[Federal Register Volume 67, Number 137 (Wednesday, July 17, 2002)]
[Rules and Regulations]
[Pages 46852-46855]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-18036]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 888

[Docket No. 02P-0294]


Medical Devices; Reclassification of Polymethylmethacrylate 
(PMMA) Bone Cement

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that it 
has reclassified the polymethylmethacrylate (PMMA) bone cement intended 
for use in arthroplastic procedures of the hip, knee, and other joints 
for the fixation of polymer or metallic prosthetic implants to living 
bone from class III to class II (special controls). The agency is also 
announcing that it has issued an order in the form of a letter to the 
Orthopedic Surgical Manufacturers Association (OSMA) reclassifying the 
device. The special control for the device is a guidance document 
entitled ``Class II Special Controls Guidance Document: 
Polymethylmethacrylate (PMMA) Bone Cement.'' The agency is 
reclassifying this device into class II because special controls, in 
addition to general controls, would provide reasonable assurance of the 
safety and effectiveness of the device, and there is sufficient 
information to establish special controls.

DATES: The reclassification was effective October 14, 1999. The 
revision of Sec. 888.3027 is effective August 16, 2002.

FOR FURTHER INFORMATION CONTACT: Hany W. Demian, 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

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et. seq.), as amended by the Medical Device Amendments of 1976 (the 
1976 amendments) (Public Law 94-295), the Safe Medical Devices Act of 
1990 (the SMDA) (Public Law 101-629), and the Food and Drug 
Administration Modernization Act of 1997 (the FDAMA) (Public Law 105-
115), established a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the act (21 U.S.C. 360c) 
established three categories (classes) of devices, depending on the 
regulatory controls needed to provide reasonable assurance of their 
safety and effectiveness. The three categories of devices are class I 
(general controls), class II (special controls), and class III 
(premarket approval).
    The 1976 amendments broadened the definition of ``device'' in 
section 201(h) of the act (21 U.S.C. 321(h)) to include certain 
articles that were once regulated as drugs. Under the 1976 amendments, 
Congress classified all transitional devices, i.e., those devices 
previously regulated as new drugs, including the PMMA bone cement, into 
class III. The legislative history of the SMDA reflects congressional 
concern that many transitional devices were being overregulated in 
class III (H. Rept. 808, 101st Cong., 2d sess. 26-27 (1990); S. Rept. 
513, 101st Cong., 2d sess. 27 (1990)). Congress amended section 520(l) 
of the act (21 U.S.C. 360j(l)) to direct FDA to collect certain safety 
and effectiveness information from the manufacturers of transitional 
devices still remaining in class III to determine whether the devices 
should be reclassified into class II (special controls) or class I 
(general controls). Accordingly, in the Federal Register of November 
14, 1991 (56 FR 57960), FDA issued an order under section 520(l)(5)(A) 
of the act, requiring manufacturers of transitional devices, including 
the PMMA bone cement (21 CFR 888.3027), to submit to FDA a summary of, 
and a citation to, any information known or otherwise available to them 
respecting the devices, including adverse safety or effectiveness 
information which had not been submitted under section 519 of the act

[[Page 46853]]

(21 U.S.C. 360i). Manufacturers were to submit the summaries and 
citations to FDA by January 13, 1992. However, because of 
misunderstandings and uncertainties regarding the information required 
by the order, and whether the order applied to certain manufacturers' 
devices, many transitional class III device manufacturers failed to 
comply with the reporting requirement by January 13, 1992. 
Consequently, in the Federal Register of March 10, 1992 (57 FR 8462), 
FDA extended the reporting period to March 31, 1992.
    Section 520(l)(5)(B) of the act provides that, after the issuance 
of an order requiring manufacturers to submit a summary of, and 
citation to, any information known or otherwise available respecting 
the devices, but before December 1, 1992, FDA was to publish 
regulations either leaving transitional class III devices in class III 
or reclassifying them into class I or II. Subsequently, as permitted by 
section 520(l)(5)(C) of the act, in the Federal Register of November 
30, 1992 (57 FR 56586), the agency published a notice extending the 
period for issuing such regulations until December 1, 1993. Due to 
limited resources, FDA was unable to publish the regulations before the 
December 1, 1993, deadline.

