Federal Register / Vol. 74, No. 202 / Wednesday, October 21, 2009 / Notices 54053 

II. Significance of Guidance 

FDA is issuing this draft guidance 

document consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). The draft guidance, when 

finalized, will represent the agency’s 

current thinking on ‘‘Registration and 

Product Listing for Owners and 

Operators of Domestic Tobacco Product 

Establishments.’’ It does not create or 

confer any rights for or on any person 

and does not operate to bind FDA or the 

public. An alternative approach may be 

used if such approach satisfies the 

requirements of the applicable statute 

and regulations. 

III. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. The guidance 

document and received comments may 

be seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

IV. Paperwork Reduction Act of 1995 

This draft guidance contains proposed 

collections of information that are 

subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(PRA) (44 U.S.C. 3501–3520). As 

required by the PRA, FDA has 

published an analysis of, among others, 

the information collection concerning 

the submission of tobacco product 

establishment registration and product 

listing information (74 FR 45219, 

September 1, 2009, as corrected by 74 

FR 47257, September 15, 2009) and will 

submit them for OMB approval. 

V. Electronic Access 

An electronic version of the guidance 

document is available on the Internet at 

http://www.regulations.gov and http:// 

www.fda.gov/TobaccoProducts/ 

GuidanceComplianceRegulatory

Information/default.htm. 

Dated: October 15, 2009. 

David Horowitz, 

Assistant Commissioner for Policy. 

[FR Doc. E9–25235 Filed 10–16–09; 11:15 

am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–D–0503] 

Draft Guidances for Industry and Food 

and Drug Administration Staff; 

Computer-Assisted Detection Devices 

Applied to Radiology Images and 

Radiology Device Data—Premarket 

Notification [510(k)] Submissions and 

Clinical Performance Assessment: 

Considerations for Computer-Assisted 

Detection Devices Applied to 

Radiology Images and Radiology 

Device Data—Premarket Approval 

(PMA) and Premarket Notification 

[510(k)] Submissions; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of two related draft guidance 

documents. One is a draft guidance 

entitled, ‘‘Computer-Assisted Detection 

Devices Applied to Radiology Images 

and Radiology Device Data—Premarket 

Notification [510(k)] Submissions’’ 

(‘‘CADe 510(k) draft guidance’’). This 

draft guidance provides 

recommendations regarding premarket 

notification (510(k)) submissions of 

certain computer-assisted detection 

(CADe) devices applied to radiology 

images and radiology device data. The 

second draft guidance is entitled, 

‘‘Clinical Performance Assessment: 

Considerations for Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Approval (PMA) and 

Premarket Notification [510(k)] 

Submissions’’ (‘‘CADe clinical 

performance assessment draft 

guidance’’). This draft guidance 

provides recommendations on how to 

design and conduct clinical 

performance studies for CADe devices 

applied to radiology images and 

radiology device data. These studies 

may be part of a premarket submission 

to FDA, whether it is a 510(k) 

submission, an application for 

premarket approval (PMA), an 

application for a humanitarian device 

exemption (HDE), or an application for 

an investigational device exemption 

(IDE). These draft guidances are not 

final nor are they in effect at this time. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the agency 

considers your comment on these draft 

guidances before it begins work on the 

final versions of these guidances, submit 

written or electronic comments on the 

draft guidances by January 19, 2010. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance 

document entitled ‘‘Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Notification [510(k)] 

Submissions’’ or the draft guidance 

document entitled ‘‘Clinical 

Performance Assessment: 

Considerations for Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Approval (PMA) and 

Premarket Notification [510(k)] 

Submissions’’ to the Division of Small 

Manufacturers, International, and 

Consumer Assistance, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., WO66–4613, Silver 

Spring, MD 20993. Send one selfaddressed adhesive label to assist that 

office in processing your request, or fax 

your request to 301–847–8149. See the 

SUPPLEMENTARY INFORMATION section for 

information on electronic access to 

these draft guidances. 

Submit written comments concerning 

either of these draft guidances and the 

questions found in the supplementary 

information to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http:// 

www.regulations.gov. Identify 

comments with the docket number 

found in brackets in the heading of this 

document. Please include your rationale 

and/or scientific justification with your 

comments. 

