[Federal Register: March 5, 2004 (Volume 69, Number 44)]
[Proposed Rules]
[Page 10390-10397]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05mr04-36]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 888
[Docket No. 2003N-0561]
Orthopedic Devices; Effective Date of the Proposed Requirement
for Premarket Approval of the Hip Joint Metal/Polymer or Ceramic/
Polymer Semiconstrained Resurfacing Cemented Prosthesis
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule; opportunity to request a change in
classification.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
require the filing of a premarket approval application (PMA) or a
notice of completion of a product development protocol (PDP) for the
hip joint metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prosthesis. The agency is summarizing its proposed findings
regarding the degree of risk of illness or injury intended to be
eliminated or reduced by requiring the device to meet the statute's
approval requirements as well as the benefits to the public from the
use of the device. The agency also is proposing to revise the name and
identification of the device. In addition, FDA is announcing the
opportunity for interested persons to request the agency to change the
classification of the device based on new information. FDA is taking
this action under the Federal Food, Drug, and Cosmetic Act (the act) as
amended by the Medical Device Amendments of 1976 (the 1976 amendments),
the Safe Medical Devices Act of 1990 (the SMDA), the Food and Drug
Administration Modernization Act of 1997 (FDAMA), and the Medical
Device User Fee and Modernization Act of 2002 (MDUFMA).
DATES: Submit written or electronic comments by June 3, 2004; submit
written or electronic requests for a change in classification by March
22, 2004.
ADDRESSES: Submit written comments or requests for a change in
classification to the Division of Dockets Management (HFA-305), Food
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD
20852. Submit electronic comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments
.
FOR FURTHER INFORMATION CONTACT: Pei Sung, Center for Devices and
Radiological Health (HFZ-410), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-2036.
SUPPLEMENTARY INFORMATION:
I. Background
Section 513 of the act (21 U.S.C. 360(c)) requires FDA to classify
medical devices into one of three regulatory categories (classes):
Class I (general controls), class II (special controls), and class III
(premarket approval). Generally, FDA has classified, or is classifying,
devices that were on the market before May 28, 1976, the date of
enactment of the 1976 amendments, and devices marketed on or after that
date that are substantially equivalent to such devices. For
convenience, this preamble refers to the devices that were on the
market before May 28, 1976, and the substantially equivalent devices
that were marketed on or after that date as ``preamendments devices.''
Section 515(b)(1) of the act (21 U.S.C. 360e(b)(1)) establishes the
requirement that a preamendments device that FDA has classified into
class III is subject to premarket approval. An applicant may
commercially distribute a preamendments class III device without an
approved PMA or a notice of completion of a PDP until 90 days after the
effective date that FDA issues in a final rule requiring premarket
approval for the device, or 30 months after final classification of the
device under section 513 of the act, whichever is later. Also, an
applicant may commercially distribute a preamendments device subject to
the rulemaking procedure under section 515(b) without an approved
investigational device exemption (IDE) part 812 (21 CFR part 812) until
the date FDA identifies in the final rule requiring the submission of a
PMA or PDP for the device. At that time, an applicant must submit an
IDE if a PMA has not been submitted or a PDP has not been declared
completed.
Section 515(b)(2)(A) of the act provides a proceeding to issue a
final rule to require premarket approval. The agency must initiate the
process by publishing a notice of proposed rulemaking in the Federal
Register. The notice must contain: (1) The proposed rule, (2) the
proposed findings with respect to the degree of risk of illness or
injury designed to be eliminated or reduced by requiring the device to
have an approved PMA or a declared completed PDP and the benefit to the
public from the use of the device, (3) an opportunity to submit
comments on the proposed rule and the proposed findings, and (4) an
opportunity to request reclassification of the device based on relevant
new information.
If FDA receives a request to reclassify the device within 15 days
of publication of the notice, section 515(b)(2)(B) of the act requires
the agency to take the following action. Within 60 days of the
publication of the notice, FDA must consult with the appropriate FDA
advisory committee and publish a notice denying the requested
reclassification or announcing the agency's intent to initiate a
proceeding to reclassify the device under section 513(e) of the act. If
FDA does not initiate such a proceeding, section 515(b)(3) of the act
requires FDA, after the close of the comment period on the proposed
[[Page 10391]]
rule and consideration of any comments received, to: (1) Issue a final
rule requiring premarket approval, or (2) publish a notice terminating
the proceeding. If FDA terminates the proceeding, FDA must initiate
reclassification of the device under section 513(e) of the act. FDA
does not have to initiate reclassification of the device if the reason
for termination is that the device is a banned device under section 516
of the act (21 U.S.C. 360f).
If a proposed rule to require premarket approval for a
preamendments device becomes final, section 501(f)(2)(B) of the act (21
U.S.C. 351(f)(2)(B)) requires the applicant to file a PMA or notice of
completion of a PDP for any such device no later than 90 days after the
date that FDA identifies in the final rule, or 30 months after final
classification of the device under section 513 of the act, whichever is
later. If an applicant does not file a PMA or notice of completion of a
PDP by the later of the two dates, commercial distribution of the
device must cease. An applicant may distribute the device for
investigational use, if the applicant complies with the IDE
regulations. If the applicant does not file a PMA or notice of
completion of a PDP by the later of the two dates, and no IDE is in
effect, the device is deemed to be adulterated within the meaning of
section 501(f)(1)(A) of the act. The device also is subject to seizure
and condemnation under section 304 of the act (21 U.S.C. 334) if its
distribution continues. Shipment of the device in interstate commerce
is subject to an injunction under section 302 of the act (21 U.S.C.
