(a) Identification. A fludeoxyglucose F18-guided radiation therapy system is a device that combines the functionality of an emission computed tomography detection system and a linear accelerator. The device is intended for use with approved fludeoxyglucose F18. The emission computed tomography detection system acquires images of positron-emitting fludeoxyglucose F18 for the purpose of guiding the delivery of megavoltage X-rays for oncologic treatment with radiation therapy using an FDA-cleared, -authorized, or -approved linear accelerator.

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

(1) An analysis must be provided of any effects on safety or effectiveness based on differences that exist in the use (i.e., concentration, rate of administration, route of administration; region, organ, or system of the body; or patient population) of fludeoxyglucose F18 with the device compared to the current approved drug labeling; and adequate justification, including support from clinical performance testing and labeling, must be provided that the differences do not adversely affect the safety and effectiveness of fludeoxyglucose F18 when used with the device.

(2) Design verification and validation activities must include monitoring of changes to the labeling and formulation of fludeoxyglucose F18, and addressing such changes so that they do not adversely affect the safety and effectiveness of the device and fludeoxyglucose F18 when used with the device.

(3) Clinical performance testing must demonstrate that the system performs as intended under anticipated conditions of use, including demonstrating: adequate reader performance for distinguishing patients with eligible versus ineligible radiopharmaceutical biodistribution on imaging; reproducibility across fractions; and sufficient signal strength to meet system sensitivity requirements. Clinical performance testing under anticipated conditions of use must evaluate: dose ranging for identification of lowest safe and adequate dose; and all adverse events.

(4) Non-clinical performance testing under anticipated conditions of use must demonstrate:

(i) Compatibility of the linear accelerator and the tomography scanner;

(ii) Adequate positron emission tomography (PET) imaging performance for patient selection in comparison with a legally marketed diagnostic scanner's output;

(iii) Adequacy of the chosen imaging metrics for inter- and intra-fractional treatment delivery; and

(iv) Dosimetric concurrence between delivered dose distributions and treatment plan, including comparison of delivery isolating difference between guidance on and off conditions.

(5) Performance testing must demonstrate the electrical safety and electromagnetic compatibility of any electrical components.

(6) Software verification, validation, and hazard analysis must be performed for any software components of the device. Software documentation must include a detailed description of the dose delivery tracking algorithms, including the dose calculation methods, treatment boundaries, treatment delivery fluence calculation methods, system latency for moving targets, interface for post-treatment review, limitations of the algorithm, and accompanying verification and validation testing to ensure device and algorithm functionality as informed by the software requirements and hazard analysis.

(7) A training program must be included to ensure users can correctly interpret images to determine patient eligibility.

(8) The labeling must include the following:

(i) A detailed description of the patient population included in clinical testing specifying age, primary cancer type, cancer stage, and target volume locations and sizes;

(ii) A dedicated imaging agent section which includes a description of the use of fludeoxyglucose F18 with the device and a statement in the indications for use informing users where full prescribing information is available for fludeoxyglucose F18 in the current approved drug labeling and in the device labeling;

(iii) Detailed instructions for use of fludeoxyglucose F18 with the device to guide radiation therapy, including: uptake time needed, time window to deliver treatment, physician review of pre-delivery safety checks, image interpretation, tissue targeted for fludeoxyglucose F18 uptake, pre-treatment image criteria to determine patient eligibility, and other differences compared to the current approved fludeoxyglucose F18 drug labeling;

(iv) A detailed summary of the performance testing required under paragraphs (b)(3) and (b)(4) of this section, including test methods, dataset characteristics, and results;

(v) A detailed description of the user workflow; and

(vi) An instruction for users to plan for an alternative treatment if pre-treatment evaluation fails.

[91 FR 50710, Aug. 6, 2026]