and typically includes treatments performed three times per week for 
approximately four hours per treatment.  The therapy is administered by a trained medical 
professional. 
 
Nocturnal Home Hemodialysis (NHHD) 
NHHD is a type of chronic hemodialysis that takes place in the home while the patient is 
sleeping, typically at night, up to seven times per week, for approximately six to ten hours 
per treatment, depending on the individualized dialysis prescription.  It is administered by 
the patient or a trained partner, rather than by a trained medical professional. 
 
The scope of this document is limited to IDE applications for the device types identified below 
when used for NHHD: 
 
   876.5600 Sorbent regenerated dialysate delivery system for hemodialysis 
 
   876.5820 Hemodialysis system and accessories 
 
   876.5860 High permeability hemodialysis system 
 
The procodes for these devices are ODM, ODN, and ODO, respectively.  This guidance does not 
address the investigation of hemodialyzers, hemofilters, or hemoconcentrators. 
 
FDA believes that the NHHD systems described in this guidance document are significant risk 
devices, as defined in 21 CFR 812.3(m); therefore, any clinical investigation must be conducted 
in conformance with the Investigational Device Exemptions (IDE) regulations, 21 CFR Part 812.  
In addition to the requirement of having an FDA-approved IDE, sponsors of such trials must 
comply with the regulations governing institutional review boards (21 CFR Part 56) and informed 
consent (21 CFR Part 50).  FDA recommends that you contact us before submitting a 510(k) or 
IDE to discuss clinical data requirements unique to each system. For general information 
regarding IDEs, please refer to Investigational Device Exemptions Policies and Procedures in 
CDRH Device Advice.2
 
In addition to the information described above, we recommend that IDEs for NHHD systems 
contain the information described in the following sections. 
                                                 
1 http://www.fda.gov/cdrh/ode/hemod.pdf
2 http://www.fda.gov/cdrh/devadvice/ide/index.shtml
  2 Contains Nonbinding Recommendations 
 
3.  Device Description 
We recommend that you include detailed information describing the safety features and basic 
components of the NHHD system in your device description.  This information should include a 
description of the physical and electronic components, system features and functions, and 
software as discussed below. 
 
Physical and/or Electronic Description  
You must provide a description of the NHHD system.3  We also recommend you provide the 
information in the form of a block diagram that identifies the interconnections between the 
various sub-systems, system components, user interfaces, and networks.  
 
You must provide a description of the important individual components of the NHHD 
system.4  You should provide specifications, if applicable.  Important components of a NHHD 
system generally include the following:  
  pumps; 
  valves; 
  ultrafiltration controller mechanism; 
  air detector systems; 
  blood leak detectors; 
  patient disconnection or exsanguination preventers and detectors;  
  heat exchangers; 
  access ports for external remote monitoring devices; 
  anticoagulant pumps or supply; and 
  other safety features. 
 
Some NHHD systems may also include the following important components: 
  water treatment system; 
  integrated remote patient monitors; and 
  dedicated tubing sets. 
 
We recommend you provide a diagram (in color, if possible) that identifies the fluid paths 
(e.g., blood, dialysate, effluent) and indicate how each path interacts with the components of 
the NHHD system. 
We recommend you identify each of the system components and the corresponding materials 
that are either patient-contacting or indirect patient-fluid contacting, including dialysate 
distribution lines, monitors, and sensors applied to the patient.  For the purpose of this 
                                                 
3 See 21 CFR 812.25(d). 
4 See 21 CFR 812.25(d). 
  3 Contains Nonbinding Recommendations 
 
guidance, you should consider a system component in the dialysate fluid path to be patient-
fluid contacting.  
We recommend you provide a description of the systems patient/user interface (also called 
the device-user interface, use interface, man-machine interface or usability). 
We recommend you describe how the patient or user interacts with the system, with emphasis 
on designed-in prevention of potentially dangerous errors, detection of errors, and recovery 
from hazardous situations.  The user interface includes all components and accessories 
necessary to perform the tasks related to safe and effective use of the device (e.g., installation, 
calibration, operation, maintenance, and ultimately disposal of parts and supplies).  The user 
interface components generally include controls, displays, connections, alarms, device logic 
(software), labeling, and training materials.    
We recommend you provide a description of the dialysate used with the NHHD system (e.g., 
type of concentrate used, whether it is prepared on-line or pre-mixed).  If the dialysis solution 
is prepared on-line during the dialysis treatment, we recommend you provide the following 
information:  
  the ratio of the mixture of concentrates and water used;  
  the minimum quality of water that is to be mixed with the dialysate (e.g., following the 
American Association for Medical Instrumentation (AAMI) standard RD62:2001, 
Water treatment equipment for hemodialysis applications, or an equivalent current, 
FDA-recognized standard);  
  the type of concentrates that may be used (e.g., acid and bicarbonate, acetate); and  
  the way incoming water is fed into the NHHD system (i.e., we recommend you 
describe how connections are made, the flow path, and identify the use of flow-
limiting valves). 
 
