80 FR 51823 - In Vitro Diagnostic Testing for Direct Oral Anticoagulants; Public Workshop; Request for Comments

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 165 (August 26, 2015)

Page Range		51823-51824
FR Document		2015-21095
Federal Register, Volume 80 Issue 165 (Wednesday, August 26, 2015)
[Federal Register Volume 80, Number 165 (Wednesday, August 26, 2015)]
[Notices]
[Pages 51823-51824]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-21095]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-2919]


In Vitro Diagnostic Testing for Direct Oral Anticoagulants; 
Public Workshop; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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    The Food and Drug Administration (FDA) is announcing a public 
workshop entitled ``In Vitro Diagnostic Testing for Direct Oral 
Anticoagulants''. The objective of the workshop is to gain public input 
and to discuss analytical performance requirements for the diagnostic 
assessment of direct oral anticoagulants (DOACs) and the clinical 
circumstances under which patients receiving these agents would require 
testing. Specifically, this workshop aims to do the following: (1) 
Evaluate the impact of DOACs on traditional coagulation testing 
results; (2) identify clinical circumstances where testing of DOACs 
anticoagulant activity or concentration would be relevant; (3) discuss 
clinically meaningful interpretation of coagulation testing results for 
patients on DOACs; and (4) review the regulatory requirements for 
granting clearance for in vitro diagnostic devices intended for 
coagulation testing in patients treated with DOACs.
    Date and Time: The public workshop will be held on October 26, 
2015, from 9 a.m. to 5 p.m.
    Location: The public workshop will be held at FDA's White Oak 
Campus, 10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great 
Room (Rm. 1503), Silver Spring, MD 20993-0002. Entrance for the public 
meeting participants (non-FDA employees) is through Building 1 where 
routine security check procedures will be performed. For parking and 
security information, please refer to: http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Contact Person: Claudia Dollins, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66 Rm. 5262, Silver Spring, MD 20993-0002, 301-796-4807, 
Claudia.Dollins@fda.hhs.gov.
    Registration: Registration is free and available on a first-come, 
first-served basis. Persons interested in attending this public 
workshop must register online by 4 p.m., October 16, 2015. Early 
registration is recommended because facilities are limited and, 
therefore, FDA may limit the number of participants from each 
organization. If time and space permits, onsite registration on the day 
of the public workshop will be provided beginning at 8 a.m.
    Contact for Special Accommodations: If you need special 
accommodations due to a disability, please contact Susan Monahan, 
Center for Devices and Radiological Health, Office of Communication and 
Education, 301-796-5661, susan.monahan@fda.hhs.gov no later than 
October 9, 2015.
    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, email, and telephone number. Those without Internet 
access should contact Susan Monahan to register (see Contact for 
Special Accommodations). Registrants will receive confirmation after 
they have been accepted. You will be notified if you are on a waiting 
list.
    Streaming Webcast of the Public Workshop: This public workshop will 
also be Webcast. Persons interested in viewing the Webcast must 
register online by October 16, 2015. 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 October 20, 2015. If you have never attended a 
Connect Pro

[[Page 51824]]

event before, test your connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. 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).
    Comments: FDA is holding this public workshop to obtain information 
on in vitro diagnostic testing for direct oral anticoagulants. 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 the public workshop is November 25, 2015.
    Regardless of attendance at the public workshop, interested persons 
may submit either electronic comments regarding this document to http://www.regulations.gov or 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. 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 a.m. and 4 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. The Freedom of 
Information office address is available on the Agency's Web site at 
http://www.fda.gov. 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).

SUPPLEMENTARY INFORMATION: 

