The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis. The kit can be used to test human whole blood collected in sodium citrate or sputum collected aseptically from individuals greater than 18 years of age suspected of having septic or pneumonic plague. In addition, positive blood cultures and colonies may be tested. The JBAIDS Plague Target 2 assay is used as a supplementary test only after a positive result with the Target 1 Assay.
The JBAIDS Plague Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y. pestis in conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.

The diagnosis of plague must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of Y. pestis from cultures or directly from whole blood or sputum specimens.

The JBAIDS Plague Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit. The level of Y. pestis that would be present in blood or sputum from individuals with early systemic infection is unknown. Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague.

Device Description

The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) reagent kit, which, when used with the JBAIDS instrument and software, allows the qualitative in vitro diagnostic (IVD) detection of target DNA sequences within the pathogenic bacterium, Yersinia pestis, the causative agent of plague. The kit contains two assays, Plague Target 1 and Target 2, each of which consists of oligonucleotide primers and a fluorescent-labeled target assay probe that specifically detect Y. pestis DNA. The Target 2 assay is reserved for samples that test positive with the Target 1 assay. The kit is designed for use with the JBAIDS instrument, a portable thermocycler and real-time fluorimeter that performs PCR in glass capillaries.

Before testing, samples are purified using Idaho Technology's 1-2-3TM Sample Purification Kits (or validated equivalent). The resulting purified sample is added to an Unknown reagent vial and an Inhibition Control reagent vial, along with reconstitution buffer. When the organism is present, a fragment of Y. pestis DNA is amplified. The amplicon is detected by fluorescence using a specific hydrolysis probe. The hydrolysis probe contains a short oligonucleotide that hybridizes to an internal sequence of the amplified fragment during the annealing phase of the PCR cycle. This probe has the 5' and 3' ends labeled with a reporter dye and a quenching dye, respectively. When the probe hybridizes to the specific DNA target, the Taq polymerase enzyme replicating the target-specific DNA hydrolyzes the probe, separating the two fluorophores and allowing the reporter dye to fluoresce.

The JBAIDS instrument measures the level of fluorescence from each unknown sample and control. JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, inhibited, or uncertain. A failure of the Positive or Negative Control will result in the entire run being called invalid. Failure of the Inhibition Control yields an inhibited result when the associated sample has a negative result for the target assay and requires retesting of that sample.

AI/ML Overview

Due to the nature of the provided document (a 510(k) summary for a diagnostic test kit), the study performed is a diagnostic accuracy study rather than a study evaluating the performance of an AI/ML device. Therefore, many of the requested fields (MRMC study, effect size of human readers improving with AI, number of experts for ground truth establishment, etc.) are not applicable and will be marked as "N/A".

Here's an analysis of the provided text based on your request:

JBAIDS Plague Detection Kit Performance Study Analysis

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for the clinical trial in terms of specific performance metrics that needed to be met for FDA clearance. However, it details the design of the clinical specificity study and the resulting performance. For analytical studies, it provides "LOD" (Limit of Detection) and inclusivity/exclusivity data which serve as performance measures.

Metric	Acceptance Criteria (Not explicitly stated as such, but inferred goals)	Reported Device Performance (JBAIDS Plague Detection Kit)
Analytical Sensitivity (LOD)	Lower limit of detection for Y. pestis	- Citrated Whole Blood: 50 CFU/mL
		- Sputum: 670 CFU/mL
Analytical Sensitivity (Inclusivity)	100% detection of virulent Y. pestis isolates	- 18/18 (100%) isolates of virulent Y. pestis gave expected test results.
		- 15 (83%) were presumptively positive (detected by both Target 1 & 2).
		- 2 had indeterminate results (missing Target 2 gene).
		- 1 had a false negative (missing Target 1 gene). (Note: The document implies this would be problematic but the overall 100% "expected result" might refer to the specific gene targets present)
Analytical Specificity (Exclusivity)	100% negative results for non-Y. pestis organisms	- Target 1 Assay: 24/24 (100%) of tested non-Y. pestis isolates gave negative results.
		- Target 2 Assay: Uncertain results were sometimes obtained for one of three Y. enterocolitica isolates. However, as Target 1 would have been negative, Target 2 would not be run, thus avoiding a false positive. Overall analytic specificity deemed "high and equivalent to the predicate."
Clinical Specificity (Whole Blood)	High specificity > predicate device	- At least 97% (95% CI, 97-100%) for whole blood samples.
	(as Y. pestis was not expected in this cohort)	- 132 whole blood samples tested: all yielded negative with Target 1.
		- Two (1.5%) whole blood samples gave false positive results with Target 2, but these would not have been processed according to the standard workflow (Target 2 is only run after a positive Target 1).
Clinical Specificity (Sputum)	High specificity > predicate device	- At least 92% (95% CI, 92-100%) for sputum samples.
	(as Y. pestis was not expected in this cohort)	- 36 (100%) sputum samples yielded negative results for both assays.