FOR FURTHER INFORMATION CONTACT: 

Nicholas Petrick, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., White Oak Bldg. 62, rm. 4116, 

Silver Spring, MD 20993, 301–796– 

2563, and Joyce Whang, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., White Oak Bldg. 66, 

rm. G318, Silver Spring, MD 20993. 

SUPPLEMENTARY INFORMATION: 

I. Background 

CADe devices are computerized 

systems that incorporate pattern 

recognition and data analysis 

capabilities (i.e., combine values, 

measurements, or features extracted 

from the patient radiological data) 

intended to identify, mark, highlight, or 

in any other manner direct attention to 

portions of an image, or aspects of 

radiology device data, that may reveal 

abnormalities during interpretation of 


jlentini on DSKJ8SOYB1PROD with NOTICES
54054 Federal Register / Vol. 74, No. 202 / Wednesday, October 21, 2009 / Notices 

patient radiology images or patient 

radiology device data by the intended 

user (i.e., a physician or other health 

care professional). In drafting these 

documents, we considered the 

recommendations made during the 

Radiological Devices Panel on March 4 

through 5, 2008. Further information on 

this public advisory committee meeting, 

including panel transcripts, can be 

found at: http://www.fda.gov/ohrms/ 

dockets/ac/cdrh08.html#radiology. 

The CADe 510(k) draft guidance 

provides recommendations on 

documentation and performance testing 

to be part of a 510(k) submission for 

Class II CADe devices applied to 

radiology images and radiology device 

data. The CADe clinical performance 

assessment draft guidance provides 

recommendations regarding clinical 

performance studies for both Class II 

and Class III CADe devices applied to 

radiology images and radiology device 

data. 

II. Frequently Asked Questions 

The agency anticipates including a 

section containing frequently asked 

questions (FAQs) in each of the 

guidances to further clarify the agency’s 

recommendations regarding premarket 

notification (510(k)) submissions of 

certain computer-assisted detection 

(CADe) devices applied to radiology 

images and radiology, and on how to 

design and conduct clinical 

performance studies for CADe devices 

applied to radiology images and 

radiology device data. The agency is 

requesting public comment on the 

proposed sample questions provided in 

this document. Suggestions for 

additional questions and answers that 

are not included below but that may be 

helpful in understanding the guidances 

are also encouraged. The public 

comments will allow the agency to 

further refine the guidance and develop 

a FAQ section to communicate the 

recommended level of evidence for 

different premarket submissions. The 

agency also wants to ensure that these 

guidances adequately address these 

anticipated questions. The agency may 

adjust, add or delete questions based on 

received comments. 

The first group of draft sample 

questions (Q1–Q7) has been developed 

to provide context to the principles 

discussed in the CADe 510(k) draft 

guidance. They may help in preparing a 

Premarket Notification [510(k)] 

Submission for your CADe device. 

Please comment on the following 

questions and what you believe would 

be the expectation of the agency based 

on the issues presented in the CADe 

510(k) draft guidance. 

Q1: Our CT CADe device is intended 

to be used on a variety of CT devices. 

Should any clinical trials we perform 

include every unit with which the CT 

CADe device is intended to be used? 

Q2: Our CADe device is designed to 

detect lung nodules. Should we power 

our standalone performance assessment 

so that statistically significant results 

can be obtained for the clinically 

relevant subgroups of lesions, for 

example, nodules near the mediastinum 

versus the peripheral lung fields? 

Q3: We have an already cleared CADe 

device and have updated one of its 

algorithms. Should we perform another 

clinical performance assessment (i.e., a 

reader study)? 

Q4: We have a new CADe device and 

have done standalone testing comparing 

it to an already cleared CADe device. 

Our new CADe identified additional 

cancers and had fewer false positive 

marks than the cleared device but ours 

missed some of the cancers detected by 

the cleared device. Should we perform 

a clinical performance assessment? 

Q5: We have an already cleared CADe 

device and have changed the prompt 

format (e.g., masses are now marked 

with a circle rather than an arrow). 

Should we perform another clinical 

performance assessment? 

Q6: In a 510(k), can I reuse the test 

dataset that supported clearance of the 

predicate CADe device and if so what 

are the constraints on this reuse? 

