ARIOL

K033200 · Applied Imaging Corp. · NQN · Mar 18, 2004 · Hematology

Device Facts

• Record ID: K033200
• Device Name: ARIOL
• Applicant: Applied Imaging Corp.
• Product Code: NQN · Hematology
• Decision Date: Mar 18, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.1860
• Device Class: Class 2
• Attributes: AI/ML

AI Performance

Output	Acceptance	Observed	Dev DS	Test DS
Estrogen Receptor (ER) status (percent positivity)	Substantial equivalence to manual microscopy readings.	Concordance with manual method at 1% threshold: 93.2-95.9%; at 5% threshold: 95.9-97.3%; at 10% threshold: 94.5-98.6%.	Not specified.	Approximately 75 clinical slides of known scoring intensity for ER (total 150 slides including PR) obtained from a commercial vendor, evaluated by three pathologists.
Progesterone Receptor (PR) status (percent positivity)	Substantial equivalence to manual microscopy readings.	Concordance with manual method at 1% threshold: 94.8-96.1%; at 5% threshold: 84.4-88.3%; at 10% threshold: 88.3-94.8%.	Not specified.	Approximately 75 clinical slides of known scoring intensity for PR (total 150 slides including ER) obtained from a commercial vendor, evaluated by three pathologists.

Intended Use

Ariol™ is an automated scanning microscope and image analysis system. It is intended for in vitro diagnostic use as an aid to the pathologist in the detection, classification, and counting of cells of interest based on particular color, intensity, size, pattern, and shape. This particular Ariol software application is intended to measure, count, and quantitate the percentage and intensity of positively stained nuclei in formalin-fixed paraffin-embedded tissue specimens immunohistochemically stained for Estrogens Receptors or Progesterone Receptors (ER/PR).

Device Story

Automated scanning microscope and image analysis system; inputs formalin-fixed, paraffin-embedded tissue specimens stained for ER/PR; transforms visual data into quantitative metrics; measures, counts, and quantitates percentage and intensity of positively stained nuclei; used in clinical laboratory settings by pathologists; output assists pathologists in breast cancer management, prognosis, and therapy prediction; provides objective quantification of immunohistochemical staining.

Clinical Evidence

No clinical data provided in the document; substantial equivalence determination based on technological characteristics and intended use as an automated aid for immunohistochemical analysis.

Technological Characteristics

System includes computer, monitor, motorized microscope with focus/filterwheels. Uses colorimetric and morphometric pattern recognition for nuclear IHC analysis. Operates via semi-automated scanning (1.25x, 5x, 20x). Calibration via user-trained positive/negative slides. Software performs image acquisition, cell counting, and intensity quantification. Connectivity includes bar-code slide identification.

Indications for Use

Indicated for use as an aid to pathologists in the management, prognosis, and prediction of therapy outcomes for breast cancer patients by measuring, counting, and quantitating positively stained nuclei in formalin-fixed, paraffin-embedded tissue specimens immunohistochemically stained for Estrogen Receptors (ER) or Progesterone Receptors (PR).

Regulatory Classification

Identification

Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.

Special Controls

(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 1 8 2004

Ms. Diane Oates Vice President, Regulatory and Quality Affairs Applied Imaging Corp. 2380 Walsh Avenue., Bldg. B Santa Clara, CA 95051

k033200 Re: Trade/Device Name: Ariol TM ER/PR Application Regulation Number: 21 CFR 864.1860 Regulation Name: Irnmunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NQN Dated: January 15, 2004 Received: January 16, 2004

Dear Ms. Oates:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the cnactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA 's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{1}------------------------------------------------

## Page 2

This letter will allow you to begin marketing your device as described in your Section 510(k) I ins lotter will and w your he FDA finding of substantial equivalence of your device to a legally premated noticated device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or guestions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I va may of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Joseph L. Hackett

Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

## STATEMENT OF INTENDED USE

## 510(K) Number (if known): KO33200

Device Name: Ariol™ ER/FR Application

## Indications for Use:

Ariol™ is an automated scanning microscope and image analysis system. It is intended for in virro diagnostic use as an aid to the pathologist in the detection, classification, and counting of cells of interest based on particular color, intensity, size, pattern, and shape.

This particular Ariol software application is intended to measure, count, and quantitate the percentage and intensity of positively stained nuclei in formalin-fixed paraffin-embedded tissue specimens immunohistochemically stained for Estrogens Receptors or Progesterone Receptors (ER/PR). ER/PR results are indicated for use as and aid in the management, prognosis, and prediction of therapy outcomes of breast cancer.

(PLEASE DO NOT WRITE BELOW THIS LINE- CONTINUE ON ANOTHER PAGE AS NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use | X | OR | Over-the-Counter Use | _____ |
|----------------------|---|----|----------------------|-------|
| (Per 21 CFR 801.109) | | | | |

A Pleeves for M. Chan

(Division Sign-Off)

Division of Clinical Laboratory Devices

| 510(k) Number | K033200 |
|---------------|---------|
|---------------|---------|