[Federal Register Volume 67, Number 204 (Tuesday, October 22, 2002)]
[Proposed Rules]
[Pages 64835-64840]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-26816]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. 02N-0370]


Neurological Devices; Classification of Human Dura Mater

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to 
classify human dura mater intended to repair defects in human dura 
mater into class II (special controls). The agency is publishing the 
recommendations of

[[Page 64836]]

FDA's Neurological Devices Panel (the Panel) regarding the 
classification of this device. After considering public comments on the 
proposed classification, FDA will publish a final regulation 
classifying this device. This action is being taken to establish 
sufficient regulatory controls to provide reasonable assurance of the 
safety and effectiveness of the device. Elsewhere in this issue of the 
Federal Register, FDA is publishing a notice of availability of a 
guidance document that FDA intends to serve as the special control for 
this device.

DATES: Submit written or electronic comments by January 21, 2003.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20857. Submit electronic comments to http://www.fda.gov/dockets/ecomments. Comments are to be identified with the docket number 
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Charles N. Durfor, Center for Devices 
and Radiological Health (HFZ-410), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-3090.

SUPPLEMENTARY INFORMATION:

I. Background

A. Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et. seq.), as amended by the Medical Device Admendments 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 (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). Under the 1976 amendments, class II devices were 
defined as those devices for which there is insufficient information to 
show that general controls themselves will ensure safety and 
effectiveness, but for which there is sufficient information to 
establish performance standards to provide such assurance.
    The SMDA broadened the definition of class II devices to mean those 
devices for which there is insufficient information to show that 
general controls themselves will ensure safety and effectiveness, but 
for which there is sufficient information to establish special controls 
to provide such assurance. Special controls may include performance 
standards, postmarket surveillance, patient registries, development and 
dissemination of guidelines, recommendations, and any other appropriate 
actions the agency considers necessary (section 513(a)(1)(B) of the 
act).
    Under section 513 of the act, devices that were in commercial 
distribution prior to May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution before May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking process. Those devices remain in class III 
and require premarket approval, unless and until: (1) The device is 
reclassified into class I or II; (2) FDA issues an order classifying 
the device into class I or II in accordance with new section 513(f)(2) 
of the act, as amended by the FDAMA; or (3) FDA issues an order finding 
the device to be substantially equivalent, in accordance with section 
513(i) of the act, to a predicate device that does not require 
premarket approval. The agency determines whether new devices are 
substantially equivalent to previously offered devices by means of 
premarket notification procedures in section 510(k) of the act (21 
U.S.C. 360(k)) and 21 CFR part 807 of the regulations.
    A preamendments device that has been classified into class III may 
be marketed, by means of premarket notification procedures, without 
submission of a premarket approval application until FDA issues a final 
regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Consistent with the act and the regulations, FDA consulted with the 
Panel, an FDA advisory committee, regarding the classification of this 
device.

B. Regulatory History

    Human dura mater derived and processed from human cadavers and 
intended for use in neurosurgical procedures to repair defects in the 
cranial and spinal cord dura mater caused by trauma and tumor resection 
was in commercial distribution before the enactment of the 1976 
amendments. Human dura mater is currently regulated as an unclassified 
medical device via premarket notification.
    In February 1987, the first of three United States cases of 
iatrogenic Creutzfeldt-Jacob Disease (CJD), a rare, degenerative, fatal 
disease of the central nervous system was reported (Ref. 1). It was 
associated with the implantation of Lyodura, an imported processed 
human dura mater manufactured in Germany that was never cleared for use 
in the United States. In April 1987, FDA issued a safety alert that 
warned of the potential risk of transmitting CJD through this imported 
dura mater product, and in June 1987, FDA issued an import alert 
banning its use in the United States.
    On July 14, 1989, and on February 2, 1990, the Panel heard 
testimony on the processing and use of human dura mater in the United 
States (Refs. 2 and 3). At the 1990 meeting, in accordance with FDA's 
device classification regulations, the Panel recommended that human 
dura mater be classified into class II.
    On June 26, 1990, FDA made available the ``Guide for 510(k) Review 
of Processed Human Dura Mater.'' The guide was based on testimony heard 
at the 1989 and 1990 Panel meetings. It recommended donor selection and 
rejection criteria, manufacturing controls, and other safeguards to 
minimize the risk of iatrogenic transmission of CJD. On November 14, 
1990, FDA also notified distributors of human dura mater of the 
requirement to register and list their products with the agency and of 
the requirement for premarket notification clearance to market new 
human dura products.
    On March 27, 1997, the World Health Organization (WHO) recommended 
that human dura mater no longer be used, especially for neurosurgery, 
unless no other alternative was available. WHO issued this 
recommendation because of over 50 cases of CJD associated with use of 
human dura mater (Ref. 4) . Most of these cases were associated with 
the dura mater product that was never cleared in the United States and 
that was under import alert in the United States. WHO also recommended 
that if human dura mater is used, it should be

