§ 866.3046 Simple in vitro diagnostic device for the detection of secreted proteins from
Bacillus species (spp.) in human clinical samples.
(a) Identification. A simple in vitro diagnostic device for the detection of secreted proteins from Bacillus species (spp.) is a prescription in vitro diagnostic device used to detect and presumptively identify B. anthracis and other Bacillus spp. in human clinical samples as an aid in the diagnosis of anthrax and other diseases caused by Bacillus spp. This device is simple to use and does not involve sample manipulation or measurement of an analyte that could be affected by conditions such as sample turbidity or cell lysis. This device may be used to aid in the presumptive diagnosis of anthrax in individuals who have signs and symptoms consistent with anthrax and a likelihood of exposure. Bacillus infections include anthrax (cutaneous, inhalational, or gastrointestinal) caused by B. anthracis, gastrointestinal disease, non-gastrointestinal infections, and an anthrax-like illness caused by B. cereus.
(b) Classification. Class II (special controls). The special controls for this device are:
(1) The distribution of these devices is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone 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.
(3) The labeling required under 21 CFR 809.10(b) of this chapter must include:
(i) An intended use statement that includes the following:
(A) A detailed description of targets the device detects and measures;
(B) The results provided to the user (i.e., whether the measurement is qualitative, semi-quantitative, or quantitative);
(C) The clinical indications appropriate for test use (e.g., in conjunction with patient history, epidemiological information, clinical observations, and other laboratory evidence to make patient management decisions);
(D) Sample types with which it is intended for use;
(E) The specific population(s) with which the device is intended to be used;
(F) The testing location(s) where the device is to be used (if not intended for all locations);
(G) A statement that the device results are for the presumptive identification of Bacillus spp., and definitive identification requires additional testing and confirmation procedures in consultation with the appropriate public health authorities;
(H) A statement that negative results do not preclude infection with Bacillus spp. and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions; and
(I) A statement that testing is to be performed and reported in accordance with current guidelines provided by the appropriate public health authorities.
(ii) Detailed instructions for minimizing the risk of user exposure to Bacillus spp. that may be present in test samples and those used as control materials.
(iii) Detailed instructions for minimizing the risk of generating false positive test results due to contamination from positive test samples and/or positive control materials.
(iv) A prominent and conspicuous precaution that interpretation of test results is intended to be performed by experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and the expertise to report results.
(v) A prominent and conspicuous warning statement that the test results alone do not conclusively establish infection and that additional testing and confirmation procedures may be necessary in consultation with the appropriate public health or other authorities to whom reporting is required.
(vi) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of samples.
(vii) Detailed descriptions of the performance characteristics of the device for all claimed sample types as shown by the analytical and clinical studies required under paragraphs (b)(4)(ii) and (b)(4)(iii) of this section, except sample stability performance characteristics.
(viii) For any devices intended for use in a near-patient setting, a brief reference sheet for healthcare professionals that accompanies the device and that includes the name and intended use of the test, step-by-step instructions of all control and sample testing procedures for the claimed sample types, the result(s) interpretation, warning and limitation statements, and information for troubleshooting or technical assistance with the device.
(ix) A statement that a nationally notifiable disease caused by a biothreat microbial agent must be reported to public health authorities in accordance with local, state, and federal law.
(x) Limiting statements indicating, as applicable:
(A) Situations where the device has been demonstrated to fail or may not perform at its expected performance level (e.g., any disease specific circumstances or circumstances identified by human factors or robustness studies);
(B) Any specific circumstances that pose significant risk to public health, and for which the device has not been validated. For example:
(1) Testing of matrices and patient populations that are not identified in the intended use; or
(2) Testing individuals without signs and symptoms of infection, including mass infection screening (such as airport or border screening) that is not limited to individuals who have signs and symptoms and a risk of exposure to biothreat microbial agents.
(4) Design verification and validation must include:
(i) A detailed device description, including all device parts, control elements incorporated into the test procedure, reagents required but not provided, the principle of device operation and test methodology, and the computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported result).
(ii) Detailed documentation of analytical studies, as applicable, including those demonstrating limit of detection, inclusivity, cross-reactivity, microbial interference, interfering substances, carryover/cross contamination, sample stability, within lab precision, hook effect, reproducibility, and other studies relevant to the technology (e.g., linearity), as determined to be appropriate by FDA.
(iii) Detailed documentation and results from either a clinical study or, when determined to be acceptable by FDA, a study with an equivalent data set. Documentation from this study must include study reports, testing results, and results of all statistical analyses, including line data of all test samples, and an appropriate justification describing how the sample set is representative of the intended use population. This study must compare the device performance to results obtained from a reference or comparator method that FDA has determined to be appropriate. This study must include prospective (sequentially collected) samples for each intended sample type that are representative of the intended use populations and may, when determined to be acceptable by FDA, include additional characterized clinical samples; or, as an alternative, when determined to be acceptable by FDA, an equivalent sample set. This study must include samples spanning all relevant analyte concentrations for all of the indicated sample type(s) and the targeted analyte(s).
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions, as applicable.
(v) For any devices that detect the presence of an analyte directly from sample, detailed documentation and results from a shelf-life assessment that includes samples formulated in the most complex clinical matrix identified in the device's intended use.
(vi) As part of the risk management activities, if the labeling includes hyperlinks to documents from public health authorities regarding sampling, sample shipment, sample testing, or clinical management of patients suspected of being infected; or if the labeling includes direct contact information for any such public health authority, then the hyperlinks and contact information must be reviewed at least annually and updated to reflect any changes to those hyperlinks or contact information.
[91 FR 36978, June 22, 2026]