[Federal Register Volume 64, Number 25 (Monday, February 8, 1999)]
[Proposed Rules]
[Pages 5987-5996]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-2689]
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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: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing for public
comment its proposal to reclassify from class III to class II the
extracorporeal shock wave lithotripter, when intended for use to
fragment kidney and ureteral calculi, and the recommendation of the
Gastroenterology and Urology Devices Advisory Panel (the Panel)
regarding this reclassification. The Panel made this recommendation
after reviewing the relevant publicly available information and the
proposed reclassification. FDA is also issuing 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 reclassify the device or retain it in class III.
FDA's decision on the proposed reclassification will be announced in
the Federal Register.
DATES: Written comments by May 10, 1999.
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: John H. Baxley, Center for Devices and
Radiological Health (HFZ-470), Food 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) (Pub. L. 94-295), the Safe Medical Devices Act of 1990
(the SMDA) (Pub. L. 101-629), and the Food and Drug Administration
Modernization Act of 1997 (the FDAMA) (Pub. L. 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 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 (21 U.S.C.
360c(f))) 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 (21 U.S.C. 360c(i)), 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 part 807 of the regulations (21 CFR part 807).
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 (21 U.S.C. 360c(f)(2)). 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 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 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 agency use of data in PMA's approved 6 or more
years before FDA undertakes certain regulatory 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 proposal. In this instance, FDA has only used
data that 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 (21 U.S.C.
360c(f)(2)(B)(i)), the Secretary, for good cause shown, may refer a
proposed reclassification to a
[[Page 5988]]
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. Regulatory History of the Device
The extracorporeal shock wave lithotripter intended for the
fragmentation of kidney and ureteral calculi is a postamendments device
classified into class III under section 513(f)(1) of the act.
Therefore, this generic type of device cannot be placed in commercial
distribution unless it is reclassified under section 513(f)(2), or is
the subject of a PMA or notice of completion of a product development
protocol (PDP) under section 515 of the act (21 U.S.C. 360e).
In accordance with section 513(f)(2) of the act, FDA, on its own
initiative, is proposing to reclassify this device from class III to
class II when intended to fragment kidney and ureteral calculi. FDA
referred the proposed reclassification to the Panel for its
recommendation on the requested change in classification. This panel
meeting was held on July 30, 1998, and is summarized further in Section
VI.
III. Device Description
An extracorporeal shock wave lithotripter is a device that focuses
ultrasonic shock waves into the body to noninvasively fragment urinary
calculi within the kidney and 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 through a water-filled rubber cushion or by direct
contact of the patient's skin with the water. After the stone has been
fragmented by the focused shock waves, the fragments pass out of the
body with the patient's urine.
IV. Recommendations of the Panel
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.
V. Risks to Health
After considering the information discussed by the Panel during the
reclassification proceedings, the published literature, data in PMA
applications available to FDA under section 520(h)(4) of the act, as
amended by FDAMA, and the Medical Device Reports, FDA believes the
following risks are associated with the use of the extracorporeal shock
wave lithotripter in the fragmentation of kidney and ureteral calculi.
A. Bleeding
Interaction between the shock waves and internal tissues can result
in bleeding within the urinary tract. Lithotripsy-induced bleeding
typically presents as either hematuria (blood in the urine) or renal
hematoma. Hematuria occurs following most treatments (Refs. 4, 69, and
85), is believed to be secondary to trauma to the renal parenchyma
(Ref. 7), and usually resolves spontaneously within 24 to 48 hours of
treatment (Refs. 8 and 69). Small, asymptomatic renal hematomas occur
with 20 to 25 percent of treatments, which resolve without intervention
(Ref. 52). In less than 1 percent of treatments, however, clinically
significant intrarenal, subcapsular, or perirenal hematomas occur
(Refs. 20 and 50). These patients typically present with severe,
chronic flank pain (Refs. 4, 50, 52, and 84), and anuria secondary to
renal compression has also been reported (Refs. 62 and 95). Although
clinically significant hematomas often resolve with conservative
management (Refs. 50, 52, and 84), severe hemorrhage (Refs. 4, 85, and
92) or death (Refs. 66 and 92) has been reported. Management of severe
renal hemorrhage includes the administration of blood transfusions
(Refs. 50, 52, 81, 85, and 92), percutaneous drainage (Ref. 72), or
surgical intervention, which may include nephrectomy (Refs. 4, 50, and
62).
Lithotripsy-induced bleeding is believed to be caused by vessel
damage secondary to the collapse of cavitation bubbles at the shock
wave focus (Refs. 17 and 65). The risk of serious bleeding is minimized
by the use of conservative treatment parameters (Ref. 17) and careful
evaluation of the patient post-treatment (Ref. 50).
Patient characteristics associated with increased risk for the
development of life threatening hemorrhage include the presence of
coagulopathy or the use of anticoagulant therapy (including aspirin)
(Refs. 45, 73, 85, and 91), presence of an arterial calcification or
vascular aneurysm (Refs. 9, 19, and 91), and poorly-controlled
hypertension (Refs. 49 and 50). For some of these high risk patients,
however, lithotripsy can still be delivered safely as long as certain
precautions are taken. Specifically, patients on anticoagulant therapy
can undergo lithotripsy provided that their anticoagulation is
temporarily reversed (Refs. 73 and 91). Furthermore, patients with an
arterial calcification or vascular aneurysm have been treated without
complication provided that the calcification or aneurysm is
sufficiently outside of the shock wave path, treatment is limited to a
minimum number of low-power shock waves, and the patient is carefully
monitored (Refs. 9 and 19).
B. Renal Injury
The focused shock waves delivered by all extracorporeal shock wave
lithotripters cause some degree of acute trauma to the treated kidney
with associated functional impairment (Refs. 1, 7, 41, and 101). As
with bleeding, renal injury is probably secondary to the effects of
cavitation at the shock wave focus (Refs. 16, 17, and 82).
It is believed that renal trauma, with associated nephron loss and/
or tubule damage, occurs during nearly all lithotripsy treatments
(Refs. 1 and 82), is dependent upon the applied shock wave dose (Refs.
74, 82, and 86), and is typically limited to the size of the shock wave
focal volume (Ref. 83). While a small region of renal scarring persists
at the treated site (Refs. 74 and 86), any associated changes in renal
function resolve within 30 days (Refs. 3, 6, 32, and 86). Although
infrequently reported and of questionable clinical significance,
permanent morphological changes to the kidney have been observed
following lithotripsy (Refs. 6 and 74). The risk of renal injury is
minimized by delivering fewer, less powerful shock waves (Refs. 70 and
74), and using a lower shock wave repetition rate (Refs. 17 and 86).
[[Page 5989]]
Patients with solitary kidneys or pre-existing impairment of renal
function may be at increased risk for long-term changes (Refs. 74 and
100). Additionally, although many short-term studies have been
published regarding the safe use of extracorporeal shock wave
lithotripsy in children (Refs. 53, 55, 69, and 70), questions still
exist regarding the long-term effects of shock waves upon the function
and growth of the immature kidney (Refs. 15, 27, 70, and 74).
