[Federal Register Volume 61, Number 237 (Monday, December 9, 1996)]
[Notices]
[Pages 64909-64912]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-31229]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 88N-0244]
Ear, Nose, and Throat Devices; Denial of Request for Change in
Classification of Endolymphatic Shunt Tube With Valve
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is denying the petition
submitted by E. Benson Hood Laboratories, Inc. (Hood Laboratories), to
reclassify the endolymphatic shunt tube with valve from class III into
class II. The agency is denying the petition because Hood Laboratories
failed to provide sufficient new information to establish special
controls that would provide reasonable assurance of the safety and
effectiveness of the device. This notice also summarizes the basis for
the agency's decision. FDA will issue a final rule requiring the filing
of premarket approval applications (PMA's) for the device in a future
issue of the Federal Register. This action is being taken under the
Federal Food, Drug, and Cosmetic Act (the act), as amended by the
Medical Device Amendments of 1976 (the 1976 amendments), and the Safe
Medical Devices Act of 1990 (the SMDA).
EFFECTIVE DATE: March 10, 1997.
FOR FURTHER INFORMATION CONTACT: Harry R. Sauberman, Center for Devices
and Radiological Health (HFZ-470), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-2080.
SUPPLEMENTARY INFORMATION:
I. Classification and Reclassification of Devices under the Medical
Device Amendments of 1976
Under section 513 of the act (21 U.S.C. 360c), as amended by the
1976 amendments (Pub. L. 94-295), FDA must classify devices into one of
three regulatory classes: Class I, class II, or class III. FDA's
classification of a device is determined by the amount of regulation
necessary to provide reasonable assurance of its safety and
effectiveness. Except as provided in section 520(c) of the act (21
U.S.C. 360j(c)), FDA may not use confidential information concerning a
device's safety and effectiveness as a basis for reclassification of
the device from class III into class II or class I.
Under the 1976 amendments, devices were classified in class I
(general controls) if there was information showing that the general
controls of the act were sufficient to assure safety and effectiveness;
into class II (performance standards) if there was insufficient
information showing that general controls would ensure safety and
effectiveness, but there was sufficient information to establish a
performance standard that would provide such assurance; and into class
III (premarket approval) if there was insufficient information to
support placing a device into class I or class II and the device was a
life-sustaining or life-supporting device or was for a use that is of
substantial importance in preventing impairment of human health.
FDA has classified into one of these three regulatory classes most
generic types of devices that were on the market before the date of the
1976 amendments (May 28, 1976) (generally referred to as preamendments
devices) under the procedures set forth in section 513(c) and (d) of
the act. Under section 513(c) and (d) of the act, FDA secures expert
panel recommendations on the appropriate device classifications for
generic types of devices. FDA then considers the panel's
recommendations and, through notice and comment
[[Page 64910]]
rulemaking, promulgates classification regulations.
Devices introduced into interstate commerce for the first time
after May 28, 1976, are classified through the premarket notification
process under section 510(k) of the act (21 U.S.C. 360(k)). Those
devices that FDA finds to be substantially equivalent to a classified
preamendments generic type of device are thereby classified in the same
class as the predicate preamendments device.
Reclassification of classified preamendments devices is governed by
section 513(e) of the act. This section provides that FDA may, by
rulemaking, reclassify a device (in a proceeding that parallels the
initial classification proceeding) based on ``new information.'' The
reclassification can be initiated by FDA or by the petition of an
interested person, and must be based on ``valid scientific evidence,''
as defined in section 513(a)(3) of the act and in 21 CFR 860.7(c)(2).
FDA relies upon ``valid scientific evidence'' in the classification
process to determine the level of regulation for devices. For the
purpose of reclassification, the valid scientific evidence upon which
the agency relies must be publicly available in accordance with section
520(c) of the act. Publicly available information excludes trade secret
and/or confidential commercial information, e.g., the confidential
contents of PMA's.