II. Recommendation of the Panel

    On January 21, 1998, FDA filed the reclassification petition 
submitted by OSMA, requesting reclassification of the PMMA bone cement 
from class III to class II. FDA consulted with the Orthopedic and 
Rehabilitation Devices Panel (the Panel) regarding reclassification of 
the PMMA bone cement. During an open public meeting on April 28, 1998, 
the Panel unanimously recommended that FDA reclassify the PMMA bone 
cement intended for use in arthroplastic procedures of the hip, knee, 
and other joints for the fixation of polymer or metallic prosthetic 
implants to living bone from class III to class II. The Panel also 
recommended that FDA guidance documents, consensus standards, and 
labeling be the special controls to reasonably assure the safety and 
effectiveness of the device.
    FDA considered the Panel's recommendation and tentatively agreed 
that the generic type of device, the PMMA bone cement intended for use 
in arthroplastic procedures of the hip, knee, and other joints for the 
fixation of polymer or metallic prosthetic implants to living bone, be 
reclassified from class III into class II. FDA agreed that guidance 
documents, consensus standards, and labeling are appropriate special 
controls for the device.
    After reviewing the data in the petition and presented before the 
Panel, and after considering the Panel's recommendation and the 
comments, FDA, based on the information set forth, issued an order to 
the petitioner on October 14, 1999, reclassifying the PMMA bone cement, 
and substantially equivalent devices of this generic type, from class 
III to class II with the implementation of special controls.
    The special controls listed in the order to the petitioner were the 
following FDA guidance documents, consensus standards, and labeling:

A. FDA Guidance Documents

    1. ``Use of International Organization for Standardization (ISO) 
10993, `Biological Evaluation of Medical Devices Part I: Evaluation and 
Testing',''
    2. ``510(k) Sterility Review Guidance and Revision of 11/18/94 K90-
1,''
    3. ``Guidance Document for Testing Orthopedic Bone Cement,'' and
    4. ``Guidance Document for the Preparation of Premarket 
Notification (510(k)) Applications for Orthopedic Devices.''

B. Consensus Standards

    1. American Society for Testing and Material (ASTM) F 451-95 
``Standard Specifications for Acrylic Bone Cement,''
    2. ASTM D 638-91 ``Standard Test Method for Tensile Properties of 
Plastics,''
    3. ASTM D 732-93 ``Standard Test Method for Shear Strength of 
Plastics by Punch Tool,''
    4. ASTM D 790-98 ``Standard Test Method for Flexural Properties of 
Unreinforced and Reinforced Plastics and Electrical Insulating 
Materials,''
    5. ASTM D 2990-95 ``Standard Tensile, Compressive, and Flexural 
Creep and Creep Rupture of Plastics,''
    6. ASTM E 399-90 ``Standard Test Method for Plane-Strain Fracture 
Toughness of Metallic Materials,''
    7. ASTM E 647-95a ``Standard Test Method for Measurement of Fatigue 
Crack Growth Rates,'' and
    8. International Organization for Standardization (ISO) 5833:1992 
``Implants for surgery--Acrylic resin cements.''

