Guidance for Industry and for FDA Reviewers 

Guidance Document for Premarket 
Notification Submissions for Nitric Oxide 
Delivery Apparatus, Nitric Oxide Analyzer 
and Nitrogen Dioxide Analyzer 
              Document Issued on:  January 24, 2000 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health
 Anesthesiology, Respiratory, and Defibrillator Devices Group
 Division of Cardiovascular, Respiratory, and Neurological Devices 
Office of Device Evaluation  Preface 
Public Comment 
For 90 days following the date of publication in the Federal Register of the notice announcing the 

availability of this guidance, comments and suggestions regarding this document should be submitted 

to Docket No. 99D-5297, Dockets Management Branch, Division of Management Systems and 

Policy, Office of Human Resources and Management Services, Food and Drug Administration, 

5630 Fishers Lane, (HFA-305), Room 1061, Rockville, MD 20852.. Such comments will be 

considered when determining whether to amend the current guidance.
 
After 90 days following the date of publication in the Federal Register of the notice announcing the 

availability of this guidance comments and suggestions may be submitted at any time for Agency 

consideration to: Michael Bazaral, M.D., Ph.D., Center for Devices and Radiological Health 

(HFZ-450), Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850. 

Comments may not be acted upon by the Agency until the document is next revised or updated. 

For questions regarding the use or interpretation of this guidance contact Michael Bazaral, M.D., 

Ph.D. at 301-443-8609. 

Additional Copies 
ii  Table of Contents 
1.   INTRODUCTION. ..................................................................................................................................................................1 
 
1.1  PURPOSE.......................................................................................................................................................................... 1
 
1.2  BACKGROUND .................................................................................................................................................................. 1
 
1.3   SCOPE  ..............................................................................................................................................................................  1
 
2.   DEVICE DESCRIPTION  .....................................................................................................................................................3 
 
2.1  NITRIC OXIDE ADMINISTRATION APPARATUS............................................................................................................. 3
 
2.2  NITRIC OXIDE GAS ANALYZER...................................................................................................................................... 3
 
2.3  NITROGEN DIOXIDE GAS ANALYZER............................................................................................................................ 4
 
3.   SPECIFIC CRITERIA AND TESTING. ...........................................................................................................................5 
 
3.1  NITRIC OXIDE DELIVERY APPARATUS ......................................................................................................................... 5
 
3.1.1  Loss of nitric oxide therapy and incorrect nitric oxide concentration................................................... 5
 
3.1.2  Insufficient or excess ventilation or oxygenation....................................................................................... 8
 
3.1.3  Excessive nitrogen dioxide administration................................................................................................... 9
 
3.1.4  Potential for catastrophic release of nitric oxide .....................................................................................10
 
3.1.5  Adulteration of the nitric oxide.......................................................................................................................11
 
3.1.6  Electrical hazards .............................................................................................................................................11
 
3.1.7  Adverse effects on other electronic devices.............................................................................................11
 
3.1.8  Release of nitric oxide and release and generation of nitrogen dioxide............................................11
 
3.2  NITRIC OXIDE ANALYZER............................................................................................................................................. 12 

3.2.1  Nitric Oxide measurement error....................................................................................................................12
 
3.2.2  Electrical hazards .............................................................................................................................................14
 
3.2.3  Adverse effects on other electronic devices.............................................................................................14
 
3.3  NITROGEN DIOXIDE ANALYZER................................................................................................................................... 14 

3.3.1  Nitrogen Dioxide measurement error...........................................................................................................15
 
3.3.2  Electrical hazards .............................................................................................................................................17
 
3.3.3  Adverse effects on other electronic devices.............................................................................................17
 
4.   GENERAL CRITERIA AND TESTING..........................................................................................................................18
 
4.1  GENERAL CRITERIA ...................................................................................................................................................... 18 

4.2  GENERAL TEST METHODS........................................................................................................................................... 18 

5.   ELECTRICAL SAFETY.....................................................................................................................................................20
 
5.1  PERFORMANCE CRITERIA ............................................................................................................................................ 20 

5.1.1  Battery power......................................................................................................................................................20
 
5.1.2  Electrical power indicators..............................................................................................................................20
 
5.1.3  Overcurrent protection .....................................................................................................................................21
 
5.1.4  Dielectric withstand...........................................................................................................................................21
 
5.1.5  AC power grounding and polarity..................................................................................................................21
 
5.1.6  Leakage current.................................................................................................................................................21
 
5.1.7  Auxiliary output...................................................................................................................................................22
 
5.2  TEST METHODS............................................................................................................................................................. 22 

5.2.1  Battery power......................................................................................................................................................22
 
5.2.2  Electrical power indicators..............................................................................................................................23
 
5.2.3  Overcurrent protection .....................................................................................................................................23
 
iii  5.2.4  Dielectric withstand...........................................................................................................................................24
 
5.2.5  AC power grounding and polarity..................................................................................................................24
 
5.2.6  Leakage current.................................................................................................................................................24
 
5.2.7  Auxiliary output...................................................................................................................................................24
 
6.   ELECTROMAGNETIC COMPATIBILITY....................................................................................................................25
 
6.1  PERFORMANCE CRITERIA ............................................................................................................................................ 25 

6.1.1  Emissions............................................................................................................................................................25
 
6.1.1.1  Radiated and conducted electromagnetic energy.............................................................................. 25
 
6.1.1.2  Magnetic fields........................................................................................................................................... 25
 
6.1.2  Immunity..............................................................................................................................................................25
 
6.1.2.1  Electrostatic discharge ............................................................................................................................ 26
 
6.1.2.2  Radiated electromagnetic fields ............................................................................................................ 26
 
6.1.2.3  AC voltage fluctuations, transients, and surges ................................................................................. 26
 
6.1.2.4  Conducted electromagnetic energy...................................................................................................... 27
 
6.1.2.5  Magnetic fields........................................................................................................................................... 28
 
6.1.2.6  Quasi-static electric fields ....................................................................................................................... 28
 
6.2  TEST METHODS............................................................................................................................................................. 28 

6.2.1  Emissions............................................................................................................................................................28
 
6.2.1.1  Radiated and conducted electromagnetic energy.............................................................................. 28
 
6.2.1.2  Magnetic fields........................................................................................................................................... 29
 
6.2.2  Immunity..............................................................................................................................................................29
 
6.2.2.1  Electrostatic discharge ............................................................................................................................ 29
 
6.2.2.2  Radiated electromagnetic fields ............................................................................................................ 30
 
6.2.2.3  AC voltage fluctuations, transients, and surges ................................................................................. 33
 
6.2.2.4  Conducted electromagnetic energy...................................................................................................... 35
 
6.2.2.5  Magnetic fields........................................................................................................................................... 36
 
6.2.2.6  Quasi-static electric fields ....................................................................................................................... 36
 
7.   PERFORMANCE SPECIFICATIONS, ENVIRONMENTAL AND MECHANICAL SAFETY. ........................38
 
7.1  PERFORMANCE CRITERIA ............................................................................................................................................ 38 

7.1.1  Controls protection............................................................................................................................................38
 
7.1.2  Connector protective incompatibility...........................................................................................................38
 
7.1.3  Mechanical safety.............................................................................................................................................38
 
7.1.4  Mechanical vibration and shock resistance..............................................................................................39
 
7.1.5  Fluid spill resistance........................................................................................................................................39
 
7.1.6  High and low temperature and humidity......................................................................................................39
 
7.1.7  Surface temperature.........................................................................................................................................39
 
7.1.8  Toxic materials...................................................................................................................................................40
 
7.1.9  Strangulation.......................................................................................................................................................40
 
7.1.10  Determination of Endurance..........................................................................................................................40
 
7.1.11  Material Compatibility.......................................................................................................................................40
 
7.1.12  Medical Gas Cylinder Connections ..............................................................................................................40
 
7.2  TEST METHODS............................................................................................................................................................. 40 

7.2.1  Controls protection............................................................................................................................................40
 
7.2.2  Connector protective incompatibility...........................................................................................................40
 
7.2.3  Mechanical safety.............................................................................................................................................41
 
7.2.4  Mechanical vibration and shock resistance..............................................................................................41
 
7.2.5  Fluid spill resistance........................................................................................................................................41
 
iv  7.2.6  High and low temperature and humidity......................................................................................................41
 
7.2.7  Surface temperature.........................................................................................................................................42
 
7.2.8  Toxic materials...................................................................................................................................................42
 
7.2.9  Strangulation.......................................................................................................................................................42
 
7.2.10  Determination of Endurance..........................................................................................................................42
 
7.2.11  Material Compatibility.......................................................................................................................................42
 
8.   HARDWARE DOCUMENTATION..................................................................................................................................43
 
9.   SOFTWARE DOCUMENTATION. .................................................................................................................................44
 
10.   LABELING........................................................................................................................................................................45
 
10.1  IDENTIFICATION OF MEDICAL GAS CYLINDERS AND CONNECTIONS ...................................................................... 45 

10.2  INSTRUCTIONS FOR USE............................................................................................................................................... 45 

10.2.1  Intended Use......................................................................................................................................................45
 
10.2.2  Validated Ventilators ........................................................................................................................................45
 
10.2.3  Installation Instructions ...................................................................................................................................46
 
v  1
Guidance  Document for Premarket 
Notification Submissions for Nitric Oxide 
Delivery Apparatus, Nitric Oxide Analyzer 
and Nitrogen Dioxide Analyzer 
SECTION 1. Introduction 
1.1  Purpose. 
The purpose of this document is to facilitate the preparation and the review of premarket 
submissions for nitric oxide delivery apparatus, nitric oxide analyzers, and nitrogen dioxide 
analyzers. 
1.2  Background 
On September 23, 1996, Ohmeda Inc. submitted a petition under section 513(f)(2) of the 
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360c(f)(2)), requesting that the 
devices included in the Ohmeda I-NOvent Delivery System intended for administration of 
inhaled nitric oxide, be reclassified from class III into class II. The system includes three 
devices which may be separately manufactured; a nitric oxide administration apparatus, a 
nitric oxide gas analyzer, and a nitrogen dioxide gas analyzer. This guidance document is 
proposed as a special control for these devices. 
This guidance document describes a means by which nitric oxide delivery and analyzing 
devices and nitrogen dioxide analyzing devices for use during the administration of nitric 
oxide may comply with the requirement of special controls for Class II devices. 
Designation of this guidance document as a special control means that manufacturers 
attempting to establish that their device is substantially equivalent to a predicate device 
should demonstrate that the proposed device complies with either the specific 
recommendations of this guidance or some alternate control that provides equivalent 
assurances of safety and effectiveness. 
1.3  Scope 
This guidance document identifies information that should be included in premarket 
notifications for the Nitric Oxide Delivery Apparatus, the Nitric Oxide Analyzers, and the 
                                                                
