[Federal Register: March 10, 2005 (Volume 70, Number 46)]
[Proposed Rules]               
[Page 11887-11893]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10mr05-27]                         

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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 from Class III to Class II of Automated Blood Cell 
Separator Device Operating by Centrifugal Separation Principle

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify from class III to class II (special controls) the automated 
blood

[[Page 11888]]

cell separator device operating on a centrifugal separation principle 
and intended for the routine collection of blood and blood components. 
This proposed rule would also modify the special control for the device 
with the same intended use but operating on a filtration separation 
principle. The reclassification is being proposed on FDA's own 
initiative under procedures set forth in FDA regulations and based on 
information provided to FDA. This action is being taken 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 proposes 
this reclassification because special controls, in addition to general 
controls, are capable of providing 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Register, FDA is publishing a notice of availability of a draft 
guidance document entitled ``Class II Special Controls Guidance 
Document: Automated Blood Cell Separator Device Operating by 
Centrifugal or Filtration Separation Principle,'' which will serve as 
the special control if this proposal becomes final.

DATES: Submit written or electronic comments by June 8, 2005. See 
section XVI of this document for the proposed effective date of a final 
rule based on this document.

ADDRESSES: You may submit comments, identified by Docket No. 2005N-
0017, by any of the following methods:
     Federal eRulemaking Portal: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. 

Follow the instructions for submitting comments.
     Agency Web site: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting comments on the agency Web site.
     E-mail: fdadockets@oc.fda.gov. Include Docket No. 2005N-
0017 in the subject line of your e-mail message.
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket No. or Regulatory Information Number (RIN) for this 
rulemaking. All comments received will be posted without change to 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, including any personal 

information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, see the Comments 
heading of the SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm 

and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

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

SUPPLEMENTARY INFORMATION:

I. Background (Regulatory Authorities)

    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 the 1976 amendments, class II devices were defined as those 
devices for which there is insufficient information to show that 
general controls themselves will assure safety and effectiveness, but 
for which there is sufficient information to establish ``performance 
standards'' to provide such assurance. The SMDA revised the definition 
of class II devices to include those devices for which there is 
insufficient information to show that general controls themselves will 
assure 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 deems necessary (section 513(a)(1)(B) of the act). The SMDA also 
directs FDA to revise the classification of such preamendments class 
III devices into class I or class II or require the device to remain in 
class III; and directs FDA to issue a schedule for section 515(b) of 
the act (21 U.S.C. 360e(b)) rulemaking within 12 months of publication 
of a regulation retaining a device in class III. However, the SMDA does 
not prevent FDA from proceeding immediately to section 515(b) 
rulemaking on specific devices, in the interest of public health, 
independent of the 515(i) process.
    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 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 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, 
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 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 requiring premarket 
approval.
    Reclassification of classified preamendments devices is governed by 
section 513(e) of the act. Section 513(e) of the act provides that FDA 
may, by rulemaking, reclassify a device (in a proceeding that parallels 
the initial classification proceeding) based upon ``new information.'' 
The reclassification can be initiated by FDA or by the

[[Page 11889]]

petition of an interested person. The term ``new information,'' as used 
in section 513(e) 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'' upon which reclassification under section 513(e) of the 
act is based must consist of ``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. For the purpose of reclassification, the valid scientific 
evidence upon which the agency 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).)

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. 
The 1976 amendments did not immediately subject preamendments devices 
classified in class III to the premarket approval process. The act 
requires FDA to publish 515(b) regulations directing the submission of 
premarket approval applications for preamendments class III devices. 
The 515(b) process involves the publication of two Federal Register 
notices, the proposed rule and the final rule. The 515(b) proposed rule 
announces FDA's intention to call for PMAs, lists the issues to be 
addressed in PMA submissions, states a deadline for the receipt of 
comments, and affords an opportunity to request reclassification. The 
final rule addresses any comments received, repeats the issues to be 
addressed in PMA submissions, and sets a deadline for the submission of 
premarket approval applications or investigational device exemptions of 
not more than 90 days after the date of publication.
    In the Federal Register of September 11, 1979 (44 FR 53050), FDA 
issued a proposed rule to classify into class III the automated blood 
cell separator device intended for routine collection of blood and 
blood components. The preamble to the proposed rule to classify the 
device included the recommendation of an FDA advisory committee, The 
Hematology Device Classification Panel, regarding the classification of 
the device.
    In the Federal Register of September 12, 1980 (45 FR 60643), FDA 
issued a final rule (Sec.  864.9245 (21 CFR 864.9245)) classifying into 
class III the automated blood cell separator operating either on a 
centrifugal or filtration separation principle intended for routine 
collection of blood and blood components.

