[Federal Register Volume 72, Number 230 (Friday, November 30, 2007)]
[Rules and Regulations]
[Pages 67640-67644]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-23285]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 864

[Docket No. 2005N-0017]


Medical Devices; Hematology and Pathology Devices: 
Reclassification of Automated Blood Cell Separator Device Operating by 
Centrifugal Separation Principle

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is reclassifying from 
class III to class II the automated blood cell separator device 
operating by centrifugal separation principle and intended for the 
routine collection of blood and blood components. FDA is taking this 
action on its own initiative based on new information. Elsewhere in 
this issue of the Federal Register, FDA is announcing the availability 
of a guidance document that will serve as the special controls for this 
device, as well as the special controls for the device with the same 
intended use but operating on a filtration separation principle.

[[Page 67641]]


DATES: This rule is effective December 31, 2007. The reclassification 
date is November 30, 2007.

FOR FURTHER INFORMATION CONTACT:  Nathaniel L. Geary, Center for 
Biologics Evaluation and Research, Food and Drug Administration (HFM-
17), 1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448, 301-
827-6210.

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 (SMDA) 
(Public Law 101-629), the Food and Drug Administration Modernization 
Act (FDAMA) (Public Law 105-115), and the Medical Device User Fee and 
Modernization Act (Public Law 107-250) 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 as follows:
     Class I (general controls),
     Class II (special controls), and
     Class III (premarket approval).
    Under the 1976 amendments, class II devices were defined as devices 
for which there was insufficient information to show that general 
controls themselves would provide reasonable assurance of safety and 
effectiveness, but for which there was sufficient information to 
establish performance standards to provide such assurance. SMDA 
broadened the definition of class II devices to mean those devices for 
which the general controls by themselves are insufficient to provide 
reasonable assurance of safety and effectiveness, but for which there 
is sufficient information to establish special controls to provide such 
assurance, including performance standards, post-market surveillance, 
patient registries, development and dissemination of guidelines, 
recommendations, and other appropriate actions the agency deems 
necessary (section 513(a)(1)(B) of the act).
    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 preamendment devices, are 
classified after FDA:
    1. Receives a recommendation from a device classification panel (an 
FDA advisory committee);
    2. Publishes the panel's recommendation for comment, along with a 
proposed regulation classifying the device; and
    3. Publishes a final regulation classifying the device.
    FDA has classified most preamendments devices under these 
procedures.
    1. 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) (21 U.S.C. 
360c(f)) into class III without any FDA rulemaking process. Those 
devices remain in class III and require premarket approval unless and 
until FDA reclassifies the device into class I or class 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 FDAMA; 
or
    3. FDA issues an order finding the device to be substantially 
equivalent, under section 513(i) of the act (21 U.S.C. 360c(i)), 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 part 807 of the regulations (21 CFR part 807).
    A preamendments device that has been classified into class III may 
be marketed through 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.
    Section 513(e) of the act governs reclassification of classified 
preamendments devices. This section provides that FDA may, by 
rulemaking, reclassify a device (in a proceeding that parallels the 
initial classification proceeding) based upon ``new information.'' FDA 
can initiate a reclassification under section 513(e) or an interested 
person may petition FDA to reclassify a preamendments device. The term 
``new information,'' as used in section 513(e)(1) of the act, includes 
information developed as a result of a reevaluation of the data before 
the agency when the device was originally classified, as well as 
information not presented, not available, or not developed at that 
time. (See, e.g., Holland Rantos v. United States Department of Health, 
Education, and Welfare, 587 F.2d 1173, 1174 n.1 (D.C. Cir. 1978); 
Upjohn v. Finch, 422 F.2d 944 (6th Cir. 1970); Bell v. Goddard, 366 
F.2d 177 (7th Cir. 1966)).
    Reevaluation of the data previously before the agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation is made in light of newly available regulatory authority 
(see Bell v. Goddard, supra, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 
F.Supp. 382, 389-91 (D.D.C. 1991)), or in light of changes in ``medical 
science.'' (See Upjohn v. Finch, supra, 422 F.2d at 951). Regardless of 
whether data before the agency are past or new data, the ``new 
information'' to support reclassification under section 513(e)(1) of 
the act must be ``valid scientific evidence,'' as defined in section 
513(a)(3) of the act and 21 CFR 860.7(c)(2). (See, e.g., General 
Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Assoc. 
v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 1062 (1985)). 
FDA relies upon ``valid scientific evidence'' in the classification 
process to determine the level of regulation for devices. To be 
considered in the reclassification process, the valid scientific 
evidence upon which FDA relies must be publicly available. Publicly 
available information excludes trade secret and/or confidential 
commercial information, e.g., the contents of a pending PMA. (See 
section 520(c) of the act (21 U.S.C. 360j(c)).
    Section 510(m) of the act (21 U.S.C. 360(m)) provides that FDA 
exempt a class II device from the premarket notification requirements 
under section 510(k) of the act if FDA determines that premarket 
notification is not necessary to provide reasonable assurance of the 
safety and effectiveness of the device. FDA believes that an automated 
blood cell separator device operating by centrifugal separation 
principle should not be exempt from premarket notification under 
section 510(m) of the act because premarket notification is necessary 
to provide reasonable assurance of the safety and effectiveness of the 
device.

