Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and Interpretation; Public Meeting; Request for Comments, 32484-32485 [2010-13768]
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Federal Register / Vol. 75, No. 109 / Tuesday, June 8, 2010 / Notices
negotiates with the regulated industry. If
a stakeholder decides to participate in
these monthly meetings at a later time,
they may still participate in remaining
monthly meetings by notifying FDA (see
ADDRESSES). These stakeholder
discussions will satisfy the requirement
in section 736B(d)(3) of the act.
II. Additional Information on PDUFA
There are several sources of
information on FDA’s Web site that may
serve as useful resources for
stakeholders participating in the
periodic consultation meetings:
• Information on the April 2010
public meeting on PDUFA
Reauthorization, the Federal Register
notice announcing the meeting, and the
transcript of the meeting are available at
https://www.fda.gov/ForIndustry/
UserFees/PrescriptionDrugUserFee/
ucm117890.htm. The slide
presentations from the meeting can be
found at https://www.regulations.gov
using Docket No. FDA–2010–N–0128.
• FDA created a webinar on the
PDUFA program, drug development,
and FDA’s drug review in PDUFA IV.
These presentations are available at
https://www.fda.gov/ForIndustry/
UserFees/PrescriptionDrugUserFee/
ucm207597.htm.
• Key Federal Register documents,
PDUFA-related guidances, legislation,
performance reports, and financial
reports and plans are posted at https://
www.fda.gov/ForIndustry/UserFees/
PrescriptionDrugUserFee/default.htm.
• The Food and Drug Administration
Amendments Act of 2007 (FDAAA)specific information is available at:
https://www.fda.gov/Regulatory
Information/Legislation/
FederalFoodDrugandCosmeticAct
FDCAct/SignificantAmendmentstothe
FDCAct/FoodandDrugAdministration
AmendmentsActof2007/default.htm
emcdonald on DSK2BSOYB1PROD with NOTICES
III. Notification of Intent to Participate
in Periodic Consultation Meetings
If you intend to participate in
continued periodic stakeholder
consultation meetings regarding PDUFA
Reauthorization, please provide
notification by e-mail to
PDUFAReauthorization@fda.hhs.gov by
June 25, 2010. Your e-mail should
contain complete contact information,
including name, title, affiliation,
address, e-mail address, phone number,
and notice of any special
accommodations required because of
disability. Stakeholders will receive
confirmation and additional information
about the first meeting once FDA
receives their notification.
VerDate Mar<15>2010
16:31 Jun 07, 2010
Jkt 220001
Dated: June 2, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–13671 Filed 6–7–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–N–0259]
Array-Based Cytogenetic Tests:
Questions on Performance Evaluation,
Result Reporting and Interpretation;
Public Meeting; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
ACTION: Notice of public meeting;
request for comments.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
following public meeting: Array-Based
Cytogenetic Tests: Questions on
Performance Evaluation, Result
Reporting and Interpretation. The
purpose of the public meeting is to seek
input on challenges related to
performance evaluation, determination
of clinical significance, result reporting,
and interpretation for array-based
cytogenetic tests.
Date and Time: The meeting will be
held on June 30, 2010, from 1:30 p.m.
to 5 p.m.
Location: The meeting will be held at
Hyatt Regency Bethesda, 7400
Wisconsin Ave., 1 Bethesda Metro
Center, Bethesda, MD.
Contact: Susan Monahan, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, rm. 4321,
Silver Spring, MD 20903, 301–796–
5661, e-mail:
Susan.Monahan@fda.hhs.gov; or Zivana
Tezak, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 66,
rm. 5668, Silver Spring, MD 20903,
301–796–6206, e-mail:
Zivana.Tezak@fda.hhs.gov.
Registration and Requests for Oral
Presentations: Send registration
information (including name, title, firm
name, address, telephone, and fax
number), and written material and
requests to make oral presentations, to
the contact person by June 21, 2010.
Registration is free and will be on a firstcome, first-served basis. Early
registration is recommended because
seating is limited. FDA may limit the
number of participants from each
organization based on space limitations.
Registrants will receive confirmation
once they have been accepted. Onsite
registration on the day of the public
PO 00000
Frm 00130
Fmt 4703
Sfmt 4703
meeting will be provided on a spaceavailable basis beginning at 7 a.m.
If you wish to make an oral
presentation during the open comment
session at the meeting, you must
indicate this at the time of registration.
FDA has included general discussion
topics and specific questions for
comment in section III of this document,
Topics for Input. You should also
identify which discussion topic you
wish to address in your presentation.