332). The individuals responsible for such shipment are subject to
prosecution under section 303 of the act (21 U.S.C. 333). In the past,
FDA has requested manufacturers to take action to prevent the further
use of devices that do not have a filed PMA. FDA may determine that
such a request is appropriate for the hip joint metal/polymer or
ceramic/polymer semiconstrained resurfacing cemented prosthesis.
If a proposed rule to require premarket approval for a
preamendments device becomes final, the act does not permit the agency
to extend the 90-day period after the rule's effective date for filing
an application or a notice. The House Report on the amendments states
``the thirty month `grace period' afforded after classification of a
device into class
III * * * is sufficient time for manufacturers and importers to develop
the data and conduct the investigations necessary to support an
application for premarket approval.'' (H. Rept. 94-853, 94th Cong., 2d
Sess. 42 (1976).)
The SMDA added section 515(i) to the act requiring FDA to review
the classification of preamendments class III devices that do not have
a final rule issued requiring the submission of PMAs. After its review,
FDA must determine whether or not each device should be reclassified
into class I or class II or remain in class III. For devices remaining
in class III, the SMDA directs FDA to develop a schedule for issuing
regulations to require premarket approval. The SMDA does not prevent
FDA from proceeding immediately to rulemaking under section 515(b) of
the act on specific devices, in the interest of public health,
independent of the procedures of section 515(i) of the act. Proceeding
directly to rulemaking under section 515(b) of the act is consistent
with Congress' objective in enacting section 515(i) of the act, i.e.,
that preamendments class III devices for which PMAs or notices of
completed PDPs have not been required either be: (1) Reclassified to
class I or II, or (2) subject to premarket approval requirements. In
this proposal, interested persons have the opportunity to request
reclassification of the hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis.
A. Classification of the Hip Joint Metal/Polymer Semiconstrained
Resurfacing Cemented Prosthesis
In the Federal Register of September 4, 1987 (52 FR 33686), FDA
issued a final rule classifying the hip joint metal/polymer
semiconstrained resurfacing cemented prosthesis into class III. The
preamble to the proposed rule to classify this device (47 FR 29052,
July 2, 1982) included the recommendation of the Orthopedic Device
Classification Panel (the Panel), an FDA advisory committee, regarding
the classification of the device. The Panel recommended that this
device be classified into class II, and identified the following risks
to health presented by the device: Loss or reduction of joint function,
adverse tissue reaction, and infection. The Panel believed that
controls to the design, material composition, and mechanical properties
of the device, such as its flexibility, rigidity, strength, and surface
finish, were necessary to address these risks to health. The Panel also
believed that the labeling of the device should include information on
the device's dimensions, kinematics, strength, and wear
characteristics. The Panel believed that sufficient information existed
to establish a performance standard to provide reasonable assurance of
the safety and effectiveness of the device.
FDA disagreed with the Panel's recommendation and proposed (47 FR
29052) that the hip joint metal/polymer semiconstrained resurfacing
cemented prosthesis be classified into class III. FDA believed that
general controls, either alone or in combination with performance
standards applicable to class II devices, were insufficient to provide
reasonable assurance of the safety and effectiveness of the device. FDA
believed that there was insufficient information to establish a
performance standard for the device and that the device presented
unreasonable risks of illness or injury because there were not adequate
data to ensure the safe and effective use of the device.
The preamble to the final rule (52 FR 33686) classifying the hip
joint metal/polymer semiconstrained resurfacing cemented prosthesis
into class III advised that the earliest date FDA could require PMAs or
notices of completion of PDPs for the device would be 90 days after FDA
issued a rule requiring premarket approval for the device. In the
Federal Register of January 6, 1989 (54 FR 550), FDA published a notice
of intent to initiate proceedings to require premarket approval of 31
preamendments class III devices. The notice described the factors FDA
took into account in establishing priorities for proceedings under
section 515(b) of the act for issuing final rules requiring that
preamendments class III devices have approved PMAs or declared
completed PDPs. In the Federal Register of May 6, 1994 (59 FR 23731),
FDA announced the availability of its preamendments class III devices
strategy document. The agency categorized the hip joint metal/polymer
semiconstrained resurfacing cemented prosthesis as a high priority
Group 3 device, a device the agency considered to have low probability
of being reclassified into class I or class II. Subsequently, FDA
determined that the ceramic/polymer semiconstrained resurfacing
cemented prosthesis is substantially equivalent to the metal/polymer
semiconstrained resurfacing cemented prosthesis. Accordingly, FDA is
commencing a proceeding under section 515(b) of the act to require that
the metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prosthesis have an approved PMA or declared completed PDP.
B. Dates New Requirements Apply
In accordance with section 515(b) of the act, FDA is proposing to
require an applicant to file a PMA or notice of completion of a PDP
with the agency for
[[Page 10392]]
the hip joint metal/polymer or ceramic/polymer semiconstrained
resurfacing cemented prosthesis by no later than 90 days after FDA
publishes a final rule based on this proposal. An applicant whose
device was in commercial distribution before May 28, 1976, or whose
device FDA has determined to be substantially equivalent to such a
device, may continue to market the hip joint metal/polymer or ceramic/
polymer semiconstrained resurfacing cemented prosthesis during FDA's
review of the PMA or notice of completion of a PDP. FDA intends to
review any PMA for the device within 180 days and any notice of
completion of a PDP for the device within 90 days of the filing date.
