[Federal Register Volume 69, Number 44 (Friday, March 5, 2004)]
[Proposed Rules]
[Pages 10390-10397]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-4885]


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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://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://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://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://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