(a) Identification. A blood collection device for cell-free nucleic acids is a device intended for medical purposes to collect, store, transport, and handle blood specimens and to stabilize and isolate cell-free nucleic acid components prior to further testing.

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

(1) Design verification and validation documentation must include appropriate design inputs and design outputs that are essential for the proper functioning of the device for its intended use, including all of its indications for use, and must include the following:

(i) Documentation demonstrating that appropriate, as determined by FDA, measures are in place (e.g., validated device design features and specifications) to ensure that users of blood collection device for cell-free nucleic acids devices are not exposed to undue risk of bloodborne pathogen exposure and operator injury during use of the device, including blood collection, transportation, and centrifugation processes.

(ii) Documentation demonstrating that appropriate, as determined by FDA, measures are in place (e.g., validated device design features and specifications) to ensure that the device reproducibly and reliably collects, transports, stabilizes, and isolates cell-free nucleic acids of sufficient yield and quality suitable for downstream applications as appropriate for its intended use. At a minimum, these measures must include:

(A) Data demonstrating that blood samples collected in the device have reproducible cell-free nucleic acid yields that are suitable, as determined by FDA, for downstream testing as appropriate for the intended use, including estimates of within-lot, within-device, and lot-to-lot variability;

(B) Data demonstrating that cell-free nucleic acid yields isolated from blood specimens collected into the device do not add clinically significant bias to test results obtained using the downstream application(s) described in the intended use. For devices indicated for use with multiple downstream applications, data demonstrating acceptable performance for each type of claimed use or, alternatively, an appropriate, as determined by FDA, clinical justification for why such data are not needed;

(C) Data demonstrating that the device appropriately stabilizes cell-free nucleic acids after sample collection, during storage, and during transport over the claimed shelf life of the device;

(D) Data demonstrating that samples collected in the device have minimal levels of contamination with other types of nucleic acids present in cells or cellular components, and that these levels of contamination do not interfere with downstream testing;

(E) Data from analytical or clinical studies that demonstrate that, when used as intended, the device consistently draws a blood sample volume that is within the indicated fill range;

(F) Data from analytical or clinical studies that demonstrate that, when used as intended, cell-free nucleic acid yield, stability, and quality are not significantly impacted by interference due to other parts of the device (such as reduced or excess active ingredient) or specimen collection and processing procedures (such as hemolysis, centrifugation, or mixing of blood with anticoagulant or additives); and

(G) Data from analytical studies that demonstrate that the device is suitable for its intended use across all storage and sample handling conditions described in the device labeling, including device shelf life and shipping conditions (e.g., temperature, humidity, duration).

(iii) A protocol, reviewed and determined acceptable by FDA, that specifies the verification and validation activities that will be performed for anticipated device modifications to reevaluate performance claims or performance specifications. This protocol must include a process for assessing whether a modification to technology, engineering, performance, materials, specifications, or indications for use, or any combination thereof, could significantly affect the safety or effectiveness of the device. The protocol must include assessment metrics, acceptance criteria, and analytical methods for the performance testing of changes.

[89 FR 72983, Sept. 9, 2024]