C. Hypertension
Early investigators reported new onset of hypertension in as many
as 8 percent of patients between 1 and 2 years following extracorporeal
shock wave lithotripsy to the kidney (Refs. 58 and 99). The
physiological basis of this finding was theorized to be caused by the
Page effect, secondary to the renal fibrosis that occurs following
resolution of lithotripsy-induced intraparenchymal hemorrhage (Refs. 52
and 99). Despite the hypertension incidence rates reported by these
early studies, however, subsequent research indicates that hypertension
is not a risk of lithotripsy. Lingeman et al. noted no difference at 2
years in the rates of new onset of hypertension between patients who
received lithotripsy and those who received alternative stone removal
therapies, although a small but statistically significant increase in
diastolic blood pressure was seen in the lithotripsy group (Ref. 61).
In a subsequent report describing 3- and 4-year followup on the same
patients, similar outcomes were observed (Ref. 60). In a similar
investigation, Vaughan et al. observed no difference in either new
onset of hypertension or blood pressure between lithotripsy and
nonlithotripsy treated patients 2 years post-treatment (Ref. 98). The
results of these controlled studies demonstrate that the development of
hypertension is not an actual risk of lithotripsy among normal, healthy
patients. However, due to the unknown effects of lithotripsy-induced
damage to the growing kidney, concern has been raised that pediatric
patients may be at increased risk of developing chronic hypertension
(Ref. 74).
D. Cardiac Arrhythmia
Cardiac arrhythmias, most commonly premature ventricular
contractions, are generally reported during extracorporeal shock wave
lithotripsy at fixed shock wave delivery in 2 to 20 percent of patients
(Refs. 14 and 30). While the specific cause of lithotripsy-induced
arrhythmias is not fully understood, researchers have postulated
several causes, including irritation or mechanical stimulation of the
myocardium by the shock wave, autonomic nerve stimulation, or the
effects of the intravenous sedatives (Refs. 14 and 43). Arrhythmias
resolve spontaneously upon synchronizing the shock waves with the
refractory period of the ventricular cycle (i.e., electrocadiograph
(ECG) gating) or terminating treatment (Refs. 14, 30, and 102).
Although these cardiac disturbances rarely pose a serious risk to the
healthy patient, there is the potential for life threatening events to
occur in those with a pre-existing history of cardiac disease (Ref.
43). Furthermore, patients with either cardiac pacemakers or
implantable defibrillators may be at additional risk due to the
possibility of the lithotripter interfering with the function of the
pulse generator (Refs. 2, 91, and 97).
The risk of serious cardiac events during lithotripsy can be
minimized by monitoring the cardiac activity of all patients during
treatment to detect any arrhythmias, and either terminating treatment
or switching to an ECG-gated mode of shock wave delivery should an
arrhythmia occur (Refs. 59 and 102). Additionally, the risks of
lithotripter interference with cardiac pacemakers and implantable
defibrillators can be minimized by temporarily reprogramming the pulse
generator prior to treatment, verifying the correct function of the
pulse generator during and after shock wave delivery, and maintaining
sufficient distance between the shock wave path and the pulse generator
(Refs. 2, 5, 91, and 97).
E. Urinary Obstruction
Urinary obstruction occurs in up to 6 percent of patients following
lithotripsy due to stone fragments becoming lodged in the ureter, and
may be the result of either a single stone fragment or the accumulation
of multiple small stone particles (i.e., Steinstrasse) (Refs. 24, 48,
and 84). Patients with urinary obstruction typically present with
persistent pain, and may be at risk of developing hydronephrosis with
subsequent renal failure if the obstruction is not promptly treated
(Ref. 29). Often, the obstructing fragments pass spontaneously and
intervention is not necessary (Refs. 48 and 84). Intervention is
indicated in the presence of severe pain, fever, sepsis, or failure of
the obstruction to spontaneously resolve, and usually includes
ureteroscopic manipulation or retrieval, electrohydraulic or laser
lithotripsy, percutaneous nephrostomy drainage, open surgery, or repeat
extracorporeal shock wave lithotripsy (Refs. 22, 48, 84, and 93).
F. Infection
Urinary tract infection (UTI) occurs in 1 to 7 percent of patients
following extracorporeal shock wave lithotripsy as a result of the
release of bacteria from the fragmentation of infected calculi (Refs.
18, 77, 80, and 84). Rarely, pyelonephritis secondary to lithotripsy
has been reported (Refs. 77 and 84). Additionally, lithotripsy shock
waves can cause local tissue trauma sufficient to permit bacteria to
enter the bloodstream from the urinary tract, resulting in sepsis
(Refs. 29 and 84). Although the incidence of sepsis following
lithotripsy is not common, typically occurring in less than 1 percent
of cases (Ref. 31), this complication has the potential for serious
consequences (Ref. 84). Patients at greatest risk of developing severe
infectious complications include those with pre-existing UTI and
infected stones, as well as those who experience urinary obstruction
due to the passage of stone fragments (Refs. 29, 38, and 84).
Additionally, patients with cardiac disease, including valvular disease
and implanted heart valves, and immunocompromised patients are at
increased risk for developing bacterial endocarditis following
lithotripsy (Ref. 68).
The risk of infectious complications secondary to extracorporeal
shock wave lithotripsy can be effectively minimized through the use of
prophylactic antibiotics in patients with pre-existing UTI, infected
stones, cardiac disease, and compromised immune systems (Refs. 18, 38,
68, and 84).
G. Injury to Adjacent Organs
Because multiple shock waves pass through the patient's body during
treatment, extracorporeal shock wave lithotripsy has the potential to
cause injury to nontarget organs. Examples of injury to adjacent organs
include splenic rupture requiring splenectomy (Refs. 63 and 78), liver
hematoma (Ref. 84), and pancreatitis (Ref. 84). In addition, the
interaction of shock waves with air-filled organs, such as the lung or
bowel, results in hemorrhage secondary to tissue damage (Refs. 36, 65,
and 84). Serious injury to adjacent organs is rare, and is minimized
through proper patient selection, careful targeting of the shock wave
focus, and the use of conservative treatment parameters and retreatment
intervals (Refs. 36, 76, and 84).
In addition to the documented risks to adjacent organs described
previously, extracorporeal shock wave lithotripsy
[[Page 5990]]
potentially represents significant hazards to other nontarget tissues.
First, the administration of shock waves to pregnant animals at
specific gestational stages has been shown to cause growth
disturbances, serious injury, or death to the fetus (Refs. 33 and 71).
As a result of these findings, pregnancy is regarded as an absolute
contraindication of lithotripsy (Refs. 12, 74, 76, and 91). The medical
community has raised the concern that lithotripsy for stones in the
lower ureter in women of childbearing potential may cause irreversible
damage to the ovary (Ref. 12). Although several investigators have
failed to detect ovarian damage in women receiving extracorporeal shock
wave lithotripsy to the lower ureter (Refs. 25 and 91), this potential
risk has not been fully assessed (Ref. 12). Lastly, Yeaman et al.
observed growth plate disturbances in the epiphyses of developing long
bones in rats subjected to shock waves, indicating that extracorporeal
shock wave lithotripsy may cause growth disturbances in children (Ref.
103). Although these same growth disturbances were not duplicated in a
subsequent animal study (Ref. 96), the long-term effects of lithotripsy
shock waves upon nontarget pediatric tissues remain unknown.