1 This guidance document represents the agencys current thinking on this 
subject.  It does not create or confer any rights for or on any person and does 
not operate to bind FDA or the public.  An alternative approach may be used if 
such approach satisfies the applicable statute, regulations, or both.  Nitrogen Dioxide Analyzers. 
A description of certain information typically provided in a premarket notification such as 
comparative performance evaluations, table of comparison, device description, discussion 
of similarities and difference, biocompatibility is not included in this guidance. Such 
information is common for all premarket notifications and is discussed in current guidances 
and manuals, including the Draft Guidance for Premarket Notification Submissions, and 
the Premarket Notification [510(k)] Manual. Both of these are available from the Division of 
Small Manufacturers Assistance (DSMA). 
2  SECTION 2. Device Descrip tion 
A complete Nitric Oxide Delivery System includes three component medical devices; a 
nitric oxide administration apparatus, a nitric oxide gas analyzer, and a nitrogen dioxide 
gas analyzer. Each of the three components of a generic nitric oxide administration system 
may be manufactured and distributed separately; for that reason this guidance document 
addresses the three component devices individually. 
2.1  Nitric Oxide Administration Apparatus 
The nitric oxide administration apparatus (product code MRN) is a device used to add 
nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration 
apparatus is to be used in conjunction with a ventilator or other breathing gas 
administration system. The concentration of nitric oxide is maintained approximately 
constant during the inspiratory flow regardless of the variation in flow rate within the 
inspiratory portion of the respiratory cycle. The concentration of inspired nitric oxide can 
be set, typically in the range of 0 to 80 parts per million (ppm). The administration 
apparatus includes a pressure regulator and connectors with fittings which are specific for 
nitric oxide gas cylinders, typically containing 400 or 800 ppm nitric oxide in nitrogen. The 
nitric oxide administration apparatus design should minimize the time that nitric oxide is 
mixed with oxygen (dwell time), and thus minimize the concentration of nitrogen dioxide in 
the gas breathed by the patient (nitrogen dioxide is a toxic reaction product which forms in 
a chemical reaction of nitric oxide with oxygen). 
The administration device should include provisions for a nitric oxide gas concentration 
gas analyzer with alarms, a nitrogen dioxide gas analyzer with an alarm, and an oxygen 
analyzer with alarms. Suitable gas analysis devices should be identified in the labeling for 
the nitric oxide gas administration device. 
The delivery system should include or indicate a nitric oxide administration apparatus for 
use as a "backup" system (product code MRO) for administration of nitric oxide when the 
main administration apparatus cannot be used. 
2.2  Nitric Oxide Gas Analyzer 
A nitric oxide gas analyzer (product code MRP) is a device intended to measure the 
concentration of nitric oxide in respiratory gas mixtures during administration of nitric oxide.
 The gas should be sampled from the inspiratory limb of the patient circuit. The nitric oxide 
gas analyzer usually includes provisions for setting upper and lower measured nitric oxide 
concentrations at which an alarm will be activated. 
3  2.3  Nitrogen Dioxide Gas Analyzer 
A nitrogen dioxide gas analyzer (product code MRQ) is a device intended to measure the 
concentration of nitrogen dioxide in respiratory gas mixtures during administration of nitric 
oxide. The gas is sampled from the inspiratory limb of the patient circuit. The nitrogen 
dioxide gas analyzer usually includes provisions for setting an upper measured nitrogen 
dioxide concentration, with an alarm to be activated when the measured concentration 
exceeds the set value. 
4  SECTION 3.  Specific Criteria and Testing 
A nitric oxide administration system has each of these three components; a nitric oxide 
delivery apparatus, a nitric oxide analyzer, and a nitrogen dioxide analyzer. The 
components may be manufactured and distributed separately; for that reason this section 
of the guidance document addresses the three component devices individually. 
3.1 	 Nitric Oxide Delivery Apparatus 
The design and testing of the nitric oxide delivery apparatus should take into consideration 
the risks associated with the device. Risks for the nitric oxide delivery apparatus and the 
applicable controls are discussed in the follow subsections. 
3.1.1 	 Loss of nitric oxide therapy and incorrect nitric oxide concentration.  Loss of 
nitric oxide therapy may result in acute respiratory failure or acute pulmonary 
hypertension. Incorrect low nitric oxide concentration may result in ineffective 
treatment, while incorrect high nitric oxide concentration may result in excess 
side effects, and generation and administration of excess nitrogen dioxide. 
The controls for this risk consist of the following elements: 
a.	  If the device is the primary nitric oxide delivery system, the device should 
include a reserve (backup) nitric oxide delivery system. Alternatively, 
labeling may specify a marketed reserve (backup) nitric oxide delivery 
system. The back-up system will minimize the risk of loss of NO therapy 
resulting from failure of the primary NO administration apparatus. 
b.	  The administration device should include provision for nitric oxide gas 
analysis with alarms. The breathing circuit location for sampling should 
sample gas which is representative of the inspired gas. Labeling should 
specify a suitable nitric oxide gas analyzer. The specified nitric oxide 
analyzer should include an alarm with settable upper and lower nitric 
oxide concentration limits. The inclusion of nitric oxide gas analysis with 
alarms will minimize the risk result from loss of nitric oxide therapy or 
incorrect therapy, by alerting the practitioner of the need to correct a 
malfunction. 
c. 	 The device should include a cylinder pressure gauge. Information provide 
by the cylinder pressure will permit verification of an adequate reserve of 
compressed nitric oxide in nitrogen and permit planning for replacement 
of near-empty cylinders without loss of therapy. 
5  d.	  The device should include provision for attachment of two nitric oxide 
cylinders which can be used alternately via a manifold, or other means to 
assure a continuous supply of nitric oxide for normal operation of a 
primary administration system during replacement of cylinders. This 
provision will minimize the risk of loss of nitric oxide therapy. 
e.	  A primary nitric oxide administration device and the gas analysis devices 
should have battery backup power if the administration device or the gas 
analysis devices require main electrical power, and if the device is 
labeled for use with a ventilator having a battery backup power supply, or 
a ventilator capable of operation without main electrical power. Backup 
power should be demonstrated to have the duration of the ventilators 
listed for use with the device, or for at least 20 minutes. Backup power 
will minimize the risk of loss of nitric oxide therapy during transient power 
failure. If the devices are intended for use only with a ventilator having no 
backup power supply, then the manual backup nitric oxide administration 
device may be used, and no battery backup power for the nitric oxide 
administration system is needed. 
f. 	 If a nitric oxide administration device is intended for use only as a backup 
or reserve system, then the device should be labeled for use only as a 
backup to a primary system, and only for use with a specified manual 
ventilator or a non-powered breathing circuit.  The manual ventilator or 
non-powered breathing circuit should be specified. The device should be 
tested under simulated conditions of use to verify accuracy and the 
delivery of near-constant concentrations of NO within the respiratory 
cycle. Nitric oxide administration devices labeled for use as backup 
devices should not require main electrical power during use. The labeling 
for the backup device need not specify compatible gas analysis devices.
 If the backup system provides only a fixed concentration of NO then the 
manual should note that the system should be used only during periods 
when the primary system has failed or cannot be used for other 
unanticipated reasons, unless the patient is known to have no adverse 
effects at the concentration provided by the backup system. The labeling 
should also note that if a patient is thought to require a concentration 
different than provided by the backup system, then a separate system 
capable of providing the required concentration should be available. A 
backup system which provides a set single concentration will reduce the 
risks resulting from failure of the primary system, since for most patients 
inhaled nitric oxide will be effective over a wide range of concentrations, 
6  and the primary system should fail only infrequently.  Although the risks 
may in principle be further minimized by the use of an adjustable 
concentration system, the use of an adjustable system may introduce 
additional hazards of complexity. Thus the use either of a fixed 
concentration system or an adjustable backup system, within the device 
labeling recommendations, can sufficiently limit the risk resulting from 
possible failure of the primary administration system. 
g.	  For either backup or primary nitric oxide administration devices the mean 
nitric oxide concentration in the inspired gas should be reasonably 
constant in the circumstances of intended use. Testing should be 
performed in simulated use to determine the accuracy with which the 
device can maintain the mean nitric oxide concentration when the mean 
inspired concentration is sampled while the device is delivering 
representative respiratory flow patterns. Testing should evaluate the 
stability of the concentration produced, and the repeatability of the 
settings. Inspired concentrations within 20% of the set concentration of 
nitric oxide will be considered sufficiently accurate, since currently 
available data typically demonstrates that within a study, the effect of nitric 
oxide is similar over a range of concentrations. The testing will establish 
that the device is capable of providing sufficient accuracy, and thus will 
control the risk of incorrect delivered concentration of nitric oxide. 
Results of testing should be included in the labeling as specifications to 
allow selection of suitable devices. 
h. 	 The device should provide nitric oxide concentrations at the patient 
connection which are well-defined at all times within the duration of each 
breath, and which correspond to available data regarding safety. Testing 
should be done under conditions of intended use to determine the 
delivered concentration at the patient connection, using a test system 
having an adequate response time. Sufficient accuracy within a breath 
cannot be defined on the basis of current data. However the currently 
available data (NINOS and Ohmeda) were developed using devices 
which provide reasonably constant concentrations within breaths. 
Transient concentrations as high as 150% of the mean concentration and 
as low as 0.0 ppm would be considered reasonably safe if the total 
duration of these transient concentrations did not exceed 10% of the 
volumetric duration of the breath. Testing may be done using a tracer gas 
in place of nitric oxide if adequate response times cannot be achieved for 
analysis of nitric oxide concentrations.  Representative test result 
tracings should be included in the device labeling. Conformance to the 
7  accuracy range stated above will control the risk of incorrect NO 
concentration, within the stated limit. Also, inclusion of the test results in 
the labeling will permit the practitioner to select devices on the basis of 
delivered concentration profile within the respiratory cycle. 
i.	  Gas-specific connectors with integral check valve which allow connection 
only to fittings (Compressed Gas Association 626 fitting) for 
pharmaceutical grade nitric oxide in nitrogen should be used for 
connections to the source gas cylinder or for other external detachable 
connections for compressed nitric oxide in nitrogen. Plans for 
commercial distribution of nitric oxide in the United States include the use 
of only a single concentration of nitric oxide; the availability of only a 
single concentration renders the use of a compressed gas cylinder 
containing an incorrect concentration of compressed nitric oxide in 
nitrogen unlikely.  Thus use of a standard gas-specific fitting (as well as 
the use of nitric oxide gas analyzer) will control the risk of incorrect drug 
administration resulting from use of the incorrect compressed gas. 
j. 	 Particular published standards or portions of published consensus 
standards, and other material in this guidance document address issues 
such as software and hardware documentation, electromagnetic 
compatibility documentation, and environmental documentation. Refer to 
the table of contents for the specific topic. 
3.1.2 	 Insufficient or excess ventilation or oxygenation may result from the effects of 
the nitric oxide administration system on the function of the ventilator or other 
respiratory gas administration system with which the nitric oxide administration 
system is used. 
To control the risk of insufficient or excess ventilation or oxygenation: 
a.	  Compatible ventilators or other respiratory gas administration systems 
should be identified in the labeling. The nitric oxide administration device 
(including specified gas analysis devices) should not adversely affect the 
triggering, cycling, alarm function, or other aspects of the safety and 
effectiveness of the listed ventilators or other respiratory gas 
administration system. Testing should be performed to demonstrate 
compatibility of the ventilator and nitric oxide administration device. 
Testing should include testing of the ventilator and nitric oxide 
administration device, and also endurance testing of the ventilator to 
evaluate the effect of nitric oxide on ventilator components. The 
8  proposed testing will control risks related to adverse interactions of the 
nitric oxide administration apparatus and ventilator or the respiratory gas 
administration system. 
b.	  The nitric oxide administration apparatus or specified ventilator should 
include an oxygen gas analyzer (or provisions for a specified oxygen 
analyzer) which samples gas representative of the inspired gas and 
which includes alarms appropriate to the intended use. Oxygen gas 
analyzers for such use should be demonstrated to maintain specified 
accuracy and useful life in the highest concentration of nitric oxide and 
nitrogen dioxide with which they will be used. The inclusion and testing of 
an oxygen analyzer will control the risk that unanticipated malfunctions of 
any part of the system will result in inhalation of hypoxic gas mixtures. 
3.1.3 	 Excessive nitrogen dioxide administration is a risk associated with nitric oxide 
administration.  Nitrogen dioxide is a toxic gas formed by reaction of nitric 
oxide with oxygen. Conditions for this reaction are well-described. The toxicity 
of nitrogen dioxide may in part be mediated by the formation of acid products 
by reaction of nitrogen dioxide with water. While levels of nitrogen dioxide less 
that 5 ppm meet OSHA standards for industrial exposure, and the 
recommended NIOSH limit is 1 ppm, patient exposure should be at a practical 
minimum. The currently available data (NINOS and Ohmeda) was developed 
using devices which provide minimal dwell time. Other devices under 
development are also capable of similar low values of nitrogen dioxide 
production. 
To control the risk of excessive nitrogen dioxide administration: 
a.	  The nitric oxide administration device should not produce excessive 
nitrogen dioxide. The labeling should specify the inhaled concentration of 
nitrogen dioxide during delivery at 40 ppm (or the highest concentration if 
less than 40 ppm) of nitric oxide in 60%; testing should support the 
accuracy of the specifications. Testing should be done for each ventilator 
listed for use with the nitric oxide administration device, under the 
simulated circumstances of use which produce the highest 
concentrations of nitrogen dioxide. Devices should produce gas that 
contains no more than 1.0 ppm nitrogen dioxide during administration of 
40 ppm of nitric oxide in 60% oxygen. If the dwell time for mixtures of 
nitric oxide oxygen differs significantly for other combinations of flows and 
concentrations, then additional labeling and testing may be necessary. 
Engineering analysis, and testing when practical, should be used to 
9  estimate the peak concentration of nitrogen dioxide within the respiratory 
cycle. If the physical configuration and other parameters contributing to 
dwell time remain unchanged, then the nitrogen dioxide concentration at 
other oxygen or nitric oxide concentrations may be estimated from known 
chemical kinetics. This information will permit control of the risks of 
excessive nitrogen dioxide production. 
During delivery of low concentrations of nitric oxide (5 ppm or less) longer 
dwell times may be acceptable. The equivalence with respect to nitrogen 
dioxide production of devices providing low concentrations of nitric oxide 
would be evaluated on the basis of clinical data, and other data which 
may become available. 
Nitrogen dioxide in the inspired gas provided by a backup system should 
also be evaluated. The inspired concentration in simulated use should be 
measured at 10 ppm NO and approximately 98% oxygen, and should 
meet specifications provided in the device labeling. If the specified 