FDA will do its best to accommodate
requests to speak. Individuals and
organizations with common interests are
urged to consolidate or coordinate their
presentations, and to request time for a
joint presentation. FDA will determine
the amount of time allotted to each
presenter and the approximate time that
each oral presentation is scheduled to
begin.
If you need special accommodations
due to a disability, please contact Susan
Monahan or Zivana Tezak (see Contact)
at least 7 days in advance.
Comments: FDA is holding this public
meeting to obtain input on a number of
questions regarding review and
interpretation issues for array-based
cytogenetic testing.
Regardless of attendance at the
meeting, interested persons may submit
either electronic or written comments
on any discussion topic(s) to the open
docket. The deadline for submitting
comments to the docket is July 30, 2010.
Submit electronic comments to https://
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.
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 III 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.
SUPPLEMENTARY INFORMATION:
I. Background
Many human genetic disorders are a
result of the gain or loss of human
genetic material, which may manifest as
congenital anomalies, dysmorphic
features, developmental disabilities, etc.
Traditionally, chromosomes were
analyzed using a method called
karyotyping. In addition, molecular
methods such as fluorescence in situ
hybridization (FISH) provide the
information about chromosome
abnormalities at specific loci. The recent
E:\FR\FM\08JNN1.SGM
08JNN1
Federal Register / Vol. 75, No. 109 / Tuesday, June 8, 2010 / Notices
development of deoxyribonucleic acid
(DNA) array methodologies, such as
microarray-based comparative genomic
hybridization (aCGH) and singlenucleotide polymorphism (SNP) arrays
allow a high-resolution evaluation of
DNA copy number alterations
associated with chromosome
abnormalities. Array-based cytogenetic
testing is currently being implemented
in the clinical setting as a method for
detecting pathological genomic copy
number changes.
FDA regulation and review of in vitro
diagnostic devices has traditionally
been a single marker-based, indicationspecific process that ensures safety and
effectiveness of the product. However,
the results obtained from array-based
cytogenetic tests are not necessarily
predefined and may not be associated
with known clinical syndromes.
Evaluating complex devices such as
array-based cytogenetic tests challenges
the traditional method of FDA review.
emcdonald on DSK2BSOYB1PROD with NOTICES
II. Meeting Overview
During the meeting, FDA staff will
present a brief background and
overview of in vitro diagnostic (IVD)
regulation. Specific questions related to
review challenges for array-based
cytogenetic tests are listed in section III
of this document, Topics for Input. After
the open comment session, the meeting
will close with a round-table discussion
between FDA staff and selected
participants representing a range of
constituencies. The participants in the
round-table discussion will engage in a
dialogue on discussion topics (see
section III of this document), and
provide closing thoughts. The
participants will not be asked to
develop consensus opinions during the
discussion, but rather to provide their
individual perspectives. Others in
attendance at the meeting will have an
opportunity to listen to the round-table
discussion.
In advance of the meeting, additional
information, including a meeting
agenda, will be made available on the
Internet. This information will be
placed on file in the public docket
(docket number found in brackets in the
heading of this document), which is
available at https://www.regulations.gov.
This information will also be available
at https://www.fda.gov/MedicalDevices/
NewsEvents/WorkshopsConferences/
default.htm (select the appropriate
meeting from the list).
III. Topics for Input
FDA seeks input on the following
issues:
1. Clinical significance
VerDate Mar<15>2010
16:31 Jun 07, 2010
Jkt 220001
a. The resolution of array-based
cytogenetic tests and the presence of
copy number variations (CNVs) in the
apparently healthy population poses
challenges for result interpretation.
What criteria should be used to
determine the clinical significance of
CNVs (e.g., when categorized as benign,
pathogenic, or of unknown
significance)?
b. Should there be different
requirements implemented for
interpreting the clinical significance of
deletions vs. duplications vs.
translocations?
2. Result reporting and interpretation
a. Should result output be limited to
results associated with known
syndromes that can be adequately
validated clinically and analytically?
b. What criteria (e.g., minimum
overlap, size, etc.) should be used to
conclude findings are indicative of
known syndrome?
c. Should the performing, ordering
and/or result interpretation of these
tests be limited to certain professionals
(e.g., clinical cytogeneticists)?
d. How does FDA ensure that the
results are interpreted correctly?
3. Additional and confirmatory testing
a. Should any array-based cytogenetic
testing of an affected individual include
testing of parents where possible?
b. Should a second followup test (e.g.,
FISH) be required for result
confirmation prior to reporting arraybased cytogenetic results?
4. Incidental findings
Laboratories are obliged to report
clinically significant findings unrelated
to the test order, when identified. How
can the reporting of results for diseases
or conditions outside of the indications
for use be restricted?
