[Federal Register Volume 68, Number 40 (Friday, February 28, 2003)]
[Rules and Regulations]
[Pages 9530-9532]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-4690]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 864

[Docket No. 96P-0484]


Medical Devices; Hematology and Pathology Devices; 
Reclassification of Automated Blood Cell Separator Device Operating by 
Filtration Principle from Class III to Class II

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is reclassifying the 
automated blood cell separator (ABCS) device operating by filtration 
principle, intended for routine collection of blood and blood 
components, from class III to class II (special controls). The special 
control requirement for this device is an annual report with emphasis 
on adverse reactions to be filed by the manufacturer for a minimum of 3 
years. The agency is taking this action in response to a petition 
submitted 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), and the Food and Drug 
Administration Modernization Act of 1997 (FDAMA). The agency is 
reclassifying the automated blood cell separator devices operating by 
filtration principle into class II (special controls) because special 
controls, in addition to general controls, are capable of providing a 
reasonable assurance of safety and effectiveness of the device.

DATES: This rule is effective March 31, 2003.

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

    The act (21 U.S.C. 301 et seq.), as amended by the 1976 amendments 
(Public Law 94-295), the SMDA (Public Law 101-629), and 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 section 513(f)(1) of the act, devices that were not in 
commercial distribution before May 28, 1976, the date of enactment of 
the 1976 amendments, generally referred to as postamendments devices, 
are classified automatically by statute 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.
    Under section 513(f)(3) of the act, FDA may initiate the 
reclassification of a device classified into class III under section 
513(f)(1), or the manufacturer or importer of a device may petition the 
Secretary of Health and Human Services 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.

II. Regulatory History of the Device

    The AUTOPHERESIS-C SYSTEM, an ABCS, 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 cannot 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 premarket approval application (PMA) under section 515 of the 
act (21 USC 360e). FDA is taking this action under section 513(f)(3) of 
the act and Sec.  860.134, based on information submitted in a petition 
by Baxter Healthcare Corp. (Baxter) on June 17, 1996, requesting 
reclassification of the AUTOPHERESIS-C SYSTEM, intended for routine 
collection of blood and blood components, from class III to class II 
(Ref. 1). 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 section 513(f)(3) of the 
act and Sec.  860.134, FDA referred the petition to the Blood Products 
Advisory Committee, Medical Devices Panel (the Panel) for its 
recommendation on the requested change in classification. The Panel met 
on September 26, 1996, at a public meeting (Ref. 2).

III. Device Description

    The AUTOPHERESIS-C 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

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functions. It uses a fully automated processing program to collect a 
preset volume of plasma from a donor. Plasma collection in the 
AUTOPHERESIS-C 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 SYSTEM is currently employed in 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.
    Any change in the indication for use, i.e., for therapeutic use, 
would require a PMA because devices for therapeutic use are not 
included in this reclassification action.

IV. 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 complement, 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.
    Some of the reported adverse donor reactions are: (1) Allergic 
reaction; (2) vasovagal or synocopal 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.
    In addition to the potential risks of the AUTOPHERESIS-C SYSTEM and 
subsequent generic types of filtration-based blood cell separators, 
there is sufficient information about the benefits of the device. 
Specifically, the AUTOPHERESIS-C SYSTEM has been used since 1986, and 
the data presented by Baxter show no evidence of cellular or protein 
damage to the donor blood; the procedure is well tolerated by the 
donor; and the instrument is 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 potential adverse event that were 
reported to Baxter.

V. Panel Recommendation

    The Panel reviewed the data and information contained in the 
petition and provided by FDA, and considered the open discussions 
during the Panel meeting. The Panel consisted of members with personal 
knowledge of and clinical experience with the device. At a public 
meeting on September 27, 1996, the Panel unanimously recommended that 
the AUTOPHERESIS-C SYSTEM and subsequent membrane-based blood cell 
separators substantially equivalent to this device, intended for 
routine collection of blood and blood components, be reclassified from 
class III to class II. 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.

