(a) Identification. A hematopoietic cell enrichment kit is an in vitro diagnostic device intended for the selection and enrichment of specific hematopoietic cells from human whole blood and/or bone marrow collected from patients with hematological malignancies using immunomagnetic bead-based selection. It is intended for use with diagnostic assays as part of the pre-analytical workflow.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (stand-alone or as part of a test system) for the collection of the sample types with which this device is intended to be used; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.

(2) The intended use statement must include:

(i) The intended use specimen type (i.e., human whole blood and/or bone marrow) for each malignancy for which acceptable enrichment has been demonstrated and documented using the minimum volume required to ensure a 95 percent accurate call rate when the cell concentration is at the limit of detection, per the device labeling.

(ii) A detailed description of the cell enrichment target(s).

(iii) A statement that the end-user is responsible for validation of this device for use with the assay.

(3) The labeling required under § 809.10(b) of this chapter must include:

(i) Detailed specifications and procedures, appropriately supported by replicate and stability data, for sample collection, processing, and storage, including acceptable ranges of deviation.

(ii) A detailed device description, including all device parts (e.g., instruments and associated user manuals, antibody(ies), reagents, and consumables) and their use within the enrichment procedure.

(iii) Prominent and conspicuous limiting statements clearly explaining:

(A) Any end-user validation required for use with specific tests and collection devices.

(B) Bone marrow stability is severely compromised after 48 hours (or, alternatively, a different timeframe supported by appropriate specimen stability data required under paragraph (4)(i)(E) of this section).

(C) The device is intended only for enriching hematopoietic cell specimens for use in further processing or analysis using additional independent methods.

(D) Results from the device do not provide information regarding any health conditions.

(E) The device is not intended for cell enumeration.

(F) A detailed summary of the studies required under paragraph (b)(4) of this section.

(4) Design verification and validation must include:

(i) Detailed documentation of the following studies for each intended specimen type and malignancy combination, including the study protocols containing descriptions of the test methods, prescribed methods of data analysis and acceptance criteria, final study reports, and data line listings:

(A) Recovery study data demonstrating the range of the device.

(B) A study demonstrating the device limit of detection by demonstrating the minimum number of cells within a prespecified volume that the device is capable of enriching and the percent enrichment when the concentration of cells is established, using a flow cytometry reference method determined to be acceptable by FDA.

(C) A study demonstrating device reproducibility, including multiple operators at each site using the specified enrichment method(s) and protocol. The evaluation must include multiple runs, different instruments, and three different reagent lots. The study must include specimens with low, medium, and high starting enrichment target levels and result in enrichment and acceptable precision at each level. The study must include specimens containing different genetic alterations representative of the cancer indication or condition.

(D) A study demonstrating device specificity, including interference, to evaluate the impact on cell enrichment.

(E) Studies performed to support the stability of samples using the indicated specimen collection method(s) under various storage times, as applicable.

(ii) Detailed documentation of studies performed to demonstrate on-board and in-use reagent stability, including studies to demonstrate reagent shelf life.

(iii) A shipping-stability study, separate from the on-board and in-use reagent stability study, that demonstrates acceptable stability of the parts that comprise the device.