[[Page 64837]]

from nonpooled sources from carefully screened donors and it should be 
inactivated by a validated method.
    On March 31, 1997, FDA announced that it would not restrict the 
distribution of FDA-cleared human dura mater because of the previously 
established safeguards and guidelines that were in effect to minimize 
the possibility of CJD transmission by human dura mater implantation. 
This decision also reflected the absence of any confirmed cases of CJD 
transmission in the United States that were related to human dura mater 
implants that were cleared for commercial distribution. In addition, 
FDA decided to hold public meetings of the agency's Transmissible 
Spongiform Encephalopathies Advisory Committee (TSEAC) to re-evaluate 
the safety of human dura mater with respect to CJD transmission.
    On October 6, 1997, the TSEAC made recommendations on the use of 
human dura mater in the context of the risks to health associated both 
with the use of human dura mater and with the use of the available dura 
mater substitute products (animal, synthetic, and patient's own tissue) 
(Ref. 5). The TSEAC also made recommendations for additional safeguards 
to minimize iatrogenic CJD transmission. On March 6, 1998, FDA 
transmitted the 1997 TSEAC recommendations in a letter to manufacturers 
of human dura mater. On April 16, 1998, the TSEAC again deliberated on 
iatrogenic CJD transmission associated with the use of human dura mater 
and made additional recommendations to minimize CJD transmission.
    On December 14, 1998, FDA issued a tracking order (21 CFR part 821 
and section 519(e) of the act (21 U.S.C. 360i(e)) for human dura mater. 
This tracking order requires each manufacture of human dura mater to 
develop and implement a program that enables the manufacturer to locate 
patients implanted with human dura mater until device explantation or 
death.
    In parallel with the Center for Devices and Radiological Health's 
(CDRH's) efforts to ensure the safety and effectiveness of human dura 
mater, FDA has considered the appropriate way to regulate all human 
cellular and tissue-based products (HCT/Ps). In the Federal Register of 
March 4, 1997 (62 FR 9721), FDA proposed a comprehensive approach to 
regulate all HCT/Ps, including human dura mater, under the authority of 
section 361 of the Public Health Act. To implement this approach, FDA 
published the following three proposed rules: (1) ``Establishment 
Registration and Listing for Manufacturers of Human Cellular and 
Tissue-Based Products'' (63 FR 26744, May 14, 1998); (2) ``Suitability 
Determination for Donors of Human Cellular and Tissue-Based Products'' 
(64 FR 52696, September 30, 1999); and (3) ``Current Good Tissue 
Practice for Manufacturers of Human Cellular and Tissue-Based Products; 
Inspection and Enforcement'' (65 FR 1508, January 8, 2001).
    In the Federal Register of January 19, 2001 (66 FR 5447), FDA 
issued a final rule for establishment registration and listing of human 
cellular and tissue-based products (HCT/Ps). This regulation became 
effective on April 4, 2001, except for 21 CFR 207.20(f) (registration 
of drug products), 21 CFR 807.20(d) (registration of medical devices), 
and Sec.  1271.3(d)(2) (21 CFR 127.3(d)(2)) (definitions), which will 
become effective on January 21, 2003. Section 1271.3(d)(2) also states 
that human dura mater is an HCT/P. In the final rule, the agency 
recognized that unanticipated delays in completing the rulemaking for 
the remainder of 21 CFR part 1271 could occur and that it could become 
necessary to delay the effective dates for some or all HCT/Ps.
    On August 15, 2001, Public Citizen's Health Research Group 
submitted a petition (docket number 01P-0354) requesting that the 
agency ban the sale of human cadaveric dura mater and recall all 
unimplanted human cadaveric dura mater. On February 11, 2002, FDA 
denied the petitioner's requests in a letter because the agency 
determined that information in the petition did not meet the statutory 
requirements to ban or recall a medical device under sections 516(a)(1) 
and (a)(2) and 518(e)(1) of the act (21 U.S.C. 360f(a)(1) and (a)(2) 
and 360h(e)(1)).
    FDA is now proposing to classify human dura mater into class II. 
The agency is also proposing that the guidance document entitled 
``Class II Special Controls Guidance Document: Human Dura Mater; 
Guidance for Industry and FDA'' be the special control to reasonably 
ensure the safety and effectiveness of the device until such time as 
the regulatory authority for this product is transferred from CDRH to 
the Center for Biologics Evaluation and Research. Elsewhere in this 
issue of the Federal Register, FDA is announcing the availability of 
this draft guidance document.