5. Clinical evaluation for approval of
array-based cytogenetic devices
a. Would validation of a group of
CNVs associated with well-known
syndromes be acceptable as a
representation of all types of detectable
CNVs?
b. If yes, then which syndromes
should be included and how many
CNVs would be a representative
number?
c. What should be used as the
reference genome?
d. What studies should be performed
to understand clinical specificity?
6. Use of database(s) in result
reporting
a. How can the accuracy of
information used in the determination
of results be assured?
i. Who should develop and maintain
a curated database of known/probable
CNV changes and benign findings in the
population?
PO 00000
Frm 00131
Fmt 4703
Sfmt 4703
32485
ii. FDA regulations require that all
aspects of a test involved in result
output are under design controls in
accordance with the Quality System
regulations. When implementing the
database for result reporting, how can it
be assured that the database is
adequately maintained and meets
appropriate quality standards?
Transcripts: Please be advised that as
soon as a transcript is available, it will
be accessible at https://
www.regulations.gov. It may be viewed
at the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD. 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 Division of
Freedom of Information (HFI–35), Office
of Management Programs, Food and
Drug Administration, 5600 Fishers
Lane, rm. 6–30, Rockville, MD 20857.
Dated: June 3, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–13768 Filed 6–7–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Diabetes and
Digestive and Kidney Diseases; Notice
of Closed Meetings
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meetings.
The meetings will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute of
Diabetes and Digestive and Kidney Diseases
Special Emphasis Panel; Planning Centers for
Interdisciplinary Research in Benign Urology
(IR–BU) (P20).
Date: July 9, 2010.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Marriott Wardman Park Washington,
DC Hotel, 2660 Woodley Road, NW.,
Washington, DC 20008.
E:\FR\FM\08JNN1.SGM
08JNN1
]]>Agencies
[Federal Register Volume 75, Number 109 (Tuesday, June 8, 2010)]
[Notices]
[Pages 32484-32485]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-13768]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0259]
Array-Based Cytogenetic Tests: Questions on Performance
Evaluation, Result Reporting and Interpretation; Public Meeting;
Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
following public meeting: Array-Based Cytogenetic Tests: Questions on
Performance Evaluation, Result Reporting and Interpretation. The
purpose of the public meeting is to seek input on challenges related to
performance evaluation, determination of clinical significance, result
reporting, and interpretation for array-based cytogenetic tests.
Date and Time: The meeting will be held on June 30, 2010, from 1:30
p.m. to 5 p.m.
Location: The meeting will be held at Hyatt Regency Bethesda, 7400
Wisconsin Ave., 1 Bethesda Metro Center, Bethesda, MD.
Contact: Susan Monahan, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, rm. 4321, Silver Spring, MD 20903, 301-796-
5661, e-mail: Susan.Monahan@fda.hhs.gov; or Zivana Tezak, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 5668, Silver
Spring, MD 20903, 301-796-6206, e-mail: Zivana.Tezak@fda.hhs.gov.
Registration and Requests for Oral Presentations: Send registration
information (including name, title, firm name, address, telephone, and
fax number), and written material and requests to make oral
presentations, to the contact person by June 21, 2010. Registration is
free and will be on a first-come, first-served basis. Early
registration is recommended because seating is limited. FDA may limit
the number of participants from each organization based on space
limitations. Registrants will receive confirmation once they have been
accepted. Onsite registration on the day of the public meeting will be
provided on a space-available basis beginning at 7 a.m.
If you wish to make an oral presentation during the open comment
session at the meeting, you must indicate this at the time of
registration. FDA has included general discussion topics and specific
questions for comment in section III of this document, Topics for
Input. You should also identify which discussion topic you wish to
address in your presentation. FDA will do its best to accommodate
requests to speak. Individuals and organizations with common interests
are urged to consolidate or coordinate their presentations, and to
request time for a joint presentation. FDA will determine the amount of
time allotted to each presenter and the approximate time that each oral
presentation is scheduled to begin.
If you need special accommodations due to a disability, please
contact Susan Monahan or Zivana Tezak (see Contact) at least 7 days in
advance.
Comments: FDA is holding this public meeting to obtain input on a
number of questions regarding review and interpretation issues for
array-based cytogenetic testing.
Regardless of attendance at the meeting, interested persons may
submit either electronic or written comments on any discussion topic(s)
to the open docket. The deadline for submitting comments to the docket
is July 30, 2010. Submit electronic comments to https://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. 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 III 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.