2. Sample Size Used for the Test Set and Data Provenance

Analytical Test Set:
- Inclusivity: 18 isolates of virulent Y. pestis (subtypes and strains)
- Exclusivity: A "panel" of 24 isolates (phylogenetically related and unrelated organisms)
- Data Provenance: Not explicitly stated, but typically research laboratory settings for analytical studies. Retrospective in nature.
Clinical Test Set:
- Whole Blood: 132 samples
- Sputum: 36 samples
- Data Provenance: The study was a "multisite clinical trial". The samples were obtained from "subjects with clinical signs and symptoms consistent with systemic plague and for whom a blood and/or sputum culture had been ordered." Since clinical plague is rare, and the document explicitly states "Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague," these samples were likely from individuals suspected of plague but ultimately found to be negative. Thus, these are clinical samples, but representative of a "negative" population in the context of plague in humans. Retrospective in nature.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

N/A. For this in vitro diagnostic (IVD) device, the ground truth for analytical studies is established by known bacterial stocks and for clinical studies, by established laboratory culture methods.
The ground truth for the clinical study was "laboratory culture results" which were considered the "gold standard." These methods are typically performed by trained microbiologists or clinical laboratory scientists, not "experts" in the sense of physicians adjudicating medical imaging or complex interpretations.

4. Adjudication Method for the Test Set

N/A. For analytical studies, the ground truth (presence/absence of specific bacteria, concentration) is determined by established microbiological methods and known samples, without adjudication.
For the clinical specificity study, the ground truth was "laboratory culture results." These are typically definitive for bacterial presence/absence. No adjudication among experts is mentioned or typically needed for this type of ground truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This is an in vitro diagnostic (IVD) device, not an AI/ML device requiring human-in-the-loop performance evaluation. The device provides an automated "positive, negative, inhibited, or uncertain" result.
Effect size of how much human readers improve with AI vs. without AI assistance: N/A.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in essence. The JBAIDS system operates as a standalone diagnostic test. The "JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, inhibited, or uncertain." This is the standalone performance of the analytical system.
While the kit is "intended for use by trained clinical laboratory personnel," their role is to operate the instrument and interpret the automated results within a clinical context, not to perform a subjective interpretation of a raw signal that the algorithm then enhances.

7. The Type of Ground Truth Used

Analytical Studies: Known strains/isolates of Y. pestis and other bacteria, with confirmed identification and concentrations (e.g., CFU/mL).
Clinical Studies: "Laboratory culture results," which are considered the "gold standard" for bacterial identification in clinical samples.

8. The Sample Size for the Training Set

Not explicitly stated in terms of a "training set." For IVDs, assay development and optimization (which can be considered analogous to training) involve numerous preliminary experiments with various dilutions, strains, and conditions, but these aren't typically documented as a formal "training set" with a defined size in the same way an AI/ML model would. The document describes the assay's design and then its validation/testing.

9. How the Ground Truth for the Training Set Was Established

N/A (as no formal "training set" is described). However, for the development of PCR assays (like this kit), the ground truth for optimizing primers and probes would be established by:
- Using purified genomic DNA of Yersinia pestis and other closely related and common organisms.
- Sequencing to confirm target regions.
- Utilizing known bacterial cultures and dilutions with confirmed concentrations.
- These foundational truths are based on established molecular biology and microbiology techniques.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus or a series of interconnected human profiles.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 20, 2019

CYNTHIA PHILLIPS, Ph.D. VICE PRESIDENT OF REGULATORY AND CLINICAL AFFAIRS BIOFIRE DEFENSE, LLC 79 W. 4500 SOUTH, SUITE 14 SALT LAKE CITY UT 84107

Re: K072631 Trade/Device Name: JBAIDS Plague Detection Kit Regulation Class: Unclassified Product Code: OIH Dated: December 17, 2007 Received: December 18, 2007

Dear Dr. Phillips:

This letter corrects our substantially equivalent letter of December 20, 2007.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing

{1}------------------------------------------------

Page 2-Dr. Phillips

(21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97).

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Uwe Scherf -S

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

{2}------------------------------------------------

Indications for Use

510(k) Number (if known): K072631 Device Name: JBAIDS Plague Detection Kit Indications for Use:

The JBAIDS Plaque Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y. pestis in conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.