H. Other Complications
Other reported complications of extracorporeal shock wave
lithotripsy include pain/renal colic, skin irritation/bruising, nausea/
vomiting, fever, vasovagal syncope, autonomic dysreflexia, embedded
stone fragments, and increased stone recurrence rate.
Pain/renal colic and skin irritation/bruising commonly occur during
and immediately after treatment (Refs. 22, 24, 47, and 84), are less
severe with lithotripters that have less powerful shock waves and
larger shock wave generator apertures (Refs. 22, 47, and 79), and
typically resolve spontaneously (Ref. 22). Temporary pain/renal colic
may also occur secondary to the passage of stone fragments, which is
often managed with medication. Chronic pain may be indicative of
ureteral obstruction or renal hematoma (Refs. 4, 84, and 92).
Transient nausea and vomiting are occasionally reported immediately
after lithotripsy (Refs. 22, 24, and 37), and may be associated with
either pain or the administration of sedatives or analgesia.
Fever has been reported after lithotripsy (Refs. 24, 31, 47, and
77), and may be secondary to infection (Ref. 23).
Vasovagal syncope (heart rate suppression concurrent with
hypotension) has been reported during lithotripsy, although its
incidence is rare (Ref. 44). Researchers attribute this serious
condition to either patient anxiety or shock wave stimulation of renal
peripheral autonomic nerve fibers, and conclude that the risks of this
condition can be minimized by closely monitoring cardiac activity
during treatment.
Kabalin et al. demonstrated that while autonomic dysreflexia may
occur in spinal cord injured patients during lithotripsy, this
condition is effectively treated by terminating shock wave delivery and
administering medical therapy (Ref. 42).
Although infrequently noted, stone fragments have the potential to
become embedded in the ureteral wall during lithotripsy (Ref. 28).
Obstructing submucosal calculi may necessitate endoscopic removal.
Some investigators have observed higher stone recurrence rates
following extracorporeal shock wave lithotripsy as compared to
alternative stone removal therapies, indicating that retained stone
particles may act as a nidus for new stone formation (Ref. 10).
However, the magnitude and significance of this finding are unclear and
continue to undergo investigation.
VI. Summary of Reasons for Recommendation
After reviewing the data provided by FDA, and after consideration
of the open discussions during the Panel meeting and the Panel members'
personal knowledge of and clinical experience with the device, the
Panel gave the following reasons in support of its recommendation to
reclassify the generic type extracorporeal shock wave lithotripter for
use in fragmenting kidney and ureteral calculi from class III into
class II: (1) The safety and effectiveness of the extracorporeal shock
wave lithotripter in the fragmentation of kidney and ureteral calculi
has become well-established since approval of the first device in 1984;
(2) extracorporeal shock wave lithotripsy is effective in treating most
kidney and ureteral calculi, with a typical stone-free rate of 75
percent; and (3) the rates of serious complications from extracorporeal
shock wave lithotripsy are low, and can be effectively minimized by:
(a) Consensus standards regarding shock wave characterization
measurements and general mechanical and electrical safety, (b) clinical
performance testing, (c) labeling restrictions, and (d) physician
training restrictions (Ref. 94). Based on information presented by FDA,
along with the Panel members' personal knowledge and clinical
experience, the Panel identified the following risks to health
regarding the use of extracorporeal shock wave lithotripsy for the
fragmentation of kidney and ureteral calculi: Bleeding and hematoma,
renal injury and scarring, cardiac arrhythmia, urinary obstruction,
urinary tract infection, and injury to adjacent organs. In addition,
the Panel stated that the safety of lithotripsy among certain subgroups
is unknown, such as pregnant women, children, and women of childbearing
potential with lower ureteral stones. Although hypertension has
historically been listed as a potential risk of extracorporeal shock
wave lithotripsy, the Panel stated that sufficient evidence now exists
to conclude that this condition should not be listed as an actual risk
to health.
The Panel believes that the extracorporeal shock wave lithotripter
should be reclassified into class II because special controls, in
addition to general controls, 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
Based on the information discussed by the Panel during the
reclassification proceedings, the published literature, and data in
premarket approval (PMA) applications available to FDA under section
520(h)(4) of the act, as amended by FDAMA, FDA believes that there is
reasonable knowledge of the benefits of the device when used for the
fragmentation of kidney and ureteral calculi. Extracorporeal shock wave
lithotripsy successfully fragments most urinary calculi. Effectiveness,
expressed as the percentage of patients rendered stone-free within 3
months, ranges between 55 to 98 percentage with a typical retreatment
rate of 1 to 25 percentage (Refs. 11, 20, 22 to 24, 47, 51, 75, 84, 87,
89, and 93). Successful treatment outcome has been achieved despite the
use of different shock wave generator designs (i.e., electrostatic
spark discharge, electromagnetically repelled membranes, piezoelectric
crystal arrays) and wide range of shock wave characteristics.
Similarly, extracorporeal shock wave lithotripter effectiveness is
comparable among the different anatomical sites of the upper urinary
tract. Specifically, similar stone-free rates are reported for stones
in the kidney and the upper, middle, and lower ureter, making
extracorporeal shock wave lithotripsy the first-line therapy for most
upper urinary calculi (Refs. 11, 13, 21, 46, 66, and 90).
Despite being capable of effectively fragmenting most urinary
stones, there
[[Page 5991]]
are several limitations to the success of extracorporeal shock wave
lithotripsy. Many studies have observed poor effectiveness with both
staghorn and large (i.e., greater than 2 centimeters in largest
dimension) stones, leading to the recommendation that alternative stone
removal therapies should be considered for these cases (Refs. 57, 64,
75, 84, and 88). Furthermore, some stone compositions, particularly
cystine calculi, are more resistant to fragmentation than others, and,
therefore, may require more shocks than other stone types (Refs. 34 and
91). Because the effectiveness of lithotripsy is predicated on the
resulting stone fragments passing from the urinary tract, patients with
an obstruction distal to the stone cannot be successfully treated until
resolution of the obstruction (Refs. 8, 29, and 57). Stones that are
embedded or impacted within the tissue of the kidney or ureter are also
not effectively treated with lithotripsy, due to the inability of the
stone fragments to pass out of the body (Refs. 29 and 46). Lastly,
lithotripsy is not effective in patients with anatomical conditions
that prevent targeting of the shock wave focus at the stone, such as
severe obesity (Refs. 29 and 91) or orthopedic deformity (Ref. 53).
Although extracorporeal shock wave lithotripsy is effective for the
treatment of most ureteral calculi, in some specific instances it is
not effective as a first-line therapy. Many authors report poor
localization of ureteral stones using ultrasound imaging, making
lithotripsy difficult or impossible if the lithotripter does not
incorporate or use an x-ray imaging system (Refs. 35, 47, and 90).
Additionally, small stones in the middle or lower ureter (i.e., 4 to 6
mm in largest dimension) have a high probability of passing
spontaneously (Ref. 67), making the use of lithotripsy unnecessary
unless immediate intervention is required.
