```

[Federal Register Volume 65, Number 185 (Friday, September 22, 2000)]
[Proposed Rules]
[Pages 57303-57307]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-24335]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 896

[Docket No. 83N-0193]

Medical Devices; Performance Standard for the Infant Apnea 
Monitor; Withdrawal Notice

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule; withdrawal.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is withdrawing the 
proposed rule it issued on February 21, 1995 (60 FR 9762). The document 
set out proposed requirements for a mandatory performance standard for 
the infant apnea monitor. In light of declining births and reduced 
mortality rates for infants at risk for death due to apparent life-
threatening events (ALTE's), including certain apneas, and after 
considering other factors, FDA no longer believes that a mandatory 
performance standard is needed for this class II device. The agency 
believes that FDA guidance to industry that identifies minimum 
performance, testing, and labeling recommendations will provide 
reasonable assurance of the safety and effectiveness of the apnea 
monitor, including infant/child monitors. FDA is making this draft 
guidance available for comment through a notice published elsewhere in 
this issue of the Federal Register. Also, elsewhere in this issue of 
the Federal Register, FDA is proposing to create a separate 
classification for the apnea monitor, with the FDA guidance document as 
the special control.

FOR FURTHER INFORMATION CONTACT: James J. McCue, Center for Devices and 
Radiological Health (HFZ-84), Food and Drug Administration, 2094 
Gaither Rd., Rockville, MD 20850, 301-594-4766, ext. 101.

SUPPLEMENTARY INFORMATION:

I. Background

    On September 10, 1982 (47 FR 39816), FDA classified devices 
intended to measure or monitor a patient's respiratory rate into class 
II (performance standards) as part of the generic group of devices 
known as breathing (ventilatory) frequency

[[Page 57304]]

monitors (21 CFR 868.2375). Under the classification scheme set forth 
in section 513 of the Federal Food, Drug, and Cosmetic Act (the act) 
(21 U.S.C. 360c), as amended by the Medical Device Amendments of 1976 
(the 1976 amendments) (Public Law 94-295), the agency determined that 
performance standards were necessary to provide reasonable assurance of 
the safety and effectiveness of these devices.
    In subsequent years, FDA initiated a series of actions to provide 
for the development of a mandatory performance standard for the subset 
of breathing frequency monitors, commonly called neonatal apnea 
monitors, that are intended to be used on infants to detect the 
cessation of respiratory air flow. Early actions included the 
initiation of a proceeding under section 514(b) of the act (21 U.S.C. 
360d(b)) (48 FR 31392, July 8, 1983), and the issuance of an invitation 
for interested persons to submit an existing standard as a proposed 
standard or to submit an offer to develop a proposed standard (51 FR 
6886, February 26, 1986).
    Thereafter, FDA issued a grant award to the Emergency Care Research 
Institute (ECRI) to develop a proposed standard for the neonatal apnea 
monitor (53 FR 13296, April 22, 1988). However, the proposed standard 
ECRI developed did not cover certain performance requirements for the 
device. As a consequence, FDA initiated notice and comment rulemaking 
to develop a performance standard for the infant apnea monitor, which 
would include the neonatal apnea monitor. FDA intended that the 
standard would encompass monitors used in hospitals and in patients' 
homes to detect and alarm upon the cessation of respiratory air flow 
(i.e., apnea) in children under 3 years old.
    In the Federal Register of January 4, 1989 (54 FR 187), FDA made 
available for public comment its ``First Draft Proposed Standard for 
the Infant Apnea Monitor, October 1988.'' In the Federal Register of 
December 6, 1989 (54 FR 50437), FDA announced the public availability 
of its ``Second Draft Proposed Standard for the Infant Apnea Monitor 
October, 1989.'' After considering comments received on these drafts, 
and comments made at public meetings, including the Seventh and Eighth 
Conference(s) on Apnea of Infancy, FDA issued a proposed rule setting 
forth requirements for a mandatory performance standard for the infant 
apnea monitor (60 FR 9762, February 21, 1995).