If the dialysis solution is not prepared on-line, we recommend you provide a complete 
description of the type of solution that may be used, how it is prepared and stored before use, 
and how it is delivered into the fluid path system.  
 
We recommend you describe the water treatment system, if one is used within the NHHD 
system to purify tap water for the preparation of dialysate.  You should explain the various 
components of this water treatment system and how they may be arranged and optimized for 
each home setting. 
 
We recommend you describe all intended clinical configurations that are mentioned in the 
device labeling (e.g., single-needle, double needle) and explain which features of the system 
are used for each configuration.  
 
We recommend you identify the accessories that may be incorporated within the NHHD 
system (e.g., patient data card, network interface, non-invasive blood pressure (NIBP) 
monitor, water treatment system, dedicated tubing sets, electrocardiogram (ECG)).  If the 
system incorporates a device component for which there is a device-specific guidance 
  4 Contains Nonbinding Recommendations 
 
document issued by FDA (e.g., NIBP monitor,5 water treatment system6) you should refer to 
those documents for additional recommendations.  
 
We recommend you indicate whether any external accessories (e.g., wetness detectors, 
external blood flow and/or hematocrit monitors) that may be used with the NHHD system in 
the clinical study are legally marketed.  For accessories that are not legally marketed, we 
recommend you provide detailed information on the accessories.  
 
If the system does not include a dedicated tubing set, we recommend you identify the legally 
marketed tubing set compatible with your device and include this information in the device 
labeling and the investigational plan for the clinical study.  Where applicable, we recommend 
you conduct the functional testing described in Section 4. Reports of Prior Investigations 
with the tubing set identified in your IDE.  
 
System Features and Functions  
We recommend you provide a list of the performance specifications for the controllable 
parameters of the NHHD system, including both the range of allowable values and the default.  
We recommend you provide information for each of the following parameters:  
  flow rate that each pump can deliver; 
  transmembrane pressure; 
  ultrafiltration rate; 
  dialysate temperature; 
  dialysate conductivity;  
  arterial and venous pressure;  
  length of treatment; 
  volume of water that can be purified, if applicable; 
  rate of production of purified water, if applicable; 
  water conductivity and purity, if applicable; and 
  volume of dialysate that can be processed.  
 
You should provide a list of the alarms in the NHHD system.  Since the study subject and the 
care partner may be sleeping during treatments, the alarms should be able to awaken them in 
the event of an alarm condition.  For each alarm, we recommend you identify the design (e.g., 
audible, visible, tactile, vibration).  In addition, we recommend you identify: 
  the hazard condition that triggers the alarm;  
  how the subject or the trained care partner should respond to and resolve the condition 
that triggered the alarm; and 
  how the machine responds to the alarm condition (e.g., system shut down). 
 
                                                 
5 http://www.fda.gov/cdrh/ode/noninvas.html  
6 http://www.fda.gov/cdrh/ode/hemodial.pdf  
  5 Contains Nonbinding Recommendations 
 
Since alarms are part of the patient/user interface, we recommend you describe the alarms 
from the perspective of human factors or usability.  In addition, we recommend you describe 
whether you followed any standard pertaining to alarms in designing or validating the alarm 
system (e.g., IEC 60601-1-8, Medical electrical equipment Part 1-8: General requirements 
for safety - Collateral standard: general requirements, tests and guidance for alarm systems 
in medical electrical equipment and medical electrical systems, Edition 1).  
 
We also recommend you describe the role of the systems integrated remote monitoring 
system, if a component of your device, or interface with an external remote monitoring 
system. 
 
Due to its inherent design and operational properties, we recommend the NHHD system 
include several key design features, associated alarms, and fail-safe responses.  We 
recommend you incorporate the following features: 
  disinfection, cleaning, and reprocessing capabilities and cycles; 
  dialysate conductivity monitor, if your device contains a dialysate mixing system; 
  water conductivity monitor; if your device contains a water treatment system; 
  pH sensor; 
  ultrafiltration controller; 
  air detector system; 
  blood leak detector; 
  patient disconnect preventers and detectors; 
  temperature monitor;  
  anticoagulant administration system; 
  access port for external remote patient monitoring device; 
  integrated remote patient monitor, if a component of your system; and 
  fail-safe design features in the event of power failure.  
 