Since its introduction in the United States in 1984, extracorporeal
shock wave lithotripsy has become the preferred treatment for kidney
and ureteral calculi (Refs. 56 and 91). Not only is lithotripsy
extremely effective, but the overall rate of serious risks from
extracorporeal shock wave lithotripsy, primarily clinically significant
renal hematoma, severe hemorrhage, chronic renal injury, and sepsis, is
low and can be effectively minimized. Treatment is noninvasive, often
delivered in an outpatient setting, and can be performed without
general or regional anesthesia with many systems (Refs. 37, 56, and
104). Compared to alternative therapies for the removal of urinary
calculi, extracorporeal shock wave lithotripsy is either associated
with less morbidity (e.g., open surgery, percutaneous nephrolithotomy,
ureteroscopy) (Refs. 8, 54, 57, and 84) or increased success (e.g.,
watchful waiting) (Ref. 67).
Based on the available information, FDA believes that the special
controls discussed in section VIII of this document are capable of
providing reasonable assurance of the safety and effectiveness of the
extracorporeal shock wave lithotripter with regard to the identified
risks to health of this device.
VIII. Special Controls
In addition to general controls, FDA believes that the
extracorporeal shock wave lithotripter should be subject to the special
controls of labeling restrictions and a FDA guidance document to
minimize the risks to health identified for this device.
A. Labeling Restrictions
Labeling restrictions can control the risks of bleeding, renal
injury, cardiac arrhythmia, urinary obstruction, infection, injury to
adjacent organs, and other reported complications by providing
information on patient selection, treatment practices, post-treatment
followup, and potential adverse events. Specifically, FDA is proposing
that extracorporeal shock wave lithotripters be subject to the labeling
statements listed in the appendix as a special control, in addition to
other required labeling information.
Under 21 CFR 801.109(b)(ii) and section 520(e) of the act, FDA also
proposes as described in the 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'' to require the following statement: ``CAUTION:
Federal law restricts this device to sale by or on the order of a
physician trained and/or experienced in the use of this device as
outlined in an appropriate training program.''
B. FDA Guidance Document
Adherence to 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'' (Ref. 26) can control the risks of bleeding, renal
injury, cardiac arrhythmia, urinary obstruction, infection, injury to
adjacent organs, and other reported complications by recommending: (1)
Conformance to consensus standards, (2) shock wave characterization
measurements, (3) assessment of localization accuracy, (4) clinical
performance testing, and (5) physician training restrictions for
premarket notifications for extracorporeal shock wave lithotripters.
These sections of the guidance document correspond to the controls
recommended by the Panel.
1. Conformance to consensus standards
The FDA guidance document recommends conformance to the following
consensus standards: (1) International Electrotechnical Commission
(IEC) 60601-2-36 Medical electrical equipment--Part 2: Particular
requirements for the safety of equipment for extracorporeally induced
lithotripsy; (Ref. 39) and (2) IEC 61846 Ultrasonics--Pressure pulse
lithotripters--Characteristics of fields (Ref. 40).
Conformance with IEC 60601-2-36 can control the risks of bleeding,
renal injury, and injury to adjacent organs by requiring that the
device accurately localize stones at the shock wave focus and be
designed to guard against unintentional shock wave delivery.
Conformance with IEC 61846 can control the risks of bleeding, renal
injury, and injury to adjacent organs by providing a standard method
for characterizing the lithotripter's acoustic output for the purpose
of determining whether its shock wave characteristics are within the
range provided by existing systems.
2. Shock wave characterization measurements
Shock wave characterization measurements can control the risks of
bleeding, renal injury, and injury to adjacent organs by having each
manufacturer assess whether the shock wave characteristics of its
lithotripter are within the range provided by existing systems.
3. Assessment of localization accuracy
Assessment of localization accuracy can control the risks of
bleeding, renal injury, and injury to adjacent organs by having each
manufacturer verify that its device accurately positions stones at the
shock wave focus.
4. Clinical performance testing
Clinical performance testing can control the risks of bleeding,
renal injury, cardiac arrhythmia, and injury to adjacent organs by
verifying that the device accurately locates the target stone, delivers
shock waves in accordance with the parameters set by the operator, and
does not present an unreasonable risk of injury to the patient. As
recommended by the Panel, this testing can take the form of either a
small, confirmatory clinical study or a larger clinical investigation
of safety and
[[Page 5992]]
effectiveness, depending upon the technological characteristics of the
particular device (Ref. 94). For extracorporeal shock wave
lithotripters that generate shock waves using a similar method to that
of legally marketed systems and have comparable shock wave
characteristics, a small, confirmatory clinical study should be
performed. However, for systems that use a novel method of shock wave
generation or have shock wave characteristics that are outside of the
range of current devices, a larger clinical investigation is necessary
to assess safety and effectiveness.
5. Physician training restrictions
Physician training restrictions can control the risks of bleeding,
renal injury, cardiac arrhythmia, urinary obstruction, infection,
injury to adjacent organs, and other reported complications by having
each manufacturer develop a training program to instruct users of their
device on both the operation of the particular lithotripsy system and
the general practices for the safe and effective use of extracorporeal
shock wave lithotripters (Ref. 76). Manufacturers should inform device
users of this physician training restriction with the following
labeling statement: ``CAUTION: Federal law restricts this device to
sale by or on the order of a physician trained and/or experienced in
the use of this device as outlined in a training program.''
IX. FDA's Tentative Findings
The Panel and FDA believe that the extracorporeal shock wave
lithotripter should be classified 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.
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. Akdas, A., L. N. Turkeri, Y. Ilker, F. Simsek, and K. Emerk,
Short-Term Bioeffects of Extracorporeal Shockwave Lithotripsy,
Journal of Endourology, 8(3):187-190, 1994.
2. Albers, D. D., F. E. Lybrand, III, J. C. Axton, and J. R.
Wendelken, ``Shockwave Lithotripsy and Pacemakers: Experience with
20 Cases,'' Journal of Endourology, 9(4):301-303, 1995.
3. Anderson, K. R., K. Kerbl, P. T. Fadden, M. R. Wick, E. M.
McDougall, and R. V. Clayman, ``Effect of Piezoelectric Energy on
Porcine Kidneys Using the EDAP LT.02,'' Journal of Urology,
153:1295-1298, 1995.
4. Antoniou, N. K., D. Karanastasis, and J. L. Stenos, ``Severe
Perinephric Hemorrhage after Shock Wave Lithotripsy,'' Journal of
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5. Asroff, S. W., T. E. Kingston, and B. S. Stein,
``Extracorporeal Shock Wave Lithotripsy in Patient with Cardiac
Pacemaker in an Abdominal Location: Case Report and Review of the
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6. Atahan, O., T. Alkibay, U. Karaoglan, N. Deniz, and I.
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7. Back, W., K. U. Kohrmann, J. Bensemann, J. Rassweiler, and P.
Alken, ``Histomorphologic and Ultrastructural Findings of Shockwave-
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Journal of Endourology, 8(4):257-261, 1994.
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Lithotripsy for Patients with Calcified Ipsilateral Renal Arterial
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1992.
10. Carr, L. K., R. J. D. Honey, M. A. S. Jewett, D. Ibanez, M.
Ryan, and C. Bombardier, ``New Stone Formation: A Comparison of
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11. Cass, A. S., ``Comparison of First Generation (Dornier HM3)
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Urology, 153:588-592, 1995.
12. Cass, A. S., ``Extracorporeal Shock Wave Lithotripsy for Mid
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13. Cass, A. S., ``Extracorporeal Shock Wave Lithotripsy for
Ureteral Calculi,'' Journal of Urology, 147:1495-1498, 1992.