II. Recommendations of the Panel

A. Device Identification

    The Panel adopted the following device identification based on the 
agency's recommendation: Human dura mater is human pachymeninx tissue 
intended to repair defects in human dura mater.

B. Recommended Classification of the Panel

    During a public meeting on February 2, 1990, the Panel recommended 
that human dura mater be classified into class II (Ref. 3). The Panel 
also identified the following risks to health associated with the 
device: Prion infection, infection in general, leakage of cerebral 
spinal fluid (CSF), and adverse tissue reaction. New information about 
the safety and effectiveness of the device became available after 1990, 
however, and a second Panel meeting was held on September 16 and 17, 
1999. At this meeting the Panel again recommended that the device be 
classified into class II (Ref. 6). The Panel recommended the following 
as potential special controls to provide reasonable assurance of safety 
and effectiveness: (1) FDA guidances, (2) postmarket surveillance, (3) 
patient registries, (4) device tracking, and (5) restrictions on donor 
selection.

C. Summary of the Reasons for the Recommendation

    After reviewing the information provided by FDA, and after 
consideration of the open discussions during the Panel meeting(s) and 
the Panel members' personal knowledge of and clinical experience with 
the device system, the Panel gave the following reasons in support of 
its recommendation to classify the generic type human dura mater for 
use in repairing defects in human dura mater into class II .
    The Panel believes that human dura mater should be classified into 
class II because special controls, in addition to general controls, 
would provide reasonable assurance of the safety and effectiveness of 
the device, and there is sufficient information to establish special 
controls to provide such assurance.

D. Summary of the Data Upon Which the Recommendation Is Based

    In addition to the potential risks associated with the use of the 
human dura mater described in section V of this document, there is 
reasonable knowledge of the benefits of the device. Specifically, this 
long-term implanted device provides mechanical support and protection 
of the brain, as well as less leakage of CSF after neurosurgery. The 
use of human dura mater rather than the use of a dura substitute device 
or a graft prepared from the patient is also

[[Page 64838]]

preferred by some neurosurgeons (Refs. 5 and 6).

