[Federal Register: September 6, 2000 (Volume 65, Number 173)]
[Notices]
[Page 54053-54056]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06se00-78]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 00P-0788]
Neurological Devices; Reclassification of the Totally Implanted
Spinal Cord Stimulator
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of panel recommendation.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing for
public comment the recommendation of the Neurological Devices Panel
(the Panel) to reclassify the totally implanted spinal cord stimulator
(SCS) for treatment of chronic intractable pain of the trunk or limbs
from class III into class II. The Panel made this recommendation after
reviewing the reclassification petition submitted by Advanced
Neuromodulation Systems, Inc. (ANS), and other publicly available
information. FDA is also announcing for public comment its tentative
findings on the Panel's recommendation. After considering any public
comments on the Panel's recommendation and FDA's tentative findings,
FDA will approve or deny the reclassification petition by order in a
letter to the petitioner. FDA's decision on the reclassification
petition will be announced in the Federal Register. Elsewhere in this
issue of the Federal Register, FDA is announcing the availability of a
draft guidance for industry entitled ``Special Control Guidance for
Premarket Notifications for Totally Implanted Spinal Cord Stimulators
for Pain Relief.''
DATES: Submit written comments by October 6, 2000.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Russell P. Pagano, Center for Devices
and Radiological Health (HFZ-410), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-1296.
SUPPLEMENTARY INFORMATION:
I. Background
The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301
et. seq.), as amended by the Medical Device Amendments of 1976 (the
1976 amendments) (Public Law 94-295), the Safe Medical Devices Act of
1990 (Public Law 101-629), and the Food and Drug Administration
Modernization Act of 1997 (Public Law 105-115), established a
comprehensive system for the regulation of medical devices intended for
human use. Section 513 of the act (21 U.S.C. 360c) established three
categories (classes) of devices, depending on the regulatory controls
needed to provide reasonable assurance of their safety and
effectiveness. The three categories of devices are class I (general
controls), class II (special controls), and class III (premarket
approval).
Under section 513 of the act, devices that were in commercial
distribution before May 28, 1976 (the 1976 amendments enactment date),
generally referred to as preamendments devices, are classified after
FDA has: (1) Received a recommendation from a device classification
panel (an FDA advisory committee); (2) published the Panel's
recommendation for comment, along with a proposed regulation
classifying the device; and (3) published a final regulation
classifying the device. FDA has classified most preamendments devices
under these procedures.
Devices that were not in commercial distribution prior to May 28,
1976, generally referred to as postamendments devices, are classified
automatically by statute (section 513(f) of the act) into class III
without any FDA rulemaking process. A postamendment device remains in
class III and requires premarket approval, unless and until the device
is reclassified into class I or II or FDA issues an order finding the
device substantially equivalent, under section 513(i) of the act, to a
predicate device that does not require premarket approval. The agency
determines whether new devices are substantially equivalent to
previously offered devices by means of premarket notification
procedures in section 510(k) of the act (21 U.S.C. 360(k)) and 21 CFR
part 807 of the regulations.
A preamendments device that has been classified into class III may
be marketed, by means of premarket notification procedures, without
submission of a premarket approval application (PMA) until FDA issues a
final regulation under section 515(b) of the act (21 U.S.C. 360e(b))
requiring premarket approval.
Reclassification of classified postamendments devices is governed
by section 513(f)(2) of the act. This section allows FDA to initiate
reclassification of a postamendments class III device under section
513(f)(1) of the act, or the manufacturer or importer of a device may
petition the Secretary of Health and Human Services (the Secretary) for
the issuance of an order classifying the device in class I or class II.
FDA's regulations in Sec. 860.134 (21 CFR 860.134) set forth the
procedures for the filing and review of a petition for reclassification
of such class III devices. To change the classification of the device,
it is necessary that the proposed new class have sufficient regulatory
controls to provide reasonable assurance of the safety and
effectiveness of the device for its intended use.
Under section 513(f)(2)(B)(i) of the act, the Secretary may, for
good cause shown, refer a petition to a device classification panel.
