[Federal Register Volume 78, Number 16 (Thursday, January 24, 2013)]
[Pages 5186-5188]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-01419]



Food and Drug Administration

[Docket No. FDA-2013-N-0046]

Clinical Flow Cytometry in Hematologic Malignancies; Public 
Workshop; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.


    The Food and Drug Administration (FDA) is announcing the following 
public workshop entitled ``Clinical Flow Cytometry in Hematologic 
Malignancies.'' The purpose of this public workshop is to seek public 
input from academia, Government, laboratorians, industry, clinicians, 
patients and other stakeholders on the role of clinical flow cytometry 
in hematologic malignancies, in order to develop a specific regulatory 
policy for this class of in vitro diagnostic devices.
    Date and Time: The workshop will be held on February 25 and 26, 
2013 from 8 a.m. to 5 p.m.
    Location: The public workshop will be held at FDA's White Oak 
Campus, 10903 New Hampshire Ave., Rm. 1503 (Section A of the Great 
Room) in Bldg. 31, Silver Spring, MD 20993-0002. All visiting public 
workshop participants (non- FDA employees) must enter through Building 
1 for routine security check procedures. For parking and security 
information, please visit the following Web site: http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Contact Person: Carol Krueger, Center for Devices and Radiological 
Health (CDRH), Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 66, Rm. 5437, Silver Spring, MD 20993-0002, 301-796-3241, 
    Registration: Registration is free and on a first-come, first-
served basis. Persons interested in attending this public workshop must 
register online by 5 p.m. on February 11, 2013. Early registration is 
recommended because facilities are limited and, therefore, FDA may 
limit the number of participants from each organization. If time and 
space permit, onsite registration on the day of the public workshop 
will be provided beginning at 7 a.m.
    To register for the public workshop, please visit FDA's Medical 
Devices News & Events--Workshops & Conferences calendar at http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. 
(Select this public workshop from the posted events list.) Please 
provide complete contact information for each attendee, including name, 
title, affiliation, mailing address, email address, and telephone 
number. Those without Internet access should contact Carol Krueger to 
register (see Contact Person). Registrants will receive confirmation 
after they have been accepted. You will be notified if you are on a 
waiting list.
    If you need special accommodations due to a disability, please 
contact Susan Monahan (email: Susan.Monahan@fda.hhs.gov or phone:

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301-796-5661) no later than February 11, 2013.
    Streaming Webcast of the Public Workshop: This workshop will also 
be available via Webcast. Persons interested in viewing the Webcast 
must register online by 5:00 p.m. on February 11, 2013. Early 
registration is recommended because Webcast connections are limited. 
Organizations are requested to register all participants, but to view 
using one connection per location. Webcast participants will be sent 
technical system requirements after registration and will be sent 
connection access information after February 20, 2013. If you have 
never attended a Connect Pro event before, test your connection at 
To get a quick overview of the Connect Pro program, visit http://www.adobe.com/go/connectpro_overview. (FDA has verified the Web site 
addresses in this document, but FDA is not responsible for any 
subsequent changes to the Web sites after this document publishes in 
the Federal Register.)
    Requests for Oral Presentations: This workshop includes public 
comment sessions. If you wish to present during a public comment 
session, you must indicate this at the time of registration. At the 
time of registration identify which discussion topic you wish to 
address. The topics under consideration for this workshop are 
identified in section II of this document. FDA will do its best to 
accommodate requests to present. Individuals and organizations with 
common interests are urged to consolidate or coordinate their comments, 
and request time to present a joint comment. Following the close of 
registration, the Agency will determine the amount of time allotted to 
each presenter, the approximate time each comment is to begin, and will 
select and notify speakers by February 20, 2013. All requests to make 
oral presentations must be received by the close of registration on 
February 11, 2013. No commercial or promotional material will be 
permitted to be presented or distributed at the workshop.
    Comments: FDA is holding this public workshop to obtain information 
on the topics identified in section II of this document.
    In order to permit the widest possible opportunity to obtain public 
comment, FDA is soliciting either electronic or written comments on all 
aspects of the public workshop topics. The deadline for submitting 
comments related to this public workshop is March 29, 2013.
    Regardless of attendance at the public workshop, interested persons 
may submit either electronic or written comments. Submit electronic 
comments to http://www.regulations.gov. Submit written comments to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. It is only necessary 
to send one set of comments. Please identify comments with the docket 
number found in brackets in the heading of this document. In addition, 
when responding to specific questions as outlined in section II of this 
document, please identify the question you are addressing. Received 
comments may be seen in the Division of Dockets Management between 9:00 
a.m. and 4:00 p.m., Monday through Friday and will be posted to the 
docket at http://www.regulations.gov.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at http://www.regulations.gov. It may 
be viewed at the Division of Dockets Management (see Comments). A 
transcript will also be available in either hardcopy or on CD-ROM, 
after submission of a Freedom of Information request. Written requests 
are to be sent to the Division of Freedom of Information (ELEM-1029), 
Food and Drug Administration, 12420 Parklawn Dr., Element Bldg., 
Rockville, MD 20857. A link to the transcripts will also be available 
approximately 45 days after the public workshop on the Internet at 
http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm. (Select this public workshop from the posted events list).