A. Centrifugal Separation Principle

    In the Federal Register of February 19, 1988 (53 FR 5108),\1\ FDA 
published a proposed rule to require the filing of a PMA or a notice of 
completion of a product development protocol (PDP) for the automated 
blood cell separator device based on a centrifugal separation principle 
and intended for the routine collection of blood and blood components. 
The February 1988 proposed rule summarized the risks and benefits 
associated with the use of the automated blood cell separator. FDA also 
announced an opportunity for interested persons to request a change in 
the classification of the device based on new information.
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    \1\ In the Federal Register of April 22, 2003 (68 FR 19766), FDA 
issued a withdrawal of certain proposed rules and other proposed 
actions; notice of intent to withdraw Hematology and Pathology 
Devices; Premarket Approval of the Automated Blood Cell Separator 
Intended for Routine Collection of Blood and Blood Components.
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    In the Federal Register of May 16, 1988 (53 FR 17227), FDA extended 
the comment period of the proposed rule from 60 days to 90 days in 
response to a letter from a medical trade association requesting 
additional time to submit comments. In response to the February 1988 
proposed rule, the agency received 17 letters of comment. New 
information in the form of scientific evidence was submitted with 
several of the comments to FDA on the automated blood cell separator 
operating on the centrifugal separation principle. The majority of the 
letters of comment indicated there is sufficient evidence to provide 
reasonable assurance of the safety and effectiveness of the automated 
blood cell separator operating on the centrifugal separation principle, 
and supported reclassifying the device into class II when intended only 
for routine collection of blood and blood components. Many of the 
comment letters provided scientific information and references in 
support of the reclassification. FDA has evaluated the information 
submitted and decided that there is valid scientific evidence 
supporting a change in classification of the centrifugal-based 
automated blood cell separator with the intended use of routine 
collection of blood and blood components from class III, requiring 
premarket approval, to class II, requiring special controls.
    Consistent with the act and regulation, FDA referred the proposed 
reclassification to a panel for its recommendation on the requested 
change in classification. FDA announced in the Federal Register of 
April 18, 1989 (54 FR 15558), that the agency would consult with the 
Blood Products Advisory Committee (BPAC) in an open meeting on May 11, 
1989 (Ref. 1), regarding the reclassification of the automated blood 
cell separator operating on a centrifugal separation principle. BPAC 
acts in the capacity of a device classification panel for such matters 
as new information regarding a device and its classification. FDA 
requested that BPAC consider the new information and provide its 
recommendation as to whether BPAC agreed that the new information was 
substantial and supported reclassification. The recommendation of BPAC 
is further discussed in section IV of this document.
    In accordance with section 513(e) of the act and Sec.  
860.130(b)(1) (21 CFR 860.130(b)(1)), based on new information with 
respect to the device, FDA, on its own initiative, is proposing to 
reclassify the centrifugal-based automated blood cell separator device 
from class III to class II (special controls) when the intended use of 
the device is for the routine collection of blood and blood components. 
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 FDA's Center for 
Devices and Radiological Health and are not part of Sec.  864.9245.

[[Page 11890]]

