[Federal Register: June 8, 2010 (Volume 75, Number 109)] [Notices] [Page 32484-32485] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr08jn10-109]
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
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 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. 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
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
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
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 http://www.regulations.gov. This information will also be available
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
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
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
5. Clinical evaluation for approval of array-based cytogenetic
a. Would validation of a group of CNVs associated with well-known
syndromes be acceptable as a representation of all types of detectable
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
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 http://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.
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-13768 Filed 6-7-10; 8:45 am] BILLING CODE 4160-01-S