FDA cautions that under section 515(d)(1)(B)(I) of the act, the agency
may not enter into an agreement to extend the review period for a PMA
beyond 180 days unless the agency finds that ``* * * the continued
availability of the device is necessary for the public health.''
Under Sec. 812.2(d), FDA intends that the preamble to any final
rule based on this proposal will inform the applicant about limits on
certain exemptions under the IDE regulations. No later than 90 days
after FDA publishes a final rule requiring an applicant to file a PMA
or notice of completion of a PDP, the exemptions in Sec. 812.2(c)(1)
and (c)(2) of the IDE regulations for preamendments class III devices
will cease to apply to any hip joint metal/polymer or ceramic/polymer
semiconstrained cemented prosthesis which is: (1) Not legally on the
market on or before that date; or (2) legally on the market on or
before that date but for which a PMA or notice of completion of a PDP
is not filed by that date, or for which PMA approval has been denied or
withdrawn.
If an applicant does not submit a PMA, notice of completion of a
PDP, or an IDE application for the hip joint metal/polymer or ceramic/
polymer semiconstrained cemented prosthesis by no later than 90 days
after FDA publishes a final rule requiring premarket approval for the
device, commercial distribution of the device must cease. FDA cautions
that manufacturers not planning to submit a PMA or notice of completion
of a PDP immediately, should submit IDE applications to FDA no later
than 60 days after the final rule publishes. FDA considers
investigations of the hip joint metal/polymer or ceramic/polymer
semiconstrained cemented prosthesis to pose a significant risk as
defined in the IDE regulation.
C. Description of the Device
The hip joint metal/polymer or ceramic/polymer semiconstrained
resurfacing cemented prosthesis is an implanted device intended to
replace a portion of the hip joint with minimal bone resection. FDA is
proposing the following device identification for the hip joint metal
or ceramic/polymer semiconstrained resurfacing cemented prosthesis to
include ceramic/polymer semiconstrained resurfacing cemented hip joint
prostheses that the agency has determined to be substantially
equivalent (cleared) under Sec. 888.3410 (21 CFR 888.3410):
A hip joint metal/polymer or ceramic/polymer semiconstrained
resurfacing cemented prosthesis is a two-part device intended to be
implanted to replace the articulating surfaces of the hip while
preserving the femoral head and neck. The device limits translation
and rotation in one or more planes via the geometry of its
articulating surfaces. It has no linkage across the joint. This
generic type of device includes prostheses that consist of a femoral
cap component made of a metal alloy, such as cobalt-chromium-
molybdenum, or a ceramic material, that is placed over a surgically
prepared femoral head, and an acetabular resurfacing polymer
component. Both components are intended for use with bone cement (21
CFR 888.3027).
D. Proposed Findings With Respect to Risks and Benefits
As required by section 515(b) of the act, FDA is publishing its
findings regarding: (1) The degree of risk of illness or injury
designed to be eliminated or reduced by requiring an approved PMA or
completed PDP for the hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis, and (2) the benefits
to the public from the use of the device.
E. Risk Factors
In the early 1950s, Townley (Ref. 1) designed a new type of hip
joint prosthesis, the total articular resurfacing arthroplasty (TARA).
The TARA is a type of hip surface replacement (HSR) prosthesis. A
metallic component covers the articulating surface of the femoral head
component of the device. The articulating surface of the acetabulum is
resurfaced with a thin ultra-high molecular weight polyethylene
(UHMWPe) shell. Because of the high failure rates of the TARA's
acetabular component and the loosening of its femoral component, this
device is no longer in use (Ref. 2). Since then, several slightly
different HSR joint prosthesis designs have been marketed and
investigated. These include metal-backed UHMWPe acetabular cups,
ceramic femoral resurfacing components, and porous-coated femoral and
acetabular components.
Based on the published literature and other publicly available
information, FDA has determined that the following risks to health are
associated with the use of the hip joint metal/polymer semiconstrained
resurfacing cemented prosthesis:
1. Revision--Due to mechanical aseptic failure, revision surgery is a
major risk to health associated with implanting the metal/polymer or
ceramic polymer semiconstrained resurfacing hip prosthesis. Revision
surgery is a second major surgery to remove the device and replace it
with a total hip replacement (THR).
Clinical investigations published before the device was classified
in 1987 reported unacceptably high revision rates. These studies and
studies published after the device was classified report revision rates
up to 11.2 to 47.0 percent for followup periods ranging from 2 to 10
years for HSR arthroplasty with metal/polymer articulation (Refs. 3 to
9). With conventional THR, the 5- to 7-year failure rates range from
1.0 to 1.7 percent and 10-year failure rates are approximately 3
percent (Ref. 3).
In 1981, Head (Ref. 4) reported a 34 percent failure rate for the
Wagner HSR prosthesis. The average time to failure of the device was
1[frac1s2] years. He concluded that the causes of its high failure rate
were: (1) A high susceptibility to avascular necrosis of the femoral
head, (2) the younger ages of the patients, and (3) the device's
biomechanical design.