We recommend you describe all prescription profiling features used within the NHHD 
treatment (e.g., dialysate, ultrafiltration, sodium).  We recommend you identify the profiles 
available to the user, describe the process for selecting a particular profile, and describe how 
the NHHD system reacts to a particular profile during machine use.  In addition, in the event 
that profiles require different operating conditions or parameters, we recommend you clarify 
whether one profile has precedence over another. 
 
Software  
We recommend you submit the information for software-controlled devices described in the 
Guidance for the Content of Premarket Submissions for Software Contained in Medical 
Devices.7  The type of information we recommend you submit is determined by the level of 
concern, which is related to the risks associated with software failure.  The level of concern 
                                                 
7 http://www.fda.gov/cdrh/ode/guidance/337.html  
  6 Contains Nonbinding Recommendations 
 
for a device may be minor, moderate, or major.  We believe the level of concern for NHHD 
systems is major.  If your device incorporates off-the-shelf software, refer to the Off-the-
Shelf Software Used in Medical Devices8 guidance.   You can find additional information on 
software validation in the General Principles of Software Validation9 guidance. 
 
4.  Reports of Prior Investigations 
IDEs for NHHD systems must include the results from pre-clinical testing performed prior to a 
clinical study.10  Your testing information should include the information described below. 
 
Bench Testing 
We recommend you conduct functional testing that demonstrates the system and its 
components perform as designed and expected.  This functional testing should include 
validation of all of the system features under both standard operating conditions and worst-
case conditions (e.g., treatment features, user interface, disinfection procedures, disconnect 
preventers and alarms, system sensors, controllers, monitors, alarms, and if applicable, water 
treatment and integrated remote monitoring capabilities). 
 
We recommend you conduct a system-level hazard analysis including use error-related 
hazards.  You should correlate this analysis to the functional testing of the system to confirm 
that the device does not perform in an unexpected or unsafe manner, or provide a declaration 
of conformity with risk management standard ISO 14972.  
 
We recommend you conduct electrical safety testing and submit the results, or provide a 
declaration of conformity with IEC 60601-1, Medical Electrical Equipment  Part 1: General 
Requirements for Safety. 
 
We recommend you conduct electromagnetic compatibility (EMC) testing, or describe 
whether you followed any EMC standard (e.g.,  IEC 60601-1-2, Medical Electrical 
Equipment  Part 1-2: General Requirements for Safety; Electromagnetic Compatibility  
Requirements and Tests) and to what extent you followed the standard.  Since the NHHD 
system is intended for use in a home environment, we recommend you conduct testing that 
addresses the potential hazards in the home environment, including radiated immunity testing 
at the 10 V/m level at all tested frequencies. 
 
We recommend you conduct performance testing demonstrating your device has the 
capability of transmitting real time alarms to a remote monitoring station (i.e., over the 
internet or direct phone line), either using an integrated remote monitoring system, if a 
component of your system, or by interfacing with an external monitor.  
 
If your device contains dedicated tubing sets, we recommend you conduct testing of those sets 
and disposable components.  For information on dialysis system tubing sets, refer to the 
guidance Hemodialysis Blood Tubing Sets  Premarket Notification (510(k)) Submissions. 
                                                 
8 http://www.fda.gov/cdrh/ode/guidance/585.pdf  
9 http://www.fda.gov/cdrh/comp/guidance/938.pdf  
10 See 21 CFR 812.20(b)(2). 
  7 Contains Nonbinding Recommendations 
 
 
Biocompatibility Testing 
We recommend you conduct biocompatibility testing, as described in the FDA-modified Use 
of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: 
Evaluation and Testing,11 for all direct and indirect patient-fluid contacting components of 
the NHHD system.  In addition, we recommend you select biocompatibility tests appropriate 
for the duration and level of patient contact with your device.  If identical materials and 
identical material processing are used in a comparable, marketed predicate device with the 
same type and duration of patient contact, you may identify the predicate device in lieu of 
providing biocompatibility testing. 
 
