[Federal Register Volume 66, Number 103 (Tuesday, May 29, 2001)]
[Notices]
[Pages 29149-29152]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-13302]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 96P-0484]


Blood Products Advisory Committee, Medical Devices Panel; 
Reclassification of Autopheresis-C<Register> System From Class III to 
Class II

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of panel recommendation.

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SUMMARY: The Food and Drug Administration (FDA) is issuing for public 
comment the recommendation of the Blood Products Advisory Committee, 
Medical Devices Panel (the Panel) to reclassify the Autopheresis-
C<Register> System, intended for routine collection of blood and blood 
components, from class III to class II. The Panel made this 
recommendation after reviewing the reclassification petition submitted 
by Baxter Healthcare Corp. (Baxter). FDA is also issuing for public 
comment its tentative findings on the Panel's recommendation. After 
considering any public comments on the Panel's recommendation and FDA's 
tentative findings, FDA will approve or deny the reclassification 
petition by order in the form of a letter to the petitioner. FDA's 
decision on the reclassification petition will be announced in the 
Federal Register.

DATES: Submit written comments by August 13, 2001.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Paula S. McKeever, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
6210.

SUPPLEMENTARY INFORMATION:

I. Background (Regulatory Authorities)

    The Federal Food, Drug, and Comestic 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

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Safe Medical Devices Act of 1990 (Public Law 101-629), and the Food and 
Drug Administration Modernization Act of 1997 (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 section 513 of the act, devices that were in commercial 
distribution before 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 prior to 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 the device is 
reclassified into class I or II or FDA issues an order finding the 
device to be substantially equivalent, under 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 (PMA) until FDA issues a 
final regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Reclassification of classified postamendments devices is governed 
by section 513(f)(3) of the act. This section provides that FDA may 
initiate the reclassification of a device classified into class III 
under section 513(f)(1) of the act, or the manufacturer or importer of 
a device may petition the Secretary of Health and Human Services (the 
Secretary) for the issuance of an order classifying the device in class 
I or class II. FDA's regulations in Sec. 860.134 (21 CFR 860.134) set 
forth the procedures for the filing and review of a petition for 
reclassification of such class III devices. In order to change the 
classification of the device, it is necessary that the proposed new 
class have sufficient regulatory controls to provide reasonable 
assurance of the safety and effectiveness of the device for its 
intended use.
    Under section 513(f)(3)(B)(i) of the act, the Secretary may, for 
good cause shown, refer a petition to a device classification panel. 
The Panel shall make a recommendation to the Secretary respecting 
approval or denial of the petition. Any such recommendation shall 
contain: (1) A summary of the reasons for the recommendation, (2) a 
summary of the data upon which the recommendation is based, and (3) an 
identification of the risks to health (if any) presented by the device 
with respect to which the petition was filed.

II. Regulatory History of the Device

    The Autopheresis-C<Register> System, intended for the routine 
collection of blood and blood components, is a postamendments device 
classified into class III under section 513(f)(1) of the act. 
Therefore, the device can not be placed in commercial distribution for 
the routine collection of blood and blood components unless it is 
reclassified under section 513(f)(3) of the act, or subject to an 
approved PMA under section 515 of the act. This action is taken in 
accordance with section 513(f)(3) of the act and Sec. 860.134 of the 
regulations, based on information submitted in a petition for 
reclassification by Baxter on June 17, 1996, requesting 
reclassification of the Autopheresis-C<Register> System, intended for 
routine collection of blood and blood components, from class III to 
class II. Although Baxter submitted its petition for reclassification 
under section 513(e) of the act, the request should have been submitted 
under section 513(f)(3), and therefore FDA has considered the petition 
filed under section 513(f)(3). Consistent with the act and the 
regulation, FDA referred the petition to the Panel for its 
recommendation on the requested change in classification. The Panel met 
on September 26, 1996, at a public meeting.