The Panel shall make a recommendation to the Secretary respecting
approval or denial of the petition. Any such recommendation shall
contain: (1) A summary of the reasons for the recommendation, (2) a
summary of the data upon which the recommendation is based, and (3) an
identification of the risks to health (if any) presented by the device
with respect to which the petition was filed.
II. Regulatory History of the Device
The totally implanted SCS intended for treatment of chronic
intractable pain of the trunk or limbs is a postamendments device
classified into class III under section 513(f)(2) of the act.
Therefore, the device cannot be placed in commercial distribution for
treatment of chronic intractable pain of the trunk or limbs unless it
is reclassified under section 513(f)(2) of the act, or subject to an
approved PMA under section 515 of the act.
This action is taken in accordance with section 513(f)(2) of the
act and Sec. 860.134 of the regulations, based on information in the
ANS petition submitted on June 16, 1999. ANS requested reclassification
of totally implanted SCS intended for treatment of chronic intractable
pain of the trunk or limbs from class III into class II. Consistent
with the act and the regulation, FDA referred the petition to the Panel
for its recommendation on the requested reclassification.
III. Device Description
The following device description is based on the Panel's
recommendations and the agency's review: The totally implanted SCS
consists of an implanted
[[Page 54054]]
pulse generator (IPG), leads, and electrodes. The IPG contains the
internal power source that is implanted in the patient. The electrodes
are placed on the patient's spinal cord and the leads from the
electrodes are connected subcutaneously to the IPG.
IV. Recommendation of the Panel
At a public meeting on September 16 and 17, 1999, the Panel
recommended that the totally implanted SCS intended for aid in the
treatment of chronic intractable pain of the trunk or limbs be
reclassified from class III into class II.
V. Risks to Health
After considering the information in the petition, the information
presented at the Panel meeting, the Panel's deliberations, the
published literature, and the Medical Device Reports (MDR's), FDA has
evaluated the risks to health associated with the use of the totally
implanted SCS intended for treatment of chronic intractable pain of the
trunk or limbs. FDA now believes that the following are risks to health
associated with use of the device: Lead migration, device failure,
tissue reaction, skin erosion, surgical procedural risks, lack of
electromagnetic compatibility (EMC), and lack of magnetic resonance
(MR) compatibility.
A. Lead Migration
Lead migration is the movement of the lead from its intended
position (Ref. 1). It can result in a change in stimulation and a
subsequent reduction in pain relief. Lead migration may require
reoperation to adjust or replace the leads or may require stimulator
reprogramming.
B. Device Failure
Device failure, including battery failure, lead breakage, hardware
malfunction, and loose connections can lessen or eliminate stimulation
and can result in ineffective pain control. Battery failure requires
reoperation to replace the battery in the IPG component of the device
(Ref. 1). The life of the battery in the totally implanted SCS is
affected by the following factors: Battery type, output characteristics
of the stimulator (i.e., voltage, pulse rate, pulse width, and
frequency), number of electrodes used, and duration of use. Replacement
of the battery earlier than the expected date is considered a battery
failure. In addition, a damaged or improperly sealed IPG case can also
result in battery leakage that could potentially cause tissue damage,
as well as device failure.
C. Tissue Reaction
Adverse tissue reaction due in part to biocompatibility concerns is
a potential risk to health associated with all implanted devices (Ref.
1). In addition, changes in stimulation can occur due to changes in the
tissue surrounding the electrodes. Suboptimal stimulation can result in
ineffective pain control.
D. Skin Erosion
Skin erosion over the IPG is a potential risk to health associated
with use of the device. When skin erosion is attributed to the IPG, the
device is usually explanted (Ref. 1).
E. Surgical Procedural Risks
Temporary pain at the implantation site is expected in any implant
surgery.
Infection is a risk to health associated with all surgical
procedures and implanted devices (Ref. 1). The best defenses against
infection are preventive measures, including selection of patients
without known local and/or systematic infection, administration of
perioperative antibiotics, implantation of a sterile device, and strict
adherence to sterile surgical technique.