SUPPLEMENTARY INFORMATION:
I. Background
Many human genetic disorders are a result of the gain or loss of
human genetic material, which may manifest as congenital anomalies,
dysmorphic features, developmental disabilities, etc. Traditionally,
chromosomes were analyzed using a method called karyotyping. In
addition, molecular methods such as fluorescence in situ hybridization
(FISH) provide the information about chromosome abnormalities at
specific loci. The recent
[[Page 32485]]
development of deoxyribonucleic acid (DNA) array methodologies, such as
microarray-based comparative genomic hybridization (aCGH) and single-
nucleotide polymorphism (SNP) arrays allow a high-resolution evaluation
of DNA copy number alterations associated with chromosome
abnormalities. Array-based cytogenetic testing is currently being
implemented in the clinical setting as a method for detecting
pathological genomic copy number changes.
FDA regulation and review of in vitro diagnostic devices has
traditionally been a single marker-based, indication-specific process
that ensures safety and effectiveness of the product. However, the
results obtained from array-based cytogenetic tests are not necessarily
predefined and may not be associated with known clinical syndromes.
Evaluating complex devices such as array-based cytogenetic tests
challenges the traditional method of FDA review.
II. Meeting Overview
During the meeting, FDA staff will present a brief background and
overview of in vitro diagnostic (IVD) regulation. Specific questions
related to review challenges for array-based cytogenetic tests are
listed in section III of this document, Topics for Input. After the
open comment session, the meeting will close with a round-table
discussion between FDA staff and selected participants representing a
range of constituencies. The participants in the round-table discussion
will engage in a dialogue on discussion topics (see section III of this
document), and provide closing thoughts. The participants will not be
asked to develop consensus opinions during the discussion, but rather
to provide their individual perspectives. Others in attendance at the
meeting will have an opportunity to listen to the round-table
discussion.
In advance of the meeting, additional information, including a
meeting agenda, will be made available on the Internet. This
information will be placed on file in the public docket (docket number
found in brackets in the heading of this document), which is available
at https://www.regulations.gov. This information will also be available
at https://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm (select the appropriate meeting from the list).
III. Topics for Input
FDA seeks input on the following issues:
1. Clinical significance
a. The resolution of array-based cytogenetic tests and the presence
of copy number variations (CNVs) in the apparently healthy population
poses challenges for result interpretation. What criteria should be
used to determine the clinical significance of CNVs (e.g., when
categorized as benign, pathogenic, or of unknown significance)?
b. Should there be different requirements implemented for
interpreting the clinical significance of deletions vs. duplications
vs. translocations?
2. Result reporting and interpretation
a. Should result output be limited to results associated with known
syndromes that can be adequately validated clinically and analytically?
b. What criteria (e.g., minimum overlap, size, etc.) should be used
to conclude findings are indicative of known syndrome?
c. Should the performing, ordering and/or result interpretation of
these tests be limited to certain professionals (e.g., clinical
cytogeneticists)?
d. How does FDA ensure that the results are interpreted correctly?
3. Additional and confirmatory testing
a. Should any array-based cytogenetic testing of an affected
individual include testing of parents where possible?
b. Should a second followup test (e.g., FISH) be required for
result confirmation prior to reporting array-based cytogenetic results?
4. Incidental findings
Laboratories are obliged to report clinically significant findings
unrelated to the test order, when identified. How can the reporting of
results for diseases or conditions outside of the indications for use
be restricted?
5. Clinical evaluation for approval of array-based cytogenetic
devices
a. Would validation of a group of CNVs associated with well-known
syndromes be acceptable as a representation of all types of detectable
CNVs?
b. If yes, then which syndromes should be included and how many
CNVs would be a representative number?
c. What should be used as the reference genome?
d. What studies should be performed to understand clinical
specificity?
6. Use of database(s) in result reporting
a. How can the accuracy of information used in the determination of
results be assured?
i. Who should develop and maintain a curated database of known/
probable CNV changes and benign findings in the population?
ii. FDA regulations require that all aspects of a test involved in
result output are under design controls in accordance with the Quality
System regulations. When implementing the database for result
reporting, how can it be assured that the database is adequately
maintained and meets appropriate quality standards?
Transcripts: Please be advised that as soon as a transcript is
available, it will be accessible at https://www.regulations.gov. It may
be viewed at the Division of Dockets Management (HFA-305), Food and
Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD. 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 Division of Freedom of Information (HFI-35), Office
of Management Programs, Food and Drug Administration, 5600 Fishers
Lane, rm. 6-30, Rockville, MD 20857.
Dated: June 3, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-13768 Filed 6-7-10; 8:45 am]
BILLING CODE 4160-01-S
