WARNING LETTER
RadLogics, Inc. MARCS-CMS 515599 —
- Recipient:
- RadLogics, Inc.
United States
- Issuing Office:
- Center for Devices and Radiological Health
United States
| |
10903 New Hampshire Avenue Silver Spring, MD 20993 |
WARNING LETTER
VIA UPS
April 5, 2018
Mr. Moshe Becker
Executive Chairman
RADLogics, Inc.
39 Wildwood Ave
Piedmont, CA 94610
Re: FDA Reference number COR16000016
Dear Mr. Becker:
The United States Food and Drug Administration (FDA) has learned that your firm, RADLogics, Inc. (“RADLogics”), is marketing AphaPoint Imaging Software (“AlphaPoint”), a radiological image analysis software application, in the United States without marketing clearance or approval, in violation of the Federal Food, Drug, and Cosmetic Act (the “Act”).
Under section 201(h) of the Act, 21 U.S.C. § 321(h), this product is a device because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.[1]
FDA has reviewed your firm’s website (www.radlogics.com) and your firm’s YouTube video published on November 21, 2017, titled “RADLogics with and without Demo 11 21 17” (https://www.youtube.com/watch?v=gF8BJSsMdeM). Based on this review, FDA has determined that AlphaPoint is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed.
AlphaPoint is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm introduced or delivered for introduction into interstate commerce for commercial distribution this device with major changes or modifications to the intended use without submitting a new premarket notification to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3)(ii).
Specifically, AlphaPoint was cleared under K120161 with the following indications:
The AlphaPoint software is a device that allows review, analysis, and interchange of CT chest images. It is intended for use with CT Chest images to assist medical professionals in image analysis. It is not intended to be the primary interpretation. The software provides segmentation, Hounsfield numerical analysis values which are indicative of various substances (i.e., air, lung, soft tissue, fat, water, transudate, exudate, blood, muscle and bone). The user can review, verify and correct the results of the system and generate a report of the findings.
This clearance describes AlphaPoint as an electronic platform, with basic image-processing functionality, that displays radiology images for physicians to review and analyze. However, your firm’s current promotion of the device goes significantly beyond the terms of the clearance and provides evidence that AlphaPoint is being marketed as providing computer-assisted detection (CADe) of abnormalities in radiology images.
Language on your firm’s website indicates that the AlphaPoint software provides CADe functionality, utilizing machine learning algorithms to automatically detect and mark abnormalities on medical images, including lung nodules, pneumothorax, and pleural effusion. Your firm’s website states that the AlphaPoint software is capable of functioning as a “Virtual Resident” because it automatically performs an initial review of radiologic images and generates a report listing and characterizing the abnormalities detected in the images, relieving the physician of the task of reviewing the images to identify abnormalities. Examples of such language include:
- “Detailed, accurate findings for each case are available in a matter of minutes. By the time you sit down to review a case, the preliminary findings are up on the screen. Instead of spending the majority of your time on detection and characterization, you can focus on the critical task of diagnostics and completing your report.”
- “The RADLogics Virtual Resident is like having a top resident preparing detailed detection and characterization findings for your review.”
- “The RADLogics Virtual Resident is not subject to human variability, minimizing the chances of errors and inconsistencies. For example, if a clinician fails to note that contrast media was used in a scan, this will not affect the accuracy of the findings. The RADLogics Virtual Resident analyzes the images and identifies, independently, whether or not a contrast media was used. The software also scans for all of the disease states that are in each scan module. In the case of Chest CT, for example, even if a referring physician has asked the radiologist to look for a rib fracture, the software will identify lung nodules, if present.”
In addition, on November 21, 2017, your firm published a video on YouTube demonstrating AlphaPoint’s CADe functionality. The 3 minute 7 second video entitled “RADLogics with and without Demo 11 21 17” shows the difference between “reading a chest CT” and “Using the RADLogics Machine-Learning Virtual Resident.” The video highlights nodules automatically marked and measured by the AlphaPoint software at 1:49, 1:53, and 1:57, and suggests the superiority of AlphaPoint’s automatic detection capability over that of a human radiologist by calling out an “Additional Nodule!” at 2:28. The video concludes with a summary indicating that AlphaPoint’s automatic detection capability could allow a radiologist to read medical images 3 minutes faster than software without such capability, stating that “Reading without RADLogics” takes 12 minutes 30 seconds, while “Reading with RADLogics” takes 9 minutes 30 seconds.”