14. Cass, A. S., ``The Use of Ungating with the Medstone
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15. Claro, J. D., F. Denardi, U. Ferreira, N. R. Netto, Jr., L.
B. Saldanha, and J. F. Figueiredo, ``Effects of Extracorporeal
Shockwave Lithotripsy on Renal Growth and Function: An Animal
Model,'' Journal of Endourology, 8(3):191-194, 1994.
16. Coleman, A. J. and J. E. Saunders, ``Review of the Physical
Properties and Biological Effects of the High Amplitude Acoustic
Fields Used in Extracorporeal Lithotripsy,'' Ultrasonics, 31(2):75-
89, 1993.
17. Delius, M., W. Mueller, A. Goetz, H. Liebich, and W.
Brendel, ``Biological Effects of Shock Waves: Kidney Hemorrhage in
Dogs at a Fast Shock Wave Administration Rate of Fifteen Hertz,''
Journal of Lithotripsy and Stone Disease, 2(2):103-110, 1990.
18. Deliveliotis, Ch., A. Giftopoulos, G. Koutsokalis, G.
Raptidis, and A. Kostakopoulos, ``The Necessity of Prophylactic
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International Urology and Nephrology, 29(5):517-521, 1997.
19. Deliveliotis, Ch., A. Kostakopoulos, N. Stavropoulos, E.
Karagiotis, P. Kyriazis, and C. Dimopoulos, ``Extracorporeal Shock
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20. Drach, G. W., S. Dretler, W. Fair, B. Finlayson, J.
Gillenwater, D. Griffith, J. Lingeman, and D. Newman, ``Report of
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Govan, J. Lingeman, S. A. Loening, D. M. Newman, J. M. Tudor, and S.
Saada, ``Extracorporeal Shock Wave Lithotripsy: Multicenter Study of
Kidney and Upper Ureter Versus Middle and Lower Ureter Treatments,''
Journal of Urology, 152:1379-1385, 1994.
22. Elabbady, A., G. Mathes, D. D. Morehouse, J. Honey, J.
Pahira, R. Zeman, J. Paquin, R. Faucher, and M. M. Elhilali,
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Treatment of Urinary Calculi,'' Journal of Endourology, 9(3):225-
231, 1995.
23. El-Damanhoury, H., T. Scharfe, J. Ruth, S. Roos, and R.
Hohenfellner, ``Extracorporeal Shock Wave Lithotripsy of Urinary
Calculi: Experience in Treatment of 3,278 Patients Using the Siemens
Lithostar and Lithostar Plus,'' Journal of Urology, 145:484-488,
1991.
24. Elhilali, M. M., M. L. Stoller, T. C. McNamara, D. D.
Morehouse, J. S. Wolf, Jr., and L. L. Keeler, Jr., ``Effectiveness
and Safety of the Dornier Compact Lithotriptor: An Evaluative
Multicenter Study,'' Journal of Urology, 155:834-838, 1996.
25. Erturk, E., A. M. Ptak, and J. Monaghan, ``Fertility
Measures in Women after Extracorporeal Shockwave Lithotripsy of
Distal Ureteral Stones,'' Journal of Endourology, 11(5):315-317,
1997.
26. FDA Guidance Document (Draft),`` Guidance for the Content of
Premarket Notifications (510(k)s) for Extracorporeal Shock Wave
Lithotripters Indicated for the Fragmentation of Kidney and Ureteral
Calculi'' (Currently available for comment.)
27. Ferreira, U., J. D. Claro, N. R. Netto, Jr., F. Denardi, J.
F. Figueiredo, and C. L. Z. Riccetto, ``Functional and Histologic
Alterations in Growing Solitary Rat Kidney as a Result of
Extracorporeal Shockwaves,'' Journal of Endourology, 9(1):45-49,
1995.
28. Grasso, M., J. Liu, B. Goldberg, and D. H. Bagley,
``Submucosal Calculi: Endoscopic and Intraluminal Sonographic
Diagnosis and Treatment Options,'' Journal of Urology, 153:1384-
1389, 1995.
29. Grasso, M., P. Loisides, M. Beaghler, and D. Bagley, ``The
Case for Primary Endoscopic Managment of Upper Urinary Tract
Calculi: I. A Critical Review of 121 Extracorporeal Shock-Wave
Lithotripsy Failures,'' Urology, 45(3):363-371, 1995.
30. Greenstein, A., I. Kaver, V. Lechtman, and Z. Braf,
``Cardiac Arrhythmias during Nonsynchronized Extracorporeal Shock
Wave Lithotripsy,'' Journal of Urology, 154:1321-1322, 1995.
[[Page 5993]]
31. Grenabo, L., K. Lindqvist, H. Adami, R. Bergstrom, and S.
Pettersson, ``Extracorporeal Shock Wave Lithotripsy for the
Treatment of Renal Stones,'' Archives of Surgery, 132:20-26 1997.
32. Groshar, D., O. Israel, J. Ginessin, D. R. Levin, B.
Moskovitz, D. Front, and A. Frenkel, ``Effect of Extracorporeal
Piezoelectric Lithotripsy Shock Waves on Renal Function Measured by
Tc-99m-DMSA Using Spect,'' Urology, 38(6):537-539, 1991.
33. Gumus, B., M. Lekili, A. R. Kandiloglu, A. Isisag, G.
Temeltas, O. Nazli, and C. Buyuksu, ``Effects of Extracorporeal
Shockwave Lithotripsy at Different Stages of Pregnancy in the
Rabbit,'' Journal of Endourology, 11(5):323-326, 1997.
34. Gupta, M., D. M. Bolton, and M. L. Stoller, ``Etiology and
Management of Cystine Lithiasis,'' Urology, 45(2):344-355, 1995.
35. Hamdy, S., D. D. Morehouse, H. Laporte, and M. M. Elhilali,
Early Experience with ``Extracorporeal Shockwave Dornier
Lithotriptor,'' Journal of Endourology, 9(3):219-223, 1995.
36. Holmberg, G., S. Spinnell, and J. Sjodin, ``Perforation of
the Bowel during SWL in Prone Position,'' Journal of Endourology,
11(5):313-314, 1997.
37. Hosking, M. P., S. A. Morris, F. A. Klein, and C. Dobmeyer-
Dittrich,`` Anesthetic Management of Patients Receiving Calculus
Therapy with a Third-Generation Extracorporeal Lithotripsy
Machine,'' Journal of Endourology, 11(5):309-311, 1997.
38. Ilker, Y., L. N. Turkeri, V. Korten, T. Tarcan, and A.
Akdas, ``Antimicrobial Prophylaxis in Management of Urinary Tract
Stones by Extracorporeal Shock-Wave Lithotripsy: Is It Necessary?,''
Urology, 46(2):165-167, 1995.
39. International Electrotechnical Commission, International
Standard IEC 60601-2-36 Medical electrical equipment--Part 2:
Particular requirements for the safety of equipment for
extracorporeally induced lithotripsy, 1997 (IEC address: 3, rue de
Varembe Geneva, Switzerland; IEC web site: ``http://www.iec.ch'').
40. International Electrotechnical Commission, International
Standard IEC 61846 Ultrasonics--Pressure pulse lithotripters--
Characteristics of fields, 1998 (IEC address: 3, rue de Varembe
Geneva, Switzerland; IEC web site: ``http://www.iec.ch'').