VI. Special Controls

    FDA believes that, in addition to general controls, the special 
controls described below address these risks and provide reasonable 
assurance of the safety and effectiveness of the device. FDA described 
the special controls in the Federal Register of May 29, 2001 (66 FR 
29149 at 29151), and provided an opportunity for public comment. FDA 
did not receive any comments on the special controls. Therefore, on 
September 5, 2001, FDA issued an order to the petitioner reclassifying 
the AUTOPHERESIS-C SYSTEM, and substantially equivalent devices of this 
generic type, from class III to class II subject to the special 
controls described below (Ref. 3). Through this final rule, FDA is 
codifying the reclassification of this device by revising 21 CFR 
864.9245. By listing the contents of the special controls, new 
manufacturers of substantially equivalent devices can comply with the 
same special controls.
    In addition to general controls of the act, automated blood cell 
separator devices operating by filtration principle are subject to the 
following special controls in order to provide reasonable assurance of 
the safety and effectiveness of the 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 to the AUTOPHERESIS-C 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 of a premarket 
notification in accordance with section 510(k) of the act should be 
included in the annual report.
    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:
    [sbull] new indications for use of the device;
    [sbull] labeling changes, including operation manual changes;
    [sbull] 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.

VII. 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.

VIII. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1501 et seq.). 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.
    Under the Regulatory Flexibility Act, if a rule has a significant 
economic impact on a substantial number of small entities, an agency 
must consider alternatives that would minimize the economic impact of 
the rule on small

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entities. Reclassification of the affected devices from class III to 
class II will relieve manufacturers of the cost of complying with the 
premarket approval requirements of section 515 of the act, and may 
permit small potential competitors to enter the marketplace by lowering 
their costs. Although the final rule requires manufacturers of these 
devices to file an annual report with FDA for 3 consecutive years, this 
is less burdensome than the current premarket approval requirement that 
annual reports be submitted to FDA on an ongoing basis. The agency, 
therefore, certifies that the final rule will not have a significant 
economic impact on a substantial number of small entities. Therefore, 
under the Regulatory Flexibility Act, no further analysis is required. 
In addition, the Unfunded Mandates Reform Act does not require FDA to 
prepare a statement of costs and benefits for the final rule because 
the rule will not impose costs of $100 million or more on State, local, 
and tribal governments in the aggregate, or the private sector, in any 
one year (adjusted annually for inflation).

IX. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

X. 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, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilites 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.

XI. References

    The following references have been placed on display in the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852, 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 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.
    3. Order to the petitioner, September 5, 2001.

List of Subjects in 21 CFR Part 864

    Blood, Medical devices, Packaging and containers.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
864 is amended as follows:

PART 864--HEMATOLOGY AND PATHOLOGY DEVICES

    1. The authority citation for 21 CFR part 864 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

    2. Section 864.9245 is amended by redesignating paragraphs (b) and 
(c) as paragraphs (c) and (d), respectively, by adding new paragraph 
(b), and by revising newly redesignated paragraphs (c) and (d) to read 
as follows:


Sec.  864.9245  Automated blood cell separator.

* * * * *
    (b) Classification of device operating by filtration separation 
principle. Class II (special controls). The special controls for the 
device are that the manufacturer must file an annual report with FDA 
for 3 consecutive years. Each annual report must include the following:
    (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 part 803 of this chapter;
    (2) Any change to the device, including but not limited to:
    (i) New indications for use of the device;
    (ii) Labeling changes, including operation manual changes;
    (iii) 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.
    (c) Classification of device operating by centrifugal separation 
principle. Class III (premarket approval).
    (d) Date PMA or notice of completion of a PDP is required. No 
effective date has been established of the requirement for premarket 
approval for the device described in paragraph (c) of this section. See 
Sec.  864.3.

    Dated: February 4, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-4690 Filed 2-27-03; 8:45 am]
BILLING CODE 4160-01-S