[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