I. Background

    Coagulation is the process of forming a clot to stop bleeding. 
Blood clotting is initiated by injury to a blood vessel resulting in 
the exposure of various proteins on the inner surface of the vessels. 
These proteins trigger the serial activation of coagulation factors 
that make up the coagulation cascade that culminates in the formation 
of the insoluble clot.
    Although immediate clot formation is critical to prevent severe 
blood loss, excessive clot formation outside of wound healing obstructs 
blood flow and poses serious medical consequences. To prevent unwanted 
coagulation, a number of anticoagulant drugs have been developed. 
Historically, anticoagulation drug therapy was limited to the 
administration of non-specific anticoagulants, such as heparin or 
vitamin K antagonists, that act by inhibiting the coagulation cascade 
at several points. Although effective, these anticoagulants have 
numerous drawbacks, such as delayed onset and offset of action, a 
narrow therapeutic window, and interactions with food and drugs that 
necessitate frequent monitoring and dose adjustments. Several tests 
have been cleared for monitoring of patients undergoing vitamin K 
antagonist therapy.
    A new class of DOACs has been developed in the last decade to 
overcome limitations of traditional anticoagulants. Thus far, FDA has 
approved four DOACs: PRAXADA (dabigatran), XARELTO (rivaroxiban), 
ELIQUIS (apixaban), and SAVAYSA (edoxaban). DOAC therapy creates a need 
for coagulation testing, which in turn poses new challenges.
    Currently there are no FDA cleared devices for the characterization 
of DOAC effects on coagulation. Differences in individual responses to 
the drugs require laboratories to develop unique testing schemes to 
assess a patient's coagulation status while on DOAC regimens. Thus, the 
first aim of this workshop is to discuss the effect of DOACs on 
traditional coagulation test methods currently on the market and the 
impact these effects may have on patient management.
    We will also examine clinical scenarios that would warrant DOAC 
testing. Instructions for coagulation monitoring as required for 
vitamin K antagonists are not specified in DOAC's instructions for use. 
However, in certain clinical settings assessment of DOAC-induced 
anticoagulation may be advantageous. The second aim of the workshop 
will focus on medical conditions that require coagulation testing of 
patients taking DOACs.
    There are a limited number of strategies to assess coagulation in 
patients taking DOACs. We will review options for quantitative and 
qualitative determination of the drug effects and discuss problems 
related to interpretation of results. Also, we will consider the 
corresponding analytical performance criteria of DOAC testing required 
to provide reliable and informative test results.
    Thus, the Center for Devices and Radiological Health plans to 
provide an overview of the scientific, clinical, and regulatory 
challenges that need to be addressed to ultimately support the 
development of in vitro testing for patients on DOAC regimens that 
would translate into clinically meaningful results.

II. Topics for Discussion at the Public Workshop

    The public workshop seeks to involve industry and academia in 
addressing analytical performance requirements for the diagnostic 
assessment of DOACs. Furthermore, the workshop aims to focus on the 
clinical circumstances under which patients receiving these agents 
would require testing, including but not limited to, the following 
topic areas:
    1. Overview of the effects of DOACs on traditional coagulation 
tests;
    2. identification of clinical scenarios that necessitate DOAC 
testing;
    3. interpretation of coagulation testing results for patients on 
DOACs; and
    4. considerations for regulatory review of devices assessing the 
effect of DOACs on coagulation.

    Dated: August 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-21095 Filed 8-25-15; 8:45 am]
BILLING CODE 4164-01-P
51824 Federal Register / Vol. 80, No. 165 / Wednesday, August 26, 2015 / Notices