Alternatively, we recommend you conduct leach testing that identifies and characterizes the 
potential leachables using appropriate chemical analyses for indirect patient-fluid contacting 
materials, such as dialysate.  In addition, we recommend you conduct a risk assessment of the 
toxic potential of these leachables.  The risk assessment should be supported by the referenced 
literature.  
 
Sterility, Disinfection, and Expiration Date Testing 
 
Sterility 
FDA recommends that you provide sterilization information described in the guidance 
entitled, Updated 510(k) Sterility Review Guidance K90-1.12  The device should be 
sterile with a sterility assurance level (SAL) of 1 x 10-6 using a sterilization cycle that has 
been validated in accordance with the quality system regulation (21 CFR Part 820). 
 
Disinfection 
We recommend you describe the complete system disinfection cycles, reprocessing 
cycles, and methods appropriate for disinfecting the NHHD system.   This description 
should include the steps the operator should follow in order to complete machine 
disinfection, and methods for determining disinfectant residuals.  If you identify a 
disinfection method, protocol, or agent not used in a legally marketed device or not used 
in a legally marketed dialysis system, you should provide validation of the method.  If you 
have any questions about the data or information needed to support the safety of your 
proposed disinfection methods or protocols, we recommend that you contact the 
Gastroenterology and Renal Devices Branch prior to the submission of your IDE.   
 
Expiration Date Testing 
We recommend you identify all components of the NHHD system labeled with expiration 
dates.  In addition, we recommend you substantiate these expiration dates with the 
appropriate testing data.  Refer to Guidance for the Content of Premarket Notifications 
                                                 
11 http://www.fda.gov/cdrh/g951.html  
12 http://www.fda.gov/cdrh/ode/guidance/361.pdf
  8 Contains Nonbinding Recommendations 
 
for Conventional and High Permeability Hemodialyzers13 for recommendations 
pertaining to expiration date testing for hemodialyzers. 
 
Human Factors Recommendations 
We recommend you provide validation of the patient/user interface, taking into account 
human factor considerations, such as potential user errors and ergonomic factors.  
 
We also recommend you conduct a non-clinical, realistic usability (human factors) study to 
validate the device, as it may not be possible to evaluate the clinical device performance in 
potentially dangerous use scenarios.  Usability testing should demonstrate that the device 
performs safely, under realistic conditions in the hands of prospective users, with minimal 
dependence on training and labeling as described in AAMI/ANSI HE74:2001, Human Factors 
Design Process for Medical Devices or equivalent methods. 
 
Previous Clinical Data 
You must submit a complete report of all prior clinical testing of the device, conducted at U.S. 
and outside U.S. (OUS) sites.14  If the clinical testing is described in literature articles, we 
recommend you provide the articles.  Foreign sites do not require IDE approval.  However, if 
you intend to study your NHHD system in foreign centers, we recommend that you indicate 
this in the IDE application related to your U.S. study and include them in your statistical 
analysis plan.  Clinical data obtained at foreign sites may be submitted in the marketing 
application as part of the primary data set.  For future marketing applications using OUS data, 
we recommend you use the same clinical protocol as the IDE study for the foreign sites to 
minimize variability. 
 
Bibliography 
You must provide a bibliography of all publications, whether adverse or supportive, that are 
relevant to an evaluation of the safety or effectiveness of the device.15  You should also 
include copies of all published or unpublished adverse event information. 
 
5.  Investigational Plan  
You must provide a complete description of the investigational plan.16  We recommend that you 
design your IDE study to obtain clinical data to demonstrate the safety of the NHHD system 
under actual use conditions.  Your study should evaluate the incidence of adverse events, the 
devices ability to deliver prescribed treatments, and the subjects or care partners ability, after 
appropriate training, to conduct the prescribed treatments in a nocturnal home hemodialysis 
setting.  In general, we recommend you compare assessments for subjects over a period of time 
in-clinic, followed by a period of home-use.  Please note that the study does not have to evaluate 
long-term effectiveness of nocturnal hemodialysis treatment as an endpoint. 
                                                 
13 http://www.fda.gov/cdrh/ode/highpermhemo.pdf
14 See 21 CFR 812.27. 
15 See 21 CFR 812.27(b)(1). 
16 See 21 CFR 812.25. 
  9 Contains Nonbinding Recommendations 
 
 
We recommend you consider the information below, specific to NHHD system clinical studies. 
 
Study Design  
We recommend that you design your study to incorporate an in-clinic period, followed by a 
home-use period.  The appropriate length of the study and sample size will be dependent on 
the study endpoints, the indication for use, and any performance characteristics and claims 
you propose to include in labeling. 
 