manual ventilator includes a reservoir which is not continuously flushed, 
then the maximum concentration of inspired nitrogen dioxide during the 
respiratory cycle should be evaluated, and the result provided for review. 
b.	  The administration device should include provision for nitrogen dioxide 
gas analysis with alarms. The breathing circuit location for sampling 
should sample gas which is representative of the inspired gas. Labeling 
should specify a suitable nitrogen dioxide gas analyzer. The analyzer 
should include an alarm with upper nitrogen dioxide concentration limits. 
Use of nitrogen dioxide analysis with alarms will permit detection and 
correction of malfunctions resulting in excess nitrogen dioxide production, 
and thus provides a supplementary method to control the risk of 
excessive nitrogen dioxide concentration. 
c. 	 Instructions for flushing the device and for operation of the device should 
be sufficient to prevent administration of nitrogen dioxide in excess of 
labeled limits. Testing should be performed to demonstrate the 
adequacy of these procedures. This testing will permit control of the risks 
of excessive nitrogen dioxide production. 
3.1.4 	 Potential for catastrophic release of nitric oxide results from the use of 
compressed gas cylinders containing substantial quantities of nitric oxide. This 
risk is limited by limiting the total quantity of nitric oxide subject to release in 
case of device failure or damage to the device or cylinder. This requirement 
10  will be met if the devices uses #82 cylinders pressurized to no more than 2200 
psi, and containing 400 ppm or 800 ppm nitric oxide. A data summary 
provided by Ohmeda lists the expected peak concentrations resulting from the 
release of the content of one cylinder (400 ppm) over 17 seconds into a 3.1 x 
6.2 x 4.65 meter room; without air exchange, the expected peak nitric oxide 
concentration is be 9 ppm and the expected peak nitrogen dioxide 
concentration is be 1.8 ppm, within OHSA standards of 25 and 5 ppm 
respectively. 
3.1.5 	 Adulteration of the nitric oxide may occur by reaction with the nitric oxide 
administration apparatus, or by reaction with the ventilator, humidifier, or other 
devices specified for use with the nitric oxide administration apparatus. The 
inspired gas at the patient connection should be tested by sensitive methods 
for the detection of adulterants. Methods may include Fourier transform 
infrared. This testing will control the risk of adulteration of the inhaled nitric 
oxide. 
3.1.6 	 Electrical hazards to patients and others may result from the use of electrical 
devices. Published standards or portions of standards are identified and 
discussed in Section 5. Compliance with these standards, or equivalent 
demonstrations of safety, are commonly used in review of medical devices, 
such as ventilators, to provide adequate control of risks related to various types 
of malfunctions, and will adequately control the electrical hazards of the nitric 
oxide administration device. 
3.1.7 	 Adverse effects on other electronic devices used for patient care may result 
from the use of electrical devices. Published standards or portions of 
standards for electromagnetic compatibility and testing are identified and 
discussed in Section 6 of this document as a special control. Compliance with 
these standards, or equivalent demonstrations of safety, are commonly used in 
review of medical devices to provide adequate control of risks related to 
electromagnetic interference, and will adequately control the electromagnetic 
interference hazards of the nitric oxide administration device. 
3.1.8 	 Release of nitric oxide and release and generation of nitrogen dioxide will result 
in the use of a nitric oxide administration device, and this may constitute a 
hazard under some circumstances. Because the concentration of nitric oxide 
concentrations used are low, generally less than 40 ppm, the nitric oxide 
concentration accumulated in room air concentrations are unlikely to exceed the 
NIOSH recommended time-weighted concentration limit of 25 ppm or the 
recommended acute exposure for nitrogen dioxide of 1 ppm. Calculations of 
11  dilution as well as experimental simulated use demonstrate that the ambient 
concentration of nitric oxide or nitrogen dioxide expected to result from use of 
the device is less than 50 ppb. Thus there is no need to scavenge the 
exhausted gas under typical circumstances. However individuals who may be 
particularly sensitive to nitric oxide or nitrogen dioxide, or who will be exposed 
for long periods should be informed of the exposure by labeling, including 
labeling on the device itself. In addition the practitioner should be instructed by 
labeling to evaluate the particular location in which the device is used, if the 
ventilation is in question. This labeling will adequately control risks which may 
result from release of nitric oxide and the release and generation of nitrogen 
dioxide in the nearby area under most circumstances. Optionally, scavenging 
devices may be fitted to ventilators if required. Scavenging devices are class II 
devices (21 CFR 868.5430). If there are circumstances in which use of the 
nitric oxide administration device results in excessive ambient nitric oxide and 
nitrogen dioxide, use of scavenging devices will adequately control risk. 
3.2 	 Nitric Oxide Analyzer 
The design and testing of the nitric oxide analyzer should take into consideration the risks 
associated with the device. Risks for the nitric oxide analyzer and the applicable controls 
are discussed in the follow subsections. 
3.2.1 	 Nitric Oxide measurement error is a particular risk of the nitric oxide analyzer. 
False low displayed or alarm values for of nitric oxide concentration can result 
in administration of excess nitric oxide, and false high displayed values for nitric 
oxide concentration can result in administration of insufficient nitric oxide. 
False display or alarm values for nitric oxide concentration will raise concerns 
that the administration device is malfunctioning, or that the nitric oxide cylinder 
contents are adulterated; the result may be interruption of essential nitric oxide 
therapy. 
To control the risk of error in measurement of nitric oxide the following 
specifications, labeling and testing should be incorporated in the design of the 
nitric oxide analyzer: 
a.	  Accuracy should be specified in the labeling. Testing should be 
performed to demonstrate the accuracy over the range of displayed 
values and under the conditions of simulated use. The testing conditions 
should include testing at 37 degrees Fahrenheit using mixtures as shown 
in table 1 below. The nitric oxide gas analyzer should measure 
concentrations of nitric oxide as low as 1 ppm. The accuracy of the 
12  displayed value should be within +/- (0.5 ppm + 20% actual 
concentration) between 1 and 20 ppm (m L/L). Above 20 ppm, the 
displayed value should be within +/- (0.5 ppm + 10% actual 
concentration). A 0-90% rise time of 30 seconds is sufficient. 
NO  0 ppm NO 0 ppm NO 5 ppm NO 0 ppm NO 0 ppm NO
2  2  2  2  2 
(ppm)  Ambient pressure  Ambient pressure  Ambient pressure  50 CmHO  Ambient pressure 
2
90% Humidification  90% Humidification  90% Humidification  90% Humidification  Dry Gas 
Balance* gas O2  Balance gas Air  Balance gas O2  Balance gas O2  Balance gas O2 
0           
1           
5   
20           
Full   
Scale 
* Balance is the gas to which the 800 or 400 ppm nitric oxide in nitrogen is added.  Balance gas should 
constitute at least 85% of the tested gas mixture, (volume %). 
Table 1 
b.  The equivalence of the nitric oxide gas analysis devices with respect to 
nitric oxide measurements at levels less than 1 ppm will be evaluated on 
the basis of the accuracy relative to the clinical indications and other data 
which may become available. 
c.  Labeling should include methods for calibration. Nitric oxide calibration 
gas suitable for use with the device should be specified by the 
manufacturer of the nitric oxide gas analyzer. The calibration gas should 
be labeled with an expiration date, and test data should be provided to 
demonstrate that the calibration gas is adequately stable for use within 
the expiration limit, and will permit calibration of the nitric oxide gas 
analyzer to the analyzer's specified accuracy. 
d.  The expected life of the sensor or other life-limited components should be 
specified. Testing to validate the endurance sensor or other life-limited 
components should include simulated use with the patient circuit as 
specified in the device labeling, with the humidifier set to simulate the 
conditions of clinical use. 
e.  Alarms, if provided, should be capable of being set over the range of 
displayed nitric oxide concentrations, and be demonstrated to alarm at 
13  set value. Note that a primary nitric oxide administration device should 
include provision for nitric oxide gas analysis with upper and lower 
concentration alarms. 
f. 	 If the device is for use within or for attachment to a patient breathing 
circuit operating at other than ambient pressure, accuracy should be 
verified by testing during simulated positive pressure ventilation generally 
in accordance with procedures used for testing of oxygen gas analyzers. 
This information can be found in ASTM F 1462 - 93 Specifications for 
Oxygen Analyzers. 
g.	  Particular published standards or portions of published consensus 
standards, and other material in this guidance document address issues 
such as; software and hardware documentation, electromagnetic 
compatibility documentation, and environmental documentation. Refer to 
the table of contents for the applicable section. 
3.2.2 	 Electrical hazards to patients and others may result from the use of electrical 
devices. Published standards or portions of standards are identified and 
discussed in Section 5. Compliance with these standards, or equivalent 
demonstrations of safety, are commonly used in review of medical devices, 
such as ventilators, to provide adequate control of risks related to various types 
of malfunctions, and will adequately control the electrical hazards of the nitric 
oxide analyzer. 
3.2.3 	 Adverse effects on other electronic devices used for patient care may result 
from the use of electrical devices. Published standards or portions of 
standards for electromagnetic compatibility and testing are identified and 
discussed in Section 6 of this document as a special control. Compliance with 
these standards, or equivalent demonstrations of safety, are commonly used in 
review of medical devices, to provide adequate control of risks related to 
electromagnetic interference, and will adequately control the electromagnetic 
interference hazards of the nitric oxide analyzer. 
3.3 	 Nitrogen Dioxide Analyzer 
The design and testing of the nitrogen dioxide analyzer should take into consideration the 
risks associated with the device. Risks for the nitrogen dioxide analyzer and the 
applicable controls are discussed in the follow subsections. 
14  3.3.1 	 Nitrogen Dioxide measurement error is a particular risk in the use of Nitrogen 
Dioxide gas analyzer. False low displayed or alarm values of nitrogen dioxide 
concentration can result in failure to detect administration of toxic 
concentrations of nitrogen dioxide. False high displayed alarm values for 
nitrogen dioxide concentration will raise concerns that the administration device 
is malfunctioning, or that the nitric oxide cylinder contents are adulterated; the 
result may be interruption of essential nitric oxide therapy. 
To control the risk of error in measurement of nitric oxide the following 
specifications, labeling and testing should be incorporated in the design of the 
nitrogen dioxide analyzer: 
a.	  Concentrations as low as 0 ppm and as high as 5 ppm should be 
measured by the analyzer with sufficient accuracy. Accuracy should be 
specified in the labeling. Testing should be performed to demonstrate 
the accuracy under the conditions of use. The testing conditions in Table 
2 shold be used (at 37 degrees Farenheit). On the basis of current data, 
accuracy can be considered sufficient if the displayed value is within 20% 
of the actual concentration, or 0.5 ppm, whichever is greater. A 0-90% 
rise time of 30 seconds is sufficient. Accuracy results should be stated in 
the device labeling. 
15  NO 0 ppm NO  0 ppm NO  20 ppm NO  0 ppm NO  0 ppm NO 
2 
(ppm)  Ambient pressure  Ambient pressure  Ambient pressure  50 CmHO  Ambient pressure 
2
90% Humidification  90% Humidification  90% Humidification  90% Humidification  Dry Gas 
Balance* gas O2  Balance gas Air  Balance gas O2  Balance gas O2  Balance gas O2 
0           
1           
5   
Full   
Scale 
* Balance is the gas to which the 800 or 400 ppm nitric oxide in nitrogen is added.  Balance gas should 
constitute at least 85% of the tested gas mixture, (volume %). 
Table 2 
b.	  Labeling should include methods for calibration. Nitrogen dioxide 
calibration gas suitable for use with the device should be specified by the 
manufacturer of the nitrogen dioxide gas analyzer. The calibration gas 
must be labeled with an expiration date, and test data must be provided 
to demonstrate that the calibration gas is adequately stable for use within 
the expiration limit, and will permit calibration of the nitrogen dioxide gas 
analyzer to the analyzer's specified accuracy. 
c. 	 The expected life of the sensor or other life-limited components should be 
specified. Testing to validate the endurance sensor or other life-limited 
components should include simulated use with the patient circuit as 
specified in the device labeling, with the humidifier set to simulate the 
conditions of clinical use. 
d.	  An upper alarm limit, if provided, should be capable of being set to levels 
as low as 1 ppm, and be demonstrated to alarm at the set value. Note 
that a primary nitric oxide administration device should include provisions 
for nitrogen dioxide gas analysis with an upper concentration alarm. 
e.	  If the device is for use within or for attachment to a patient breathing 
circuit operating at other than ambient pressure, accuracy should be 
verified by testing during simulated positive pressure ventilation generally 
in accordance with procedures used for testing of oxygen gas analyzers. 
This information can be found in ASTM F 1462 - 93 Specifications for 
Oxygen Analyzers. 
16     f. 	 Particular published standards or portions of published consensus 
standards, and other material in this guidance document address issues 
such as; software and hardware documentation, electromagnetic 
compatibility documentation, and environmental documentation. These 
testing and documentation procedures are discussed in this document in 
separate sections. Refer to the table of contents for the applicable 
section. 
3.3.2 	 Electrical hazards to patients and others may result from the use of electrical 
devices. Published standards or portions of standards are identified and 
discussed in Section 5. Compliance with these standards, or equivalent 
demonstrations of safety, are commonly used in review of medical devices, 
such as ventilators, to provide adequate control of risks related to various types 
of malfunctions, and will adequately control the electrical hazards of the nitrogen 
dioxide analyzer. 
3.3.3 	 Adverse effects on other electronic devices used for patient care may be result 
from the use of electrical devices. Published standards or portions of 
standards for electromagnetic compatibility and testing are identified and 
discussed in Section 6 of this document as a special control. Compliance with 
these standards, or equivalent demonstrations of safety, are commonly used in 
review of medical devices, to provide adequate control of risks related to 
electromagnetic interference, and will adequately control the electromagnetic 
interference hazards of the nitrogen dioxide analyzer. 
17  SECTION 4.  General Criteria and Testing 
The following subsections apply to the nitric oxide administration devices, nitric oxide 
analyzers and nitrogen dioxide analyzers. 
4.1  General Criteria 
The 510(k) premarket notification application should include testing information 
demonstrating safety and effectiveness of the performance characteristics of the device in 
the intended environment of use. The type of the device and its intended environment will 
determine the type of testing that is necessary. Recommended environmental, electrical, 
electromagnetic compatibility, and mechanical test procedures and protocols are 
discussed in the following sections. 
The submitted information should include the test procedures and protocols, an explanation 
as to how the test procedures simulate the intended environment of use and are 
comparable to the test procedures outlined below, test results, and an analysis of the 
results. If device failure occurs during the testing, a justification as to why such a failure 
does not affect safety or effectiveness, and/or a description of device modifications (i.e., 
identification of each modification, rationale for each modification) and follow-up testing 
demonstrating that the modification alleviates the problem should be provided. 
4.2  General Test Methods 
General test methods should be established and utilized for verifying that device 
performance is within specification when subjected to the environmental testing 
procedures in the subsequent sections. This testing information should be included in the 
premarket notification submission. Also, information concerning the design of, and 
rationale for, the tests used to demonstrate the safety and effectiveness of the device in the 
intended environment, together with the testing procedures and protocols, results, and 
analyses of the results, should be provided in the 510(k) premarket notification submission. 
  