event before, test your connection at resulting in the exposure of various determination of the drug effects and
https://collaboration.fda.gov/common/ proteins on the inner surface of the discuss problems related to
help/en/support/meeting_test.htm. To vessels. These proteins trigger the serial interpretation of results. Also, we will
get a quick overview of the Connect Pro activation of coagulation factors that consider the corresponding analytical
program, visit http://www.adobe.com/ make up the coagulation cascade that performance criteria of DOAC testing
go/connectpro_overview. (FDA has culminates in the formation of the required to provide reliable and
verified the Web site addresses in this insoluble clot. informative test results.
document, but FDA is not responsible Although immediate clot formation is Thus, the Center for Devices and
for any subsequent changes to the Web critical to prevent severe blood loss, Radiological Health plans to provide an
sites after this document publishes in excessive clot formation outside of overview of the scientific, clinical, and
the Federal Register). wound healing obstructs blood flow and regulatory challenges that need to be
Comments: FDA is holding this public poses serious medical consequences. To addressed to ultimately support the
workshop to obtain information on in prevent unwanted coagulation, a development of in vitro testing for
vitro diagnostic testing for direct oral number of anticoagulant drugs have patients on DOAC regimens that would
anticoagulants. In order to permit the been developed. Historically, translate into clinically meaningful
widest possible opportunity to obtain anticoagulation drug therapy was results.
public comment, FDA is soliciting limited to the administration of non-
either electronic or written comments specific anticoagulants, such as heparin II. Topics for Discussion at the Public
on all aspects of the public workshop or vitamin K antagonists, that act by Workshop
topics. The deadline for submitting inhibiting the coagulation cascade at The public workshop seeks to involve
comments related to the public several points. Although effective, these industry and academia in addressing
workshop is November 25, 2015. anticoagulants have numerous analytical performance requirements for
Regardless of attendance at the public drawbacks, such as delayed onset and the diagnostic assessment of DOACs.
workshop, interested persons may offset of action, a narrow therapeutic Furthermore, the workshop aims to
submit either electronic comments window, and interactions with food and focus on the clinical circumstances
regarding this document to http:// drugs that necessitate frequent under which patients receiving these
www.regulations.gov or written monitoring and dose adjustments. agents would require testing, including
comments to the Division of Dockets Several tests have been cleared for but not limited to, the following topic
Management (HFA–305), Food and Drug monitoring of patients undergoing areas:
Administration, 5630 Fishers Lane, Rm. vitamin K antagonist therapy. 1. Overview of the effects of DOACs
1061, Rockville, MD 20852. It is only A new class of DOACs has been on traditional coagulation tests;
necessary to send one set of comments. developed in the last decade to 2. identification of clinical scenarios
Identify comments with the docket overcome limitations of traditional that necessitate DOAC testing;
number found in brackets in the anticoagulants. Thus far, FDA has 3. interpretation of coagulation testing
heading of this document. In addition, approved four DOACs: PRAXADA results for patients on DOACs; and
when responding to specific questions (dabigatran), XARELTO (rivaroxiban), 4. considerations for regulatory
as outlined in section II of this ELIQUIS (apixaban), and SAVAYSA review of devices assessing the effect of
document, please identify the question (edoxaban). DOAC therapy creates a DOACs on coagulation.
you are addressing. Received comments need for coagulation testing, which in Dated: August 20, 2015.
may be seen in the Division of Dockets turn poses new challenges. Leslie Kux,
Management between 9 a.m. and 4 p.m., Currently there are no FDA cleared
devices for the characterization of Associate Commissioner for Policy.
Monday through Friday, and will be
posted to the docket at http:// DOAC effects on coagulation. [FR Doc. 2015–21095 Filed 8–25–15; 8:45 am]
www.regulations.gov. Differences in individual responses to BILLING CODE 4164–01–P
Transcripts: Please be advised that as the drugs require laboratories to develop
soon as a transcript is available, it will unique testing schemes to assess a
be accessible at http:// patient’s coagulation status while on DEPARTMENT OF HEALTH AND
www.regulations.gov. It may be viewed DOAC regimens. Thus, the first aim of HUMAN SERVICES
at the Division of Dockets Management this workshop is to discuss the effect of
Indian Health Service
(see Comments). A transcript will also DOACs on traditional coagulation test
be available in either hardcopy or on methods currently on the market and Meeting on American Indian/Alaska
CD–ROM, after submission of a the impact these effects may have on Native Lesbian, Gay, Bisexual, and
Freedom of Information request. The patient management. Transgender Health Issues
Freedom of Information office address is We will also examine clinical
available on the Agency’s Web site at scenarios that would warrant DOAC AGENCY: Indian Health Service.
http://www.fda.gov. A link to the testing. Instructions for coagulation ACTION: Notice of meeting.
transcripts will also be available monitoring as required for vitamin K
approximately 45 days after the public antagonists are not specified in DOAC’s SUMMARY: The Indian Health Service
workshop on the Internet at http:// instructions for use. However, in certain (IHS) is continuing to seek broad public
www.fda.gov/MedicalDevices/ clinical settings assessment of DOAC- input as it continues efforts to advance
NewsEvents/WorkshopsConferences/ induced anticoagulation may be and promote the health needs of the
default.htm. (Select this public advantageous. The second aim of the American Indian/Alaska Native (AI/AN)
rmajette on DSK7SPTVN1PROD with NOTICES

workshop from the posted events list). workshop will focus on medical Lesbian, Gay, Bisexual, and Transgender
SUPPLEMENTARY INFORMATION: conditions that require coagulation (LGBT) community.
testing of patients taking DOACs. DATES: The meeting will be held as
I. Background There are a limited number of shown below:
Coagulation is the process of forming strategies to assess coagulation in 1. September 11, 2015 from 12:00
a clot to stop bleeding. Blood clotting is patients taking DOACs. We will review p.m. EST to 2:00 p.m. EST.
initiated by injury to a blood vessel options for quantitative and qualitative ADDRESSES: The meeting location is:

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Document Created: 2015-12-15 10:58:21
Document Modified: 2015-12-15 10:58:21
Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of public workshop; request for comments.
FR Citation		80 FR 51823
80 FR 51823 - In Vitro Diagnostic Testing for Direct Oral Anticoagulants; Public Workshop; Request for Comments

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 165 (August 26, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