Cerebrospinal fluid (CSF) leakage is also a potential risk to
health and can cause a severe headache, which usually occurs in the
early postoperative period. CSF leakage can occur from accidental dural
puncture by an epidural needle, guide wire, or the leads during the
surgical procedure. The headache may be frontal or occipital, and it
may be accompanied by tinnitus, diplopia, neck pain, and nausea. A post
procedural headache may be treated with injection of autologous blood
into the patient's epidural space if conservative measures are
unsuccessful (Ref. 1).
Although rare, epidural hemorrhage, seroma, hematoma, and paralysis
are potential risks to health associated with totally implanted SCS
(Ref. 1).
F. EMC
External sources of electromagnetic interference may cause the
device to malfunction and the stimulation parameters to change. This
suboptimal stimulation can result in ineffective pain control or an
increase in stimulation resulting in induced pain.
G. MR Compatibilty
If the device is not designed to be compatible with magnetic
resonance procedures, various adverse consequences could result. First,
a needed imaging study may not be able to be performed, and second, if
a MR procedure is performed, the results may be compromised by the
device artifact or the device itself may be adversely affected (e.g.,
movement and/or heating).
VI. Summary of Reasons for Recommendation
The Panel believed that the device should be reclassified into
class II because special controls, in addition to general controls,
would provide reasonable assurance of the safety and effectiveness of
the device, and there is sufficient information to establish special
controls to provide such assurance.
VII. Summary of Data Upon Which the Panel Recommendation is Based
The Panel based its recommendations on the information contained in
the petition, information provided by FDA, and their personal knowledge
of the device. In addition to information concerning the potential
risks associated with the use of the totally implanted SCS device
described in section V of this document, there is reasonable knowledge
of the benefits of the device (Refs. 1 and 2). Specifically, the device
can provide pain relief resulting in an overall improved quality of
patient life.
VIII. Special Controls
FDA believes that the draft guidance document special control
identified below, in addition to general controls, is sufficient to
control the identified risks to health for this device. FDA agrees with
the Panel that FDA guidances are appropriate special controls to
provide reasonable assurance of the safety and effectiveness of the
device. However, FDA disagrees with the Panel that consensus standards,
postmarket surveillance, preclearance manufacturing inspections, device
tracking, and patient registries are necessary special controls for the
device.
A. Guidance Document
Elsewhere in this issue of the Federal Register, FDA is announcing
the availability of a draft guidance document entitled ``Special
Control Guidance for Premarket Notifications for Totally Implanted
Spinal Cord Stimulators for Pain Relief.''
The draft guidance document has sections on intended use and
indications for use, device description, labeling, technological
characteristics, testing, and manufacturing that control the risks to
health associated with use of the device identified in section V of
this document. The draft guidance document addresses the risks to
health associated with the use of the device in the following ways:
[[Page 54055]]
1. The risk of lead migration is addressed by design controls under
the Quality Systems Regulation. The labeling section of the draft
guidance also ensures that there are adequate directions for
implantation of the leads and that there is a warning about this risk
to health.
2. The risk of device failure is also addressed by design controls
under the Quality Systems Regulation. The labeling section in the draft
guidance document also ensures that there are adequate directions for
use, a battery life table, and shelf life information. It also
addresses the warnings, precautions, and adverse effects statements
related to device failure that should appear in the labeling.
3. The risk of tissue reaction is addressed in the testing section
of the draft guidance document to ensure that the device materials and
the finished device are biocompatible.
4. The risk of skin erosion is addressed in the labeling section of
the draft guidance document to ensure that adequate directions for
implantation of the device are provided in the labeling and that this
risk is noted in the adverse effects statements of the labeling.