41. Janetschek, G., F. Frauscher, R. Knapp, G. Hofle, R.
Peschel, and G. Bartsch, ``New Onset of Hypertension after
Extracorporeal Shock Wave Lithotripsy: Age Related Incidence and
Prediction by Intrarenal Resistive Index,'' Journal of Urology,
158:346-351, 1997.
42. Kabalin, J. N., S. Lennon, H. S. Gill, V. Wolfe, and I.
Perkash, ``Incidence and Management of Autonomic Dysreflexia and
Other Intraoperative Problems Encountered in Spinal Cord Injury
Patients Undergoing Extracorporeal Shock Wave Lithotripsy without
Anesthesia on a Second Generation Lithotriptor,'' Journal of
Urology, 149:1064-1067, 1993.
43. Kataoka, H., ``Cardiac Dysrhythmias Related to
Extracorporeal Shock Wave Lithotripsy Using a Piezoelectric
Lithotripter in Patients with Kidney Stones,'' Journal of Urology,
153:1390-1394, 1995.
44. Kataoka, H. and T. Tanigawa, ``Vasovagal Syncope Elicited by
Extracorporeal Shock Wave Lithotripsy,'' American Heart Journal,
126:258-259, 1993.
45. Katz, R., D. Admon, and D. Pode, ``Life-Threatening
Retroperitoneal Hematoma Caused by Anticoagulant Therapy for
Myocardial Infarction after SWL,'' Journal of Endourology, 11(1):23-
25, 1997.
46. Kim, H. H., J. H. Lee, M. S. Park, S. E. Lee, and S. W. Kim,
``In Situ Extracorporeal Shockwave Lithotripsy for Ureteral Calculi:
Investigation of Factors Influencing Stone Fragmentation and
Appropriate Number of Sessions for Changing Treatment Modality,''
Journal of Endourology, 10(6):501-505, 1996.
47. Kim, S. C. and Y. T. Moon, ``Experience with EDAP LT02
Extracorporeal Shockwave Lithotripsy in 1363 Patients: Comparison
with Results of LT01 SWL in 1586 Patients,'' Journal of Endourology,
11(2):103-111, 1997.
48. Kim, S. C., C. H. Oh, Y. T. Moon, and K. D. Kim, ``Treatment
of Steinstrasse with Repeat Extracorporeal Shock Wave Lithotripsy:
Experience with Piezoelectric Lithotriptor,'' Journal of Urology,
145:489-491, 1991.
49. Knapp, P. M., and T. B. Kulb, ``Extracorporeal Shock Wave
Lithotripsy Induced Perirenal Hematomas,'' Journal of Urology,
137:142A, abstract 155, 1987.
50. Knapp, P. M., T. B. Kulb, J. E. Lingeman, D. M. Newman, J.
H. O. Mertz, P. G. Mosbaugh, and R. E. Steele, ``Extracorporeal
Shock Wave Lithotripsy-Induced Perirenal Hematomas,'' Journal of
Urology, 139:700-703, 1988.
51. Kohrmann, K. U., J. J. Rassweiler, M. Manning, G. Mohr, T.
O. Henkel, K. P. Junemann, and P. Alken, ``The Clinical Introduction
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Urology, 153:1379-1383, 1995.
52. Krishnamurthi, V. and S. B. Streem, ``Long-Term Radiographic
and Functional Outcome of Extracorporeal Shock Wave Lithotripsy
Induced Perirenal Hematomas,'' Journal of Urology, 154:1673-1675,
1995.
53. Kroovand, R. L., ``Pediatric Urolithiasis,'' Urologic
Clinics of North America, 24(1):173-184, 1997.
54. Lehtoranta, K., ``Cost Effectiveness of Different Treatment
Alternatives in Urinary Stone Practice,'' Scandinavian Journal of
Urology and Nephrology, 29:437-447, 1995.
55. Lim, D. J., R. D. Walker, III, P. I. Ellsworth, R. C.
Newman, M. S. Cohen, M. A. Barraza, and P. S. Stevens, ``Treatment
of Pediatric Urolithiasis between 1984 and 1994,'' Journal of
Urology, 156:702-705, 1996.
56. Lingeman, J. E., ``Extracorporeal Shock Wave Lithotripsy:
Development, Instrumentation, and Current Status,'' Urologic Clinics
of North America, 24(1):185-211, 1997.
57. Lingeman, J. E., ``Lithotripsy and Surgery,'' Seminars in
Nephrology, 16(5):487-498, 1996.
58. Lingeman, J. E. and T. B. Kulb, ``Hypertension following
Extracorporeal Shock Wave Lithotripsy,'' Journal of Urology,
137:142A, abstract 154, 1987.
59. Lingeman, J. E., D. M. Newman, Y. I, Siegel, T. Eichhorn,
and K. Parr, ``Shock Wave Lithotripsy with the Dornier MFL 5000
Lithotripter Using an External Fixed Rate Signal,'' Journal of
Urology, 154:951-954, 1995.
60. Lingeman, J. E., J. R. Woods, and D. R. Nelson, ``Commentary
on ESWL and Blood Pressure,'' Journal of Urology, 154:2-4, 1995.
61. Lingeman, J. E., J. R. Woods, and P. D. Toth, ``Blood
Pressure Changes Following Extracorporeal Shock Wave Lithotripsy and
Other Forms of Treatment for Nephrolithiasis,'' The Journal of the
American Medical Association, 263(13):1789-1794, 1990.
62. Lipski, B., J. Miller, G. Rigaud, G. Stack, and C. Marsh,
``Acute Renal Failure from a Subcapsular Hematoma in a Solitary
Kidney: An Unusual Complication of Extracorporal Shock Wave
Lithotripsy,'' Journal of Urology, 157:2245, 1997.
63. Marcuzzi, D., R. Gray, and T. Wesley-James, ``Symptomatic
Splenic Rupture following Extracorporeal Shock Wave Lithotripsy,''
Journal of Urology, 145:547-548, 1991.
64. Meretyk, S., O. N. Gofrit, O. Gafni, D. Pode, A. Shapiro, A.
Verstandig, T. Sasson, G. Katz, and E. H. Landau, ``Complete
Staghorn Calculi: Random Prospective Comparison Between
Extracorporeal Shock Wave Lithotripsy Monotherapy and Combined with
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1997.
65. Miller, D. L. and R. M. Thomas, ``Thresholds for Hemorrhages
in Mouse Skin and Intestine Induced by Lithotripter Shock Waves,''
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66. Mobley, T. B., D. A. Myers, J. McK. Jenkins, W. B. Grine,
and W. R. Jordan, ``Effects of Stents on Lithotripsy of Ureteral
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Lithotripter,'' Journal of Urology, 152:53-56, 1994.
67. Morse, R. M. and M. I. Resnick, ``Ureteral Calculi: Natural
History and Treatment in an Era of Advanced Technology,'' Journal of
Urology, 145:263-265, 1991.
68. Muller-Mattheis, V. G. O., D. Schmale, M. Seewald, H. Rosin,
and R. Ackermann, ``Bacteremia During Extracorporeal Shock Wave
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1991.