B. Filtration Separation Principle

    The automated blood cell separator device operating on a filtration 
separation principle and intended for the routine collection of blood 
and blood components is a postamendments device originally classified 
into class III under section 513(f)(1) of the act. On June 17, 1996, 
the Baxter Healthcare Corp. submitted to FDA a petition requesting 
reclassification from class III to class II of its AUTOPHERESIS-C 
SYSTEM device. The petition contained information in the form of 
scientific evidence to provide reasonable assurance of the safety and 
effectiveness of the filtration-based AUTOPHERESIS-C SYSTEM device. 
Consistent with section 513(f)(3) of the act and 21 CFR 860.134, FDA 
referred the petition to the BPAC medical devices panel for its 
recommendation on the requested change in classification. At a public 
meeting held on September 27, 1996, BPAC 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.
    FDA published a notice of BPAC's recommendation in the Federal 
Register of May 29, 2001 (66 FR 29149). In this notice, FDA issued its 
tentative findings on BPAC's recommendation and requested from the 
public comments on BPAC's recommendation. The comment period closed 
August 13, 2001. After receiving no comments on BPAC's recommendation 
for reclassification or our tentative findings on BPAC's 
recommendation, FDA approved the reclassification petition by order in 
the form of a letter to the petitioner.
    In the Federal Register of February 28, 2003 (68 FR 9530), FDA 
published a final rule announcing the decision to reclassify from class 
III to class II the filtration-based automated blood cell separator 
device intended for routine collection of blood and blood components 
(the February 2003 final rule). In addition to general controls of the 
act, the February 2003 final rule also provided for special controls 
applicable to the filtration-based devices in order to provide 
reasonable assurance of the safety and effectiveness of the device.
    In this rule, we are proposing to change the special control listed 
in the February 2003 final rule for the filtration-based device. We 
propose the special control to be a draft guidance entitled ``Class II 
Special Controls Guidance Document: Automated Blood Cell Separator 
Device Operating by Centrifugal or Filtration Separation Principle.'' 
This draft guidance, if finalized, 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.

III. Device Description

    Current Sec.  864.9245 provides a brief description of the 
automated blood cell separator device operating on either a centrifugal 
separation principle or a filtration separation principle. The current 
section describes the automated blood cell separator as a device that 
automatically withdraws whole blood from a donor, separates the blood 
into components (red blood cells, white blood cells, plasma, and 
platelets), retains one or more of the components, and returns the 
remainder of the blood to the donor. The components obtained are 
transfused or used for further manufacturing to prepare blood products 
for administration. The separation bowls of centrifugal blood cell 
separators may be reusable or disposable.
    The current section classifies the centrifugal-based automated 
blood cell separator into class III (premarket approval). This proposed 
rule reclassification from class III to class II (special controls) 
applies to the automated blood cell separator device that operates by 
centrifugal separation principle and is intended for the routine 
collection of blood and blood components for transfusion or further 
manufacturing use. The proposed rule removes in the identification of 
the automated blood cell separator the words that were in parentheses--
red blood cells, white blood cells, plasma, and platelets.

IV. Recommendation of the Panel

    At a public meeting held on May 11, 1989, the BPAC panel considered 
the new information presented in the letters of comment and unanimously 
recommended that the centrifugal-based automated blood cell separator 
be reclassified from class III (premarket approval) to class II 
(performance standards; now included in special controls). The panel 
believed that class II with performance standards (now included in 
special controls) would provide reasonable assurance of the safety and 
effectiveness of the automated blood cell separator and that there is 
sufficient information publicly available to establish a performance 
standard (special control) to assure safety and effectiveness of the 
device.
    We believe another device classification panel recommendation is 
not necessary since, prior to the SMDA, a panel recommended 
classification into class II. If a panel recommended that a device be 
reclassified from class III into class II under the 1976 definition of 
class II, which included only performance standards as a class II 
control, then the panel's recommendation for class II status would not 
change if special controls are required that would include performance 
standards, among other controls. Under the SMDA, FDA may establish 
special controls, including performance standards, postmarket 
surveillance, patient registries, guidelines, and other appropriate 
actions it believes necessary to provide reasonable assurance of the 
safety and effectiveness of the device.

V. Summary of Reasons for Recommendation (Reclassification)

    The panel believes that the centrifugal-based automated blood cell 
separator device should be reclassified into class II because 
performance standards (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.

VI. Risks to Health

    In the February 1988 proposed rule, FDA outlined its proposed 
findings regarding potential risks associated with the automated blood 
cell separator intended for routine collection of blood and blood 
components. FDA's proposed findings showed the following: A major risk 
to health of donors is that the process of removing blood, handling the 
blood outside the body, and returning the blood to the donor's 
circulatory system could injure the cellular components of the blood 
and activate the body's complement system (a series of enzymatic 
proteins capable, when activated, of destroying intact cells). Another 
potential donor reaction is fever, due to a breakdown of granulocytes 
(leukocytes containing granules) during the pump cycle of the automated 
blood cell separator.
    Also, if the automated blood cell separator fails to perform 
satisfactorily, the donor may have one or more of the following adverse 
reactions: (1) Shock resulting from blood loss; (2) toxic reaction to 
high levels of anticoagulants,

