[Federal Register Volume 65, Number 173 (Wednesday, September 6, 2000)]
[Notices]
[Pages 54053-54056]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-22618]


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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.

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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draft guidance for industry entitled ``Special Control Guidance for 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