Unless otherwise specified, the test conditions should be as follows: 
Temperature: 15 to 35C 
Humidity: 30 to 90 percent 
Barometric pressure: 68 to 106 kPa 
Line voltage: 110 V rms to 125 V rms 
18  For modular devices, test in more than one typical module configuration with the other 
modules operating. 
The following should be used to verify proper device alarming capabilities and self test 
functions in the subsequent sections of the test methods. 
a.  Visual status indicators (alarms) 
Determine by inspection the presence and proper operation of warning 
indicators and device status indicators. 
b.  Audible status indicators (alarms) 
Determine by inspection the presence and proper operation of the audible 
status indicators. Measure and record the frequency, temporal characteristics, 
and sound level of the indicators at 1 meter. Devices intended for home use 
should feature continuously sounding warning indicators with sound levels not 
less than 85 dB(A) and warning indicators of devices intended for hospital use 
should feature sound levels not less than 70 dB(A). 
c.  Remote alarm 
Determine proper operation of the remote alarm by connecting the remote 
alarm during the testing of the device and verifying proper response. Also, 
verify that use of remote alarms does not disable the device's alarms. 
d.  Self test 
It a self test capability is part of the device design, the self test capability should 
be verified. Determine by inspection the presence and proper operation of an 
indicator self-test capability that exercises all indicators upon turn-on. 
Determine by inspection, the presence or absence of a sensing and/or 
functional self-test. If a functional self-test is present, verify its operation. 
19  SECTION 5.  Electrical Safety 
5.1  Performance Criteria 
5.1.1  Battery power 
a.  When a line-powered medical device is equipped with a battery power 
back-up, this battery back-up should, unless the overcurrent protection 
mechanism described in paragraph 5.1.3 of this section has activated, 
automatically activate when power fails for any other reason. The device should 
operate within its specification within 5 seconds or less after the battery backup 
power activates. 
b.  On medical devices equipped with a battery back-up system, the battery, when 
charged fully, should be capable of supplying power for normal operation for the 
time duration specified in the device specifications, and consistent with its 
intended use. 
c. 	 When a battery back-up is provided, audible and visual battery depletion 
warning indicators should be provided that activate when the battery depletes to 
a level of charge that is approaching the lower limit of power that can operate 
the device within its specification. The operating time between the onset of the 
battery depletion alarm and the end of normal device operation should be 
stated in the device specification. The alarm should remain activated during 
this period. 
d.	  Housings containing batteries from which gases can escape during charging or 
discharging should be ventilated to minimize the risk of accumulation and 
ignition. Battery compartments should be designed to prevent the risk of 
accidentally short-circuiting the battery. 
e.	  If a safety hazard or device malfunction might develop by the incorrect 
connection or replacement of a battery, the device should be fitted with a 
means of preventing incorrect polarity of connection. 
5.1.2  Electrical power indicators 
a.	  Power visual status indicators should be provided to indicate that the device is 
energized. Such indicators should be located conspicuously on the device and 
should distinguish between battery power and line power sources when both 
sources are provided. 
20  b.  In devices incorporating a means for battery charging, the charging mode 
should be visibly indicated to the operator. 
5.1.3  Overcurrent protection 
a.	  Overcurrent protection should be provided for all line-powered devices. 
b.	  An audible warning status indicator should be activated if the overcurrent 
protection mechanism is activated and operation of the device cannot occur. 
This status indicator (alarm) should be capable of sounding for the time 
duration identified in device specifications. 
c. 	 Medical devices should not be fitted with protective mechanisms which cause 
disconnection of the device from the power line (supply mains) by producing a 
short-circuit which results in operation of an overcurrent protection mechanism. 
5.1.4  Dielectric withstand 
Power source conductors, patient contact circuits, and transducer circuits should be 
adequately insulated to assure protection of the patient and device from over voltages. 
Therefore, the device should meet the requirements of IEC 601-1, Clause 20. 
5.1.5  AC power grounding and polarity 
If the device power connector is not polarized, the device should operate within its 
specification in both polarities of power line connector insertion. Devices that operate or 
recharge batteries from the ac power line should operate within specifications when 
operating from a grounded or an ungrounded power source (i.e., with the third-wire ground 
connected and with it disconnected at the plug end of the power cord). 
5.1.6  Leakage current 
The leakage current testing procedures and protocols, test results including leakage 
current measurements, and identification of standards to which the measured leakage 
current complies should be provided in the 510(k) premarket application. Devices should 
meet the requirements of IEC 601-1. 
21  5.1.7  Auxiliary output 