The diagnosis of plaque must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of Y. pestis from cultures or directly from whole blood or sputum specimens.

The JBAIDS Plague Detection Kit is intended for use by trained clinical laboratory personnel who have received specific training on the use of the JBAIDS Plague Detection Kit. The level of Y, pestis that would be present in blood or sputum from individuals with early systemic infection is unknown. Due to the difficulty in obtaining clinical specimens, these assays were not evaluated with blood or sputum from individuals with septic or pneumonic plague.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Freddie Poole Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and S

510(k) K072631

{3}------------------------------------------------

K072631

510(k) Summary

510(k) Summary Idaho Technology Inc. JBAIDS Plague Detection Kit

Introduction: According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
Submitted by: Idaho Technology Inc.390 Wakara WaySalt Lake City, UT 84108	DEC 2 0 2007
Telephone: 801-736-6354Facsimile: 801-588-0507
Contact Person: Beth Lingenfelter, ext. 407
Date Prepared: September 14, 2007
Device Name: Trade Name: JBAIDS Plague Detection Kit
Common Name:
Real-time PCR assay for targeted Yersinia pestis DNA sequences
Classification Name:
Reagent Kit: Y. pestis DNA reagents (Unclassified)
DeviceDescription:	The Joint Biological Agent Identification and Diagnostic System (JBAIDS)Plague Detection Kit is a real-time polymerase chain reaction (PCR) reagent kit,which, when used with the JBAIDS instrument and software, allows thequalitative in vitro diagnostic (IVD) detection of target DNA sequences withinthe pathogenic bacterium, Yersinia pestis, the causative agent of plague. The kitcontains two assays, Plague Target 1 and Target 2, each of which consists ofoligonucleotide primers and a fluorescent-labeled target assay probe thatspecifically detect Y. pestis DNA. The Target 2 assay is reserved for samples thattest positive with the Target 1 assay. The kit is designed for use with the JBAIDSinstrument, a portable thermocycler and real-time fluorimeter that performs PCRin glass capillaries.
	Before testing, samples are purified using Idaho Technology's 1-2-3TM SamplePurification Kits (or validated equivalent). The resulting purified sample is addedto an Unknown reagent vial and an Inhibition Control reagent vial, along withreconstitution buffer. When the organism is present, a fragment of Y. pestis DNA

is amplified. The amplicon is detected by fluorescence using a specific hydrolysis

{4}------------------------------------------------

probe. The hydrolysis probe contains a short oligonucleotide that hybridizes to an internal sequence of the amplified fragment during the annealing phase of the PCR cycle. This probe has the 5' and 3' ends labeled with a reporter dye and a quenching dye, respectively. When the probe hybridizes to the specific DNA target, the Taq polymerase enzyme replicating the target-specific DNA hydrolyzes the probe, separating the two fluorophores and allowing the reporter dye to fluoresce.

Intended Use: The Joint Biological Agent Identification and Diagnostic System (JBADS) Plague Detection Kit is a real-time polymerase chain reaction (PCR) test kit intended for the qualitative in vitro diagnostic (IVD) detection of target DNA sequences of Yersinia pestis. The kit can be used to test human whole blood collected in sodium citrate or sputum collected aseptically from individuals greater than 18 years of age suspected of having septic or pneumonic plague. In addition, positive blood cultures and colonies may be tested. The JBAIDS Plague Target 2 assay is used as a supplementary test only after a positive result with the Target 1 Assay.
The JBAIDS Plague Target 1 and Target 2 assays are run on the JBAIDS instrument using the Diagnostic Wizard. Results are for the presumptive identification of Y. vestis in conjunction with culture and other laboratory tests. The definitive identification of Y. pestis from colony growth, liquid blood culture growth, or from blood or sputum specimens requires additional testing and confirmation procedures in consultation with public health or other authorities for whom reports are required.

{5}------------------------------------------------

The JBAIDS Plague Detection Kit is substantially equivalent to direct Substantial immunofluorescence assays (DFA) using fluorescein-labeled antibodies against Equivalence: the Fraction 1 (F1) capsular antigen of Y. pestis. This preamendment device was considered at the FDA's Microbiology Devices Advisory Panel meeting on March 7, 2002 and was determined to be a Class II device.