III. Device Description

    The Autopheresis-C<Register> System, intended for routine 
collection of blood and blood components, is an automated 
plasmapheresis system. It utilizes a spinning membrane separation 
device to achieve rapid and gentle separation by filtration of whole 
blood into concentrated cellular components for reinfusion and into 
plasma for collection.
    The instrument uses a system of pumps and sensors controlled by a 
microprocessor and it incorporates a variety of safety and alarm system 
functions. It uses a fully automated processing program to collect a 
preset volume of plasma from a donor. Plasma collection in the 
Autopheresis-C<Register> System involves sequential phases of 
collection of plasma from the donor and reinfusion of the residual red 
blood cell concentrate back to the donor.
    The Autopheresis-C<Register> System is currently employed in 
commercial plasma centers where it is used to collect Source Plasma, 
and it is also found in blood centers and hospital blood banks where it 
is used for the collection of plasma for preparation of fresh frozen 
plasma.

IV. Recommendations of the Panel

    At a public meeting on September 27, 1996, the Panel unanimously 
recommended that the Autopheresis-C<Register> System, intended for 
routine collection of blood and blood components, be reclassified from 
class III to class II. The Panel also recommended that subsequent 
membrane-based blood cell separators be classified as class II devices, 
if in the opinion of FDA they are substantially equivalent to the 
Autopheresis-C<Register> System, the predicate device. The Panel 
believed that class II with the special controls of a periodic report 
filed annually for a minimum of 3 years with emphasis on adverse 
reactions would provide reasonable assurance of the safety and 
effectiveness of the device.

V. Risks to Health

    FDA has identified the following risks associated with apheresis 
blood donation and processing: (1) The potential loss of blood due to 
leaks; (2) thrombosis due to activation of factors by foreign surfaces; 
(3) toxic reaction to citrate or heparin anticoagulant; (4) damage to 
red cells, activation of compliment, and denaturation of proteins; (5) 
potential for sepsis and fever due to bacterial contamination of the 
donor's blood returned to the donor; (6) infectious disease risk to the 
donor or to the operator due to leaks; (7) electrical shock hazard; (8) 
donor stress reaction due to removal or loss of blood; and (9) 
reservoir rupture.

[[Page 29151]]

    Some of the reported adverse donor reactions are: (1) Allergic 
reaction; (2) vasovagal or syncopal reaction; (3) citrate toxicity; (4) 
hematoma; (5) hematuria or hemoglobinuria; (6) hypovolemic reaction; 
(6) myocardial infarct in three cases unrelated to the donation 
procedure; (7) mesenteric thrombosis unrelated to the donation 
procedure; (8) chest pains; (9) high blood pressure; (10) blood 
clotting; (11) nonresponsive donor during or after the donation 
procedure; (12) death of a donor several days following an apheresis 
unrelated to the procedure; (13) blood spray; and (14) tubing 
separation.

VI. Summary of Reasons for Recommendation

    After reviewing the data and information contained in the petition 
and provided by FDA, and after consideration of the open discussions 
during the Panel meeting and the Panel members' personal knowledge of 
and clinical experience with the device, the Panel gave the following 
reasons in support of its recommendation to reclassify the 
Autopheresis-C<Register> System, intended for routine collection of 
blood and blood components, as the predicate device and the subsequent 
generic type of filtration-based blood cell separator for use in 
routine collection of donor plasma from class III to class II.
    The Panel believes that the Autopheresis-C<Register> System and 
subsequent generic type of filtration-based blood cell separator should 
be reclassified into class II because special controls, in addition to 
general controls, provide reasonable assurance of the safety and 
effectiveness of the device, and there is sufficient information to 
establish special controls to provide such assurance.