Where an auxiliary output is provided: 

a.  The device should operate within its specification during and after application 
of a short-circuit applied to the auxiliary output for 1 minute. 
b.  The leakage current requirements of 5.1.6 should not be exceeded upon proper 
connection of an auxiliary device to the auxiliary output. This proper connection 
should be described in the operator's manual. 
5.2  Test Methods 
For modular devices, test in more than one typical module configuration with the other 
modules operating. 
5.2.1  Battery power 
a.	  For ac powered devices with battery back-up, with the device powered from the 
ac line, simulate normal operation. Remove ac power and determine if battery 
back-up power activates within 5 seconds.  With the device operating on 
battery power, test as discussed in Sections 4.1 and 4.2. Failure of the device 
to perform within its specification should constitute failure of this test. 
b.	  Operate the device from a fully charged battery. After operation for 90 percent 
of the battery power time duration specified in the device specifications, test in 
accordance with Sections 4.1 and 4.2. Failure of the device to perform within 
its specification should constitute failure of this test. 
c. 	 Operate the device from a fully charged battery. Record the start time and the 
time at which battery depletion is indicated. Test in accordance with Sections 
4.1 and 4.2 and verify that battery depletion to the level at which the device fails 
to operate occurs no less than the minimum time duration defined in the device 
specifications after indication of battery depletion. Failure of the device to 
perform within its specification should constitute failure of this test. 
d.	  Determine by inspection that housings containing batteries from which gases 
can escape during charging or discharging are adequately vented. Determine 
by inspection that battery compartments are designed to prevent accidental 
22  short-circuiting of the battery. 
e.  For user-replaceable batteries, attempt to incorrectly connect, insert, or replace 
the battery. Determine by inspection that there is clear indication that the 
device is not functioning. Then insert or connect the battery correctly and test 
the device in accordance with Sections 4.1 and 4.2. Failure of the device to 
perform within its specification should constitute failure of this test. 
5.2.2  Electrical power indicators 
a.  Determine by inspection that visual status indicators indicate when the device 
is energized and that they distinguish between battery power and line power 
sources when both sources are provided. 
b.  For devices incorporating a means for battery charging, place the device in the 
charging mode and determine by inspection that the charging mode is visibly 
indicated. 
5.2.3  Overcurrent protection 
a.  For ac line-powered devices, determine by inspection the presence of 
overcurrent protection. 
b.  For ac line -powered devices, activate the overcurrent protection mechanism. 
Record the time at which the audible warning status indicator activates and the 
time at which it ceases to sound. Failure of the alarm to activate or to sound for 
at least the time duration identified in the device specifications should 
constitute failure of this test. 
c.  For ac line -powered devices, operate from a power distribution strip that 
incorporates a slow-blow fuse or a circuit breaker appropriately rated for the 
device under test. Activate the device overcurrent protection mechanism. 
Activation of the power distribution strip fuse or circuit breaker should constitute 
failure of this test. 
23  5.2.4  Dielectric withstand 
Test for dielectric withstand in accordance with Clause 20 and Appendix E of IEC 601-1. 
5.2.5  AC power grounding and polarity 
For devices that recharge batteries or operate from the ac power line, disconnect all 
connections to ground and test the device in accordance with Sections 4.1, 4.2, 5.2.1.a, 
and 5.2.3. If the ac power connector is not polarized, reverse the polarity of the ac 
connection and repeat the test. Failure of the device to perform within its specification 
should constitute failure of this test. 
5.2.6  Leakage current 
Test the device in accordance with IEC 601-1 or in accordance wi th other applicable 
standards with leakage current specifications. 
5.2.7  Auxiliary output 