E. Risks to Health

    After considering the Panel's deliberations, as well as the 
published literature and medical device reports (MDRs), FDA has 
evaluated the risks to health associated with the use of human dura 
mater intended to repair defects in human dura mater. FDA now believes 
the following are risks to health associated with the use of the 
device: Infection related to patient condition and treatment, 
transmission of spongiform encephalopathies, leakage of CSF, and 
adverse tissue reaction:
1. Infection Related to Patient Condition and Treatment
    Bacterial, fungal, and viral infection is a risk to health 
associated with all surgical procedures and implanted devices. 
Regarding human dura mater implantation, infection may occur because 
the device was improperly sterilized or because of a pre-existing 
patient condition (i.e., whether the wound is clean, contaminated, or 
infected). After the implantation of human dura mater, the probability 
of infection that may occur has been reported to vary from 1.9 percent 
to 19 percent (Refs. 7 to 9).
2. Transmission of Spongiform Encephalopathies
    Transmission of CJD and related diseases can occur from either 
inadequate donor selection or inappropriate human dura mater processing 
(Refs. 10 to 12). As of July 2000, the worldwide incidence of 
iatrogenic CJD associated with the use of implanted human dura mater 
was reported to be 114 cases, including three United States cases (Ref. 
13). Most of these cases were related to the use of implanted Lyodura, 
a product that is not cleared for use in the United States.
3. Leakage of CSF
    Leakage of CSF after neurosurgery may occur due to device failure 
or the incomplete repair of suture holes in the patient's dura mater 
created during implantation of human dura mater. Leakage of CSF can 
cause secondary complications, such as meningitis or encephalitis, 
pneumocephalus, and chronic subdural hematoma. Persistent accumulation 
of CSF may require additional surgical intervention and can be a 
significant cause of morbidity and mortality (Ref. 14).
4. Adverse Tissue Reaction
    Human dura mater implantation may elicit an undesirable 
immunological reaction (Ref. 15) and an inflammatory or cytotoxic 
tissue reaction (Ref. 16). These reactions may result in adverse 
clinical outcomes, such as adhesion formation, hydrocephalus, foreign 
body reactions, and seizure (Ref. 17).

F. Special Controls

    Based on the available information, FDA believes that the FDA 
guidance document entitled ``Class II Special Controls Guidance 
Document: Human Dura Mater; Guidance for Industry and FDA'' in addition 
to general controls, can provide reasonable assurance of the safety and 
effectiveness of the device. FDA agrees with the Panel that careful 
donor selection and testing guidelines are appropriate special controls 
to address the risks to health described in section II.E of this 
document. In addition, as noted below, device tracking, prescription 
labeling, and a form of postmarket surveillance that are already in 
effect provide additional controls to reasonably ensure the safety and 
effectiveness of human dura mater.
    FDA notes that this proposed special control guidance document 
updates and will supersede the ``Guidance for the Preparation of a 
Premarket Notification Application for Processed Human Dura Mater'' 
issued on July 31, 1999, and reissued in October 1999.
1. Guidance Document
    FDA believes that the guidance document addresses the Panel's 
concerns on donor selection and testing guidelines.
    a. Infection related to patient condition and treatment. Adherence 
to the sections in the guidance document on: (1) Donor qualification; 
(2) qualification of other components; (3) manufacturing processing 
methods; (4) manufacturing controls; and (5) final sterilization may 
control the risk of bacterial, fungal, and viral infection by helping 
to ensure that the device is sterile and safe for long-term 
implantation.
    b. Transmission of spongiform encephalopathies. Adherence to the 
sections in the guidance document on: (1) Donor qualification, (2) 
qualification of other components, (3) manufacturing processing 
methods, (4) manufacturing controls, and (5) labeling may control the 
risk of spongiform encephalopathy transmission by helping ensure the 
preparation of devices that have a lower risk of CJD transmission and 
can remind users of potential risks and alternative products.
    c. Leakage of CSF.Adherence to the sections in the guidance 
document on: (1) Manufacturing processing methods, and (2) 
manufacturing controls can control the risk of CSF leakage by having 
the manufacturer demonstrate that the device is safe for long-term 
implantation.
    d. Adverse tissue reactions. Adherence to the sections in the 
guidance document on: (1) Manufacturing processing methods, (2) 
manufacturing controls, and (3) final sterilization can control the 
risk of adverse tissue reactions by having the manufacturer demonstrate 
that the device is safe for long-term implantation.
2. Device Tracking
    The Panel also identified device tracking as a potential special 
control for human dura mater. Tracking is a compliance mechanism to 
facilitate notification and recall actions in the event of a serious 
risk to health presented by a device. FDA notes that the agency has 
already issued a tracking order for human dura mater on December 14, 
1998. Because device tracking is a regulatory control already in effect 
for human dura mater, it is not necessary that tracking also be 
considered a special control necessary to provide reasonable assurance 
of the safety and effectiveness of the device.
3. Postmarket Surveillance and Patient Registries
    The Panel stated that it was important to track adverse device 
outcomes through postmarket surveillance. FDA agrees with the Panel 
that adverse device outcomes should be reported to FDA. However, FDA 
believes that the existing mandatory MDR system is an appropriate 
mechanism to report such adverse events. Therefore, it is not necessary 
that postmarket surveillance be designated a special control.
    The Panel also recommended patient registries as a special control 
for the device. Because the tracking regulation already requires 
manufacturers to develop and implement programs to locate patients 
implanted with human dura mater until device explantation or death, it 
is not necessary that patient registries be designated as a special 
control.
4. Prescription Labeling
    The Panel also recommended that the prescription statement be a 
special control for the device. Prescription labeling is already 
required for human dura mater under 21 CFR 801.109. Therefore, it is 
not necessary that the prescription statement be designated a special 
control.