In 1984, Head (Ref. 5) reported an overall anticipated failure rate
for another HSR prosthesis. The rate was 34 percent (11.9 percent
actual and 22 percent anticipated) after an average patient followup of
3.3 years. He predicted the ``anticipated'' device failure rate from
radiographic evidence indicating device component failure in 15
patients who had experienced intermittent but not significant pain.
Head believed that the radiographic evidence and pain were predictive
of future failure and revision. He attributed the high incidence of
component failure to: (1) The patients' high activity level, (2) poor
cement distribution with resultant micro motion, and (3) increased
frictional torque of the larger-diameter acetabular component.
Also in 1984, Capello et al. (Ref. 6) reported a 14.5 percent
revision rate and a 10 percent loosening rate for the Indiana
Conservative HSR prosthesis at 2 to 7 year's followup. They believed
that this failure rate and non-traumatic loosening rate were
unacceptable.
[[Page 10393]]
In 1986, Ritter and Gioe (Ref. 7) compared the Indiana Conservative
HSR prosthesis and the Trapezoidal 28 (T-28) conventional THR implanted
in the same patient. After an average patient followup of 5.4 years,
failure rates were six times greater in patients implanted with the
resurfacing design hip joint prosthesis (26 percent) than in patients
implanted with the T-28 THR (4 percent). The complications of the
resurfacing hip joint prosthesis group included femoral and acetabular
loosening and femoral neck fracture.
In 1987, Kim et al. (Ref. 8) reported a comparison between the
THARIES hip joint prosthesis, a type of HSR prosthesis, and two
conventional THRs, the Biomet Charnley and the T-28 hip joint
prostheses, in patients younger than 40 years old. Patient followup was
up to 8.5 years. Kaplan-Meier failure rates were calculated at 3 and 5
years. In the highest risk patients, the younger non-rheumatoid
arthritis (non-RA) and non-juvenile rheumatoid arthritis (non-JRA)
patients, the conventional THR patients had significantly better hip
functions than the patients with the THARIES prosthesis. In the lowest
risk RA or JRA patients, the THARIES prosthesis appeared to perform as
well as conventional THR. Kim et al. predicted that all acrylic-fixed
hip joint prostheses, THARIES or THRs, would undergo early mechanical
loosening in non-RA, non-JRA patients younger than 30 years old. They
advised against the use of acrylic cement fixation of THARIES
prostheses in patients younger than 30.
In 1990, Faris et al. (Ref. 9) reported on 64 Indiana Conservative
HSR prostheses implanted in 61 patients with an average followup of 6.8
years. There was a 47 percent failure rate. Acetabular failure occurred
in 20 patients, femoral failure occurred in 18 patients, and both
acetabular and femoral failure occurred in 13 patients. Faris et al.
concluded, ``There seems to be little or no place for this design in
contemporary hip joint arthroplasty.''
In 1994, Mesko et al. (Ref. 3) reported a 13.2 percent revision
rate for the TARA prosthesis at a mean patient followup of 8 years. The
revised patients were an average of 7 years younger than the non-
revised patients. The cemented TARA prosthesis had better intermediate
to long-term success than other cemented resurfaced hip joint
prostheses. However, the TARA prosthesis did not compare favorably to
the conventional THR's lower 5- to 7-year failure rates of 1.0 to 1.7
percent and 10-year failure rates of 3 percent.
HSR was developed as an alternative to conventional THRs because of
its minimal requirements for bone removal. However, the failure rates
of the HSRs reported in section E.1. of this document (Refs. 3 to 9)
are significantly higher compared to the failure rates of conventional
THRs. In addition, due to the inadequate UHMWPe thickness of some early
HSR designs, biomechanical analyses indicated that device loosening is
the predominate reason for the high failure rates of the HSR prosthesis
compared to conventional THRs.
Potential etiologies for the high loosening rates cited previously
include the following (Refs. 10 to 16): (1) Inadequate device design--
impingement between the rim of the acetabular cup and the femoral neck,
increased friction torque of the larger acetabular component, and
inadequate implant-cement and/or cement-bone interfaces, (2) UHMWPe
wear debris associated with macrophage response, cellular membrane
development, granuloma formation and/or bone resorption, (3) surgical
technique error such as inadequate cementing technique or cement
distribution, inadequate bone strength beneath the components, various
placement positions of the device, i.e., varus or valgus positions that
cause toggling within the femoral intramedullary canal, and (4) higher
physical activity levels of younger patients.
2. Loss or Reduction of Hip Joint Function--Improper design or
inadequate mechanical properties of the device, such as lack of
strength and resistance to wear, may result in a loss or reduction of
hip joint function due to excessive wear, fracture, dislocation and/or
deformation of the device components.
3. Adverse Tissue Reaction--Inadequate biological or mechanical
properties of the device, such as lack of biocompatibility and
resistance to wear, may result in an adverse tissue reaction. This
reaction is due to dissolution or erosion of the device's articulating
surfaces and release of debris to surrounding tissues and the systemic
circulation.
4. Infection--The presence of an implanted device within the body may
lead to an increased risk of infection.
FDA notes that loss or reduction of hip joint function, adverse
tissue reaction, and infection are risks to health common to all
implanted hip joint prostheses.