Subject Selection  
To avoid a possible bias from a recent hemodialysis initiation, we recommend you select 
subjects from a pool of established hemodialysis patients.  We also recommend you include 
subjects with an established vascular access for hemodialysis and exclude subjects in 
transition from a cuffed catheter to an arteriovenous fistula. 
 
We also recommend you consider the physical ability of the subject or care partner to perform 
the hemodialysis treatment.   
 
Your investigational plan should include procedures for an inspection of the subjects home 
environment to ensure that the environment has appropriate electrical connections, water 
supply, and any other features necessary for the use of the device.  You should exclude 
subjects whose home environments are not suitable.   
 
Endpoints 
We recommend your study provide a comparison between in-clinic use and home-use, 
including: 
  adverse events; 
  ability to deliver the prescribed treatment, (e.g., delivery of prescribed parameters, 
achieving desired kt/V in prescribed treatment time); and 
  the reliability of the device to provide each treatment as scheduled. 
 
Statistical Plan 
We recommend you provide a complete description of the statistical plan, addressing the 
sample size, proposed randomization scheme (if applicable), proposed interim analysis and 
early stopping procedures (if applicable), poolability of the data, and proposed analytical 
methods.  For additional guidance on statistical methods for evaluation of clinical trial data, 
refer to Statistical Guidance for Clinical Trials of Non-Diagnostic Medical Devices.17
 
                                                 
17 http://www.fda.gov/cdrh/ode/odeot476.html  
  10 Contains Nonbinding Recommendations 
 
Subject Monitoring and Monitoring by the Care Partner  
Your IDE application should include a description of the treatment monitoring plan and 
specify which features of the NHHD system will be used for subject monitoring.  In order to 
address the safety concerns associated with dialyzing in a nocturnal hemodialysis setting, we 
recommend all studies incorporate the use of a care partner regardless of whether the device is 
used with real time remote monitoring.  We recommend you design the study so that the care 
partner will be present throughout the dialysis treatment.  We also recommend you not use 
remote monitoring as the sole method of subject monitoring.   
 
Monitoring of Dialysate Chemistries and Water Quality 
For NHHD systems that do not use pre-mixed dialysate solutions, the investigational plan 
should include procedures for monitoring the microbiological quality of the water coming into 
the system after purification.  We recommend you perform periodic sampling and testing of 
the water quality (i.e., surveillance cultures, to ensure the water is within acceptable 
microbiological limits, as described in your protocol). We also recommend the investigational 
plan include instructions for monitoring the dialysate prepared by the NHHD system (i.e., 
instructions should be included to check dialysate conductivity, including the frequency of 
checks). 
 
Training 
We recommend subjects selected to participate in your clinical study undergo training on how 
to perform the entire hemodialysis treatment and vascular access procedures.  You should 
evaluate the success of the training as part of your clinical study.  We recommend you use a 
training team to observe the subjects or care partners ability to perform the procedure in the 
clinic before starting the home period of study.  The training team's observations should 
include observing the subjects or care partners ability to troubleshoot the device and other 
procedure-related issues.  
 
FDA believes that the actual time needed for successful training depends on factors specific to 
each subject (e.g., familiarity with hemodialysis, ability to follow directions, compliance, 
motivation).  We recommend you use a practical test or written questions to assess the 
subjects comprehension and retention of the training received.  
 
We recommend you outline the responsibilities of the care partner during the training sessions 
and provide instructions to subjects and care partners on emergency procedures, such as the 
procedures necessary if a serious adverse event occurs.   
 
We recommend you provide training for the care of the vascular access (e.g., arteriovenous 
fistulas, grafts, cuffed catheters).  In addition, we recommend you instruct subjects on 
procedures to avoid needle sticks, the use of aseptic techniques, and measures necessary to 
prevent hemodialysis related emergencies (e.g., disconnections, air emboli).   
 
In addition, we recommend you include training on the regular maintenance of the device, 
management of supplies, necessary environmental features, such as the availability of 
electrical outlets and water supply, and sampling of dialysate chemistries and water quality. 
  11 Contains Nonbinding Recommendations 
 
 
Your IDE application should include copies of the training manual, questionnaires, checklists 
and any other training materials you plan to use in the study. 
 
Labeling  
The IDE application must comply with the labeling requirements described in 21 CFR 812.5.  
Your IDE application must include draft device labeling for the NHHD system (e.g., the 
operator's manual, patient labeling, any labels that will be affixed directly to the system or its 
accessories).18
 
We recommend your labeling include information about the safe use of the NHHD system, 
including device descriptions, instructions for the use of the system, and recommendations on 
what to do in the event of a problem.  
 