II. Reclassification under the Safe Medical Devices Act of 1990
The SMDA (Pub. L. 101-629) further amended the act to change the
definition of a class II device. Under the SMDA, class II devices are
those devices for which there is insufficient information to show that
general controls themselves will assure safety and effectiveness, but
there is sufficient information to establish special controls to
provide such assurance, including the promulgation of a performance
standard or other special controls, such as postmarket surveillance,
patient registries, guidelines, and other appropriate actions necessary
to provide reasonable assurance of the safety and effectiveness of the
device. Thus, the definition of a class II device was changed from
``performance standards'' to ``special controls.'' In order for a
device that is intended to be implanted in the human body (such as an
endolymphatic shunt with valve) to be reclassified from class III into
class II, the agency must determine that premarket approval is not
necessary to provide reasonable assurance of its safety and
effectiveness.
III. Background
In the Federal Register of November 6, 1986 (51 FR 40378), FDA
issued a final rule classifying the endolymphatic shunt tube with valve
into class III (21 CFR 874.3850). The preamble to the proposal to
classify the device included the recommendation of the Ear, Nose, and
Throat Devices Panel (the Panel). The Panel's recommendation, among
other things, identified certain risks to health (inoperative and
clogged valves) presented by the device. In the Federal Register of
January 6, 1989 (54 FR 550), FDA published a notice of intent to
initiate proceedings to require premarket approval for 31 preamendments
class III devices assigned a high priority for the application of
premarket approval requirements, including the endolymphatic shunt tube
with valve.
In the Federal Register of May 4, 1990 (55 FR 18830), FDA issued a
proposed rule under section 515(b) of the act (21 U.S.C.
360e(b)(2)(A)), to require the filing of a PMA or a notice of
completion of a product development protocol (PDP) for the
endolymphatic shunt tube with valve. The preamble to the proposal
included, among other things, the proposed findings with respect to the
degree of risk of illness or injury designed to be eliminated or
reduced by requiring the device to meet the statute's premarket
approval requirements and the expected benefit to the public health
from the use of the device. The proposal also provided an opportunity
for interested persons to request the agency to change the
classification of the device based on new information. On July 27,
1990, FDA received a petition (Ref. 1) from the petitioner requesting
that the classification of the endolymphatic shunt tube with valve be
changed from class III to class II.
IV. Device Description
The endolymphatic shunt tube with valve is a device that consists
of a pressure-limiting valve associated with a tube intended to be
implanted in the inner ear to relieve the symptoms of vertigo and
hearing loss due to endolymphatic hydrops of Meniere's disease. The
device directs excess endolymph from the distended end of the
endolymphatic system into the mastoid cavity where resorption occurs.
The function of the pressure-limiting inner ear valve is to maintain
the physiologically normal endolymphatic pressure and to assure a
unidirectional flow of endolymph.
Hood Laboratories' endolymphatic shunt tube with valve is the only
device of its type in commercial distribution legally in the United
States. It consists of a SupramidTM catheter tube connected to a
silicone tube that is inside a silicone molded body. The inside
silicone tube has a slit valve at one end that allows the endolymph to
exit. The SupramidTM tube is inserted into the end of the
endolymphatic sac so that the endolymph will flow through the valve and
into the mastoid cavity via the tail-like portion of the molded
silicone body.
V. Recommendation of the Panel
In a public meeting held on June 11, 1992, the Panel met to discuss
the reclassification petition submitted by Hood Laboratories. The Panel
noted the similarities between the valved and nonvalved shunts. Both
the valved shunt device (class III) and the nonvalved shunt device
(class II) drain excess endolymph from the distended end of the
endolymphatic system into the mastoid cavity where resorption occurs.
Both devices are intended to relieve the symptoms of Meniere's disease.
The nonvalved shunt (class II device) permits the unrestricted flow of
excess endolymph, while the valved shunt (class III device) is intended
to control the flow of endolymph so that a normal endolymphatic
pressure is maintained.
The Panel acknowledged the difficulty in diagnosing, treating, and
assessing the treatment plans for Meniere's disease and could not agree
that the valved shunt is effective, but believed the device ``does
something worthwhile'' in treating the symptoms. They also noted the
lack of objective scientific data establishing that the device operates
as a one-way valve to regulate the endolymphatic pressure. While
acknowledging that the petitioner had not presented sufficient
information to establish special controls to provide reasonable
assurance of safety and effectiveness of the devices, three of the five
voting members recommended reclassifying the generic endolymphatic
shunt with valve from class III into class II.