The statements cited above provide evidence that you have made a major change or modification to the intended use of your device (see 21 CFR 807.81(a)(3)(ii)) that requires a new premarket submission. We also note that your firm’s device may not be found substantially equivalent to a legally marketed device (predicate) currently classified under 21 CFR 884.2980(a) if your firm’s device has different technological characteristics from the predicate device that raise different questions of safety and effectiveness from the predicate device (e.g., a significant change in the materials, design, energy source, or other features of the device (see 21 U.S.C. 360c(f)(1), 21 U.S.C. 360c(i)(1), and the implementing regulations found at 21 CFR 807.100).
None of your firm’s claims relating to AlphaPoint’s CADe capability is supported by the original report cleared for K120161. Your firm has provided no evidence to FDA supporting the safety and efficacy of AlphaPoint’s CADe capabilities, and FDA is currently unaware of any literature that could support RADLogics’ claims regarding AlphaPoint’s CADe functionality. The lack of evidence demonstrating the safety and efficacy of AlphaPoint’s automatic detection and characterization capabilities raises public health concerns. Specifically, the risks for the device as advertised are low sensitivity and specificity (i.e., the device has unknown false positive and false negative rates). For example, if there is a false negative, a risk to the patient is that lung nodules may go undetected or untreated, which may increase the risk of late diagnosis of lung cancer. For a false positive, there is a risk that the patient may be referred for unnecessary biopsy and/or other surgical procedures. Both biopsy and lung surgery have a risk of significant complications. Similar risks to patients exist for other conditions that your website claims the AlphaPoint software can detect/characterize (e.g., cardiomegaly, pneumothorax, pleural effusion, enlarged mediastinum, pleural air, and pleural fluid). Your firm’s promotional materials increase these public health concerns further because they market AlphaPoint as a physician replacement that can make an initial review of radiology images and provide automatic detection and characterization of abnormalities, which leaves the physician to only review the software’s findings and provide a diagnosis. These new risks are serious, and are not effectively mitigated because the AlphaPoint software was not cleared for computer-assisted detection intended use.
During a teleconference held on April 14, 2016, and in follow up communications with the FDA, your firm indicated an understanding that the AlphaPoint software was not cleared for the intended uses being marketed on your website and YouTube video referred to above. Additionally, during that teleconference, your firm concurred that a new 510(k) was necessary, (b)(4).
Following the April 14, 2016 teleconference, your firm took down its website, software demonstration, and marketing videos discussing the CADe capabilities of the AlphaPoint software. However, you have since reactivated your website (including the language and content described above) updated your YouTube marketing video, and issued a press release dated November 21, 2017 (http://www.prweb.com/releases/2017/11/prweb14937168.htm) that includes language addressing the automatic diagnostic capabilities of AlphaPoint; for example:
“‘The solution provides the computational equivalent of a medical resident that traditionally prepares preliminary findings for radiologists in academic medical centers,’ says Moshe Becker, CEO and co-founder, RADLogics.”
These materials and activities are evidence that your firm continues to market the modified AlphaPoint for a new intended use (i.e., CADe capability) without the required FDA premarket clearance or approval in violation of the Act.
Our office requests that RADLogics immediately cease activities that result in the misbranding or adulteration of the AlphaPoint software, such as the commercial distribution of the device for the uses discussed above.
Your firm should take prompt action to correct the violations addressed in this letter. For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(k), is deemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)]. The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties. Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. If your firm does not believe that the AlphaPoint software is in violation of the Act (as described herein), please include your reasoning and any supporting information for our consideration. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.
Your firm’s response should be sent to:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
Attn: Division of Radiological Health
Document Control Center -- WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
Refer to the reference number COR16000016 when replying. We remind you that only written communication is considered as official. If you have any questions about the contents of this letter, please contact: Alex Cadotte, PhD at 301-796-6661.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm. It is your firm’s responsibility to ensure compliance with the applicable laws and regulations administered by FDA.
Sincerely yours,
/S/
Donald J. St. Pierre, Ph.D.
Acting Director
Office of In Vitro Diagnostics and Radiological Health
Center for Devices and Radiological Health
[1] Software such as AlphaPoint, that is intended for interpretation or analysis of medical image data for the purpose of the diagnosis, cure, mitigation, prevention, or treatment of a disease or condition, was not affected by the amendments to Section 201(h) of the Act made by Section 3060(a) of the 21st Century Cures Act on December 13, 2016, which excluded certain software functions from the definition of device. See 21 U.S.C. § 360j(o)(1)(E). Software functions that process or analyze medical images remain devices and continue to be subject to FDA oversight.