In general, we recommend the operators manual include the elements described below. 
 
Therapy Background 
We recommend you provide an overview of the therapies and modalities performed by the 
system, the target population, and general principle of operation.  In addition, we 
recommend you include indications for use, contraindications, warnings, and precautions. 
 
Device Description  
We recommend you provide an overall description of the device and individual 
components.  You should describe:   
  the safety-related components included in the system (e.g., ultrafiltration 
controller, arterial and venous pressure sensors, disconnection preventers and 
sensors); and   
  the accessories that need to be used with the system (e.g., extracorporeal tubing, 
replacement fluids).  
We also recommend you identify:   
  the dialysate solution to be prescribed by a physician and indicate whether it 
conforms to the AAMI RD62:2001 standard, or the equivalent current, FDA-
recognized standard, in terms of chemical purity and microbiological quality;   
  the operational parameters (e.g., flow rates, monitoring pressure) and, where 
appropriate, the accuracy of these parameters; and 
  the model number and current software version of the machine.  
 
Device Operation  
We recommend you describe the pre-treatment, peri-treatment, and post-treatment steps 
needed to safely perform each available therapy mode.  If the system may be used in 
                                                 
18 See 21 CFR 812.20(b)(10). 
  12 Contains Nonbinding Recommendations 
 
different configurations (e.g., single-needle vs. double needle) we recommend labeling 
include clear instructions to distinguish between the configurations.  
 
Alarms and Troubleshooting  
We recommend you clearly identify the system alarms, their design and format, the 
suspected cause of the alarm condition, and how the subject or care partner should 
respond to the alarm.  
 
Cleaning, Disinfection, and Preventative Maintenance  
We recommend you provide detailed instructions for the subject or care partner to clean, 
disinfect, and maintain the dialysis machine.  The disinfection instructions should be 
consistent with the information discussed in Section 4. Reports of Prior Investigations. 
 
In addition, the operator's manual should include the following user-related instructions:   
  instructions for the subject or their care partner to properly use, monitor, and verify 
the conductivity and temperature of the dialysate used in the NHHD system; and 
  instructions for the subject or their care partner to properly monitor and adjust the 
dialysis treatment to ensure proper fluid balance. 
 
The operator's manual should also include the following user-related precautions: 
  a precaution regarding the possible susceptibility to electromagnetic interference 
and possible electrical hazards associated with the use of the NHHD system;   
  a precaution to use high-permeability dialyzers only if the NHHD system is 
equipped with an ultrafiltration controller; and  
  a precaution that the subject or care partner should not over-ride or bypass the air 
embolism/foam detector during treatment. 
 
Because NHHD systems are designed for use at home and treatments are administered by 
subjects or their care partners, we recommend you provide patient labeling for subjects 
participating in the clinical study.  For recommendations about preparing patient labeling, please 
refer to Guidance on Medical Device Patient Labeling.19  Your patient labeling should include 
the same elements recommended above for the operators manual, but written in laymans terms, 
that is, in a clear, concise fashion, directed to subjects or their care partners, who may not have 
any medical training.  In addition, we recommend you provide detailed instructions for use, 
including:  
  turning the device on and performing its setup; 
  installing tubing sets; 
  priming; 
  setting up patient connections and disconnections; 
  performing and monitoring treatments; 
  cleaning and disinfecting the device; and 
                                                 
19 http://www.fda.gov/cdrh/ohip/guidance/1128.pdf 
  13 Contains Nonbinding Recommendations 
 
  turning off the device. 
 
In addition, we recommend you provide a pre-treatment device setup reference sheet, or task 
checklist, for subjects and their care partners.  
 
We recommend you provide a list of settings and ranges of operation for all parameters that the 
subject or care partner may program or change at home, and explanations of these parameters 
functions.  In addition, we recommend you provide an easy-reference list of alarms, error 
conditions, and general troubleshooting directions. 
 
We also recommend your patient labeling include a list of environmental features and supplies 
necessary to perform NHHD treatments, such as information on the home environment and 
preparations necessary to accommodate the NHHD system (e.g., electrical outlets, voltage, 
ground fault interrupters, water supply, drainage, phone line connection (if applicable), volume 
and type of dialysate concentrates or pre-mixed dialysate, information on disposables and 
consumables). 
 
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