II. Summary of Requirements in the Proposed Standard

    The mandatory performance standard proposed by FDA on February 21, 
1995, specified requirements for infant apnea monitors in four areas: 
Patient monitoring, electrical characteristics, mechanical and 
environmental characteristics, and labeling. Certain provisions 
required conformance, to the extent specified, with identified 
international standards.
    Proposed patient monitoring provisions included: Requirements for 
primary and secondary monitoring modalities, visual and audible alarms 
(status indicators), a remote alarm unit for monitors intended for home 
use, and a self-test mechanism. Proposed electrical requirements 
included: Provisions for battery backup, operation from ungrounded 
power sources, limitation of leakage current, and operational 
specifications and test procedures ensuring electromagnetic 
compatibility. Proposed mechanical and environmental requirements 
mandated: Tamper proof controls, protection against misconnections, and 
resistance to normal shock, vibration, temperature extremes, and fluid 
spills. Proposed labeling provisions specified: Information that 
manufacturers would be required to provide to operators and health care 
practitioners, including specific product labels.

III. Summary of Comments Received on the Proposed Standard

    FDA received more than 100 comments from manufacturers, hospitals, 
physicians, medical societies, and national trade associations. A 
number of comments objected to the 1-year effective date of the 
standard. One comment claimed that the cost of compliance would exceed 
$100 million. Another maintained that the need for the standard was 
based on outdated data and that FDA had not established that the 
standard was necessary to provide reasonable assurance of the device's 
safety and effectiveness.
    Most comments addressed terms, definitions, specifications, and/or 
technical requirements proposed in the standard. Many commented on the 
terms ``breath,'' ``breathing,'' ``cessation of breathing,'' and 
``breathing effort;'' others on the definitions of infant apnea 
monitor, operator, primary monitoring modality, and secondary 
monitoring modality. Comments concerning primary and secondary 
monitoring modalities focused on proposed requirements for apnea 
duration settings, activation times for warning indicators, and sensor 
fault alarms.
    Some comments questioned the adequacy of requirements for visual 
and audible warning indicators. Others objected to requirements for 
resetting silenced alarms, low battery warning indicators, and minimum 
battery capacity. Comments on proposed electromagnetic compatibility 
requirements included objections to three levels of radiated 
electromagnetic testing and three voltage levels of fast transient 
burst testing. Comments also suggested that alarming or degradation of 
the monitor during immunity testing should be considered an acceptable 
response and testing endpoint.
    Some comments wanted temperature ranges raised for monitor 
operations and surfaces contacting patients. Comments about labeling 
objected generally that some of the proposed requirements were 
duplicative, or unnecessary, or were not a manufacturer responsibility.

IV. Withdrawal of the Proposed Standard

    FDA is withdrawing the proposed rule issued on February 21, 1995 
(60 FR 9762), and terminating the proceeding for the development of a 
mandatory performance standard for the infant apnea monitor, in 
accordance with section 514(b)(3)(A) of the act. FDA no longer believes 
that the special control of a mandatory standard is necessary, at this 
time, to provide reasonable assurance of the safety and effectiveness 
of this device (i.e., an apnea monitor used on an infant/child under 3 
years old). The agency considered the following factors in reaching 
this conclusion: (1) Reductions in at-risk infant populations, (2) few 
deaths and serious injuries reported to FDA for infant/child apnea 
monitors attributed to monitor design problems or malfunctions, (3) 
improved technology, (4) alternative development of consensus 
standards, and (5) compliance costs versus risks and benefits.

A. Declining Death Rates Within At-Risk Infant Populations

    Current U.S. medical opinion continues to support the consensus 
statement and report issued on the subject of infantile apnea and home 
monitoring, in accordance with the National Institutes of Health (NIH) 
Consensus Development Conference, held on September 29 to October 1, 
1986. There was consensus agreement, at that conference, with respect 
to the relationship of neonatal and infant apnea to each other and to 
infant morbidity, especially from sudden infant death syndrome (SIDS). 
The conferees agreed that apnea of

[[Page 57305]]

prematurity is not a risk factor for SIDS. The conferees also agreed 
that an ALTE would encompass any episode experienced by infants 
characterized by some combination of apnea (central or occasionally 
obstructive), color change, marked change in muscle tone, choking, or 
gagging. The conferees agreed that such an episode is considered a risk 
factor for sudden death (including SIDS).\1\ Thus, while the conferees 
generally agreed that there was no evidence of a direct relationship 
between apnea experienced by infants and SIDS deaths, certain 
pathophysiological consequences of apnea were not excluded as possible 
contributors to sudden infant death.