If the device is provided with an auxiliary output: 

a.  This output should be short-circuited (all pins connected together) for at least 1 
minute, with the device in the standard operating modes. During and after 
application of the short-circuit, the device should operate within its 
specification. 
b.  With the auxiliary output connected as specified by the manufacturer, test 
device per 5.2.6. 
24  SECTION 6.  Electromagnetic Compatibility 
6.1  Performance Criteria 
Devices should meet the electromagnetic compatibility requirements contained in sections 
6.1 and 6.2 and should also meet these requirements when recharging batteries (if 
applicable) from or operating from a grounded or an ungrounded ac power source (i.e., 
with the third-wire ground connected and with it disconnected at the plug end of the power 
cord). 
6.1.1  Emissions 
The device should operate within its specification without emitting electromagnetic energy 
in excess of the levels specified below. The required emission limit should be that 
specified by the referenced document, adjusted downward by the rms sum of all errors in 
the measurement of that quantity. 
6.1.1.1                 Radiated and conducted electromagnetic energy 
The device should comply with the relevant requirements of CISPR 11 when tested 
according to the specified test methods of this guidance document. 
6.1.1.2                 Magnetic fields 
The device should comply with the relevant requirements of RE101 (Army, 7-cm distance) 
of MIL-STD-461D from 30 Hz to 100 kHz when tested at the 7-cm distance according to 
RE101 of MIL-STD-462D. 
6.1.2  Immunity 
The device should operate within its specification during and after exposure to 
electromagnetic interference at the levels specified below. The required immunity level 
should be the level stated, adjusted upward by the rms sum of all errors in the 
measurement of that quantity, with the exception of the lower steady-state ac voltage limit 
and the line-voltage sag level, which should be adjusted downward by the rms sum of the 
measurement errors. The device should not, as a result of the specified test condition: 
indicate an equipment alarm, exhibit temporary degradation or loss of function or 
performance which requires operator intervention or system reset, or exhibit loss or 
corruption of stored data. Details of test conditions are specified in section 6.2 of this 
guidance document. 
25  6.1.2.1  Electrostatic discharge 
The device should operate within its specification within 5 seconds of air discharges of 2, 
4, 6, and 8 kV applied to insulating surfaces and contact discharges of 2, 4, and 6 kV 
applied to conductive surfaces, both positive and negative, to include any point on the 
device accessible to the operator or patient, when tested according to IEC 801-2, as 
specified in section 6.2. The device should operate within its specification within 5 
seconds of contact discharges applied to horizontal and vertical conducting planes in the 
vicinity of the device, as specified in section 6.2. 
6.1.2.2  Radiated electromagnetic fields 
The device should operate within its specification during and after exposure to 
electromagnetic fields at frequencies between 26 MHz and 1 GHz at field strengths up to 3 
V/m (when unmodulated), amplitude modulated 80 percent with a sine wave or 100 percent 
with a square wave. A modulation frequency that is within each significant signal-
processing passband of the device should used. For devices not having a defined 
passband, a modulation frequency of 0.5 Hz should be used. The modulation frequency 
should be specified in 510(k) premarket notification. 
6.1.2.3  AC voltage fluctuations, transients, and surges 
The following items apply to all devices that recharge batteries from or operate from the ac 
power line: 
a.  Steady-state voltage 
The device should operate within its specification, without changing a voltage 
selection switch, when powered from line voltages between 95 and 132 volts 
rms. The battery power back-up, if featured, should automatically activate when 
the line voltage falls below the minimum level necessary for line-powered 
device operation, which should be no greater than 95 volts rms, and line-
powered operation should automatically resume when the line voltage returns to 
the 95-to-132-volt range. 
b.  Dropout 
The device should operate within its specification during and after line voltage 
dropouts for durations of 10 milliseconds and less. 
26  c.  Slow sags and surges 
The device should operate within its specification during and after line voltage 
surges to 150 V rms and sags to 90 V rms for durations of 500 ms and less. 
d.  Fast transient bursts 
The device should operate within its specification during and after bursts of 
transients of 0.5, 1, and 2 kV applied to ac power leads and transients of 0.25, 
0.5, and 1 kV coupled by way of a capacitive clamp to signal leads, when 
tested according to IEC 801-4, with the exception that the burst repetition 
frequency should not exceed 30 per minute. 
e.  Fast surges 
The device should operate within its specification during and after exposure to 
combination voltage/current transients applied to AC power leads as specified 
in section (m) from a test generator as follows: 
Open-circuit voltage, differential mode: 1 kV 

Open-circuit voltage, common mode: 2 kV 

Open-circuit voltage risetime: 1.2 microseconds 

Open-circuit voltage falltime: 50 microseconds 

Generator source impedance: 2 ohms 

Short-circuit current risetime: 8 microseconds 

Short-circuit current falltime: 20 microseconds 

Surge repetition rate: 1 per minute 

6.1.2.4  Conducted electromagnetic energy 
The device should operate within its specification during and after exposure of each 
interconnecting cable, including power cables, to conducted electromagnetic energy at 
frequencies between 10 kHz and 100 MHz at the levels specified in CS114, Curve #3, of 
MIL-STD-461D, when tested according to CS114 of MIL-STD-462D. A modulation 
frequency that is within each significant signal-processing passband of the device should 
be used. For devices not having a defined passband, a modulation frequency of 0.5 Hz 
should be used. The modulation frequency should be specified in the 510(k) premarket 
notification. 
27  6.1.2.5  Magnetic fields 
The device should operate within its specification during and after exposure to magnetic 
fields at frequencies between 30 Hz and 100 kHz as specified in RS101 (Army) of MIL
STD-461D, when tested according to RS101 of MIL-STD-462D. A modulation frequency 
that is within each significant signal-processing passband of the device should be used. 
For devices not having a defined passband, a modulation frequency of 0.5 Hz should be 
used. The modulation frequency should be specified in the 510(k) premarket notification. 
6.1.2.6  Quasi-static electric fields 
The device should operate within its specification during and after exposure to a 
sinusoidally varying electric field at 0.5 Hz with peak field strengths up to 2000 volts per 
meter. Note: This test simulates the movement of electrostatically charged fabrics and 
objects that could come into close proximity to the device. 
6.2  Test Methods 
Devices should be tested for electromagnetic emissions and immunity to electromagnetic 
interference as described herein. Devices should be tested with the third wire ground 
connected at the plug end of the power cord. Devices intended for home use should be 
tested with the third wire ground connected and with it disconnected at the plug end of the 
power cord. 
6.2.1  Emissions 
Emissions measurements should be made as specified in the referenced document. The 
required emission limit should be that specified by the referenced document, adjusted 
downward by the rms sum of all errors in the measurement of that quantity. Emission in 
excess of the adjusted limit should constitute failure of this test. These tests should be 
conducted using passive patient simulators, which in general are not capable of simulating 
normal patient signals. 
6.2.1.1  Radiated and conducted electromagnetic energy 
The device should be tested according to CISPR 11. 
28  6.2.1.2  Magnetic fields 
The device should be tested for radiated magnetic field emissions between 30 Hz and 100 
kHz as specified in RE101 of MIL -STD -462D, using the Army 7-cm limit.  Measurements 
should be made at the 7-cm distance only. 
6.2.2  Immunity 
Immunity of the device to electromagnetic interference should be determined as specified 
in the referenced document, with the modifications listed below. The required immunity 
level should be the level stated, adjusted upward by the rms sum of all errors in the 
measurement of that quantity, with the exception of the lower steady-state ac voltage limit 
and the line-voltage sag level, which should be adjusted downward by the rms sum of the 
measurement errors. Any of the following should constitute failure of this test: an 
equipment alarm, temporary degradation or loss of function or performance which requires 
operator intervention or system reset, or loss or corruption of stored data. Patient 
simulators should be used to provide simulated normal stimulus to sensors during 
electromagnetic immunity testing. 
6.2.2.1  Electrostatic discharge 
The device should be tested with air discharges at 2, 4, 6, and 8 kV applied to insulating 
surfaces and contact discharges at 2, 4, and 6 kV applied to conductive surfaces. Failure 
to resume normal operation (with no operator intervention) within 5 seconds of a discharge 
should constitute failure of this test. All test failure conditions listed above apply. The 
device should be tested according to IEC 801-2, with the following conditions and 
modifications: 
a.  The device should be tested according to the test method described in IEC 
801-2 for table-top equipment. 
 
b.  The relative humidity should not exceed 50 percent during air discharges. 
c.  Air discharges should b e conducted at 2, 4, 6, and 8 kV.  Contact discharges 
should be conducted at 2, 4, and 6 kV. Discharges of both positive and 
negative polarity should be conducted at each voltage. 
d.  In addition to air and contact discharges directly to the device, conta ct 
discharges should be made to the horizontal coupling plane under the device 
and to the vertical coupling plane positioned parallel to the faces of the device. 
At least 10 single discharges at each test voltage and polarity should be 
29  applied to each test point. 
6.2.2.2  Radiated electromagnetic fields 
a.	  Test conditions 
i.	  The device should be tested for immunity to radiated electromagnetic 
energy over the frequency range 26 MHz to 1 GHz at a field strength of 3 
V/m. The RF carrier should be amplitude modulated 80 percent by a sine 
wave or 100 percent with a square wave. A modulation frequency that is 
within each significant signal-processing passband of the device should 
be used. For devices not having a defined passband, a modulation 
frequency of 0.5 Hz should be used. The modulation frequency should be 
specified in the 510(k) premarket application. 
ii.	  If a continuous sweep of the test frequency is used, the sweep rate should 
not exceed 0.1 MHz/second. If the sweep is incremental, the step size 
should not exceed 1 MHz and the dwell time at each frequency should be 
10 seconds. 
iii.	  Devices which can operate from both line and battery power should be 
tested both with the ac power connection (e.g., power cord, battery 
charger) attached and detached from the device. 
iv. 	 Patient simulators used during the test should be either simple passive 
devices, isolated from earth ground using fiber optics, or battery 
operated and shielded. 
v. 	 Connections not normally used during device operation that are made to 
the device to assess performance during the test should be isolated 
using fiber optics. 
vi.	  The radiated electric field should be linearly polarized. The test should be 
performed with both horizontal and vertical polarization. 
vii.	  A planar area of uniform field should be established, that contains the 
front surface of all components of the device under test, including cables.
 The boundaries of the area of uniform field should include the maximum 
planar area occupied in any orientation of the parts of the device. The E-
field should be measured at multiple points within the area of uniform 
field, with all accessories and physical components of the device 
30  removed from the field. 
Within the area of uniform field, the uniformity of the component of the 
electric field that is aligned with the intended E-field polarization should 
be -0, +6 dB, measured with no amplitude modulation present on the 
exposure field. At a minimum, point measurements should be performed 
at every incremental frequency in the 26 to 1000 MHz frequency range as 
specified in 6.2.2.2.ii. E-field measurements should be made at 
uniformly spaced points throughout the entire surface of the area of 
uniform field for both horizontal and vertical polarization. The spacing 
between these points in both the vertical and horizontal directions should 
be 0.5 m or less. At each point, the component of the E-field that is 
aligned with the intended polarization should not differ from the total E-
field at that point by more than 3 dB. 
For a given facility, if placement of absorber, antennas, and area of 
uniform field are carefully reproduced, it should be necessary to map the 
area of uniform field only occasionally, e.g. once per year. Prior to a 
series of tests, the area of uniform field should be checked along a 
vertical line near the center, with measurements made at uniformly 
spaced points having a spacing of 0.5 m or less. The E-field measured 
at these points should meet the uniformity requirements specified above. 
 