5. The risks common to the surgical procedure for implanting the
device, temporary pain and infection, are addressed in the labeling
section of the draft guidance document. As noted in section V.E of this
document, infection may also be caused by implantation of a nonsterile
device, as well as by nonsterile technique. The risk of infection from
a nonsterile device is addressed in the testing and manufacturing
section of the draft guidance document to ensure that the device is
sterile. The potential risks of CSF leakage, epidural hemorrhage,
seratoma, hematoma, and paralysis are addressed in the labeling section
of the draft guidance by warning of these possible potential adverse
effects in the device labeling.
6. The risks associated with EMC are addressed in the testing
section of the draft guidance to ensure that the device's EMC is
properly characterized. The labeling section of the draft guidance also
states that appropriate warnings about EMC should be in the device's
labeling.
7. The risks associated with MR are addressed in the testing
section of the draft guidance to ensure that the device's MR
compatibility is properly characterized. The labeling section of the
draft guidance also states that appropriate warnings about MR
compatibility should be in the device's labeling.
FDA believes that the draft guidance document addresses the Panel's
recommendation for a guidance document special control.
B. Consensus Standards
The Panel recommended that consensus standards be a special control
for the totally implanted SCS. The draft guidance document testing
section references the use of biocompatibility, electrical, EMC, and
packaging consensus standards to help provide reasonable assurance of
the safety and effectiveness of the totally implanted SCS. An FDA
guidance concerning device sterility is also referenced in the current
guidance document. FDA believes that these sections in the guidance
address the Panel's concern.
C. Postmarket Surveillance
The Panel stated that it was important that adverse device outcomes
be tracked through postmarket surveillance. FDA agrees with the Panel
that adverse device outcomes should be reported to FDA. However, FDA
believes that the existing mandatory MDR system is the appropriate
mechanism to report such adverse events. Therefore, additional
postmarket surveillance is unnecessary to address the Panel's concerns
to provide reasonable assurance of the safety and effectiveness of the
device. The Panel also recommended that annual reporting of battery
failures to FDA would be an appropriate special control to provide
reasonable assurance of the safety and effectiveness of the device. FDA
believes that the MDR system captures reporting of device malfunctions
that could cause a serious injury, including battery failure.
Therefore, FDA does not believe that annual reports of device failures
should be a special control for the device.
D. Preclearance Manufacturing Inspections
The Panel also recommended that preclearance manufacturing
inspections ``at the class III device level'' be a special control for
the totally implanted SCS. FDA notes that the Quality System Regulation
(QSR) (21 CFR part 820) that sets forth current good manufacturing
practice requirements applies to all devices except certain devices
exempted by regulation from the QSR. FDA also notes that there are no
device class-related levels of QSR inspections. Prior to premarket
approval of a class III device, FDA conducts a QSR inspection of the
class III device manufacturing site as part of the premarket approval
process. Class II device manufacturing sites are periodically inspected
after FDA clears the device for marketing. The difference between QSR
inspection of a class II manufacturing site and a class III device
manufacturing site is the timing of the inspection and not the nature
of the inspection. FDA believes that safety and effectiveness of the
totally implanted SCS can be reasonably assured by the manufacturing
section in the draft guidance document and by general controls
applicable to all medical devices, including QSR inspections.
Therefore, FDA does not think a QSR inspection prior to FDA marketing
clearance is necessary to provide reasonable assurance of the safety
and effectiveness of the totally implanted SCS.
E. Device Tracking
The Panel also recommended that device tracking be a special
control for the device. Tracking is a compliance mechanism intended to
facilitate notification and recall in the event of serious risks to
health presented by a device. The totally implanted SCS does not meet
the three criteria for a tracked device: (1) The likelihood of sudden
catastrophic failure, (2) the likelihood of significant adverse
clinical outcome, and (3) the need for prompt professional
intervention. Therefore, FDA does not believe that device tracking is
necessary to provide reasonable assurance of the safety and
effectiveness of the device.
F. Patient Registries
The Panel also recommended patient registries be a special control
for the totally implanted SCS. FDA notes that the use of patient
registries is a type of postmarket surveillance to answer a particular
question related to a device's performance or to track patients when
particular clinical issues are identified. Neither the Panel nor FDA
has identified a clinical issue requiring patient registries.