[[Page 64839]]

III. Proposed Classification

    FDA concurs with the Panel's recommendation that human dura mater 
should be classified into class II. FDA believes that the special 
control described in section II.F of this document, in addition to 
general controls, would provide reasonable assurance of the safety and 
effectiveness of the device, and there is sufficient information to 
establish special controls to provide such assurance.
    The agency proposes to amend Sec.  882.1 by adding paragraph (e) to 
provide availability information for guidance documents.

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 proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), 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.
    FDA has also examined the impact of the proposed rule under the 
Regulatory Flexibility Act. The purpose of this proposed rule is to 
change the classification of human dura mater from an unclassified 
medical device into a class II medical device subject to special 
controls. As an unclassified device, this device is already subject to 
premarket notification and the general labeling provisions of the act. 
There are currently five to seven manufacturers of human dura mater 
medical devices. All of the firms meet the Small Business 
Administration's definition of a small entity (fewer than 500 
employees). FDA believes that manufacturers presently marketing this 
device generally conform to the proposed special controls guidance 
document. New manufacturers of human dura mater will only need to 
submit 510(k)s, as the statute now requires them to do, and demonstrate 
that they meet the recommendations of the guidance or in some way 
provide equivalent assurances of safety and effectiveness. In addition, 
biocompatibility and structural testing recommendations are eliminated 
from the proposed guidance, which will decrease the premarket 
notification costs for manufacturers introducing new human dura mater 
devices into commercial distribution. The agency therefore certifies 
that this proposed rule, if finalized, will not have a significant 
economic impact on a substantial number of small entities. In addition, 
this proposed 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 analysis under 
section 202(a) of the Unfunded Mandates Reform Act of 1995 is not 
required.

VI. Paperwork Reduction Act of 1995

    The premarket notification information collections addressed in the 
guidance document have been approved by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (the 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.

VII. Submission of Comments and Proposed Dates

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments regarding this proposal. You 
must submit two copies of any mailed comments except that individuals 
may submit one copy. You must identify comments with the docket number 
found in brackets in the heading of this document. You may see any 
comments received in the Dockets Management Branch between 9 a.m and 4 
p.m., Monday through Friday. FDA proposes that any final rule that may 
issue based on this proposal become effective 30 days after its date of 
publication in the Federal Register.