VI. Agency Decision
Based on its review of the information contained in the petition
and presented at the panel meeting, as well as the Panel's discussion,
the agency respectfully disagrees with the Panel's recommendation. FDA
finds that the petition contains insufficient valid scientific evidence
to determine that special controls, in addition to the general controls
applicable to all devices, would provide reasonable assurance of the
device's safety and
[[Page 64911]]
effectiveness for its intended use. FDA, therefore, is denying the
petition.
VII. Reasons for the Denial
FDA has determined that Hood Laboratories has not presented
sufficient new scientific information to support the requested change
in classification of this device. FDA has further determined that Hood
Laboratories did not adequately address the issues of normal
endolymphatic sac pressure, the mode of action of the endolymphatic
shunt tube with valve, flow characteristics, nor the risks associated
with the use of the device. The endolymphatic shunt tube with valve is
intended to relieve the symptoms of Meniere's disease by employing a
unidirectional valve, which reportedly opens at 10 millimeters of
mercury (mm Hg) pressure to maintain the normal physiological pressure
of the endolymphatic system. The lack of information addressing the
issues of normal physiological pressure within the endolymphatic
system, as noted in the preamble to the final rule classifying the
device (51 FR 40378 at 40385), remains a concern. FDA believes that
objective scientific data, including clinical studies, are necessary to
establish that the device is effective for its intended purpose. FDA
also believes that clinical and nonclinical data are necessary to
define the full range of physiological pressures present within the
endolymphatic system and to define the flow characteristics
attributable to the device and to the valve component. These issues
remain unresolved. The agency further believes that an alternative
treatment exists for the relief of Meniere's disease.
Current literature suggests that the natural flow of endolymph is
very slow and that the pressure increases associated with endolymphatic
hydrops may not be large in magnitude. Because current technology does
not exist to allow the measurement of endolymph flow rates or
endolymphatic pressure in humans, the animal studies discussed below
provide the only information available to determine if the valve
functions to maintain normal endolymphatic pressure. In the first
study, Long and Morizono employed a micropressure system to measure the
hydrostatic pressure of endolymph and perilymph in a guinea pig model
of endolymphatic hydrops (Ref. 2). The authors reported the magnitude
of the pressure difference between perilymph and endolymph that could
be attributed to endolymphatic hydrops to be less than 0.5 mm Hg
(within 95 percent confidence limits). In another study, Salt and
Thalmann reported the average flow rate (velocity) of endolymph in the
basal turn of the guinea pig cochlea to be 0.005 mm per minute using
ionic tracers measured by ion-selective electrodes (Ref. 3).
Alec N. Salt, an invited guest speaker at the June 11, 1992, Panel
meeting, concluded that the reported low flow rate of endolymph
demonstrated that endolymph flow is not a significant homeostatic
mechanism in the inner ear. He noted that, based on measurements of
calcium ion levels within the cochlea of guinea pigs, the induction of
endolymphatic hydrops elevated endolymph calcium ion concentration by
an amount likely to impair hair cell function. Alec N. Salt concluded
that these data suggest that an elevated calcium ion level may have a
major role in the development of hearing impairment associated with
endolymphatic hydrops in guinea pigs (Ref. 4). In a study of the long-
term effects of destruction of the endolymphatic sac in a primate
species (monkeys), none of the animals developed severe endolymphatic
hydrops or the cochleo-vestibular symptoms that occur in human subjects
with Meniere's disease (Ref. 5).
The animal studies cited above do not support an increase in
endolymphatic pressure as the sole mechanism inducing the clinical
findings observed in humans. The claim of maintenance of normal
endolymphatic pressure by means of the endolymphatic shunt tube with
valve has not been established despite numerous nonclinical and
clinical studies involving the use of this device over the last 15
years. FDA believes that the mode of operation of the valved shunt is
not supported by valid scientific evidence and remains to be
established.
FDA notes that the benefits resulting from implantation of the
endolymphatic shunt tube with valve, i.e., relief of vertigo,
fluctuating hearing loss, tinnitus, and aural fullness, which typify
Meniere's disease, appear to be very similar to those resulting from
implantation of nonvalved shunts (Refs. 6, 7, and 8). Huang and Lin
reported that risks such as the incidence of infections, iatrogenic
deaf ears, and clogging have a similar occurrence in valved and
nonvalved endolymphatic shunts (Ref. 6). However, the risk concerns
raised in the proposed rule about any build up of fluid pressure in the
inner ear because of a clogged or inoperative valved device or about
the risk of infection from revision surgery were not addressed by Hood
Laboratories and remain unanswered (55 FR 18830).