F. Benefits of the Device
The hip joint metal/polymer or ceramic/polymer semiconstrained
resurfacing cemented prosthesis is an implanted device intended to
replace a portion of the hip joint with minimal bone resection. The
potential benefits intended from implantation of the device are relief
of intense, disabling pain and restoration of hip joint function. This
would result in a return to daily activities and an improved quality of
life, especially in young patients.
In 1984, Amstutz et al. (Ref. 17) reported on the THARIES TARA
prosthesis and T-28 THR for the treatment of primary hip osteoarthritis
after a 6-year followup period. They concluded that the THARIES
prosthesis appeared to be an acceptable alternative to THR after
intermediate followup for 38 months. They stated that HSR could become
a preferred treatment for primary osteoarthritis, ``if these results
are maintained after longer follow-up or are improved using better
technique and a metal backing.''
In 1987, Kim et al. reported that for low risk non-RA, non-JRA
patients younger than 40 years old, the THARIES prosthesis appeared to
perform as well as conventional THR after 3 to 5 years of followup
(Ref. 8).
FDA has determined from review of the literature that the major
causes of device loosening and subsequent device failure necessitating
revision appear to be: (1) UHMWPe or metal particulate wear debris-
induced bone resorption, and (2) high patient activity levels. Both
cause increased wear and subsequent device failure necessitating
revision.
Based on its evaluation of the benefits and risks described
previously, FDA has concluded that the safety and effectiveness of the
hip joint metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prosthesis have not been established by valid scientific
evidence as defined in 21 CFR 860.7.
II. PMA Requirements
A PMA for the hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis must include the
information required by section 515(c)(1) of the act and Sec. 814.20
(21 CFR 814.20) of the PMA regulations. The PMA should include a
detailed discussion of risks as well as a discussion of the
effectiveness of the device for which premarket approval is sought. In
addition, a PMA should include all data and information on: (1) Any
risks known, or that should be reasonably known to the applicant that
were not identified in this proposed rule; (2) the effectiveness of the
specific hip joint metal/polymer or ceramic/polymer semiconstrained
resurfacing cemented prosthesis that is the subject of the submission;
and (3) full reports of all device preclinical and clinical
[[Page 10394]]
information from the safety and effectiveness investigations for which
premarket approval is sought.
A PMA should include valid scientific evidence as defined in 21 CFR
860.7, obtained from well-controlled clinical studies or another form
of valid scientific evidence. In addition to the basic requirements for
a PMA described in Sec. 814.20(b)(6)(ii), the agency recommends that
studies use a protocol that meet the criteria described further in
section II of this document.
An applicant should submit the PMA in accordance with FDA's
``Premarket Approval Manual,'' which is available on the Internet at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/devadvice.
A. Preclinical Testing
FDA recommends the following types of preclinical testing to
establish reasonable assurance of the safety and effectiveness of the
hip joint metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prosthesis:
1. Materials Information--This information should include, but is
not limited to, chemistry; impurities identification and
quantification; physical, chemical, and mechanical properties; and
manufacturing process description. If the acetabular component is
modular, you should include locking mechanism characterization. (See
the FDA guidance document entitled ``Guidance Document for Testing Non-
Articulating, `Mechanically Locked' Modular Implant Components,'' which
is available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://fda.gov/cdrh/devadvice (Facts-
on-Demand No. 916).
2. Device Characteristics--These characteristics should include,
but are not limited to: Wear rates; debris size, geometry, and
distribution; wear mechanism and wear markings; frictional torque
measurement, axial and shear loading characteristics per American
Society for Testing and Materials consensus standards and impingement
latitude; implant-cement and cement-bone interfacial bonding strength,
e.g., shear and tensile strengths; and UHMWPe thickness.
3. Biocompatibility Information--Biocompatibility information for
finished devices made of a new hip-resurfacing material should be in
accordance with ISO-10993 standards, ``Biological Evaluation of Medical
Devices,'' 21 CFR parts 1 to 16.
B. Clinical Testing
FDA believes that clinical testing is necessary to establish the
reasonable assurance of the safety and effectiveness of the hip joint
metal/polymer or ceramic/polymer semiconstrained resurfacing cemented
prosthesis. The clinical study should distinguish between the intended
function of the device and the clinical benefit to the patient. The
study also should demonstrate both statistical significance and
clinical utility.
FDA recommends that device specific considerations include the
following:
1. Primary and Secondary Endpoints--The applicant should identify
the primary endpoints, such as reduced pain, improved function, and
radiographic confirmation of device placement and secondary endpoints,
such as improved quality of life and return to activities.
2. Patient Evaluation--Validated patient evaluation system(s)
should be capable of demonstrating both patient improvement and
deterioration. After enrolling patients, you should obtain baseline
measurements. Subsequently, at each patient followup interval, you
should measure the variables using the same patient evaluation
method(s) and the same radiographic evaluation showing the position of
the prosthesis in the skeleton and the condition of the surrounding
bone.
3. Patient Evaluation Systems--These systems should include patient
demographics (osteoarthritis or rheumatoid arthritis disease severity
classification, comorbidities, medications, allergies, prior surgery,
smoking, etc.); Harris Hip Score Evaluation or Western Ontario and
McMaster University (WOMAC) Osteoarthritis Index; radiographic
evaluation for subsidence and fracture; and quality of life evaluation,
such as the SF-36 or SF-12 Health Survey.