---------------------------------------------------------------------------

    \1\ ``Infantile Apnea and Home Monitoring,'' NIH Consensus 
Statement Online 1986, September 29 to October 1; 6(6): 1-10, pp. 1-
3.
---------------------------------------------------------------------------

    Regarding home monitoring, the consensus conference concluded that 
there were no reports of scientifically designed studies of the 
effectiveness of electronic home monitoring of premature infants for 
ALTE's, or for other pathologic conditions. However, there was 
agreement that cardiorespiratory monitoring was effective in preventing 
death due to apnea for certain infants, such as those with a history of 
recurrent or severe apnea. It was also agreed that cardiorespiratory 
monitoring, or an alternative therapy, was medically indicated for 
certain groups of infants at high risk for sudden death, such as 
infants with one or more ALTE's, symptomatic preterm infants, siblings 
of multiple SIDS victims, and others.\2\
---------------------------------------------------------------------------

    \2\ ID. at pp. 6-7.
---------------------------------------------------------------------------

    FDA also notes the dramatic drop that has occurred in SIDS deaths 
as increased numbers of healthy infants have been placed on their backs 
to sleep, as a method of reducing the risk of SIDS, under the 1992\3\ 
and 1996 recommendations of the American Academy of Pediatrics and the 
national ``Back to Sleep'' campaign launched in 1994 under the 
coordination of the National Institute of Child Health and Human 
Development. The number of SIDS deaths has declined by over 48 percent 
from 4,891 deaths in 1992\4\ to 2,529 deaths in 1998.\5\
---------------------------------------------------------------------------

    \3\ American Academy of Pediatrics, Task Force on Infant 
Positioning and SIDS, ``Positioning and SIDS,'' Pediatrics 89 (6): 
1120-1126, June 1992.
    \4\ U.S. Department of Health and Human Services, ``Reduction in 
SIDS Deaths Helps Bring Low Infant Mortality,'' Washington, DC, 
Press Release, October 9, 1996.
    \5\ National Center for Health Statistics, ``Births and Deaths: 
Preliminary Data for 1998,'' National Vital Statistics Reports; vol. 
47, No. 25, table 15, p. 32. Hyattsville, MD, National Center for 
Health Statistics, 1999.
---------------------------------------------------------------------------

    FDA is also aware of the general reductions over the past 7 years 
in infant mortality rates. The infant (under 1 year) mortality rate has 
dropped from 8.5 infant deaths per 1,000 live births in 1992\6\ to a 
7.2 rate in 1998.\7\ FDA believes that these reductions in infant 
mortality rates, in conjunction with reduced numbers of SIDS deaths, 
serve to reduce the population, and attendant risks, of infants subject 
to apnea of infancy (i.e., ``pathological'' apnea of 20 seconds or 
longer associated with bradycardia, cyanosis, pallor, and/or marked 
hypotonia), and infants subject to ALTE's, including prone sleeping, 
and other risk factors for SIDS.
---------------------------------------------------------------------------

    \6\ National Center for Health Statistics, ``Deaths: Final Data 
for 1997,'' National Vital Statistics Reports; vol. 47, No. 19, 
table 27, p. 86. Hyattsville, MD, National Center for Health 
Statistics, 1999.
    \7\ See National Center for Health Statistics, note 5, supra.
---------------------------------------------------------------------------

B. Deaths, and Serious Injuries Attributable to Infant/Child Apnea 
Monitors

    Under the Medical Device Reporting (21 CFR part 803) and Medical 
Device Distributor Reporting (21 CFR part 804) regulations, FDA has 
received manufacturer MDR reports, user facility reports, distributor 
MDR reports (until February 1998), and voluntary reports and complaints 
of alleged adverse events associated with the use of apnea detectors, 
breathing frequency monitors, respiratory monitors, and related 
devices. From 1986 through 1991, FDA received approximately 150 reports 
of deaths, and 31 reports of serious injuries allegedly associated with 
these devices.
