Nikkiso Medical America, Inc

The United States Food and Drug Administration (FDA) has learned that your firm is marketing the Nikkiso DBB-06 (DBB-06) in the United States without the necessary 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.

FDA reviewed on February 5, 2021 Nikkiso’s marketing materials for DBB-06. This review revealed that DBB-06 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. The DBB-06 is also misbranded under section 502(o) of 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 a significant change or modification, specifically the introduction of a physiological closed loop controller (PCLC) system (also referred to as PCLC function or functionality in this letter) which is a change or modification in the device that could significantly affect the safety or effectiveness of the device, 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).

Specifically, your firm’s marketing materials for DBB-06 provide evidence that the device is intended for dialysis with a PCLC system, which would constitute a significant change or modification to the device, for which your firm lacks clearance or approval. Examples include: • In the online version of your firm’s product brochure found at http://nikkisoamerica.com/wp-content/uploads/2011/08/NIKKISO-DBB06-RV09262016-V3.pdf, your firmclaims that the DBB-06 Haemo-Master Blood Volume Monitor (BVM) uses “adaptive feedback” to regulate the “blood volume trend.”

• The website also includes the following statement: “The unique adaptive feedback feature of the BVM allows for automatic changes of fluid removal to achieve desired outcomes.”

Although the DBB-06 device was cleared via the 510(k) pathway under K091978 and K152938, neither K091978 nor K152938 adequately described the PCLC function. For example, there is no mention of PCLC functionality in the 510(k) summary or in the Indications for Use statement for either 510(k). Notably, on page 6 of the 510(k) summary for K091978, the Blood Volume Monitor’s intended use is described as follows: “The healthcare provider may increase or decrease the rate at which fluid is removed from the blood based on the data that blood volume monitor provides.” This description contrasts with your firm’s current marketing materials, which describe PCLC functionality, i.e., the use of “adaptive feedback” to change dialysis therapy parameters (e.g., ultrafiltration rate) automatically with no clinician involvement. As discussed above, the introduction of a PCLC system is considered a change or modification in the device that could significantly affect the safety or effectiveness of the device, and therefore, requires clearance or approval. For example, the introduction of a PCLC system creates new risks, including reduced monitoring and adjustment of dialysis therapy by the clinician due to increased reliance on automation technology to monitor and adjust dialysis therapy.

This is not the first time that FDA has communicated with your firm that the PCLC function was not cleared under either K091978 or K152938 for the device. (b)(4). Please provide a justification for inclusion of this feature with supportive performance data for its safe and effective use. If your intent is to reference the DBB-06 device (K091978 and K152938), we do not believe this function was cleared.” On August 16, 2019, FDA issued your firm an “It has come to our attention” letter advising your firm that FDA believed the “Haemo-Master Blood Volume Monitor as an adaptive feedback controller of the ultrafiltration rate for a patient” was not cleared under the 510(k) pathway. In additional correspondence in 2019, Nikkiso continued to take the position that the PCLC function had been addressed by validation testing included in an Appendix to K091978 and that the PCLC function had been cleared. Nonetheless, (b)(4).

Regardless of whether the (b)(4), along with all the previous communication, illustrates that the firm understands FDA’s position on the regulatory status of the DBB-06 device with the PCLC function. Based on the information reviewed by FDA, Nikkiso’s marketing of the DBB-06 device with the PCLC function, which has not been cleared or approved, has resulted, as noted above, in the misbranding and adulteration of the device.

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 on the Internet 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.

Our office requests that Nikkiso America, Inc. immediately cease activities that result in the misbranding or adulteration of the Nikkiso DBB-06, such as the commercial distribution of the device with the PCLC function as discussed above.

Your firm should take prompt action to correct the violations addressed in this letter. 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. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.

Your firm’s response should be sent to:

Food and Drug Administration Center for Devices and Radiological Health Office of Regulatory Programs Division of Regulatory Programs 2: Establishment Support Regulatory Inspections and Audits Team White Oak Building 66 10903 New Hampshire Ave. Silver Spring, MD 20993

Refer to the identification number CPT1900751 and CMS# 613109 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 Carolyn Y. Neuland, Ph.D. at 301-796-6523.

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.