Therefore, FDA does not believe that patient registries are necessary
to provide reasonable assurance of the safety and effectiveness of the
device.
IX. FDA's Tentative Findings
FDA believes that the totally implanted SCS intended for treatment
of chronic intractable pain of the trunk or limbs should be
reclassified into class II because special controls, in addition to
general controls, would provide reasonable assurance of the safety and
effectiveness of the device, and there is sufficient information to
establish special controls to provide such assurance. FDA believes that
the draft guidance document entitled ``Special Control Guidance for
Premarket Notifications for Totally Implanted Spinal Cord Stimulators
for Pain Relief''
[[Page 54056]]
is an appropriate special control to provide reasonable assurance of
the safety and effectiveness of the device.
FDA notes that it has considered a comment from a manufacturer of a
totally implanted SCS for pain relief and a comment from the petitioner
after the September 16 and 17, 1999, Panel meeting in its formulation
of these tentative findings. These comments have been placed in the
docket referenced in the heading of this document.
X. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Advanced Neuromodulation Systems, Inc., Plano, TX,
Classification Proposal and Summary of Safety and Effectiveness
Information for the Totally Implanted Spinal Cord Stimulator,
received June 16, 1999.
2. Transcript of the September 16 and 17, 1999, Neurological
Devices Panel Meeting, September 17, 1999, volume, pp. 153-284.
XI. Environmental Impact
The agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
XII. Analysis of Impacts
FDA has examined the impacts of the notice under Executive Order
12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as amended
by subtitle D of the Small Business Regulatory Fairness Act of 1996
(Public Law 104-121), and the Unfunded Mandates Reform Act of 1995
(Public Law 104-4)). Executive Order 12866 directs agencies to assess
all costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety, and other advantages; distributive impacts; and
equity). The agency believes that this potential reclassification
action is consistent with the regulatory philosophy and principles
identified in the Executive Order. In addition, this potential
reclassification action is not a significant regulatory action as
defined by the Executive Order and so is not subject to review under
the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Reclassification of the device from class III to
class II will relieve manufacturers of the cost of complying with the
premarket approval requirements in section 515 of the act. Because
reclassification will reduce regulatory costs with respect to this
device, it will impose no significant economic impact on any small
entities, and it may permit small potential competitors to enter the
marketplace by lowering their costs. The agency therefore certifies
that this reclassification action, if finalized, will not have a
significant economic impact on a substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement of anticipated costs and
benefits before proposing any rule that may result in an expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100 million in any one year (adjusted annually for
inflation). The Unfunded Mandates Reform Act does not require FDA to
prepare a statement of costs and benefits for the reclassification
action, because the proposed rule is not expected to result in any 1-
year expenditure that would exceed $100 million adjusted for inflation.
XIII. Paperwork Reduction Act of 1995
FDA concludes that this reclassification action contains no new
collections of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
XIV. Federalism
FDA has analyzed this reclassification action in accordance with
the principles set forth in Executive Order 13132. FDA has determined
that the reclassification action does not contain policies that have
substantial direct effects on the States, on the relationship between
the National Government and the States, or on the distribution of power
and responsibilities among the various levels of government.
Accordingly, the agency has concluded that the action does not contain
policies that have federalism implications as defined in the order and,
consequently, a federalism summary impact statement is not required.
XV. Request for Comments
Interested persons may submit to the Dockets Management Branch
(address above) written comments regarding this document by October 6,
2000. Two copies of any comments are to be submitted, except that
individuals may submit one copy. Comments are to be identified with the
docket number found in brackets in the heading of this document.
Received comments may be seen in the office above between 9 a.m. and 4
p.m., Monday through Friday.
Dated: August 22, 2000.
Linda S. Kahan,
Deputy Director for Regulations Policy, Center for Devices and
Radiological Health.
[FR Doc. 00-22618 Filed 9-5-00; 8:45 am]
BILLING CODE 4160-01-F