    In MDR reports received by FDA during the past 8 years, few deaths 
or serious injuries of children have been reported for apnea monitor 
usage that could be attributed to monitor problems as the cause of the 
adverse events. From July 1992 to October 1997, the MDR data base lists 
receipt of reports alleging 20 deaths and 16 serious injuries that 
might be associated with apnea monitors. Sixteen deaths and 5 serious 
injury incidents could be identified as involving infants and children 
under 3 years old. For 1998 and 1999, data base reports identify six of 
six alleged deaths and three of four serious injuries as involving 
patients under 3 years of age. Since 1992, 22 deaths and 8 serious 
injuries have allegedly occurred during the use of infant/child apnea 
monitors.
    In two of those deaths reported since July 1992 were device 
problems considered to have caused or contributed directly to the 
reported event. In a February 1993 incident (User Report No. 
3200010000-1993-0008), the audible alarm of a respiration rate monitor 
reportedly did not sound at the decrease in respiration during the 
seizure of a 3-month-old infant who subsequently could not be 
resuscitated. In an August 1993 incident (User Report No. 1402080000-
1993-0002), the electrical power source of an apnea monitor allegedly 
changed from the battery mode to the alternating current mode, 
resulting in the electrocution of the infant.
    Similarly, in three of the serious injury events reported after 
July 1992 were monitor problems thought to be causal factors. In 1992 
(User Report No. 3300270000-1992-002) and 1998 (Voluntary Report No. 
MW1014260) incidents, electrode connections reportedly caused red skin 
irritations, with skin breakdowns or burns. Multiple false bradycardia 
alarming resulted in unnecessary hospitalization of an infant in one 
October 1997 incident (Voluntary Report No. MW1012327).
    FDA considers the continuing low number of reported deaths and 
serious injuries in which a monitor problem is the possible cause of 
the adverse event to be a factor that lessens the need for a mandatory 
performance standard for the infant/child apnea monitor at this time. 
Moreover, as discussed below, the agency believes that newer 
technologies will reduce these small numbers even further.

C. Improved Technology

    Monitors to detect apnea in infants have been used in hospitals and 
patients' homes since the early 1970's. Methods to detect respiration 
have included mattress motion sensors, capnometry, impedance 
pneumography, inductive plethysmography, and others. Impedance 
pneumography, utilizing electrodes, leads, and patient cables, remains 
the most prevalent method, but other methods have been developed, 
including those that utilize nonelectrical or pneumatic sensors and 
telemetric respiratory detection.
    Various detection modalities and features have been added to 
improve apnea monitor designs, including: Heart rate; oxygen saturation 
and airway carbon dioxide monitoring; noise suppression; automatic 
sensitivity adjustments; signal processing algorithms; and the capacity 
to record, display, print, and retain in memory, both patient and 
equipment data. The use of heart rate monitoring modalities in 
impedance pneumography units and the inclusion of recording and memory 
capabilities have improved the general performance of home-use infant/
child apnea monitors. For example, the introduction in the late 1980's 
of home-use monitors with internal memory has aided in determining 
monitor activity

[[Page 57306]]

during adverse events. These newer technologies are in most hospital 
units, in configurable modules that include programmable apnea 
detection modalities. Approximately 90 percent of hospital monitoring 
systems in current use already comply with the February 21, 1995, 
proposed standard for infant/child apnea monitors (now withdrawn).
    Moreover, apnea monitors for home use that were introduced into 
commercial distribution after November 1993 were cleared for marketing 
under evaluation criteria described in a guidance document\8\ used by 
reviewers in the Center for Devices and Radiological Health's (CDRH's) 
Office of Device Evaluation (ODE). This ``Reviewer Guidance'' was made 
available to industry through the Center's Division of Small 
Manufacturers' Assistance and is still used by ODE reviewers in 
evaluating 510(k) submissions for home-use respiratory devices. Many 
performance, labeling, and testing recommendations included in the 
guidance document correspond to requirements in the proposed standard. 
Thus, CDRH believes that most home-use apnea monitors that received 
510(k) clearance after November 1993 already meet most of the 
provisions of the proposed standard. Some apnea monitors distributed 
before this time, however, may not conform to certain requirements of 
the proposed standard.