ELEMENT	JBAIDS Plague Detection Kit	DFA using a Fluorescein-labeledantibody to F1 capsular antigen(Preamendment)
Intended Use	Qualitative detection of Y. pestis.	Same
Indications for Use	Identification of Y. pestis in individualssuspected of having septic or pneumonicplague.	Identification of Y. pestis in individualssuspected of having septic, pneumonic orbubonic plaque.
TechnologicalPrinciples	Real-time PCR using hydrolysis probes.	Microscopic visualization of Y. pestisbacteria via specific binding of afluorescently labeled antibody.
Assay Target	DNA sequences unique to Y. pestis	F1 antigen
Specimen Types	Whole blood (collected in 3.2% sodiumcitrate), sputum, blood culture or bacterialcolonies.	Whole blood, sputum, CSF, bubo aspirates,skin lesion scrapings and bacterial cultures,or blood culture media in which gram-negative organisms can be seen.
Instrumentation	JBAIDS instrument (K051713)	Fluorescent microscope
Time Required forAnalysis ofSpecimen	Less than 3 hours	Same
Test Interpretation	Automated test interpretation and reportgeneration.	Subjective interpretation by user.
Physical Properties	Freeze dried reagents with reconstitutionbuffer and water provided in kit.	Liquid reagent
Storage and ShelfLife	One year at room temperature (18-28 ℃).	Refrigerator temperature (2-8 ℃),manufacture defined expiration date.

JBAIDS Plaque Detection Kit vs. Fluorescein-labeled antibody to F1 antigen

The predicate device and the JBAIDS Plague Detection Kit have the same intended use. Both provide test results that aid in the diagnosis of plague when considered with other clinical and microbiological evidence, both test for Y. pestis infection directly from patient specimens or cultures, and both provide qualitative test results.

While the basic intended use is the same for the predicate device and the JBAIDS Kit, the technological characteristics are quite different. The sensitivity and specificity of DFA assays rely on the titer and specificity of the labeled antibody. Because there are no specific test kits available, each laboratory develops its own assay using different antibodies. Further, the antibodies are sold as 'research use only' reagents, so the manufacturers do not supply performance data with regard to detection of Y. pestis. As a result, the safety and efficacy of the predicate test is largely unknown, although some literature exists that can aid in comparing the two devices.

In a recent study, Tomaso et al. evaluated the analytic performance of several different immunologic methods, including ELISA, flow cytometry and DFA, for the detection of the F1 capsular antigen. The lower limit of detection (LOD) for DFA was 10' CFU/mL of Y. pestis in phosphate buffered saline (PBS) when using a monoclonal antibody labeled with OregonGreen™. In the same study, this assay demonstrated 100% (10/10)

{6}------------------------------------------------

inclusivity by detecting all isolates of Y. pestis tested and 100% (45/45) exclusivity by giving negative results for all other bacteria, including 10 non-pestis Yersinia species.

In contrast to the predicate, the sensitivity and specificity of the JBAIDS Plague Detection Kit relies on adequate recovery and purification of nucleic acids from patient specimens and on the specificity of the PCR primers and probes. The LOD for the JBAIDS Plague Detection System is 50 CFU/mL of citrated whole blood and 670 CFU/mL of sputum.

The analytic sensitivity, or inclusivity, of the JBAIDS Plague Detection Kit was determined by testing colonies and purified DNA from various subtypes and strains of Y. pestis. Given the plasmid status of the tested strains, all 18 (100%) isolates of virulent Y. pestis tested with the JBAIDS Plague Detection System gave the expected test result. Fifteen (83%) would have been considered presumptively positive for Y. pestis because they were detected by both assays. Two isolates would have given an indeterminate result because they are missing the gene target for the Target 2 assay while, one isolate would have tested false negative because it is missing the gene target for the Target 1 assay.

Analytic specificity, or exclusivity, of the JBAIDS Plague Detection System was determined by testing panels containing organisms that are phylogenetically related to Y. pestis (nearest neighbors), as well as unrelated organisms that are likely to be found in clinical samples. The JBAIDS Target 1 assay gave negative results for 100% (24/24) of the tested isolates; however, uncertain results were sometimes obtained when testing one of three isolates of Y. enterocolitica with the Target 2 assay. As the result for Target 1 was negative when testing this strain, Target 2 would not be tested and a false positive result would not be obtained. These data support that the overall analytic specificity for the JBAIDS Plague Detection Kit is high and equivalent to the predicate.