I. Background

    The earliest determination of B and T cell subsets was based on 
microscopic counting of cells expressing surface immunoglobulins for B 
cell enumeration, and sheep red blood cells rosette formation was used 
to enumerate T cells. The subsequent development of leukocyte-specific 
monoclonal antibodies and flow cytometry contributed to the automation 
of lymphocyte subset analysis. Flow cytometric lymphocyte subset 
analysis was initially used to immunophenotype hematological 
malignancies; however, the HIV epidemic led to a large number of 510(k) 
submissions addressing use for HIV immune monitoring in AIDS.
    In response to these submissions, Draft Guidance for 510(k) 
Submission of Lymphocyte Immunophenotyping Monoclonal Antibodies was 
issued September 26, 1991. Prior to this draft document, reagents for 
CD2 and CD20 were 510(k) cleared based on methodological correlation 
with accepted reference methods. Following the issuance of the 1991 
draft guidance, several test systems identifying CD3 T cells, CD4 and 
CD8 T cell subsets, NK cells and B cells were cleared under 510(k), 
with either single reagents or combination of reagents based on the 
previous clearance of CD2 and CD20 reagents. These clearances for flow 
cytometry system devices included flow cytometers, reagents, controls, 
and associated software for data acquisition and data analysis.
    In 1997, the FDA issued the Analyte Specific Reagent (ASR) Rule (21 
CFR 864.4020) to provide some assurance that 1) critical reagents 
manufacturers provided to laboratories for use in tests developed by 
the laboratories were made under current Good Manufacturing Practices 
(cGMP), 2) manufacturers registered with the FDA and listed such 
reagents, and 3) manufacturers reported malfunctions, injuries and 
deaths related to the use of such reagents to the FDA (62 FR 62260, 
November 21, 1997). Subsequent to publication of the ASR rule in 1997, 
some manufacturers began to bundle individual ASRs together in the form 
of reagent panels (``cocktails'') creating devices that went beyond the 
single reagent ASRs that the rule had anticipated. In 2007, the Agency 
reiterated and clarified the intentions of the ASR rule in the Guidance 
for Industry and FDA Staff on Commercially Distributed Analyte Specific 
Reagents (ASRs): Frequently Asked Questions http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm078423.htm. The 2007 guidance clarifies that the bundling of ASRs 
into a panel of multi-analytes is inconsistent with the definition of 
an ASR per 21 CFR 864.4020. Subsequent to issuance of the guidance, 
many uncleared, multi-analyte panels were withdrawn from distribution 
in order to comply with the interpretation of the ``ASR rule.''
    Clinical flow cytometry plays a major role world-wide in the 
diagnosis of leukemia and lymphoma and more recently in the detection 
of minimal residual disease (MRD). Because there are currently no FDA 
cleared or approved in vitro diagnostics (IVD) panels for the 
diagnostic evaluation of hematological malignancies, FDA recognizes 
that there is an unmet need for such products to assist clinical 
laboratories in performing this testing. FDA has been working to define 
the regulatory guidelines for the review of this family of devices and 
has been actively working with industry and

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academia to help bring additional products for clinical flow cytometry 
to market that are safe and effective.
    In partnership with the National Institutes of Health (NIH) and 
National Institute of Standards and Technology (NIST), CDRH intends to 
utilize the findings of this workshop in the development of an 
appropriate, risk-based regulatory framework for Clinical Flow 
Cytometry, which promotes innovation and protects patient safety.

II. Topics

    Topics for discussion during this workshop include: (1) Overview of 
Quality control and standardization issues associated with Clinical 
Flow Cytometry (FCM), including discussion of a NIST traceable 
standard; (2) Biological controls in Clinical FCM: The use of 
stabilized whole blood samples and cryopreserved cells for normals and 
chronic lymphocytic leukemia (CLL); (3) Third-party flow cytometry data 
analysis software; and (4) Overview of FDA regulation of Clinical FCM 
using the 510(k) clearance process.
    The FDA is seeking representation from both North American and 
European clinical investigators at this workshop. This Clinical FCM 
Workshop is being planned to occur just prior to a CDER Workshop on the 
role of MRD in CLL which will be held February 27, 2013 (77 FR 76051, 
December 26, 2012). An FDA workshop for acute lymphocytic leukemia 
(ALL) MRD was held April 18, 2012, and a separate workshop on acute 
myelogenous leukemia (AML) MRD will be held March 4, 2013 (77 FR 76050, 
December 26, 2012).

    Dated: January 17, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-01419 Filed 1-23-13; 8:45 am]