`[Federal Register Volume 75, Number 109 (Tuesday, June 8, 2010)]
[Notices]
[Pages 32484-32485]
From the Federal Register Online via the Government Publishing 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: [email protected]; or Zivana Tezak, Food and Drug 

Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 5668, Silver 

Spring, MD 20903, 301-796-6206, e-mail: [email protected].

    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`