II. Regulatory History of the Device

    The automated blood cell separator device operating by centrifugal 
separation principle intended for the routine collection of blood and 
blood components is a preamendments device classified into class III.
    In the Federal Register of March 10, 2005 (70 FR 11887), based on 
new information with respect to the device, FDA proposed, on its own 
initiative, to reclassify from class III to class II the automated 
blood cell separator device

[[Page 67642]]

operating by centrifugal separation principle, when the intended use of 
the device is for the routine collection of blood and blood components. 
Interested persons were invited to comment on the proposed rule by June 
8, 2005. FDA received one comment on the proposed rule and draft 
guidance and that comment was considered as the rule and guidance were 
finalized.
    Also, FDA is correcting a regulatory citation in the proposed rule 
of March 10, 2005 (70 FR 11887), on page 11892, in the first column, 
starting in the second line; ``21 CFR 803.50(b)(2)'' is corrected to 
read ``21 CFR 803.50(b)(3))''.
    FDA also identified the draft guidance entitled ``Guidance for 
Industry and FDA Staff: Class II Special Controls Guidance Document: 
Automated Blood Cell Separator Device Operating by Centrifugal or 
Filtration Separation Principle'' as the proposed special controls 
capable of providing reasonable assurance of safety and effectiveness 
for these devices.

III. Summary of Final Rule

    Under section 513(e) of the act and Sec.  860.130 (21 CFR 860.130), 
based on new information and on its own initiative, FDA is 
reclassifying from class III to class II (special controls) the 
automated blood cell separator device operating by centrifugal 
separation principle and intended for the routine collection of blood 
and blood components. The special controls in conjunction with general 
controls will provide reasonable assurance of the safety and 
effectiveness of the device. For all other uses, including therapeutic 
apheresis, the device remains in its current classification as class 
III. All therapeutic apheresis (blood cell separator) devices are 
regulated by the Center for Devices and Radiological Health and are not 
part of Sec.  864.9245 (21 CFR 864.9245).
    The automated blood cell separator device operating by centrifugal 
separation principle is assigned the generic name, automated blood cell 
separator. It is identified as a device that automatically withdraws 
whole blood from a donor, separates the blood into components, retains 
one or more components, and returns the remainder of the blood to the 
donor. This final rule removes reference in Sec.  864.9245, to the 
words that were in parentheses, specifically, red blood cells, white 
blood cells, plasma, and platelets. The components obtained are 
transfused or used for further manufacturing. The separation bowls of 
centrifugal blood cell separators may be reusable or disposable, as 
specified by the device manufacturer.
    Also in this rule, we are removing from Sec.  864.9245(b), the list 
of special controls for the class II automated blood cell separator 
device operating by filtration separation principle and intended for 
the routine collection of blood and blood components. The special 
controls guidance entitled ``Guidance for Industry and FDA Staff: Class 
II Special Controls Guidance Document: Automated Blood Cell Separator 
Device Operating by Centrifugal or Filtration Principle'' will provide 
the special controls for both filtration- and centrifugal-based 
automated blood cell separator devices intended for the routine 
collection of blood and blood components. The availability of this 
guidance is announced elsewhere in this issue of the Federal Register.
    The special controls guidance document recommends that the 
manufacturer file with FDA for 3 consecutive years an annual report on 
the anniversary date of the final rule for reclassification or on the 
anniversary date of 510(k) clearance. Each annual report should 
include, at a minimum, the following information:
     A summary of anticipated and unanticipated donor adverse 
events that have occurred and that are not required to be reported by 
manufacturers under part 803 (21 CFR part 803) Medical Device Reporting 
(MDR);
     Any subsequent change to the device requiring the 
submission of a premarket notification in accordance with section 
510(k) of the act;
     Any subsequent change to the preamendments class III 
device requiring a 30-day notice in accordance with Sec.  814.39(f) (21 
CFR 814.39(f)).
    For this type of device, FDA has determined that premarket 
notification is necessary to provide reasonable assurance of the safety 
and effectiveness of the device and, therefore, the type of device is 
not exempt from premarket notification requirements. Prior to marketing 
the device, persons must submit to FDA a premarket notification 
containing information about the automated blood cell separator device 
they intend to market. Following the effective date of this final rule, 
any firm submitting a 510(k) premarket notification for an automated 
blood cell separator device operating by filtration or centrifugal 
separation principle and intended for the routine collection of blood 
and blood components will need to address the issues covered in the 
special controls guidance. However, the firm need only show that its 
device meets the recommendations of the guidance or in some other way 
provides equivalent assurance of safety and effectiveness.

