[Federal Register Volume 65, Number 154 (Wednesday, August 9, 2000)]
[Rules and Regulations]
[Pages 48609-48612]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-20089]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. 98N-1134]


Gastroenterology and Urology Devices; Reclassification of the 
Extracorporeal Shock Wave Lithotripter

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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

SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
to reclassify from class III to class II the extracorporeal shock wave 
lithotripter, when intended for use to fragment kidney and ureteral 
calculi. FDA is taking this action on its own initiative in order to 
assure that these devices are regulated according to the appropriate 
degree of regulatory control needed to provide reasonable assurance of 
their safety and effectiveness. Elsewhere in this issue of the Federal 
Register, FDA is publishing a notice of availability of a guidance 
document, which will serve as the special control for the reclassified 
device.

DATES: This rule is effective September 8, 2000.

FOR FURTHER INFORMATION CONTACT: John H. Baxley, Center for Devices and 
Radiological Health (HFZ-470), Food

[[Page 48610]]

and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850, 
301-594-2194.

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 
(the SMDA) (Public Law 101-629), and the Food and Drug Administration 
Modernization Act of 1997 (the FDAMA) (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, reflecting 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 date of enactment of the 1976 
amendments), 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. Those devices remain in class III 
and require premarket approval, unless and until the device is 
reclassified into class I or II or FDA issues an order finding the 
device to be 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 marketed 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 provides that FDA may 
initiate the reclassification of a device classified into class III 
under section 513(f)(1) of the act, or the manufacturer or importer of 
a device may petition for the issuance of an order classifying the 
device in class I or class II. FDA's regulations in 21 CFR 860.134 set 
forth the procedures for the filing and review of a petition for 
reclassification of such class III devices. In order 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.
    Section 216 of FDAMA replaced the ``four of a kind'' rule in the 
old section 520(h)(4) of the act (21 U.S.C. 360j(h)(4)) with a 
provision that frees safety and effectiveness data in PMA's approved 6 
or more years earlier for use by the agency in certain actions, 
including device reclassifications. Under section 520(h)(4) of the act, 
as amended by FDAMA, the agency has supplemented other sources of 
information that support reclassification of the extracorporeal shock 
wave lithotripter with data contained in PMA's approved 6 or more years 
before the date of this rule. Although FDA has sufficient information 
to support this reclassification without relying upon data available 
under section 520(h)(4) of the act, the agency decided to use such data 
in taking this action. In this instance, the data used would have been 
available to the agency under the superseded four of a kind rule.
    Under section 513(f)(2)(B)(i) of the act, the Secretary of Health 
and Human Services (the Secretary), for good cause shown, may refer a 
proposed reclassification to a device classification panel. The panel 
shall make a recommendation to the Secretary respecting approval or 
denial of the proposed reclassification. 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 proposed reclassification was initiated.

II. Response to Comments

    FDA referred the issue of reclassification of the extracorporeal 
shock wave lithotripter to the Gastroenterology and Urology Devices 
Advisory Panel (the Panel) for review and recommendation. At a public 
meeting on July 30, 1998, the Panel unanimously recommended that the 
extracorporeal shock wave lithotripter indicated for the fragmentation 
of kidney and ureteral calculi be reclassified from class III to class 
II. The Panel believed that the special controls of consensus 
standards, clinical performance testing, labeling restrictions, and 
physician training restrictions would provide reasonable assurance of 
the safety and effectiveness of the device. In the Federal Register of 
February 8, 1999 (64 FR 5987), FDA published a summary of the Panel 
recommendation and a proposed rule to reclassify the extracorporeal 
shock wave lithotripter. FDA invited interested persons to submit 
written comments by May 10, 1999. FDA received one comment that raised 
several issues. The following is FDA's response to the issues raised by 
the comment.
    (Comment 1) The comment suggested that FDA should identify the 
PMA's and PMA supplements that FDA relied upon in reclassifying the 
device and make the summaries of safety and effectiveness for those 
submissions available in the Dockets Management Branch.
    FDA agrees. The PMA's that FDA relied upon are listed in section 
VII ``References'' below and the summaries of safety and effectiveness 
are available in the Dockets Management Branch, as stated there. 
Section 520(h)(4)(b) of the act states that the summaries of safety and 
effectiveness shall be available for use by FDA as the evidentiary 
basis for a reclassification action. FDA notes, however, that section 
520(h)(2) of the act provides that the summaries of safety and 
effectiveness may not be used to establish the safety or effectiveness 
of another device by any person other than the person who submitted the 
information. In the case of certain supplements for which a summary of 
safety and effectiveness was not prepared, FDA will make available a 
redacted version of the supplement.
    (Comment 2) The comment questions whether FDA believes that section 
520(h)(4) of the act allows for the use of information from PMA 
supplements as well as original PMA's.
    Yes. Section 520(h)(4) of the act authorizes FDA to use data 
contained in applications for premarket approval submitted under 
section 515(c) of the act. The 6-year provision, then, applies equally 
to initial PMA submissions and PMA supplements, which are applications 
for premarket approval of a changed device and are submitted under