C. Labeling

1. Contraindication
    Do not use PMMA bone cement in the presence of active or 
incompletely treated infection that could involve the site where the 
device will be implanted.
2. Warnings
    a. Adverse cardiovascular reactions, including hypotension, 
hypoxaemia, cardiac arrhythmia, bronchspasm, cardiac arrest, 
myocardical infarction, pulmonary embolism, cerebrovascular accident, 
and possible death: Hypotensive reactions can occur between 10 and 165 
seconds after application of the PMMA bone cement and can last for 30 
seconds to 5 or more minutes. Some hypotensive reactions have 
progressed to cardiac arrest. The blood pressure of patients should be 
monitored carefully during and immediately following the application of 
the PMMA bone cement. In addition, overpressurization of the PMMA bone 
cement should be avoided during insertion of the PMMA bone cement and 
implant in order to minimize the occurrence of pulmonary embolism.
    b. Surgeon training and experience: The surgeon should be 
thoroughly familiar with the properties, handling characteristics and 
application of the PMMA bone cement. Because the handling and curing 
characteristics of this cement vary with temperature and mixing 
technique, they are best determined by the surgeon's actual experience.
    c. Device volatility and flammability and electrocautery devices: 
The operating room should be adequately ventilated to eliminate monomer 
vapors. Ignition of monomer vapors caused by the use of electrocautery 
devices in surgical sites near freshly implanted bone cement has been 
reported.
    d. Irritation of the respiratory tract, eyes, and the liver: 
Caution should be exercised during the mixing of the liquid and powder 
components of the PMMA bone cement to prevent excessive exposure to the 
concentrated vapors of liquid monomer, which may produce irritation of 
the respiratory tract, eyes, and possibly the liver. Personnel wearing 
contact lenses should not mix PMMA bone cement or be near the mixing of 
the PMMA bone cement.
3. Precautions
    a. Contact dermatitis: The liquid monomer has caused contact 
dermatitis in those handling and mixing PMMA bone cement. Strict 
adherence to the instructions for mixing the powder and liquid 
components may reduce the incidence of contact dermatitis.
    b. Hypersensitivity reactions: The liquid component of PMMA bone 
cement is a powerful lipid solvent. It should not contact rubber or 
latex gloves. Double gloving and strict adherence to the mixing 
instructions may diminish the possibility of hypersensitivity 
reactions. The mixed PMMA bone cement should not contact the gloved 
hand until the cement has

[[Page 46854]]

acquired the consistency of dough, about 1 to 2 minutes after mixing.
    c. Inadequate postoperative fixation: Inadequate fixation or 
unanticipated postoperative events may affect the PMMA bone cement-bone 
interface and lead to micromotion of cement against the bone surface. A 
fibrous tissue layer may develop between the PMMA bone cement and the 
bone that may cause loosening of the prosthesis. Thus, continued, 
periodic followup is advised for all patients.
    d. Exothermic reaction: Polymerization of the PMMA bone cement is 
an exothermic reaction that occurs while the PMMA bone cement is 
hardening in situ. The released heat may damage bone or other tissue 
adjacent to the implant.
    e. Extrusion: Extrusion of the PMMA bone cement beyond the region 
of its intended application may occur resulting in the following 
complications: Hematuria, dysuria, bladder fistula, delayed sciatic 
nerve entrapment from extrusion of the bone cement beyond the region of 
its intended application, local neuropathy, local vascular erosion and 
occlusion, and intestinal obstruction because of adhesions and 
stricture of the ileum from the heat released during the exothermic 
polymerization.
    f. Use in pregnant women and children: The safety and effectiveness 
of the PMMA bone cement in pregnant women and in children is not 
established.
    g. Expiration dating: PMMA bone cement should not be used after the 
expiration date because the effectiveness of the device may be 
compromised.
    h. Disposal: Because of the volatility and flammability of the 
liquid monomer of the PMMA bone cement, the liquid monomer should be 
evaporated in a well-ventilated hood or absorbed by an inert material 
and transferred into a suitable container (one that does not react with 
the PMMA bone cement) for disposal.
4. Adverse Events
    a. Serious adverse events, some with fatal outcome, associated with 
the use of the PMMA bone cement include myocardial infarction, cardiac 
arrest, cerebrovascular accident, and pulmonary embolism.
    b. The most frequent adverse reactions associated with the use of 
PMMA bone cement are transitory decreased blood pressure, elevated 
serum gamma-glutamyl-transpeptidase (GGTP) up to 10 days postoperation, 
thrombophlebitis, hemorrhage and hematoma, pain and/or loss of 
function, loosening or displacement of the prosthesis, superficial or 
deep wound infection, trochanteric bursitis, short-term cardiac 
conduction irregularities, heterotopic new bone formation, and 
trochanteric separation.
    c. Other potential adverse events associated with the use of PMMA 
bone cement include allergic pyrexia, hematuria, dysuria, bladder 
fistula, delayed sciatic nerve entrapment from extrusion of the bone 
cement beyond the region of its intended application, local neuropathy, 
local vascular erosion and occlusion, intestinal obstruction because of 
adhesions and stricture of the ileum from the heat released during the 
exothermic polymerization.
    FDA incorporated the four FDA guidance documents, eight consensus 
standards, and labeling into a class II special controls guidance 
entitled ``Class II Special Controls Guidance Document: 
Polymethylmethacrylate (PMMA) Bone Cement'' that issued on August 2, 
2001. The guidance document also referenced updated versions of six of 
the eight consensus standards listed as special controls in the 
reclassification order. FDA has further revised the guidance document 
to include the risk to health of polymerization setting problems and to 
clarify the warnings, precautions, and adverse reactions sections of 
the labeling. This class II special controls guidance document, is now 
the special control for this generic device.
    Accordingly, as required by 21 CFR 860.136(b)(6) of the 
regulations, FDA is announcing the reclassification of the generic the 
PMMA bone cement intended for use in arthroplastic procedures of the 
hip, knee, and other joints for the fixation of polymer or metallic 
prosthetic implants to living bone from class III into class II.