VII. Summary of Data Upon Which the Panel Recommendation Is Based

    In addition to the potential risks of the Autopheresis-C<Register> 
System and subsequent generic types of filtration-based blood cell 
separators described above, there is sufficient information about the 
benefits of the device. Specifically, the Autopheresis-C<Register> 
System has been used since 1986, and the data presented by Baxter 
showed no evidence of cellular or protein damage to the donor blood; 
the procedure was well tolerated by the donor; and the instrument was 
safe and effective for plasma collection. The period from 1986 to 1996 
showed that a 0.03 percent of donations were associated with some type 
of event which were reported to Baxter.
    Based on the available information, FDA believes that the special 
controls discussed below are capable of providing reasonable assurance 
of the safety and effectiveness of the Autopheresis-C<Register> System, 
intended for routine collection of blood and blood components, and 
subsequent generic types of filtration-based blood cell separators with 
regard to the identified risks to health of this device.

VIII. Special Controls

    In addition to general controls, FDA believes that the following 
special control is adequate to address the risks to health described 
for this device. The manufacturer must file an annual report with FDA 
on the anniversary date of reclassification for 3 consecutive years. A 
manufacturer of a device determined to be substantially equivalent\1\ 
to the Autopheresis-C<Register> System, intended for routine collection 
of blood and blood components, also is required to comply with the same 
general and special controls. Any subsequent change to the device 
requiring the submission a premarket notification in accordance with 
section 510(k)\2\ of the act, should be included in the annual report.
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    \1\ For assistance see the guidance document entitled ``The New 
510(k) Paradigm: Alternate Approaches to Demonstrating Substantial 
Equivalence in Premarket Notifications,'' March 1998, at http://www.fda.gov/cdrh.
    \2\ For assistance see the guidance document entitled ``Deciding 
When to Submit a 510(k) for a Change to an Existing Device,'' 
January 1997, at http://www.fda.gov/cdrh.
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    Unless FDA specifies otherwise, each annual report (special 
control) must include:
    1. A summary of adverse donor reactions reported by the users to 
the manufacturer that do not meet the threshold for medical device 
reporting under 21 CFR part 803;
    2. Any change to the device, including but not limited to:
    <bullet>  new indications for use of the device;
    <bullet>  labeling changes, including operation manual changes;
    <bullet>  computer software changes, hardware changes, and 
disposable item changes, e.g., collection bags, tubing, filters;
    3. Equipment failures, including software, hardware, and disposable 
item failures, e.g., collection bags, tubing, filters.

IX. FDA's Tentative Findings

    The Panel and FDA believe that the Autopheresis-C<Register> System, 
intended for routine collection of blood and blood components, and 
subsequent generic types of filtration-based blood cell separators 
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.
    However, any change in the indication for use, i.e., for 
therapeutic purposes, would require a PMA since these devices are not 
included in the reclassification action.

X. References

    The following references have been placed on display in the Dockets 
Management Branch and may be seen by interested persons between 9 a.m. 
and 4 p.m., Monday through Friday.

    1. Petition for reclassification of the Autopheresis-C<Register> 
System from class III to class II by Baxter Healthcare Corp., June 
17, 1996.
    2. Transcript of the Blood Products Advisory Committee, 52d 
Meeting, September 27, 1996.

XI. 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.

XII. Analysis of Impacts

    FDA has examined the impacts of the notice 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 reclassification action is 
consistent with the regulatory philosophy and principles identified in 
the Executive order. In addition, the reclassification action 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

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entities. Reclassification of the device from class III to class II 
will relieve manufacturers 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 reclassification action, if finalized, will not have a 
significant economic impact on a substantial number of small entities. 
In addition, this reclassification action 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 
of analysis under section 202(a) of the Unfunded Mandates Reform Act of 
1995 is not required.

XIII. Request for Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written comments regarding this document by August 13, 
2001. Two copies of any comment are to be submitted, except that 
individuals may submit one copy. Comments are to be identified with the 
docket number found in brackets in the heading of this document. 
Received comments may be seen in the Dockets Management Branch between 
9 a.m. and 4 p.m., Monday through Friday.

    Dated: May 17, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-13302 Filed 5-25-01; 8:45 am]
BILLING CODE 4160-01-S