69. Myers, D. A., T. B. Mobley, J. McK. Jenkins, W. B. Grine,
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70. Newman, D. M., and M. Kaefer, ``Pediatric ESWL: Suitability
Hinges on Long-Term Renal Effects,'' Contemporary Urology, pp. 71-
76, September, 1992.
71. Ohmori, K., T. Matsuda, Y. Horii, and O. Yoshida, ``Effects
of Shock Waves on the Mouse Fetus,'' Journal of Urology, 151:255-
258, 1994.
72. Pacik, D., T. Hanak, P. Kumstat, M. Turjanica, P. Jelinek,
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73. Phillips, M. T., W. H. Merrell, and R. P. Knobloch,
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[[Page 5994]]
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74. Preminger, G. M., ``Review: In Vivo Effects of
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75. Psihramis, K. E., M. A. S. Jewett, C. Bombardier, D. Caron,
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76. Radiation Safety Committee of the European Federation of
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77. Rahav, G., H. Strul, D. Pode, and M. Shapiro, ``Bacteriuria
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78. Rashid, P., D. Steele, and J. Hunt, ``Splenic Rupture after
Extracorporeal Shock Wave Lithotripsy,'' Journal of Urology,
156:1756-1757, 1996.
79. Rassweiler, J., A. Westhauser, P. Bub, and F. Eisenberger,
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80. Raz, R., A. Zoabi, M. Sudarsky, and J. Shental, ``The
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81. Robertson, J. B., M. O. Koch, F. K. Kirchner, Jr., and J. A.
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82. Roessler, W., P. Steinbach, R. Seitz, F., Hofstaedter, and
W. F. Wieland, ``Mechanisms of Shockwave Action in the Human
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83. Roessler, W., W. F. Wieland, P. Steinbach, F. Hofstaedter,
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84. Roth, R. A. and C. F. Beckmann, ``Complications of
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85. Ruiz, H. and B. Saltzman, ``Aspirin-Induced Bilateral Renal
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87. Schmidt, A., J. Seibold, P. Bub, and F. Eisenberger,
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88. Segura, J. W., G. M. Preminger, D. G. Assimos, S. P.
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151:1648-1651, 1994.
89. Simon, D., ``Experience with 500 Extracorporeal Shockwave
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Urology, 157:1197-1203, 1997.
92. Stoller, M. L., L. Litt, and R. G. Salazar, ``Severe
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94. Transcripts of the Gastroenterology and Urology Devices
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95. Tuteja, A. K., J. P. Pulliam, T. H. Lehman, and L. W.
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50(4):606-608, 1997.
96. Van Arsdalen, K. N., S. Kurzweil, J. Smith, and R. M. Levin,
``Effects of Lithotripsy on Immature Rabbit Bone and Kidney
Develoment,'' Journal of Urology, 146:213-216, 1991.
97. Vassolas, G., R. A. Roth, and F. J. Venditti, Jr., ``Effect
of Extracorporeal Shock Wave Lithotripsy on Implantable Cardioverter
Defibrillator,'' PACE, 16:1245-1248, 1993.
98. Vaughan E. D., Jr., J. N. Tobin, M. H. Alderman, R. E. Sosa,
G. W. Drach, and the NEMA Kidney Stone Blood Pressure Study Group
(KSBPS), ``Extracorporeal Shock Wave Monotherapy Does Not Cause
Renal Dysfunction or Elevated Blood Pressure,'' Journal of Urology,
155:539A, abstract 915, 1996.
99. Williams, C. M., J. V. Kaude, R. C. Newman, J. C. Peterson,
and W. C. Thomas, ``Extracorporeal Shock Wave Lithotripsy: Long-Term
Complications,'' American Journal of Roentgenology, 150:311-315,
1988.
100. Willis, L. R., A. P. Evan, B. A. Connors, N. S. Fineberg,
and J. E. Lingeman, ``Effects of SWL on Glomerular Filtration Rate
and Renal Plasma Flow in Uninephrectomized Minipigs,'' Journal of
Endourology, 11(1):27-32, 1997.
101. Willis, L. R., A. P. Evan, B. A. Connors, G. Reed, N. S.
Fineberg, and J. A. Lingeman, ``Effects of Extracorporeal Shock Wave
Lithotripsy to One Kidney on Bilateral Glomerular Filtration Rate
and PAH Clearance in Minipigs,'' Journal of Urology, 156:1502-1506,
1996.
102. Winters, J. C. and J. N. Macaluso, Jr., ``Ungated Medstone
Outpatient Lithotripsy,'' Journal of Urology, 153:593-595, 1995.
103. Yeaman, L. D., C. P. Jerome, and D. L. McCullough,
``Effects of Shock Waves on the Structure and Growth of the Immature
Rat Epiphysis,'' Journal of Urology, 141:670-674, 1989.
104. Zommick, J., R. Leveillee, A. Zabbo, L. Colasanto, and D.
Barrette, ``Comparison of General Anesthesia and Intravenous
Sedation-Analgesia for SWL,'' Journal of Endourology, 10(6):489-491,
1996.
XI. Environmental Impact
The agency has determined under 21 CFR 25.34(b) that this
reclassification 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 proposed 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 (Pub. L. 104-121), and the Unfunded Mandates Reform Act of 1995
(Pub. L. 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 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 by lowering their costs. The agency therefore certifies
that this reclassification action, if finalized, will
[[Page 5995]]
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.
XIII. Request for Comments
Interested persons may, on or before May 10, 1999 submit to the
Dockets Management Branch (address above) written comments regarding
this document. 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.
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, it is
proposed that 21 CFR part 876 be 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. Sec. 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 and 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 through a water-filled rubber cushion or by direct
contact of the patient's skin with the water. 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).
(1) Labeling that contains the statements listed in the appendix in
addition to other required labeling information.
(2) 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.''
APPENDIX TO Sec. 876.5990: Labeling Restrictions
a. Contraindications:
Do not use the device in patients with:
Anatomy which precludes focusing the device at the target stone,
such as severe obesity or excessive spinal curvature.
Arterial calcification or vascular aneurysm in the lithotripter's
shock wave path.
Coagulation abnormalities (as indicated by abnormal prothrombin
time, partial thromboplastin time, or bleeding time) or those currently
receiving anticoagulants (including aspirin).
Confirmed or suspected pregnancy.
Urinary tract obstruction distal to the stone.
b. Warnings:
Air-filled interfaces in shock wave path: Do not apply shock waves
to air-filled areas of the body, i.e., intestines or lungs. Shock waves
are rapidly dispersed by passage through an air-filled interface, which
can cause bleeding and other harmful side effects.
Anticoagulants: Patients receiving anticoagulants (including
aspirin) should temporarily discontinue such medication prior to
extracorporeal shock wave lithotripsy to prevent severe hemorrhage.
Bilateral stones: Do not perform bilateral treatment of kidney
stones in a single treatment session, because either bilateral renal
injury or total urinary tract obstruction by stone fragments may
result. Patients with bilateral kidney stones should be treated using a
separate treatment session for each side. In the event of total urinary
obstruction, corrective procedures may be needed to ensure drainage of
urine.