Q7: Our colon CADe device can be 

used for both 2D and 3D interpretation. 

Should we perform clinical tests using 

both interpretation modes? 

The second set of draft sample 

questions (Q8–Q11) has been developed 

to provide context to the principles 

discussed in the CADe clinical 

performance assessment draft guidance. 

They may help in developing and 

conducting a clinical performance 

assessment of your CADe device to 

support clearance or approval. Again, 

please comment on these questions and 

what you believe would be the 

expectation of the agency based on the 

issues presented in the CADe clinical 

performance assessment draft guidance. 

Q8: The guidance calls for the trial 

readers to be ‘‘representative of the 

intended population of clinical users.’’ 

Can you give some examples and should 

the number of readers in each of the 

subgroups be proportional to the 

numbers in the population of clinical 

users? 

Q9: We have a new breast CADe 

device and would like to market it for 

use with all legally marketed Full Field 

Digital Mammography (FFDM). Should 

we perform reader studies with each 

legally marketed FFDM? 

Q10: We have a breast CADe device 

approved for use with a specific legally 

marketed Full Field Digital 

Mammography (FFDM) based on a 

robust MRMC study. We would like to 

market it for use with an additional 

legally marketed FFDM. Should we 

perform a clinical performance 

assessment (i.e., reader study) to assess 

the CADe for use with the new FFDM 

or is standalone performance data 

enough to demonstrate comparable 

results based on the specifications of the 

device? 

Q11: We have improved our legally 

marketed CADe device and will be 

submitting a new 510(k) for the 

upgraded version. Is image reading 

without CADe a suitable control arm 

against which to compare the upgraded 

CADe device? 

The agency is seeking input to the 

previous sample questions and 

suggestions on additional questions so 

that it can further refine the guidance 

and develop a FAQ section to 

communicate the recommended level of 

evidence for different premarket 

submissions. Your input would allow us 

to consider multiple viewpoints of what 

is the adequacy of evidence for these 

devices. 

III. Significance of Guidance 

These draft guidances are being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). The draft guidances, when 

finalized, will represent, respectively, 

the agency’s current thinking on ‘‘ 

Computer-Assisted Detection Devices 

Applied to Radiology Images and 

Radiology Device Data—Premarket 

Notification [510(k)] Submissions’’ and 

on ‘‘Clinical Performance Assessment: 

Considerations for Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Approval (PMA) and 

Premarket Notification [510(k)] 

Submissions.’’ The guidance documents 

do not create or confer any rights for or 

on any person and do not operate to 

bind FDA or the public. Alternative 

approaches may be used if such 

approaches satisfy the requirements of 

the applicable statute and regulations. 

IV. Electronic Access 

Persons interested in obtaining a copy 

of either draft guidance may do so by 

using the Internet. To receive 

‘‘Computer-Assisted Detection Devices 

Applied to Radiology Images and 

Radiology Device Data—Premarket 

Notification [510(k)] Submissions,’’ you 

may either send an e-mail request to 

dsmica@fda.hhs.gov to receive an 

electronic copy of the document or send 


jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 74, No. 202 / Wednesday, October 21, 2009 / Notices 54055 

a fax request to 301–847–8149 to receive 

a hard copy. Please use the document 

number 1697 to identify the draft 

guidance you are requesting. To receive 

‘‘Clinical Performance Assessment: 

Considerations for Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Approval (PMA) and 

Premarket Notification [510(k)] 

Submissions,’’ you may either send an 

e-mail request to dsmica@fda.hhs.gov to 

receive an electronic copy of the 

document or send a fax request to 301– 

847–8149 to receive a hard copy. Please 

use the document number 1698 to 

identify the draft guidance you are 

requesting. 

CDRH maintains an entry on the 

Internet for easy access to information 

including text, graphics, and files that 

may be downloaded to a personal 

computer with Internet access. Updated 

on a regular basis, the CDRH home page 

includes device safety alerts, Federal 

Register reprints, information on 

premarket submissions (including lists 

of approved applications and 

manufacturers’ addresses), small 

manufacturer’s assistance, information 

on video conferencing and electronic 

submissions, mammography matters, 

and other device-oriented information. 