During the June 11 panel meeting, the Panel questioned whether the
valve component of the shunt tube actually functions as a pressure-
regulating valve. Questions regarding the true range of physiological
pressures that one may expect to find within the endolymphatic sac, as
well as the flow characteristics that one would find attributable to an
effective functioning of the valve remain unanswered. In its
deliberations, the Panel determined that Hood Laboratories had not
presented sufficient valid scientific evidence as to whether the valve
actually functions as a valve in vivo.
Another invited guest speaker, Douglas E. Mattox, reviewed the
histology and ultrastructure of four failed, explanted valved shunts.
Using scanning electron microscopy, multiple erosions along the length
of the SupramidTM tube and liner and irregular erosion of the tip
(Ref. 9) were shown. This finding calls into question the long-term
functioning and integrity of the endolymphatic shunt tube with valve as
currently marketed by Hood Laboratories.
Despite the potential benefits of the device in improving hearing,
relief of vertigo, reduction of the fullness in the ear, and mitigation
of tinnitus, FDA believes that little new information is available
about the physiological functions and mode of operation of the device
and therefore, the device presents serious potential risks. FDA
believes that the petition lacks sufficient valid scientific evidence
to determine that special controls would provide reasonable assurance
of the safety and effectiveness of the endolymphatic shunt tube with
valve for its intended use. Therefore, the endolymphatic shunt tube
with valve shall be retained in class III (premarket approval). In a
future issue of the Federal Register, FDA will promulgate a final rule
under section 515(b) of the act to require the filing of a PMA by each
manufacturer of this device.
VII. References
The following information has been placed on display in the Dockets
Management Branch (HFA-305), Food and Drug Administration, 12420
Parklawn Dr., rm. 1-23, Rockville, MD 20857, and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. E. Benson Hood Laboratories, Inc., Reclassification Petition,
Docket No. 88N-0244.
2. Long, C. H., and T. Morizono, ``Hydrostatic Pressure
Measurement of Endolymph and Perilymph in a Guinea Pig Model of
Endolymphatic Hydrops,'' Otolaryngology Head and Neck Surgery,
96:83-95, 1987.
[[Page 64912]]
3. Salt, A. N., and R. Thalmann (Review Chapter), ``Cochlear
Fluid Dynamics,'' Physiology of the Ear, edited by A. F. Jahn, and
J. R. Santos-Sacchi, Raven Press, New York, pp. 341-357, 1988.
4. Salt, A. N., and J. E. DeMott, ``Endolymph Calcium Increases
with Time in Hydropic Guinea-Pigs,'' Abstracts of the Fifteen
Midwinter Research Meeting, Association for Research in
Otolaryngology, p. 128, 1992.
5. Swart, J. G., and H. F. Schuknect, ``Long-Term Effects of
Destruction of the Endolymphatic Sac in a Primate Species,''
Laryngoscope, 98:1183-1189, 1988.
6. Huang, T. S., and C. C. Lin, ``Endolymphatic Sac Surgery for
Meniere's Disease: A Composite Study of 339 Cases,'' Laryngoscope,
95:1082-1086, 1985.
7. Huang, T. S., ``Valve Implants Compared to Other Surgical
Methods,'' American Journal of Otology, 8:301-305, 1987.
8. Wright, J. W., and G. W. Hicks, ``Valved Implants in
Endolymphatic Surgery,'' American Journal of Otology, 8:307-312,
1987.
9. Cohen, E. J., and D. E. Mattox, ``Histology and
Ultrastructure of Explanted Arenberg Shunts,'' Presented at the
Annual Meeting of the American Otologic Society, Palm Desert, CA,
April 12-13, 1992.
Dated: November 27, 1996.
D. B. Burlington,
Director, Center for Devices and Radiological Health.
[FR Doc. 96-31229 Filed 12-6-96; 8:45 am]
BILLING CODE 4160-01-F