4. Patient Evaluation Schedule--Patient evaluations should occur at
regular intervals, such as baseline preoperative, intraoperative, and
postoperative at 6 weeks, 3 months, 6 months, 12 months, and 24 months.
FDA recommends that the general clinical study considerations
include the following:
1-1. Study Design--The applicant should evaluate the device in a
prospective, randomized, clinical trial that uses adequate controls or
other form of valid scientific evidence. The trial should answer all
safety and effectiveness questions concerning the device, including its
risk to benefit ratio. These questions should relate to the
pathophysiologic effects that the device produces, as well as the
primary and secondary endpoints used to analyze safety and
effectiveness. You should define study endpoints and success. The study
should have objectively measurable endpoints. The study design should
include an appropriate rationale, supported by background literature,
and a clear study hypothesis statement.
The study should obtain statistical and clinical significance for
the primary and secondary endpoints. For example, for each primary
endpoint, you should use an alpha level of 0.05 and a beta level of
0.2. However, under certain restricted circumstances, a clinically
significant result may be documented without statistical significance.
FDA recommends that the applicant conduct the study in three
phases: enrollment, baseline measurement, and followup. A preferred
method for subject enrollment is randomization by a central monitor.
The study should have a well-defined patient population. The
patient population should be as homogenous as possible to minimize
selection bias and reduce variability. Sample size justification should
show that enough patients are enrolled to attain statistically and
clinically meaningful results. You should carefully define inclusion
and exclusion criteria. Inclusion criteria should include the patient's
potential for benefit, the ability to detect a benefit in the patient,
the absence of contraindications and competing risk, and assurance of
patient compliance.
In a heterogeneous sample, stratification of patient groups
participating in a multicenter clinical trial may be necessary to
analyze homogeneous subgroups and minimize potential bias. FDA
recommends that the applicant include a sufficient number of patients
from each subgroup analysis to allow for stratification by pertinent
demographic characteristics. Initial patient screening according to the
inclusion and exclusion criteria and compliance of the patient
population is recommended to minimize dropout. Patient exclusion due to
dropout or loss more than 15 percent may invalidate the study due to
bias potential. You should account for all missing data, such as
dropouts. In the data analysis, you should document circumstances and
procedures used to ensure patient compliance.
FDA recommends that the applicant evaluate and minimize potential
sources of error, including selection bias, information bias, disease
misclassification bias, comparison bias, or any other potential bias.
The validity of these measurement scales should ensure that the
treatment effect being measured reflects the intended use.
The applicant should measure baseline variables, e.g., age, gender,
activity level, and other variables at the time of treatment. You
should measure
[[Page 10395]]
other variables during the study as needed to completely characterize
the particular device's safety and effectiveness. Also, throughout the
study, you should record and evaluate adverse effects, complications,
failure, revisions, and deaths.
FDA recommends rigorous monitoring to assure that the study data
are collected in accordance with the study protocol. Attentive,
unbiased monitors contribute prominently to a successful study.
For any other testing needed to assure a well-controlled study and
meaningful results, you should describe the testing sufficiently to
demonstrate its utility and adequacy. This is dependent on what the
applicant intends to measure or what the expected treatment effect is
based on each device's intended use.
The agency recommends the involvement of a biostatistician to
provide proper guidance in the planning, design, conduct, and analysis
of a clinical study.
1-2. Data Analysis--The agency recommends analyzing the following
types of data: Effectiveness primary endpoints measured by patient
evaluation systems and radiography; effectiveness secondary endpoints;
safety endpoints, including adverse events, complications, device
failures, revisions, and deaths; survival analyses (time to event or
revision; and patient satisfaction. The analyses should include actual
patient data.
There should be sufficient description and documentation of the
statistical analysis methods, their appropriateness, and the test
results. This should include complete descriptions of the methods,
comparison group selection, sample size justification, stated
hypothesis test(s), underlying assumptions, population demographics,
study site pooling justification, clear data presentation, and clear
discussion of the conclusions. The data analysis should relate to the
medical claims. It should evaluate the comparability between treatment
groups and control groups, including historical controls. The analysis
should also account for all enrolled patients, including those lost to
followup for any reason and a discussion of the impact of their loss.
This should include both the evaluable population and the intent to
treat population. The applicant should report actual patient data used
to determine the result.
1-3. Data Presentation--The applicant should present effectiveness
clinical findings in a series of tables that include complete patient
accounting. FDA recommends using a table for each followup time point.
Each table should show the number of patients in each treatment group,
the number of patients actually evaluated, the number of patients with
missing data, and reasons for the missing data.
If the evaluation uses subcategories of rating specific clinical
observations, (e.g., the pain, function, motion, subcategories of the
Harris Hip Scoring System), you should include the number of patients
in each disease rating category.
Similarly, FDA recommends that you present safety data in a series
of tables for each time point, including the number of patients
expected at that time point and the number of patients with adverse
effects, complications, device failures, and revisions. You should
include the types of adverse events, complications, device failures,
and revisions.
Use of Kaplan Meier life tables to present actuarial survivorship
data for the acetabular component and femoral component and the
complete device is recommended. You should include the actual patient
data used to generate the presentation.
The applicant should analyze and explain the reasons for missing
data and the impact of the missing data.