[[Page 48611]]

section 515(c) of the act, the general PMA authority.
    (Comment 3) The comment also said that persons submitting a 
premarket notification (510(k)) other than holders of approved PMA's 
and PMA supplements should only be able to use as predicate devices 
model numbers or modified versions of extracorporeal shock wave 
lithotripters legally marketed under a 510(k), PMA, or PMA supplement 
no sooner than 6 years before the applicant's 510(k) submission for a 
new or modified device. Holders of an approved PMA or PMA supplement 
should be the only applicants permitted to cite as a predicate the 
device for which they have an approved application fewer than 6 years 
old.
    FDA disagrees with this comment. Section 513(i) of the act provides 
that substantial equivalence may be determined based upon comparison 
with any legally marketed device. The intent of section 520(h)(4) of 
the act is to provide an additional source of information upon which 
certain actions can be based. Section 520(h)(4) of the act does not 
place any limitations on the type of device that may be used as a 
predicate device.
    (Comment 4) The comment said that the indications for use in the 
proposed rule are inconsistent with those in the approved PMA's and PMA 
supplements to date. The comment also said that the labeling 
restrictions in the rule do not address indications for use and 
questioned how manufacturers may switch to the broad intended use in 
the rule.
    FDA disagrees. The intended use in the rule (i.e., ``fragmentation 
of urinary calculi within the kidney and ureter'') is consistent with 
prior approvals. Although some devices were restricted in their 
intended use to certain stone locations or size ranges based on the 
results or circumstances of their specific clinical studies, others had 
adequate data supporting the more general intended use. Therefore, the 
broad intended use in the rule incorporates both of the individual 
intended uses that have been approved to date. This approach was based 
on findings in the literature that the differences in intended use of 
approved lithotripters were not primarily related to differences in 
technological characteristics. Because FDA is reclassifying a broad 
intended use, FDA believes that it is appropriate to list the various 
stone characteristics known to be associated with reduced effectiveness 
as precautions in the labeling. Manufacturers who have cleared devices 
with the limited intended uses can seek clearance to market their 
devices for the broad intended use by submitting a 510(k) comparing the 
device to a predicate that has the broad intended use.
    (Comment 5) The comment noted that the guidance suggests that a 
confirmatory clinical study should enroll at least 20 patients at 2 
sites. The comment questioned whether this means 20 patients at each 
site or 20 patients total at both sites. The comment further said that, 
in either case, the number is insufficient. The comment suggested that 
FDA should require 30 patients each at 3 sites and the study should 
include an assessment of treatment success and adverse effects 
immediately post-procedure and at 2 weeks and 1 month thereafter.
    The guidance has been revised to clarify that clinical testing of 
devices that are similar in technological characteristics to legally 
marketed devices should include at least 20 patients total at 2 sites. 
FDA disagrees with the comment that there is a need to assess device 
safety and effectiveness outcomes in a statistically justified sample 
size. FDA believes that clinical testing in these circumstances is 
intended only to confirm device functionality and the adequacy of the 
proposed labeling rather than to assess device safety and 
effectiveness. FDA believes that the characterization testing described 
in the guidance is sufficient to demonstrate safety and effectiveness 
with respect to clinical outcomes for devices with similar 
technological characteristics. As noted in the proposed rule and 
guidance document, however, 510(k)'s for devices that have different 
technological characteristics from legally marketed predicates will 
likely require larger, statistically justified, clinical studies to 
investigate the effect of the new technological characteristics on 
safety and effectiveness outcomes. For these cases, the study design 
should be tailored to the specifics of the new characteristics; 
therefore, we do not believe that a standard detailed study design 
should be spelled out.
    (Comment 6) The comment suggested that the restricted device legend 
for the device should be revised to read: ``CAUTION: Federal law 
restricts this device to sale, distribution, and use only upon the 
lawful order of a physician trained and/or experienced in the use of 
this device as outlined in the required training program.'' The comment 
also suggested that this statement should be included in the regulation 
and not just in the guidance.
    FDA agrees in part with this comment. FDA has added the words 
``distribution or use'' after ``sale'' so as to track the language in 
section 520(e) of the act. FDA does not believe that it would not be 
correct to replace the phrase ``appropriate training program'' with 
``required training program'' as suggested by the comment, because FDA 
does not regulate all aspects of the training program. Also, FDA does 
not believe that it is necessary to add the language to the regulation, 
because the requirement is already covered by 21 CFR 801.109(b)(1). FDA 
has decided not to include the labeling in an appendix to Sec. 876.5990 
(21 CFR 876.5990). Instead, the labeling will be included in the 
guidance document only. FDA also slightly revised the identification 
section in Sec. 876.5990(a) by removing the words ``through a water-
filled rubber cushion or by direct contact of the patient's skin with 
the water'' and replacing them with ``using an appropriate acoustic 
interface.''

