§ 866.6110 Circulating tumor cell enrichment device.
(a) Identification. A circulating tumor cell enrichment device is an in vitro diagnostic device used to enrich circulating tumor cells from the peripheral blood of patients diagnosed with cancer for subsequent in vitro diagnostic testing.
(b) Classification. Class II (special controls). The special controls for this device are:
(1) Any device used for specimen collection and transport must be FDA-cleared, -approved, or -classified as 510(k) exempt for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) Detailed specifications and procedures for sample collection, processing, and storage.
(ii) An intended use statement that includes:
(A) The intended specimen type(s) for which acceptable, as determined by FDA, validation data has been provided (e.g., peripheral whole blood).
(B) The identification of, or the specifications for, the collection device or devices to be used for sample collection.
(C) Information on the device output(s) (e.g., circulating tumor cells (CTCs), other blood cells).
(D) The specific tumor type(s) for which the device is intended to be used.
(E) A statement for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices.
(F) A statement that the standalone device is not intended for diagnostic, prognostic, or monitoring use with CTCs, including as an aid in any disease management and/or treatment decisions.
(iii) Prominent and conspicuous limiting statements clearly explaining:
(A) The use of the device is intended for the collection of CTCs from previously diagnosed cancer patients.
(B) The standalone device is not intended for cell enumeration.
(C) The users for whom the device is intended, including any training specifications.
(D) The performance characteristics of this device have not been established for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices.
(E) An insufficient number of CTCs or even no circulating tumor cells may be collected.
(F) Results from the standalone device do not provide information to the patient regarding their current state of health.
(G) The standalone device does not diagnose any health conditions and is not a substitute for visits to a doctor or other healthcare professional.
(H) The device is intended only for enriching CTC content in specimens so that the enriched specimens can then be used in further processing/analysis using additional independent methods.
(I) The variability of the number of CTCs and other cells harvested by the device may impact the success of any subsequent analysis.
(iv) A troubleshooting section that includes clear instructions for resolving any common device-related issues.
(v) A description of the device mechanism of action to enrich CTCs.
(vi) A detailed summary of the analytical and clinical performance studies required under paragraph (b)(3) of this section.
(3) Design verification and validation must include the following:
(i) Documentation of studies that provide:
(A) Data demonstrating acceptable, as determined by FDA, analytical device performance using samples representative of the range of those with which the device is intended for use. The number of specimens tested must be sufficient to obtain estimates of device performance that is representative of the device performance within the full spectrum of the device's intended use.
(B) Data demonstrating acceptable precision, as determined by FDA, to adequately evaluate intra-run, inter-run, and total variability across operator, instrument, lot, day, and site, as applicable.
(C) Data demonstrating the detection limit of the device.
(D) Recovery study data demonstrating the range of the device.
(E) Data demonstrating appropriate validation of device design features and specifications such that the device reproducibly and reliably collects and isolates CTCs. At a minimum, the data must include:
(1) Data, as appropriate for the intended use, including estimates of within-lot, within-device, and lot-to-lot variability, demonstrating that samples collected from the intended use population using the device provide CTCs that are suitable, as determined by FDA, for the intended downstream testing.
(2) Data demonstrating that the device output has no contamination or minimal levels of contamination from other sources, and that any such contamination does not interfere with the recovery of CTCs.
(3) Data demonstrating that the presence of clinically relevant levels of potential interfering substances in the intended specimen type(s) and intended use population, including endogenous and exogenous substances, does not interfere with the recovery of CTCs.
(4) Data demonstrating that blood samples collected for use with the device remain stable under certain storage conditions (e.g., temperature, time) and do not impact the output of representative downstream testing.
(ii) Documentation of clinical studies using the device on intended use clinical specimens that demonstrate the device can enrich or capture an appropriate number of CTCs, as determined by FDA, to support the intended use of the device.
[91 FR 24345, May 6, 2026]