RF electric field instruments and measurement procedures should meet 
the requirements of ANSI/IEEE C95.3 - 1991. The instruments should not 
perturb the E-fields being measured by more than 2 dB and should 
measure local E-field strength with an error of less than 3 dB over the 
frequency range of use. The field-sensing elements of the instrument 
should fit within a spherical volume with a diameter of 15 cm. The 
instrument should be capable of measuring the magnitude of each of the 
three orthogonal components of the electric field. In addition, the 
instrument should be capable of determining the total electric field 
strength (the square root of the sum of the squares of the three E-field 
vector components). The above measurements should be measured 
accurately (1 dB) regardless of the direction of the radiated electric field 
(i.e., the field measuring instrument should be isotropic). 
viii.	  When practical, the test should be repeated with each of the six faces of 
the device facing the antenna. To the extent possible, all cables should 
be horizontal over the majority of their length throughout the test. 
31  ix. 	 One or more of the following exposure methods should be used: (1) an 
open-area test site, with the signal and power leads fully extended 
horizontally; (2) an anechoic chamber; (3) a parallel-plate line; (4) a 
screen room; (5) a semi-anechoic chamber; or (6) a TEM cell. In order to 
cover the entire frequency range, combinations of several exposure 
methods may be used over the portions of the range for which they are 
most appropriate. Where the methods yield different results, the open-
site test should take precedence from 26 to 200 MHz and the anechoic 
chamber test should take precedence from 200 MHz to 1 GHz. 
a.	  Test setup 
i.	  When practical, all device components and cables should be elevated at 
least 0.8 m above any conducting ground plane by low dielectric constant 
(<2.5), nonconducting RF-transparent material. When this is not 
possible, device components should be mounted on a bulk non
conducting support at least 0.1 m high. All device components should be 
at least 0.8 m away from any RF-reflecting objects (e.g., walls of the 
exposure facility). The distance may need to be increased at certain 
frequencies to achieve the required field uniformity. 
ii.	  For exposure methods in which the device cables cannot be extended 
fully, if the length of any conducting cable is 1 m or less, it should be 
arranged horizontally in the planar area of uniform field. If the length of 
any conducting cable is greater than 1 m in length, up to the first three 
meters should be bundled in a serpentine configuration in the planar area 
of uniform. Conductive leads should be configured on a clean, dry, 
plastic foam (e.g., StyrofoamR) sheet with the dimensions and 
construction. Support pegs should be made of dielectric (e.g., TeflonR) 
rods (one quarter inch in diameter). Cables in excess of 3 m should be 
bundled low-inductively and placed on the non-conducting support. 
iii.	  RF/EMI filters should be used at the device's ac power plug. 
32  6.2.2.3  AC voltage fluctuations, transients, and surges 
The tests described below should be performed on all devices intended to recharge 
batteries or operate from the ac power line. 
a.	  Steady-state voltage 
i.	  Raise the line voltage to 132 volts rms and allow the device to stabilize. 
Test device operation according to sections (k) and (l). Repeat for a 
voltage of 95 volts rms. 
ii.	  For devices with battery backup, simulate normal patient signals while 
reducing the line voltage to zero. Record the voltage at which the device 
switches to battery power. In addition to the failure criteria listed above, 
failure of the device to automatically switch to battery power, or switching 
to battery power before the line voltage reaches 95 volts rms should 
constitute failure of this test. Continue to test device operation while 
raising the line voltage to 120 volts rms. In addition to the failure criteria 
listed above, failure of the device to automatically switch to line power 
when the line voltage exceeds 95 volts rms should constitute failure of this 
test. 
b.	  Dropout 
Operate the device at 95 volts rms, lower the line voltage to 0 volts for 10 
milliseconds, and then restore it to 95 volts rms, doing so 10 times at a rate not 
to exceed 30 per minute. 
c. 	 Slow sags and surges 
Operate the device at 120 volts rms. Raise the line voltage to 150 volts rms for 
500 ms. Repeat at 10-second intervals for a total of 10 times. Again operate 
the device at 120 volts rms. Lower the line voltage to 90 volts rms for 500 ms. 
Repeat at 10-second intervals for a total of 10 times. 
d.	  Fast transient bursts 
Test ac power leads and signal leads according to IEC 801-4 for type test of 
table-top equipment, with the exception that the burst repetition frequency 
should not exceed 30 per minute. Test supply leads at 0.5, 1, and 2 kV, and 
signal leads at 0.25, 0.5, and 1 kV. 
33  e.  Fast surges 
i.  Test generator 
(a) The values of elements R , R , R , L, and C  are such that the 
s1 s2 m r c
generator delivers at a single output a combination voltage/current wave 
characterized by a 1.2/50 s voltage surge when measured across a 
high-resistance load (more than 100 ohms) and a 8/20 s current surge 
when measured into a short circuit, i.e. the generator has an effective 
output impedance of 2 ohms. 
(b) The generator should be capable of producing an open circuit output 
voltage of up to 2 kV, both positive and negative polarity, with wave. The 
generator should be capable of delivering short circuit output current of at 
least 1 kA. 
The generator should be triggerable so that the phase angle of the 
discharge can be set at 0, 90, 180, and 270 degrees with respect to the 
ac line voltage. 
ii.  Test setup 
(a) Capacitive coupling should be used to apply the combination wave to 
the ac power leads of the device under test. 
(b) A decoupling network should be used to isolate the device under test 
from the ac power network. Residual test pulse voltage on unsurged 
leads should not exceed 15 percent of the maximum applied test voltage 
when the device is disconnected. Residual test pulse voltage on the 
inputs of the decoupling network when the device and the power supply 
network are disconnected should not exceed 10 percent of the applied 
test voltage or twice the peak value of the power line voltage, whichever 
is greater. 
(c) Surges should be applied at the point where the device would 
normally be connected to ac line power. 
(d) For the line-to-line test, an 18-uF coupling capacitor should be used. 
(e) For the line-to-ground tests, a 10-ohm resistor should be used in 
34  series with the test generator and a 9-uF coupling capacitor should be 
used. 
iii.	  Test procedure 
(a) The line-to-line test should be performed using 1-kV surges of both 
positive and negative polarity applied using a generator source 
impedance of 2 ohms and coupling capacitance of 18 uF with the 
generator output floating. 
(b) The line-to-ground test should be performed using 2-kV surges of 
both positive and negative polarity applied using a generator source 
impedance of 12 ohms and coupling capacitance of 9 uF with the 
generator output grounded. The test should be repeated with surges 
applied successively between each line and ground. 
(c) Surges at each amplitude and polarity should be applied at phase 
angles of 0, 90, 180, and 270 degrees with respect to the ac line. 
(d) Each test should be repeated 10 times at a rate of 1 surge per 
minute. 
6.2.2.4 	 Conducted electromagnetic energy 
The device should be tested for immunity to conducted electromagnetic energy on each 
power and signal lead at frequencies between 10 kHz and 100 MHZ at the levels specified 
in curve #3 of CS114 of MIL-STD-461D, using the test methods specified in CS114 of 
MIL-STD-462D, with the modifications and additions listed below. 
a.	  If continuous sweep of the test frequency is used, the sweep rate should not 
exceed 1 x 10-3 decades/second. If the sweep is incremental, the step size 
should not exceed 1 percent of decade, and the minimum dwell time is 10 
seconds per step. 
b.	  A modulation frequency that is within each significant signal-processing 
passband of the device should be used. For devices not having a defined 
passband, a modulation frequency of 0.5 Hz should be used. 
c. 	 The leads under test should be elevated 5 cm above the ground plane. 
d.	  For power cables, the interference signal should be injected at a distance of 5 
35  cm from the point at which ac line power enters the device. For battery 
chargers which plug directly into ac outlets, a 10 cm length of wire should be 
added between the LISN and the charger, and the test signal should be injected 
5 cm from the charger. The low-voltage output cable of the charger should be 
elevated 5 cm above the ground plane. 
6.2.2.5  Magnetic fields 
Test according to RS101 of MIL-STD-462D. The test should be performed from 30 Hz to 
100 kHz. 
6.2.2.6 	 Quasi-static electric fields 
a.	  Test setup 
i.	  The device should be tested between parallel horizontal planes. They 
should be metallic sheets (copper or aluminum) of 0.25 mm minimum 
thickness which extend at least 0.1 m beyond the device.  The horizontal 
planes should be separated by insulating material, with a separation at 
least three times the height of the device in the position of normal use. 
ii.	  The device should be supported by insulating material so that it is 
positioned entirely between 1/3 and 2/3 the distance between the 
horizontal planes. 
iii.	  Cables and tubing should be supported by insulating material at a height 
above the bottom horizontal plane of 1/3 the distance between the planes 
and should exit the test apparatus and continue at this height for at least 
0.1 meter beyond the horizontal planes. 
iv. 	 The output of a signal generator capable of producing a sinusoidally 
varying voltage at a frequency of 0.5 Hz with amplitude sufficient to 
produce peak electric field strengths up to 2000 V/m between the 
horizontal planes should be connected to the horizontal planes. 
Note: Ep = Vp/D, where Ep is the peak field strength in V/m, Vp is the 
peak of the signal generator output voltage waveform, and D is the 
distance between the horizontal planes in meters. 
36  b.  Test procedure 
Adjust the signal generator peak output voltage such that the device is exposed to a 
sinusoidally varying electric field at 0.5 Hz with peak field strength of 500 V/m. Gradually 
increase the peak field strength to 2000 V/m. 
37  SECTION 7.  Performance Specifications, Environmental and Mechanical Safety 
7.1  Performance Criteria 
7.1.1  Controls protection 
The controls of medical devices should be protected from inadvertent or unauthorized 
changes or adjustment. The means of protection should be such as to preclude their 
defeat by patients, or other unauthorized persons. 
All controls which increase or decrease a function should be marked with a legible 
indication to inform the operator which action(s) is (are) required to increase/decrease the 
controlled function. Controls and their associated markings should be visible or legible, or 
both, to an operator having a visual acuity of at least 1.0 when the operator is located at 
lest 1 meter in front of the device and the ambient illuminance level is 215 lx, when viewing 
the information, marking, etc. perpendicular to, and including 15 degrees above, below, left 
and right. Controls should be identified with their associated markings. 
For controls, movement upwards, to right, or in a clockwise direction should increase the 
control function. Movement downwards, to the left, or a counterclockwise direction should 
decrease the control function. Rotary gas flow controls are exempt from this performance 
criterion. 
7.1.2  Connector protective incompatibility 
a.	  Device connectors, including those on wires and tubing, should be designed 
such that insertion into a receptacle other than the one into which they are 
intended to be inserted or into a receptacle using an improper orientation 
should not be possible. 
b.	  Electrical connectors of a device (e.g., electrical lead wires) should include a 
mechanism to prevent connection of the patient to a power source that may 
cause a current flow in excess of that specified in paragraph (h)(6). 
7.1.3  Mechanical safety 
Each device should: 
a.	  Not have any exposed sharp edges. 
b.	  Be mechanically stable in the intended position(s) of use. 
38    c.  Provide protection to the operator and patient from moving parts. 
7.1.4  Mechanical vibration and shock resistance 
The device (i.e., the complete system suitable for its intended use) should withstand the 
mechanical shocks and vibrations expected in the environments of intended use as 
defined by the test methods contained herein, and should remain operational within its 
specification. 
7.1.5  Fluid spill resistance 
The device should be so constructed that it continues to operate within its specification 
after fluids have been dripped on the device. Therefore, the device should meet the 
requirements for drip-proof equipment as specified in Clause 44.6 of IEC 601-1 and IEC 
529. 
7.1.6  High and low temperature and humidity 
a.  The device should operate within its specification when operating in the 
environmental temperature range of 5C to 40C, and in the environmental 
humidity range of 15 percent to 95 percent, noncondensing. 
b.  The device should not be damaged and should remain operational within its 
specification after storage in the environmental temperature range of -20?C to 
60C and at relative humidity up to 95 percent, non-condensing. 
7.1.7  Surface temperature 
Temperature of surfaces of a device an operator can contact during operation should not 
exceed 50 degrees C in an ambient of 35 degrees C. The temperature of surfaces that 
may come in contact with the patient should not exceed 41 degrees C in an ambient of 35 
degrees C. Any surface temperature that may come in contact with the patient exceeding 
41 degrees C, should be justified with a scientifically valid explanation and data should be 
provided which demonstrates that the safety of the patient is not compromised. 
39  7.1.8  Toxic materials 
No toxic material from a device should come in contact with patient or operator during 
normal use. 
7.1.9  Strangulation 
Provision should be made in routing, retention devices, or other means to minimize the risk 
of strangulation of the patient by wires or tubing. This may also be accomplished by 
providing instructions for routing of patient wires and tubing in the device labeling. 
7.1.10  Determination of Endurance 
Compliance with device specifications should be determined with one or more samples of 
production system or components of the system (Nitric Oxide analyzer or Nitrogen Oxide 
analyzer). Each system or component should be tested for endurance as described in 
7.2.11. The system should run for 2000 h. 
7.1.11  Material Compatibility 
Parts should be made of materials that are compatible with the gases and agents with 
which those components are designed to come into contact, and minimize health risks due 
to substances leached from the device in use. 
7.1.12  Medical Gas Cylinder Connections 
Connectors of calibration gas cylinders not already specified in relevant national standards 
such as CGA C-9-1982 should be designed differently from the connectors specified for 
other medical gases. 
7.2  Test Methods 
7.2.1  Controls protection 
Test by inspection. 
7.2.2  Connector protective incompatibility 
Test by inspection and by attempting the prohibited connections. 
40  7.2.3  Mechanical safety 
Test by inspection. 
7.2.4  Mechanical vibration and shock resistance 
Test the device (i.e., the complete system suitable for its intended use) to the following 
severity levels as specified in the following IEC 68-2 Basic Environmental Testing 
Procedures. Following each of these tests, the device should be visually inspected. Any 
evidence of damage or inability to perform within specification should constitute failure of 
the test. 
a.	  IEC 68-2-27: SHOCK 