IV. Analysis of Comments on the Proposed Rule and FDA's Response

    FDA received one comment on the proposed rule. The comment 
supported the reclassification of the automated blood cell separator 
device operating by centrifugal separation principle and intended for 
the routine collection of blood and blood components. In addition, the 
comment provided specific questions about the reporting requirements in 
the special controls guidance document and asked FDA to clarify these 
reporting requirements.
    We first provide a general response to the comment and then respond 
to the questions submitted in the comment. To make it easier to 
identify the questions provided in the comment and our responses, the 
word ``Comment,'' in parentheses, will appear before the description of 
the question, and the word ``Response,'' in parentheses, will appear 
before our response. We numbered the comments to distinguish the 
questions.
    When the device is reclassified, all manufacturers of currently 
marketed automated blood cell separators operating by centrifugal 
separation principle not approved under the premarket approval process 
should file annual reports for 3 consecutive years on the anniversary 
date of reclassification of the device from class III to class II, or 
on the anniversary date of the 510(k) clearance. Within the 3-year 
reporting period, any subsequent change to the device requiring a 
510(k) should be included in the annual report. The criteria for 
reporting changes to the device and its labeling under 510(k) are 
delineated in FDA's guidance ``Deciding When to Submit a 510(k) for a 
Change to an Existing Device,'' January 10, 1997.
    However, manufacturers of automated blood cell separator devices 
operating by filtration separation principle that were classified into 
class II (68 FR 9530, February 28, 2003) were subject to the special 
controls of Sec.  864.9245 issued in 2003, requiring 3 consecutive 
years of submitting annual reports. These devices are not required to 
initiate another cycle of annual reports as a result of the change of 
special controls for those devices codified by this rule.
    Under Sec. Sec.  606.160(b)(1)(iii) and 606.170 (21 CFR 
606.160(b)(1)(iii) and 606.170), the facility using the device to 
collect blood and blood components is required to keep records of donor 
adverse reaction complaints and reports, including results of all 
investigations

[[Page 67643]]

and followup. Under Sec.  803.50(b)(3), manufacturers are responsible 
for conducting an investigation of each event and evaluating the cause 
of the event. The special controls would have the manufacturer 
summarize this information and submit it to FDA in the annual report.

Specific questions submitted in the comment and FDA's responses:

    (Comment 1) Do you intend to request 3-year annual reporting only 
for the initial 510(k) clearance for the automated blood cell separator 
device?
    (Response) Yes. The 3-year annual reporting described in the 
special controls guidance document recommends annual reporting only for 
the initial 510(k) clearance. Any subsequent change to the device 
within this 3-year reporting period requiring the submission of a 
premarket notification in accordance with section 510(k) of the act 
should be included in the annual report. However, the submission of 
this 510(k) information concerning a change to the device would not 
restart the 3-year reporting period.
    (Comment 2) Is it correct that for a device originally approved 
under the PMA process, then switched to a 510(k), annual reporting 
would not be required?
    (Response) Yes, this is correct, if an automated blood cell 
separator device intended for the routine collection of blood and blood 
components was originally approved under the PMA process.
    (Comment 3) Does this reporting requirement apply to all automated 
blood cell separator devices operating by centrifugal or filtration 
separation principle intended for the routine collection of blood and 
blood components regardless of when the original clearance was granted? 
Would any preamendments devices be ``grandfathered'' in so that the 
reporting would not be required?
    (Response) The reporting recommended in the special controls 
guidance applies to currently marketed products not approved under the 
PMA process. The 3-year annual reporting for these products should 
begin on the anniversary date of the device reclassification from class 
III to class II, or, on the anniversary date of 510(k) clearance.
    In this rulemaking, we are reclassifying the automated blood cell 
separator device operating by centrifugal separation principle from 
class III to class II. Therefore, the reclassification date from class 
III to class II for the automated blood cell separator device operating 
by centrifugal separation principle and intended for the routine 
collection of blood and blood components is the date of publication in 
the Federal Register of this final rule (see DATES). The 
reclassification date from class III to class II for the automated 
blood cell separator device operating by filtration separation 
principle and intended for the routine collection of blood and blood 
components is February 28, 2003.
    Devices in commercial distribution before May 28, 1976, are also 
referred to as preamendments devices. On September 12, 1980 (45 FR 
60643), FDA issued a final rule classifying these preamendment 
automated blood cell separator devices as class III (premarket 
approval). The 1976 amendments did not immediately subject preamendment 
devices classified in class III to the preamendment process. In the 
regulation (Sec.  864.9245), FDA did not set a deadline for the 
submission of premarket approval applications for the device. That 
regulation is amended in this rulemaking to reclassify the device from 
class III to class II. Therefore, preamendments devices are subject to 
this rulemaking, and the special controls guidance document as of the 
anniversary date of device reclassification from class III to class II.

V. FDA's Conclusion

    Therefore, under section 513 of the act, FDA is adopting the 
summary of reasons for the Panel's recommendation and the summary of 
data upon which the Panel's recommendation is based (70 FR 11887 at 
11890). FDA is also adopting the risks to public health stated in the 
proposed rule (70 FR 11887 at 11891). Furthermore, FDA is issuing a 
final rule that revises Sec.  864.9245, thereby, reclassifying the 
generic type of device, automated blood cell separator operated by 
centrifugal separation principle and intended for the routine 
collection of blood and blood components from class III into class II.

VI. 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), 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 not a significant regulatory action 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. The reclassification of automated blood cell 
separator devices 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. Although the special controls guidance document 
recommends that manufacturers of these devices file with FDA an annual 
report for 3 consecutive years, this is less burdensome than the 
current premarket approval requirements, including the submission of 
periodic reports (21 CFR 814.84). By eliminating the need for premarket 
approval applications, reclassification will reduce regulatory costs 
with respect to these devices, impose no significant economic impact on 
any small entities, and may permit small potential competitors to enter 
the marketplace by lowering their costs. The agency therefore certifies 
that this final rule will not have a significant impact on a 
substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $127 million, using the most current (2006) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

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. 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

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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.

IX. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) is not required. FDA concludes 
that the special controls guidance document contains information 
collection provisions that are subject to review and clearance by OMB 
under the PRA. Elsewhere in this issue of the Federal Register, FDA is 
publishing a notice announcing the availability of the guidance 
document entitled ``Class II Special Controls Guidance Document: 
Automated Blood Cell Separator Device Operating by Centrifugal of 
Filtration Separation Principle.'' The notice contains an analysis of 
the paperwork burden for the guidance.

List of Subjects in 21 CFR Part 864

    Blood, Medical devices, Packaging and containers.

0
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

0
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.

0
2. Section 864.9245 is revised to read as follows:


Sec.  864.9245   Automated blood cell separator.

    (a) Identification. An automated blood cell separator is a device 
that uses a centrifugal or filtration separation principle to 
automatically withdraw whole blood from a donor, separate the whole 
blood into blood components, collect one or more of the blood 
components, and return to the donor the remainder of the whole blood 
and blood components. The automated blood cell separator device is 
intended for routine collection of blood and blood components for 
transfusion or further manufacturing use.
    (b) Classification. Class II (special controls). The special 
control for this device is a guidance for industry and FDA staff 
entitled ``Class II Special Controls Guidance Document: Automated Blood 
Cell Separator Device Operating by Centrifugal or Filtration Separation 
Principle.''

    Dated: November 26, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-23285 Filed 11-29-07; 8:45 am]
BILLING CODE 4160-01-S