C. Labeling
The applicant should provide copies of all proposed labeling for
the device. You should include any information, literature, or
advertising that constitutes labeling under section 201(m) of the act
(21 U.S.C. 321(m)). The general labeling requirements for medical
devices are in 21 CFR part 801. Information in the PMA should
completely support the intended use statement in the labeling,
including specific indications for use, specific patient populations,
and directions for use. This information should include a detailed
step-by-step illustrated surgical technique manual.
III. PDP Requirements
An applicant may submit a PDP for the hip joint metal/polymer or
ceramic/polymer semiconstrained resurfacing cemented prosthesis in lieu
of a PMA. A PDP must follow the procedures outlined in section 515(f)
of the act and should include the following: A description of the
device, preclinical trial information, clinical trial information, a
description of the manufacturing and processing of the device, labeling
of the device, all relevant information about the device, progress
reports, and records of the trials conducted under the protocol on the
safety and effectiveness of the device for which the completed PDP is
sought.
FDA's Device Advice Web site has comprehensive updated information
on PDP approval, including the guidance document entitled ``Contents of
a Product Development Protocol'' issued on July 27, 1998, on the
Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/devadvice. The guidance document is
also available from CDRH's Facts on Demand at 1-800-899-0381 or 301-
827-0111. Specify number 473 when prompted for the document shelf
number.
IV. Opportunity to Request Reclassification
Before requiring the filing of a PMA or a notice of completion of a
PDP for a device, section 515(b)(2)(A)(i) through (b)(2)(A)(iv) of the
act and 21 CFR 860.132 require FDA to provide an opportunity for
interested persons to request reclassification of the device based on
new information. Any proceeding to reclassify the device is under the
authority of section 513(e) of the act.
You may submit a reclassification request for the hip joint metal/
polymer or ceramic/polymer semiconstrained resurfacing cemented
prosthesis in a reclassification petition that contains the information
required under Sec. 860.123 (21 CFR 860.123). This includes any new
information relevant to the reclassification of the device.
To ensure timely filing of a reclassification petition, submit your
petition to the Division of Dockets Management (see ADDRESSES) and not
to the address provided in Sec. 860.123(b)(1). If you submit a timely
reclassification petition for the hip joint metal/polymer or ceramic/
polymer semiconstrained resurfacing cemented prosthesis, FDA will: (1)
Consult with the Orthopedic and Rehabilitation Devices Advisory Panel
about reclassifying the device, and (2) publish an order in the Federal
Register either denying the request or announcing the agency's intent
to reclassify the device in accordance with section 513(e) of the act
and 21 CFR 860.130 of the regulations.
V. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 5 p.m., Monday through Friday.
1. Townley, C.O., ``Hemi and Total Articular Replacement
Arthroplasty of the Hip With the Fixed Femoral Cup,'' Orthopedic
Clinics of North America, 13: 869-894, 1982.
2. Mont, M.A., A.D. Rajadhyaksha, and D.S. Hungerford, ``Outcomes
of Limited Femoral Resurfacing
[[Page 10396]]
Arthroplasty Compared With Total Hip Arthroplasty for Osteonecrosis of
the Femoral Head,'' Journal of Arthroplasty, 16 suppl. 1: 134-139,
2001.
3. Mesko, J.W., F.G. Goodman, and S. Stanescu, ``Total Articular
Replacement Arthroplasty: A Three- to Ten-Year Case-Controlled Study,''
Clinical Orthopaedics and Related Research, No. 300: 168-177, 1994.
4. Head, W.G., ``Wagner Surface Replacement Arthroplasty of the Hip
- Analysis of Fourteen Failures in Forty-One Hips,'' Journal of Bone
and Joint Surgery, 63-A: 420-427, 1981.
5. Head, W.C., ``Total Articular Resurfacing Arthroplasty--Analysis
of Component Failure in Sixty-Seven Hips,'' Journal of Bone and Joint
Surgery, 66-A: 28-34, 1984.
6. Capello, W.N., G.W. Misamore, and T.M. Trancik, ``The Indiana
Conservative (Surface Replacement) Hip Arthroplasty,'' Journal of Bone
and Joint Surgery, 66-A: 518-528, 1984.
7. Ritter, M.A. and T.J. Gioe, ``Conventional Versus Resurfacing
Total Hip Arthroplasty: A Long-Term Prospective Study of Concomitant
Bilateral Implantation of Prostheses,'' Journal of Bone and Joint
Surgery, 68-A: 216-225, 1986.
8. Kim, W.C., T. Grogan, H.C. Amstutz, et al., ``Survivorship
Comparison of THARIES and Conventional Hip Arthroplasty in Patients
Younger Than 40 Years Old,'' Clinical Orthopaedics and Related
Research, No. 214: 269-277, 1987.
9. Faris, P.M., M.A. Ritter, R. Bicknell, et al., ``Long-Term
Follow-Up of the Indiana Conservative Resurfacing Hip Arthroplasty,''
Seminars in Arthroplasty, 1: 12-15, 1990.
10. D.W. Howie, B.L. Cornish, and B. Vernon-Roberts, ``Resurfacing
Hip Arthroplasty: Classification of Loosening and the Role of
Prosthesis Wear Particles,'' Clinical Orthopaedics and Related
Research, 255: 144-159, 1990.