Peak acceleration: 100 g (980 m/s2)
 
Duration: 6 msec 

Pulse shape: half sine 

b.	  IEC 68-2-6 SINUSOIDAL VIBRATION 

Frequency range: 10 to 500 Hz 

  Acceleration amplitude: 1 g (9.8 m/s2) 

Type and duration of endurance: 10 sweep cycles in each axis. 

c. 	 IEC 68-2-34  RANDOM VIBRATION, WIDE BAND 

Frequency range: 20 Hz - 500 Hz 

Acceleration spectral density: 0.02 g2/Hz 

Degree of reproducibility: low 

Duration of conditioning: 9 minutes 

7.2.5  Fluid spill resistance 
Test the device as specified in Clause 44.6 of IEC 601-1 for drip-proof and equipment. 
Following each of these tests, the device should be visually inspected. Any evidence of 
damage or inability to perform within specification should constitute failure of the test. 
7.2.6  High and low temperature and humidity 
Test the device as specified in Method Numbers 501.3, 502.3, and 507.3 of MIL-STD
810E according to the requirements of section (i)(6) of this document. Failure of the 
device to perform within its specification should constitute failure of these tests. 
41  7.2.7  Surface temperature 
Operate the device in an ambient temperature of 35C. Measure the temperature of the 
device surfaces which are not intended to contact the patient. The presence of any 
temperature greater than 50C should constitute failure of this test. Measure the 
temperature of device surfaces which are likely to contact the patient in normal use. Any 
temperature above 41C should constitute failure of this test. 
7.2.8  Toxic materials 
Determine by inspection that listed and any other known toxic materials used in the device 
are packaged in a manner that prevents patient and operator contact. 
7.2.9  Strangulation 
Test by inspection. 
7.2.10  Determination of Endurance 
Simulated testing should be performed using a ventilator, test lung, humidifier, delivery 
apparatus and analyzers. The inspriatory/expiratory phase time ratio should be as close to 
1:2 as possible, and run the test system for 2000 hours with appropriate patient population 
settings. The delivery apparatus should titrate at least 20 ppm of Nitric Oxide throughout 
the duration of the testing. 
7.2.11  Material Compatibility 
Parts which come in contact with the gases and agents should be revalidated to ensure 
that the specifications are met after the endurance testing. Simulated testing should 
address issues such as corrosion and chemical interaction which could affect mechanical 
or electrical properties. 
42  SECTION 8.  Hardware Documentation 
This information should include a description of the hardware requirements, device 
performance requirements, the potential system hazards, and the hardware and/or 
software functions implemented as a result of such potential hazards. Documentation of 
the hardware development process including quality assurance activities, configuration 
management plan, and verification activities and summaries, in accordance with the 
appropriate level of concern, should also be provided. The hardware information should 
include the most recent verification and validation test plans/protocols, identification of 
which activities were performed prior to and after hardware/software integration, 
verification and validation results, and analyses showing that specifications were met at 
each appropriate level of hardware. Written affirmation stating that the described 
hardware was developed and tested according to the stated procedures/methods and test 
showed requirements were met should be provided. The hardware information should also 
identify of the version level featured in the final design of the device. 
43  SECTION 9.  Software Documentation 
If the device is software-driven, the premarket notification should include software 
information in accordance with the  Guidance for the content of Premarket Submissions for 
Software Contained in Medical Devices. This information should include a description of 
the software requirements, device performance requirements, the potential system 
hazards, and the software and/or hardware functions implemented as a result of such 
potential hazards. Documentation of the software development process including quality 
assurance activities, configuration management plan, and verification activities and 
summaries, in accordance with the appropriate level of concern, as discussed in the 
current guidance for software, should also be provided. The level of concern should be 
identified with the hazard analysis. The software information should include the most 
recent verification and validation test plans/protocols, identification of which activities were 
performed prior to and after software/hardware integration, verification and validation 
results, and analyses showing that specifications were met at each appropriate level of 
software. Written affirmation stating that the described software was developed and tested 
according to the stated procedures/methods and test showed requirements were met 
should be provided. The software information should also identify of the software version 
level featured in the final design of the device. 
44  SECTION 10.  Labeling 
The premarket notification should include all labeling (i.e., device labels, instructions for 
use, promotional material) for the device under review. Recommendations for labeling 
content are included in the Device Labeling Guidance (ODE Blue Book #G91-1) and 
specific labeling discussed in this guidance. 
The nitric oxide administration apparatus, nitric oxide gas analyzer, and nitrogen dioxide 
gas analyzer are restricted to use only upon the written or oral authorization of a 
practitioner licensed by law to use the device and that the device be restricted to use by 
persons with experience or training in its use. In accordance with 21 CFR 801.109(b)(1), 
the labeling for prescription devices is required to bear the required caution prescription 
statement. This statement should read, "Caution: Federal law restricts this device to sale 
by or on the order of a physician or other licensed medical practitioner. 
The nitric oxide administration apparatus, nitric oxide gas analyzer, and nitrogen dioxide 
gas analyzer labeling should include a warning that Persons using this device should be 
trained and experienced in the use of this device, to assure effective administration of nitric 
oxide, and to avoid injury to the patient or to others resulting from inhalation of excess nitric 
oxide, nitrogen dioxide or other reaction products. 
10.1 Identification of Medical Gas Cylinders and Connections 
Colors of calibration gas cylinders not already specified in relevant national standards such 
as CGA C-9-1982 should be color-coded differently from the colors specified for medical 
gases. 
10.2 Instructions for Use 
10.2.1  Intended Use 
The instructions for use should include a description of the intended use and a description 
of the principles of operation of the components of the Nitric Oxide System 
10.2.2  Validated Ventilators 
The instructions for use should include a list of ventilators that have been validated for use 
with the nitric oxide administration device, nitric oxide analyzer and nitrogen dioxide 
analyzer. 
45  10.2.3  Installation Instructions 
The instructions for use should include a description of the correct installation of the Nitric 
Oxide System or any of its components. 
46