---------------------------------------------------------------------------

    \8\ ``Reviewer Guidance For Premarket Notification Submissions 
November 1993, Anesthesiology and Respiratory Devices Branch, 
Division of Cardiovascular, Respiratory, and Neurological Devices.''
---------------------------------------------------------------------------

D. Alternative Development of Consensus Standards

    In 1995 (60 FR 9762), FDA proposed to make compliance with certain 
requirements of the infant apnea monitor standard contingent upon 
meeting specified provisions of 13 standards developed by other 
organizations. Since then, global efforts to harmonize standards and 
domestic efforts to develop consensus standards have increased. FDA's 
historical support of these efforts has also been strengthened by the 
FDA Modernization Act of 1997, which added new section 514(c) to the 
act, allowing FDA to recognize consensus standards that may be used to 
satisfy device review requirements identified by the agency. In the 
Federal Register of February 25, 1998 (63 FR 9561), FDA provided public 
notice of its policy on this use of standards and published its first 
list of FDA-recognized consensus standards related to medical devices.
    FDA believes global harmonization and domestic standardization are 
producing widely accepted consensus standards embodying the latest 
scientific developments. In a draft guidance to industry, providing 
recommended criteria for infant/child apnea monitors, FDA will identify 
the latest versions of 17 international and domestic consensus 
standards that have some applicability to performance and testing 
criteria, particularly electromagnetic compatibility test methods, 
which the agency considers appropriate for these devices. The agency 
believes these consensus standards are applicable as well to apnea 
monitors used on patients of any age. After considering comments on the 
draft guidance and further evaluating clinical study criteria, FDA will 
modify the draft document and issue final guidance setting out minimum 
performance, testing, labeling, and clinical criteria that it considers 
necessary to assure the safety and effectiveness of any apnea monitor 
type of device.
    Manufacturers will have the flexibility to follow the consensus 
standards, and other recommendations, set out in the agency's apnea 
monitor guidance or to use alternative approaches of equal or better 
merit (e.g., in the use of test procedures). As standards referenced in 
the agency's guidance become FDA-recognized consensus standards, 
industry will be able to obtain expedited marketing clearance by 
certifying conformance to them. FDA believes this process will provide 
reasonable assurance of the safety and effectiveness of the apnea 
monitor type of device used on patient populations of any age, 
including the infant/child apnea monitor.

E. Compliance Costs versus Risks and Benefits

    Following its review of comments on the proposed standard, FDA 
assessed the cost and analyzed the economic impact of various modified 
versions of the proposed standard. FDA concluded that, if the standard 
were issued as a final regulation with a 1-year effective date, the 
one-time cost of complying with the modified standard would be 
approximately $146.8 million. Annual compliance costs would be about 
$2.7 million. Extending the effective date to 3 years would reduce the 
one-time compliance cost to an estimated $89.7 million, while annual 
costs would remain at $2.7 million.
    The largest portion of estimated one-time costs were costs that 
would be associated with the market removal and correction of infant 
apnea monitors that did not meet the requirements of the standard. CDRH 
made the assessment that certain home-use infant apnea monitors 
marketed before November 1993 would not meet some recommendations set 
forth in the guidance made available on that date. CDRH also believed 
that some of these monitors would not meet certain requirements of the 
February 21, 1995, proposed standard. After a final standard based on 
the proposed one went into effect, noncompliant monitors would have to 
be removed from the market and corrected, for example, to provide 
visual indication of a change in apnea duration from a setting of 20 
seconds, to change the color of some visual indicators, to change the 
volume level for audible alarms, and/or to add shielding and/or 
filtering to provide additional electromagnetic compatibility.
    In light of reductions in at-risk infant populations, few recent 
deaths or serious injuries attributable to malfunctions, improvements 
in post-1993 monitor technology, and standardization developments, FDA 
has concluded that a mandatory performance standard is not necessary to 
provide reasonable assurance of the safety and effectiveness of the 
infant(/child) apnea monitor, and that the benefit to the public health 
would not justify the costs to industry to comply with the standard.