11. R. Huiskes, P. Strens, W. Vroemen, et al., ``Post-Loosening
Mechanical Behavior of Femoral Resurfacing Prostheses,'' Clinical
Materials, 6: 37-55, 1990.
12. Wiadrowski, T.P., M. McGee, B.L. Cornish, et al., ``Peripheral
Wear of Wagner Resurfacing Hip Arthroplasty or Arthroplasty Acetabular
Components,'' Journal of Arthroplasty, 6: 103-107, 1991.
13. Kilgus, D.J., F.J. Dorey, G.A.M. Finerman, et al., ``Patient
Activity, Sports Participation, and Impact Loading on the Durability of
Cemented Total Hip Replacements,'' Clinical Orthopaedics and Related
Research, 269: 25-31, 1991.
14. Mai, M.T., T.P. Schmalzried, F.J. Dorey, et al., ``The
Contribution of Frictional Torque to Loosening at the Cement-Bone
Interface in Tharies Hip Replacements,'' Journal of Bone and Joint
Surgery, 78-A: 505-510, 1996.
15. Campbell, P., J. Mirra, and H.C. Amstutz, ``Viability of
Femoral Heads Treated With Resurfacing Arthroplasty,'' Journal of
Arthroplasty, 15: 120-122, 2000.
16. Watanabe, Y., N. Shiba, S. Matsuo, et al., ``Biomechanical
Study of the Resurfacing Hip Arthroplasty: Finite Element Analysis of
the Femoral Component,'' Journal of Arthroplasty, 15: 505-511, 2000.
17. Amstutz, H.C., B.J. Thomas, R. Jinnah, et al., ``Treatment of
Primary Osteoarthritis of the Hip,'' Journal of Bone and Joint Surgery,
66-A: 228-241, 1984.
VI. Effective Date
FDA proposes that any final rule that may issue based on this
proposal become effective 90 days after its date of publication in the
Federal Register.
VII. Environmental Impact
The agency has determined under 21 CFR 25.24(a)(8) that this action
is of a type that does not individually or cumulatively have a
significant effect upon the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
VIII. 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. 610-612), 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 proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive order. In addition, the proposed
rule 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. FDA does not expect to receive any PMAs or notices
of completion of PDPs if this rule becomes final. The device has fallen
out of use and is less safe and less effective than other available hip
joint prostheses. The agency certifies that the proposed rule will not
have a significant impact on a substantial number of small entities.
Therefore, under the Regulatory Flexibility Act, no further analysis is
required. Additionally, this proposed rule will not impose costs of
$100 million or more on the private sector, State, local, and tribal
governments in the aggregate. As a result, a summary statement or
analysis under section 202(a) of the Unfunded Mandates Reform Act of
1995 is not required.
IX. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The
burden hours required for Sec. 888.3410(c), included in the collection
entitled ``Premarket Approval of Medical Devices'' (66 FR 42664, August
14, 2001), are reported and approved under OMB control number 0910-
0231.
X. Comments
You may submit written or electronic comments regarding this
proposal or requests for a change in classification of the device to
the Division of Dockets Management (see ADDRESSES). Submit a single
copy of electronic information or two paper copies of any mailed
information, except that individuals may submit one paper copy.
Comments or requests are to be identified with the docket number found
in brackets in the heading of this document. Received comments or
requests may be seen in the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 888
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 888 be amended as follows:
PART 888--ORTHOPEDIC DEVICES
1. The authority citation for 21 CFR part 888 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
2. Section 888.3410 is revised to read as follows:
[[Page 10397]]
Sec. 888.3410 Hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis.
(a) Identification. A hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis is a two-part device
intended to be implanted to replace the articulating surfaces of the
hip while preserving the femoral head and neck. The device limits
translation and rotation in one or more planes via the geometry of its
articulating surfaces. It has no linkage across the joint. This generic
type of device includes prostheses that consist of a femoral cap
component made of a metal alloy, such as cobalt-chromium-molybdenum, or
a ceramic material, that is placed over a surgically prepared femoral
head, and an acetabular resurfacing polymer component. Both components
are intended for use with bone cement (Sec. 888.3027).
(b) Classification. Class III.
(c) Date PMA or notice of completion of a PDP is required. A PMA or
a notice of completion of a PDP is required to be filed with the Food
and Drug Administration on or before [date 90 days after date of
publication of the final rule in the Federal Register], for any hip
joint metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prosthesis that was in commercial distribution before May 28,
1976, or that has, on or before [date 90 days after date of publication
of the final rule in the Federal Register], been found to be
substantially equivalent to a hip joint metal/polymer or ceramic/
polymer semiconstrained resurfacing cemented prosthesis that was in
commercial distribution before May 28, 1976, or that has, on or before
[date 90 days after date of publication of the final rule in the
Federal Register], been found to substantially equivalent to a hip
joint metal/polymer or ceramic/polymer semiconstrained resurfacing
cemented prothesis that was in commercial distribution before May 28,
1976. Any other hip joint metal/polymer or ceramic/polymer
semiconstrained resurfacing cemented prosthesis must have an approved
PMA or a declared completed PDP in effect before being placed in
commercial distribution.
Dated: February 13, 2004.
Beverly Chernaik Rothstein,
Acting Deputy Director for Policy and Regulations, Center for Devices
and Radiological Health.
[FR Doc. 04-4885 Filed 3-4-04; 8:45 am]
BILLING CODE 4160-01-S