VIII. References

    The following references have been placed on display in the Dockets 
Management Branch (see ADDRESSES) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Centers for Disease Control, ``Rapidly Progressive Dementia 
in a Patient Who Received a Cadaveric Dura Mater Graft,'' Morbidity 
and Mortality Weekly Report, 36:49-50, 1987.
    2. Neurological Devices Panel meeting, transcript, July 14, 
1989, pp. 1-141.
    3. Neurological Devices Panel meeting, transcript, February 2, 
1990, pp. 5-111.
    4. Centers for Disease Control, ``Creutzfeldt-Jakob Disease 
Associated With Cadaveric Dura Mater Grafts-Japan, January 1979-May 
1996,'' Morbidity and Mortality Weekly Report, 46: 1066-1069, 1997.
    5. Transmissible Spongiform Encephalopathies Advisory Committee 
meeting, transcript, October 6 and 7, 1997, pp. 210-269.
    6. Neurological Devices Panel meeting, transcript, September 16, 
1999, pp. 1-3 and 77-99, and September 17, 1999, pp. 9-11 and 17-
101.
    7. Abbott, W. M. and E. L. Dupree, ``Clinical Results of 
Lyophilized Human Cadaver Dura Transplantation,'' Journal of 
Neurosurgery, 34: 770-773, 1971.
    8. Cantore, G., G. B. Guidetti, and R. Delfini, ``Neurosurgical 
Use of Human Dura Mater Sterilized by Gamma Rays and Stored in 
Alcohol: Long-Term Results,'' Journal of Neurosurgery, 66: 93-95, 
1987.
    9. Laun, A., J. C. Tonn, and C. Jerusalem, ``Comparative Study 
of Lyophilized Human Dura Mater and Lyophilized Bovine Pericardium 
as Dural Substitutes in Neurosurgery,'' Acta Neurochirurgica (Wien), 
107: 1621, 1990.
    10. Thadani, V., P. L. Penar, J. Partington, R. Kalb, R. 
Janssen, L. B. Schonberger, C. S. Rabkin, and J. W. Prichard, 
``Creutzfeldt-Jakob Disease Probably Acquired From a Cadaveric Dura 
Mater Graft, Case Report,'' Journal of Neurosurgery, 69: 766-769, 
1988.
    11. Lang, C. J., J. G. Heckman, and B. Neundorfer, 
``Creutzfeldt-Jakob Disease Via Dural and Corneal Transplants,'' 
Journal of Neurological Science, 160: 128-139, 1998.
    12. Dobbins, J. G., E. D. Belay, J. Malecki, B. E. Buck, M. 
Bell, J. Cobb, and L. B. Schonberger, ``Creutzfeldt-Jakob Disease in 
a Recipient of a Dura Mater Graft Processed in the U.S.: Cause or 
Coincidence?'' Neuroepidemiology, 19: 62-66, 2000.
    13. Brown, P., M. Preece, J. P. Brandel, T. Sato, L. McShane, I. 
Zerr, A. Fletcher, R. G. Will, M. Pocchiari, N. R. Cashman, J. H. 
d'Aignaux, L. Cervenakova, J. Fradkin, L. B. Schonberger, and S. J. 
Collins, ``Iatrogenic Creutzfeldt-Jacob Disease at the Millenium,'' 
Neurology, 55: 1075-1081, 2000.
    14. Sawamura, Y., K. Asaoka, S. Terasaka, M. Tada, and T. 
Uchida, ``Evaluation of Application Techniques of Fibrin Sealant to 
Prevent Cerebrospinal Fluid Leakage: A New Device for the 
Application of Aerosolized Fibrin Glue,'' Neurosurgery, 44: 332-337, 
1999.
    15. Alleyne, C. H. and D. L. Barrow, ``Immune Response in Hosts 
With Cadaveric Dural Grafts,'' Journal of Neurosurgery, 81: 610-613, 
1994.
    16. Rosomoff, H. L. and T. I. Malinin, ``Freeze-Dried Allografts 
of Dura Mater--20 Years Experience,'' Transplantation

[[Page 64840]]

Proceedings, VIII: No. 2 Supplement 1, 133-138, 1976.
    17. Sharkey, P. C., F. C. Usher, R. C. L. Robertson, and C. 
Pollard, ``Lyophilized Human Dura Mater as a Dural Substitute, '' 
Journal of Neurosurgery, 15: 192-198, 1958.

List of Subjects in 21 CFR Part 882

    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 882 be amended as follows:

PART 882--NEUROLOGICAL DEVICES

    1. The authority citation for 21 CFR part 882 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c 360e, 360j, 371.
    2. Section 882.1 is amended by adding paragraph (e) to read as 
follows:


Sec.  882.1  Scope.

* * * * *
    (e) Guidance documents in this part may be obtained on the Internet 
at http://www.fda.gov/cdrh/guidance.html.
    3. Section 882.5975 is added to subpart F to read as follows:


Sec.  882.5975  Human dura mater.

    (a) Identification. Human dura mater is human pachymeninx tissue 
intended to repair defects in human dura mater.
    (b) Classification. Class II (special controls). The special 
control for this device is FDA's ``Class II Special Controls Guidance 
Document: Human Dura Mater; Guidance for Industry and FDA.'' (See Sec.  
882.1 for availability information for guidances.)

    Dated: September 30, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-26816 Filed 10-21-02; 8:45 am]
BILLING CODE 4160-01-S