Cardiac arrhythmia during treatment: If a patient experiences
cardiac arrhythmia during treatment at a fixed shock wave repetition
rate, shock wave delivery should either be terminated or switched to an
ECG-gated mode (i.e., delivery of the shock wave during the refractory
period of the patient's cardiac cycle). As a general practice, patients
with a history of cardiac arrhythmia should be treated in the ECG-gated
mode. (If the system is capable of delivering shock waves at a fixed
frequency.)
Cardiac disease, immunosuppression, and diabetes mellitus:
Prophylactic antibiotics should be administered prior to extracorporeal
shock wave lithotripsy treatment to patients with cardiac disease
(including valvular disease), immunosuppression, and diabetes mellitus,
to prevent bacterial and/or subacute endocarditis.
Cardiac monitoring: Always perform cardiac monitoring during
lithotripsy treatment, because the use of extracorporeal shock wave
lithotripsy has been reported to cause ventricular cardiac arrhythmias
in some individuals. This warning is especially important for patients
who may be at risk of cardiac arrhythmia due to a history of cardiac
irregularities or heart failure.
Infected stones: Prophylactic antibiotics should be administered
prior to treatment whenever the possibility of stone infection exists.
Extracorporeal shock wave lithotripsy treatment of pathogen-harboring
calculi could result in systemic infection.
Pacemaker or implantable defibrillator: To reduce the incidence of
malfunction to a pacemaker or implantable defibrillator, the pulse
generator should be programmed to a single chamber, non-rate responsive
mode (pacemakers) or an inactive mode (implantable defibrillators)
prior to lithotripsy, and evaluated for proper function post-treatment.
Do not focus the lithotripter's shock wave through or near the pulse
generator.
c. Precautions:
Impacted or embedded stones: The effectiveness of extracorporeal
shock wave lithotripsy may be limited in patients with impacted or
embedded stones. Alternative procedures are recommended for these
patients.
Radiographic followup: All patients should be followed
radiographically after treatment until stone-free or there are no
remaining stone fragments which are likely to cause silent obstruction
and loss of renal function.
Renal injury: To reduce the risk of injury to the kidney and
surrounding tissues, it is recommended that: (1) The number of shock
waves administered during each treatment session be minimized; (2)
retreatment to the same
[[Page 5996]]
kidney/anatomical site occur no sooner than 1 month after the initial
treatment; and (3) each kidney/anatomical site be limited to a total of
three treatment sessions.
Small ureteral stones: Small middle and lower ureteral stones, 4 to
6 mm in largest dimension, are likely to pass spontaneously. Therefore,
the risks and benefits of extracorporeal shock wave lithotripsy should
be carefully assessed in this patient population.
Staghorn stones: The effectiveness of extracorporeal shock wave
lithotripsy may be limited in patients with either staghorn or large
( 20 mm in largest dimension) stones. Alternative procedures
are recommended for these patients.
d. Patient Selection and Treatment:
Children: The safety and effectiveness of this device in the
treatment of urolithiasis in children have not been demonstrated.
Although children have been treated with shock wave therapy for upper
urinary tract stones, experience with lithotripsy in such cases is
limited. Studies indicate that there are growth plate disturbances in
the epiphyses of developing long bones in rats subjected to shock
waves. The significance of this finding to human experience is unknown.
Women of childbearing potential: The treatment of lower ureteral
stones should be avoided in women of childbearing potential. The
application of shock wave lithotripsy to this patient population could
possibly result in irreversible damage to the female reproductive
system and to the unborn fetus in the undiagnosed pregnancy.
e. Adverse Events:
Potential adverse events associated with the use of extracorporeal
shock wave lithotripsy include those listed below, categorized by
frequency and individually described:
1. Potential Adverse Events of Extracorporeal Shock Wave Lithotripsy
Categorized by Frequency:
a. Commonly reported (> 20 percentage of patients): Hematuria,
pain/renal colic, skin redness at shock wave entry site.
b. Occasionally reported (1 to 20 percentage of patients): Cardiac
arrhythmia, urinary tract infection, urinary obstruction/steinstrasse,
skin bruising at shock wave entry site, fever (> 38EC), nausea/
vomiting.
c. Infrequently reported (< 1 percentage of patients): Hematoma
(perirenal/intrarenal), renal injury.
2. Description of Adverse Events of Extracorporeal Shock Wave
Lithotripsy:
Cardiac arrhythmia: Cardiac arrhythmias, most commonly premature
ventricular contractions, are generally reported during extracorporeal
shock wave lithotripsy at fixed shock wave delivery in 2 to 20
percentage of patients. These cardiac disturbances rarely pose a
serious risk to the healthy patient, and typically resolve
spontaneously upon synchronizing the shock waves with the refractory
period of the ventricular cycle (i.e., ECG gating) or terminating
treatment.
Fever (> 38 C): Fever is occasionally reported after lithotripsy,
and may be secondary to infection.
Hematoma (perirenal/intrarenal): Clinically significant intrarenal
or perirenal hematomas occur in < 1 percentage of lithotripsy
treatments. Typically patients who experience this complication present
with severe flank pain. Although clinically significant hematomas often
resolve with conservative management, severe hemorrhage and death have
been reported. Management of severe renal hemorrhage includes the
administration of blood transfusions, percutaneous drainage, or
surgical intervention.
Hematuria: Hematuria occurs following most treatments, is believed
to be secondary to trauma to the renal parenchyma, and usually resolves
spontaneously within 24 to 48 hours of treatment.
Nausea/vomiting: Transient nausea and vomiting are occasionally
reported immediately after lithotripsy, and may be associated with
either pain or the administration of sedatives or analgesia.
Pain/renal colic: Pain/renal colic commonly occurs during and
immediately after treatment, and typically resolves spontaneously.
Temporary pain/renal colic may also occur secondary to the passage of
stone fragments, and can be managed with medication.
Renal injury: Extracorporeal shock wave lithotripsy procedures have
been known to cause damage to the treated kidney. The potential for
injury, its long-term significance, and its duration are unknown.
Skin bruising at shock wave entry site: Skin bruising at the shock
wave entry site occasionally occurs after treatment, and it typically
resolves spontaneously.
Skin redness at shock wave entry site: Skin redness at the shock
wave entry site commonly occurs during and immediately after treatment,
and typically resolves spontaneously.
Urinary obstruction/steinstrasse: Urinary obstruction occurs in up
to 6 percent of patients following lithotripsy due to stone fragments
becoming lodged in the ureter, and may be the result of either a single
stone fragment or the accumulation of multiple small stone particles
(i.e., steinstrasse). Patients with urinary obstruction typically
present with persistent pain, and may be at risk of developing
hydronephrosis with subsequent renal failure if the obstruction is not
promptly treated. Intervention is necessary if the obstructing
fragments do not pass spontaneously.
Urinary tract infection: Urinary tract infection (UTI) occurs in 1
to 7 percent of patients following extracorporeal shock wave
lithotripsy as a result of the release of bacteria from the
fragmentation of infected calculi, and infrequently results in
pyelonephritis or sepsis. The risk of infectious complications
secondary to extracorporeal shock wave lithotripsy can be minimized
through the use of prophylactic antibiotics in patients with UTI and
infection stones.
Dated: January 21, 1999.
Linda S. Kahn,
Deputy Director for Regulations Policy, Center for Devices and
Radiological Health.
[FR Doc. 99-2689 Filed 2-5-99; 8:45 am]
BILLING CODE 4160-01-F