
[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 
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 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 
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 http://www.regulations.gov. This information will also be available 
at http://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 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.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-13768 Filed 6-7-10; 8:45 am]
BILLING CODE 4160-01-S