III. Access to Special Controls

    Persons interested in obtaining a copy of ``Class II Special 
Controls Guidance Document: Polymethylmethacrylate (PMMA) Bone Cement'' 
may do so using the Internet. The Center for Devices and Radiological 
Health (CDRH) maintains an entry on the Internet for easy access to 
information including text, graphics, and files that may be downloaded 
to a personal computer with access to the Internet. The CDRH home page 
may be accessed at http://www.fda.gov/cdrh. Guidance documents are also 
available from the Division of Small Manufacturers, International, and 
Consumer Assistance (DSMICA) (HFZ-220), Food and Drug Administration, 
Center for Devices and Radiological Health, 1350 Piccard Dr., 
Rockville, MD 20850. In order to receive the guidance document via your 
fax machine call the CDRH Facts-On-Demand (FOD) system at 800-899-0381 
or 301-827-0111 from a touch-tone telephone. Press 1 to enter the 
system and enter the document number (668) followed by the pound sign 
([]). 
Follow the remaining voice prompts to complete your request.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

V. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Public Law 104-121)), and the Unfunded Mandates Reform Act of 
1995 (Public Law 104-4)). Executive Order 12866 directs agencies to 
assess all costs and benefits of available regulatory alternatives and, 
when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, and other advantages; distributive impacts; 
and equity). The agency believes that this final rule is consistent 
with the regulatory philosophy and principles identified in the 
Executive order. In addition, the final 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. Reclassification of the device from class III to 
class II will relieve all manufacturers of the device of the cost of 
complying with the premarket approval requirements in section 515 of 
the act. Because reclassification will reduce regulatory costs with 
respect to this device, it will impose no significant economic impact 
on any small entities, and it may permit small potential competitors to 
enter the marketplace by lowering their costs. The agency, therefore, 
certifies that this rule will not have a significant economic impact on 
a substantial number of small entities. In addition, this rule will not 
impose costs of $100 million or more on either the private sector or 
State, local, and tribal governments in the aggregate, and therefore a 
summary statement or

[[Page 46855]]

analysis under section 202(a) of the Unfunded Mandates Reform Act of 
1995 is not required.

VI. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, or on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

VII. Paperwork Reduction Act of 1995

    The premarket notification information collections addressed in the 
guidance have been approved by the Office of Management and Budget 
(OMB) under the Paperwork Reduction Act of 1995 (PRA) under OMB control 
number 0910-0120. The labeling provisions addressed in the guidance 
have been approved by OMB under the PRA under OMB control number 0910-
0485.

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, 21 CFR 
part 888 is 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 888.3027 is revised to read as follows:


Sec. 888.3027  Polymethylmethacrylate (PMMA) bone cement.

    (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a 
device intended to be implanted that is made from methylmethacrylate, 
polymethylmethacrylate, esters of methacrylic acid, or copolymers 
containing polymethylmethacrylate and polystyrene. The device is 
intended for use in arthroplastic procedures of the hip, knee, and 
other joints for the fixation of polymer or metallic prosthetic 
implants to living bone.
    (b) Classification. Class II (special controls). The special 
control for this device is the FDA guidance document entitled ``Class 
II Special Controls Guidance Document: Polymethylmethacrylate (PMMA) 
Bone Cement.''

    Dated: July 5, 2002.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 02-18036 Filed 7-16-02; 8:45 am]
BILLING CODE 4160-01-S