V. Alternative Actions--Classification, Industry Guidance, and 
Education Program

A. Classification

    Elsewhere in this issue of the Federal Register, FDA is proposing 
to create a separate classification for the generic type of device 
known as the apnea monitor. The generic apnea monitor would include the 
infant/child apnea monitor intended for use on infants less than 12 
months old and children less than 3 years old to detect and alarm upon 
apnea and its pathophysiological consequences. The apnea monitor device 
will remain classified in class II, but will be subject to a special 
control. The special control is a FDA guidance to industry. FDA 
believes that this special control will provide reasonable assurance of 
the safety and effectiveness of the apnea monitor device, including the 
infant/child apnea monitor.

B. FDA Guidance to Industry (Special Controls)

    Elsewhere in this issue of the Federal Register, FDA is announcing 
the availability for comment of a draft guidance document for industry

[[Page 57307]]

concerning infant/child apnea monitors. This draft guidance sets forth 
the agency's current position regarding minimum performance 
characteristics, test procedures and criteria, labeling, and, as 
appropriate, clinical testing that will provide reasonable assurance of 
the safety and effectiveness of this kind of apnea monitor device. This 
guidance includes basic concepts that were included in the proposed 
standard for infant apnea monitors, but updates, consolidates, or 
eliminates certain elements of the proposed standard on the basis of 
comments received in response to the proposal and the continuing 
development and FDA recognition of appropriate consensus standards. 
Although the proposed standard did not require clinical testing, the 
guidance document addresses this subject.
    As noted above, FDA believes the performance, testing, labeling, 
and clinical parameters in the draft industry guidance for infant/child 
apnea monitors are applicable as well to apnea monitors used on 
patients in every age group. After considering comments on this 
guidance and further evaluating clinical criteria, FDA will issue final 
industry guidance identifying minimum performance, testing, labeling, 
and clinical criteria as the special control for the entire apnea 
monitor group of devices. Once this special control is established, new 
products seeking to enter the market will be required to conform with 
the special control. The final guidance document will describe a means 
by which an apnea monitor device may comply with the requirements of 
special controls for class II devices.
    Designation of the agency's guidance document as a special control 
means that manufacturers attempting to establish that their device is 
substantially equivalent to a predicate apnea monitor, including one 
used to monitor apnea in children under 3 years of age, should 
demonstrate that the proposed device complies with either the specific 
recommendations of this guidance or some alternative control that 
provides equivalent assurances of safety and effectiveness. FDA 
recognizes that older products already on the market will not be 
required to meet this special control. The agency expects, however, 
that labeling on the newer devices and other market forces will 
encourage manufacturers of these older devices to comply with the 
guidance. FDA also expects the education program, described below, to 
accelerate the improvement of these older products.
    FDA is participating with the Association for the Advancement of 
Medical Instrumentation in a separate effort to develop clinically-
based test methods and clinically-derived bench tests for measuring the 
effectiveness of monitoring modalities in detecting apnea. At the 
conclusion of this effort, the agency may consider these tests to be 
referee test methods.

C. Education Program

    FDA intends to develop an education program targeted to reach 
manufacturers of the infant/child apnea monitor, manufacturers of 
accessories marketed for use with this device, distributors and rental 
companies handling the devices, users, including hospitals and other 
health care services, and other consumers. This particular audience is 
targeted initially because infants and children under 3 years of age 
are particularly subject to the pathophysiological consequences of 
prolonged apneas lasting over 20 seconds in duration.
    The purpose of this program will be to inform the target audience 
of FDA's current position regarding performance characteristics and 
specifications, test methods and results, and labeling information the 
agency believes are appropriate for the infant/child apnea monitor. The 
program also will advise the target audience that some monitors 
previously cleared for marketing prior to November 1993 may not meet 
the agency's current recommendations and, although they may adequately 
detect and alarm upon prolonged episodes of central apnea, they may not 
be adequate for detection of episodes of obstructive apnea or mixed 
apnea.
    As circumstances warrant, FDA may direct additional educational 
efforts at parties involved with apnea monitors used on patient 
populations of other ages.

    Dated: September 12, 2000.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 00-24335 Filed 9-21-00; 8:45 am]
BILLING CODE 4160-01-F
```