Department of Health and Human Services
Public Health Service
2098 Gaither Rd
November 28, 2000
Douglas S. Barrington, MD, President & CEO
ChromaVision Medical Systems, Incorporated
33171 Paseo Cerveza
San Juan Capistrano, CA 92675-4824
Dear Sir or Madam:
The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) has reviewed a press release distributed by ChromaVision Medical Systems, Incorporated (ChromaVision) and the ChromaVision Internet site found at www.chromavision.com. The product referenced in this material is the Automated Cellular Imaging System (ACISTNi). The ACISTN1system is a device as defined within the meaning of section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act). The intended use of the ACIS™ System that was cleared in ChromaVision's 510(k) premarket notification submission designated K984188 was as follows: "The Automated Cellular Imaging System (ACIS) device is intended to detect, count, and classify cells of clinical interest based on recognition of cellular objects of particular color, size, and shape."
According to the data presented in the premarket notification for the ACIS™ it is to be used as a staining device for cytokeratin 18 which is present in the cytoplasm of normal and malignant breast cancer cells. The determination of the nature of the stained cell (malignant or benign) requires a clinical assessment by a pathologist. Although your device was intended to detect, count, and classify cells of interest, we have reviewed some promotional material that makes clinical claims regarding the ACIS™ device.
In a June 26, 2000, press release found on your Internet site at www.chromavision.com/ic/pr/pr062600.htm you imply that the ACIS™ device can be used for cancer staging and determining patient prognosis. This implication is evident in the title of the press release, "ChromaVision Launches new Automated Test for Cancer Staging and Patient Prognosis." Chromavision continues this claim within the body of the press release by stating the following: "Additionally, ACIS makes it practical to examine a greater number of lymph node sections … Lymph node status is well established as a principal determinant in the staging and prognosis of various solid tumor types…" Statements such as these are inappropriate. Both the staging of a disease and the prognosis are clinical claims beyond the intended use of the ACIS™ device Additionally, the data provided by ChromaVision in support of the ACIS™ 510(k) were derived fJrom bone marrow preparations and not from lymph nodes Your claim of the determination of lymph node status through the use of the ACIS™ device is also beyond your cleared intended use.
At www.chromavision.com/pc/apps/mm/mmmrd.htm, Chromavision again ascribes clinical claims to the ACIS™ device Under the subheading, "Clinical Use" the ACIS™ device is described as being able to provide "Testing for occult micrometastases [that] can bring greater accuracy to disease staging and can provide a more realistic assessment of prognosis."
In a brochure found at www.chromavision.com/pc/acis_brochure/acis_bro.htm, ChromaVision makes the following claim, "ChromaVision delivers a unique and definitive picture of health by providing a direct and visual assessment of disease at the cellular level…"
Clinical claims such as these are inappropriate. The ACIS™ device was cleared as a tool to assist the pathologist. The pathologist makes clinical assessments. To make clinical claims regarding this device is inappropriate.
In addition to making inappropriate clinical claims, ChromaVision also lists on its website a panel of tests as though they were all currently available. On a page titled, "ACIS™ Breast Cancer Panel," found at www.chromavision.com/pc/apps/bcp/bcp.htm, you state that ChromaVision has "[I]n current or impending release … several ACIS-based sofhvare applications that provide for comprehensive, quantitative analysis of paraffin-embedded, immunohistochem cally-stained breast and lymph node tissues. ACIS also performs rare event detection and enumeration in bone marrow and peripheral blood cytospin preparation." You then list the following tests: Estrogen Receptor, Progesterone Receptor, HER2/neu, Ki-67, p53, Angiogenesis, DNA Ploidy, Micrometastases/Minimal Residual Disease, and Sentinel Lymph Node. This list is misleading because some of the tests are not yet cleared or approved for use. ChromaVision does not make it clear which tests are currently available.
Making clinical claims regarding the use of the ACIS™ device such as those claims that imply that the ACIS™ device can be used to detect the prognosis and staging of a disease have misbranded and adulterated the device within the meanings of sections 502(o) and 501(f)(1)(B) of the Act. The ACIS™ device is misbranded because a notice or other information respecting the device was not provided to the FDA as required by section 510(k) and it has not been found to be substantially equivalent to a predicate device for the uses claimed. The device is adulterated for the HER2/neu claim because it is a class III device under section 513(o) and does not have approved applications for premarket approval in effect pursuant to section 515(a) or approved applications for investigational device exemptions under section 520(g).
FDA's regulations at 21 CFR 801.4 provide that the term "intended uses" of a device refers to the objective intent of the persons legally responsible for the labeling ofa device. That intent may be shown by labeling claims or advertising matter or oral or written statements by such persons or their representatives. Making claims that your device can be used as a tool to provide a clinical assessment of a patient's disease state changes the intended use for which the ACIS™ device was cleared. Pursuant to section 510(k) of the Act and as provided in 21 CFR 807.81(a)(3)(ii), claims that constitute a major change in the cleared intended use of a device require the submission of premarket notification to FDA.
A copy of this letter is being sent to FDA's Los Angeles District Office. Please send a copy of your response to the District Director, Los Angeles District Office (HFRPA-240), 19900 MacArthur Blvd #300, Irvine, CA 92715.
Byron L. Tart for
Larry D. Spears
Acting Director, Office of Compliance
This page was posted on August 20, 2006.