III. Final Rule

    Therefore, FDA is finalizing the rule reclassifying the 
extracorporeal shock wave lithotripter into class II with the FDA 
guidance document entitled ``Guidance for the Content of Premarket 
Notifications (510(k)'s) for Extracorporeal Shock Wave Lithotripters 
Indicated for the Fragmentation of Kidney and Ureteral Calculi,'' as 
the special control. Elsewhere in this issue of the Federal Register, 
FDA is publishing a notice of availability of the guidance document.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.24(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.

V. Analysis of Impacts

    FDA has examined the impacts of the final rule 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 reclassification action is 
consistent with the regulatory

[[Page 48612]]

philosophy and principles identified in the Executive Order. In 
addition, the 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 at lower costs. The agency 
therefore certifies that this reclassification action will not have a 
significant economic impact on a substantial number of small entities. 
In addition, this reclassification action will not impose costs of $100 
million or more on either the private sector or state, local, and 
tribal governments in the aggregate, and therefore a summary statement 
of analysis under section 202(a) of the Unfunded Mandates Reform Act of 
1995 is not required.

VI. Paperwork Reduction Act of 1995

    FDA concludes that this final rule contains no information that is 
subject to review by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995. The special controls do not require 
the respondent to submit additional information to the public. 
Therefore, no burden is placed on the public.

VII. References

    The following references have been placed on display in the Dockets 
Management Branch, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, 
and may be seen by interested persons between 9 a.m. and 4 p.m., Monday 
through Friday.

    1. P840008/S24, MFL 5000 Lithotripter, Dornier Medical Systems, 
Inc., July 3, 1991.
    2. P840008/S26, MFL 9000 Lithotripter, Dornier Medical Systems, 
Inc., August 12, 1991.
    3. Summary of Safety and Effectiveness, P890013, Piezolith 
Lithotripter, Model 2300, Richard Wolf Medical Instruments Corp., 
September 9, 1991.
    4. Summary of Safety and Effectiveness, P880042, LT.01 
Lithotripter, EDAP International Corp., December 12, 1991.
    5. Summary of Safety and Effectiveness, TP890006, Therasonic 
Lithotripsy Treatment System, Diasonics, Inc., December 20, 1991.

List of Subjects in 21 CFR Part 876

    Medical devices.


    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
876 is amended as follows:

PART 876--GASTROENTEROLOGY-UROLOGY DEVICES

    1. The authority citation for 21 CFR part 876 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.


    2. Section 876.5990 is added to subpart F to read as follows:


Sec. 876.5990  Extracorporeal shock wave lithotripter.

    (a) Identification. An extracorporeal shock wave lithotripter is a 
device that focuses ultrasonic shock waves into the body to 
noninvasively fragment urinary calculi within the kidney or ureter. The 
primary components of the device are a shock wave generator, high 
voltage generator, control console, imaging/localization system, and 
patient table. Prior to treatment, the urinary stone is targeted using 
either an integral or stand-alone localization/imaging system. Shock 
waves are typically generated using electrostatic spark discharge 
(spark gap), electromagnetically repelled membranes, or piezoelectric 
crystal arrays, and focused onto the stone with either a specially 
designed reflector, dish, or acoustic lens. The shock waves are created 
under water within the shock wave generator, and are transferred to the 
patient's body using an appropriate acoustic interface. After the stone 
has been fragmented by the focused shock waves, the fragments pass out 
of the body with the patient's urine.
    (b) Classification. Class II (special controls) (FDA guidance 
document: ``Guidance for the Content of Premarket Notifications 
(510(k)'s) for Extracorporeal Shock Wave Lithotripters Indicated for 
the Fragmentation of Kidney and Ureteral Calculi.'')

    Dated: July 12, 2000.
Linda S. Kahan,
Deputy Director for Regulations Policy, Center for Devices and 
Radiological Health.
[FR Doc. 00-20089 Filed 8-8-00; 8:45 am]
BILLING CODE 4160-01-F