[[Page 11891]]

such as citrate, that the automated blood cell separator adds to the 
blood as it is collected and before the blood is returned to the donor; 
(3) stress reaction due to the removal or loss of blood; (4) thrombosis 
due to activation of clotting factors in the blood by surfaces within 
the automated blood cell separator; or (5) sepsis and fever due to 
bacterial contamination of the blood returned to the donor.
    Lastly, an unexpected or an undetected leak in the blood handling 
system of the device presents risks of infections to donors, patients, 
and operators of the device. The device presents a risk of electrical 
shock or injury to operators and donors if the device has an electrical 
malfunction. If the automated blood cell separator fails to perform 
satisfactorily, the blood or blood components collected from a donor 
may not be suitable for use because of cellular damage to blood or 
blood components during the collection process. One form of cellular 
damage is red blood cell hemolysis (destruction of the cell membrane 
accompanied by the release of hemoglobin).
    Public comments received in response to the proposed rule indicated 
that the occurrence of these risks was very low, referred to ample 
evidence showing the safety and effectiveness of the automated blood 
cell separator, and supported reclassification of the device into class 
II.
    Presently, 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 anticoagulant; (4) 
damage to red blood 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; (9) air embolism; (10) hemolysis; and (11) reservoir 
rupture.
    In addition to the potential risks of the centrifugal-based 
automated blood cell separator, there is sufficient information about 
the benefits of the device. Extensive experience with the device 
indicates that the centrifugal-based automated blood cell separator is 
safe and effective for the intended use of routine collection of blood 
and blood components.

VII. Summary of Data Upon Which the Recommendation (Reclassification) 
is Based

    In response to the February 1988 rule proposing to place the device 
in class III, we received 17 letters of comment from manufacturers and 
the blood banking community (Ref. 1 at 103). These commenters included 
such organizations as the Health Industry Manufacturers Association and 
the American Association of Blood Banks (Ref. 1 at 104). The comments 
received indicated the risk to benefit ratio is low. In proposing this 
reclassification, we considered these industry comments and the history 
for over 30 years of safe use of the centrifugal-based automated blood 
cell separator device.

VIII. FDA's Tentative Findings

    FDA believes that the special controls discussed in section IX of 
this document are capable of providing reasonable assurance of the 
safety and effectiveness of the automated blood cell separator device 
operating on a centrifugal separation principle with regard to the 
identified risks to health of this device. Based on FDA's evaluation of 
the additional information received in the letters of comment, as well 
as the 1989 BPAC panel recommendation and the safety record of the 
device in actual use, the agency has reconsidered the February 1988 
proposed rule, and believes that the centrifugal-based automated blood 
cell separator device should be classified into class II (special 
controls). FDA, through an agency-wide action of proposed rule 
withdrawals (April 22, 2003, 68 FR 19766), announced its intention to 
withdraw the February 1988 proposed rule. Now, FDA is proposing to 
amend the device regulations by reclassifying from class III to class 
II (special controls guidance) the centrifugal-based automated blood 
cell separator device intended for the routine collection of blood and 
blood components. FDA is also changing the special control for the 
automated blood cell separator device using the filtration separation 
principle for the routine collection of blood and blood components. The 
same special control guidance will apply to the filtration and 
centrifugal-based devices when these devices are used for the routine 
collection of blood and blood components.

IX. Special Controls

    Based on available information and in addition to general controls, 
FDA believes that the FDA 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,'' can provide reasonable assurance of the safety and 
effectiveness of the device. Elsewhere in this issue of the Federal 
Register, FDA is announcing the availability of this draft guidance 
document.
    For currently marketed products not approved under the PMA process, 
the draft guidance document recommends that the manufacturer file with 
FDA for three consecutive years an annual report on the anniversary 
date of the final rule for reclassification or on the anniversary date 
of 510(k) clearance. 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. A 
manufacturer of a device that is determined to be substantially 
equivalent to the automated blood cell separator device operating by 
centrifugal or filtration separation principles intended for routine 
collection of blood and blood components, also would be required to 
comply with the same general and special controls. The firm would need 
to show that its device meets the recommendations of the guidance or in 
some other way provides equivalent assurances of safety and 
effectiveness.
    The draft guidance document (special control) recommends that each 
annual report include, at a minimum, the following information:
     A summary of anticipated and unanticipated donor adverse 
device events that have occurred and that are not required to be 
reported by manufacturers under Medical Device Reporting (MDR).\2\ We 
recommend summarizing and reporting donor adverse device events such as 
those required under Sec.  606.160(b)(1)(iii) (21 CFR 
606.160(b)(1)(iii))\3\\,\\4\ to be recorded and maintained by the 
facility\5\ using