The CDRH web site may be accessed at 

http://www.fda.gov/cdrh. A search 

capability for all CDRH guidance 

documents is available at http:// 

www.fda.gov/cdrh/guidance.html. 

Guidance documents are also available 

at http://www.regulations.gov. 

V. Paperwork Reduction Act of 1995 

These draft guidances contain 

information collection provisions that 

are subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(44 USC 3501–3520) (the PRA). The 

collections of information addressed in 

these draft guidance documents have 

been approved by OMB in accordance 

with the PRA under the regulations 

governing premarket notification 

submissions (21 CFR part 807, subpart 

E, OMB No. 0910–0120), premarket 

approval applications (21 CFR part 814, 

OMB No. 0910–0231), investigational 

device exemptions (21 CFR part 812, 

OMB No. 0910–0078), and humanitarian 

use devices (21 CFR part 814, OMB No. 

0910–0332). The labeling provisions 

addressed in the ‘‘Computer-Assisted 

Detection Devices Applied to Radiology 

Images and Radiology Device Data— 

Premarket Notification [510(k)] 

Submissions’’ draft guidance have been 

approved by OMB under OMB No. 

0910–0485. 

VI. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES), written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

Dated: October 15, 2009. 

David Horowitz, 

Assistant Commissioner for Policy. 

[FR Doc. E9–25233 Filed 10–20–09; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–D–0473] 

Guidance for Industry and Food and 

Drug Administration Staff; Class II 

Special Controls Guidance Document: 

Cardiac Allograft Gene Expression 

Profiling Test Systems; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the special controls 

guidance document entitled ‘‘Class II 

Special Controls Guidance Document: 

Cardiac Allograft Gene Expression 

Profiling Test Systems.’’ This guidance 

document describes a means by which 

cardiac allograft gene expression 

profiling test systems may comply with 

the requirement of special controls for 

class II devices. It includes 

recommendations for validation of 

performance characteristics and 

recommendations for product labeling. 

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

codifying the classification of cardiac 

allograft gene expression profiling test 

systems into class II (special controls), 

and establishing this guidance 

document as the special control for this 

device. 

DATES: Submit electronic or written 

comments on this guidance at any time. 

General comments on agency guidance 

documents are welcome at any time. 

ADDRESSES: Submit written requests for 

single copies of the guidance document 

entitled ‘‘Class II Special Controls 

Guidance Document: Cardiac Allograft 

Gene Expression Profiling Test 

Systems’’ to the Division of Small 

Manufacturers, International, and 

Consumer Assistance, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 66, rm. 4613, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request, or fax your request to 301–847– 

8149. See the SUPPLEMENTARY

INFORMATION section for information on 

electronic access to the guidance. 

Submit electronic comments to http:// 

www.regulations.gov. Submit written 

comments concerning this guidance to 

the Division of Dockets Management 

(HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Identify 

comments with the docket number 

found in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Kellie B. Kelm, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, rm. 5625, Silver Spring, 

MD 20993, 301–796–6145. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

codifying the classification of cardiac 

allograft gene expression profiling test 

systems into class II (special controls) 

under section 513(f)(2) of the Federal 

Food, Drug, and Cosmetic Act (the act) 

(21 U.S.C. 360c(f)(2)) and establishing 

this guidance document as the special 

control for cardiac allograft gene 

expression profiling test systems 

classified under that regulation. Section 

513(f)(2) of the act provides that any 

person who submits a premarket 

notification under section 510(k) of the 

act (21 U.S.C. 360(k)) for a device that 

has not previously been classified may, 

within 30 days after receiving an order 

classifying the device in class III under 

section 513(f)(1), request FDA to classify 

the device under the criteria set forth in 

section 513(a)(1). FDA shall, within 60 

days of receiving such a request, classify 

the device by written order. This 

classification shall be the initial 

classification of the device. Within 30 

days after the issuance of an order 

classifying the device, FDA must 

publish a notice in the Federal Register 

announcing such classification. Under 

this authority, on August 26, 2008, FDA 

by order classified into class II, subject 

to this special control guidance 

document, the XDx AlloMap Test. 


jlentini on DSKJ8SOYB1PROD with NOTICES