[[Page 11892]]

the device for the routine collection of blood and blood components. 
Under 21 CFR 803.50(b)(2), manufacturers are responsible for conducting 
an investigation of each event and evaluating the cause of the event. 
Therefore, this information should be available to the manufacturer to 
summarize and provide to FDA in the annual report. We emphasize that 
safety information submitted to FDA is not to be considered an 
admission of causation or liability (October 27, 1994, 59 FR 54046 at 
54051).
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    \2\ 21 CFR 803.1(a) -- ``* * * device user facilities, 
importers, and manufacturers, as defined in Sec.  803.3, must report 
deaths and serious injuries to which a device has or may have caused 
or contributed * * * .''
    \3\ Section 606.160(b) -- ``Records shall be maintained that 
include, but are not limited to, the following when applicable: * * 
* (1)(iii) Donor adverse reaction complaints and reports, including 
results of all investigations and followup.''
    \4\ In a separate proposed rulemaking (Safety Reporting 
Requirements for Human Drug and Biological Products; Proposed Rule 
(68 FR 12405, March 14, 2003)), FDA has proposed amending 21 CFR 
606.170 to require the investigation and recording by blood 
establishments of any complaint of a serious adverse reaction 
related to the collection or transfusion of blood or blood 
components.
    \5\ ``Facility'' means any area used for the collection, 
processing, compatibility testing, storage or distribution of blood 
and blood components (21 CFR 606.3(h)). Also, applicable is ``device 
user facility'' under Sec.  803.3(f), meaning ``a hospital, 
ambulatory surgical facility, nursing home, outpatient diagnostic 
facility, or outpatient treatment facility * * *.'' (Note: The donor 
becomes a patient when he or she experiences and is treated for an 
adverse event contributed to or caused by the medical device.)
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     Any subsequent change to the device requiring the 
submission of a premarket notification in accordance with section 
510(k) of the act.\6\
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    \6\ 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh.

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     Any subsequent change to the preamendments class III 
device requiring a 30-day notice in accordance with 21 CFR 814.39(f).
    The reporting of adverse device events summarized in an annual 
report will alert FDA to trends or clusters of events that might be a 
safety issue otherwise unreported under the MDR regulation. Adverse 
reactions contributed to or caused by an apheresis blood donation 
device, such as operator infection or injury; equipment failures, 
including software, hardware, and disposable item failures; thrombosis; 
sepsis; and shock resulting from blood loss, may be reportable under 
MDR. The annual report need not include MDR reports.

X. References

    The following reference has been placed on display in the Division 
of Dockets Management (see ADDRESSES) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Blood Products Advisory Committee Meeting Transcript, May 11, 
1989.

XI. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this proposed 
reclassification 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. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed 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 
responsibilities among the various levels of government. Accordingly, 
the agency tentatively concludes that the proposed rule does not 
contain policies that have federalism implications as defined in the 
Executive order and, consequently, a federalism summary impact 
statement has not been prepared.

XIII. Analysis of Impacts

    FDA has examined the impacts of this 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.
    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 entities. Reclassification of this device 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 proposed rule special control 
guidance document recommends that manufacturers of these devices file 
with FDA an annual report for three consecutive years, this is less 
burdensome than the current premarket approval requirements including 
the submission of periodic reports (21 CFR 814.84).
    The agency, therefore, certifies that this proposed rule, if 
finalized, will not have a significant economic impact on a substantial 
number of small entities, and no further analysis is required under the 
Regulatory Flexibility Act. In addition, the Unfunded Mandates Reform 
Act does not require FDA to prepare a statement of costs and benefits 
for this proposed rule because the proposed 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).

XIV. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 (44 
U.S.C. 3501-3520) is not required.

XV. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper 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 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

XVI. Proposed Effective Date

    The agency is proposing that any final rule that may issue based 
upon this proposed fule become effective 30 days after its date of 
publication in the Federal Register.

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, it is 
proposed that 21 CFR part 864 be 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:

[[Page 11893]]

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: March 1, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-4758 Filed 3-9-05; 8:45 am]

BILLING CODE 4160-01-S