In addition to analytic studies, a multisite clinical trial was conducted. Due to the near absence of clinical samples from individuals with a diagnosis of systemic plague, the clinical trial was limited to an assessment of the system's clinical specificity. Blood and/or sputum samples obtained from subjects with clinical signs and symptoms consistent with systemic plague and for whom a blood and/or sputum culture had been ordered were tested for Y. pestis using both assays of the JBAIDS Plague Detection Kit. The results were compared to the laboratory culture results, which were considered the gold standard. As expected, Y. pestis was not identified in any of the blood or sputum cultures. All 132 whole blood samples yielded negative test results with the Target 1 assay; however, two (1.5%) whole blood samples gave false positive results when tested with the Target 2 assay due to non-specific amplification that occasionally affects this assay. As the standard testing procedure is to reserve the Target 2 assay for use with samples that tested positive with Target 1 and all whole blood samples provided the correct negative test result with Target 1, the clinical specificity of the JBAIDS Plague Detection Kit is at least 97% (95% CI, 97-100%) for whole blood samples. All 36 (100%) sputum samples vielded negative results for both assays resulting in a clinical specificity of at least 92% (95% CI, 92-100%) for sputum.

Based on the available literature, the JBAIDS Plague Detection Kit appears to be as safe and effective as the predicate assay. A positive result with either DFA or the JBAIDS Plague Detection Kit provides presumptive identification of Y. pestis. Both tests have a high sensitivity and high specificity. However, the JBAIDS offers some advantages over the predicate. DFA tests can be difficult to interpret and require subjective evaluation. In

{7}------------------------------------------------

addition, the F1 capsular antigen is only formed when the organism is grown at or near body temperature.2 Storage and transport of samples can result in loss of the F1 antigen and a false negative test result. In contrast, the JBAIDS software automatically interprets the assay results, reducing the opportunity for user error and the freeze-dried assay format minimizes assay setup errors. The JBAIDS Plague Detection Kit could identify infected individuals days before DFA, reducing the time to treatment and limiting person-toperson spread of the disease.

In summary, the JBAIDS assay, while technologically distinct from the predicate, is as safe and effective as the predicate, but could provide a more rapid diagnosis.

References

1. Tomaso H, Thullier P, Seibold E, et al. Comparison of hand-held test kits, immunofluorescence microscopy, ELISA, and flow cytometric analysis for the rapid presumptive identification of Yersinia pestis. J. Clin. Microbiol. 2007; doi:10.1128/JCM.00458-07
1. Perry RD, Fetherstone JD. Yersinia pestis etiologic agent of plague. Clin Microbiol Rev. 1997;10:35-66.

Regulation Number and Section

§ 866.3045 In vitro diagnostic device for

Bacillus spp. detection.(a)
Identification. An in vitro diagnostic device forBacillus species (spp.) detection is a prescription device used to detect and differentiate amongBacillus spp. and presumptively identifyB. anthracis and otherBacillus spp. from cultured isolates or clinical specimens as an aid in the diagnosis of anthrax and other diseases caused byBacillus spp. This device may consist ofBacillus spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to presumptively identify bacillus-like organisms in clinical specimens; bacteriophage used for differentiatingB. anthracis from otherBacillus spp. based on susceptibility to lysis by the phage; or antigens used to identify antibodies toB. anthracis (anti-toxin and anti-capsular) in serum. Bacillus infections include anthrax (cutaneous, inhalational, or gastrointestinal) caused byB. anthracis, and gastrointestinal disease and non-gastrointestinal infections caused byB. cereus. (b)
Classification. Class II (special controls). The special controls are set forth in FDA's special controls guideline document entitled “In Vitro Diagnostic Devices forBacillus spp. Detection; Class II Special Controls Guideline for Industry and Food and Drug Administration Staff.” For availability of the guideline document, see § 866.1(e).(c)
Restriction on Distribution. 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.(d)
Restriction on Use. The use of this device is restricted to prescription use and must comply with the following:(1) The device must be in the possession of:
(i)(A) A person, or his agents or employees, regularly and lawfully engaged in the manufacture, transportation, storage, or wholesale or retail distribution of such device; or
(B) A practitioner, such as a physician, licensed by law to use or order the use of such device; and
(ii) The device must be sold only to or on the prescription or other order of such practitioner for use in the course of his professional practice.
(2) The label of the device shall bear the statement “Caution: Federal law restricts this device to sale by or on the order of a ____”, the blank to be filled with the word “physician” or with the descriptive designation of any other practitioner licensed by the law of the State in which he practices to use or order the use of the device.
(3) Any labeling, as defined in section 201(m) of the Federal Food, Drug, and Cosmetic Act, whether or not it is on or within a package from which the device is to be dispensed, distributed by, or on behalf of the manufacturer, packer, or distributor of the device, that furnishes or purports to furnish information for use of the device contains adequate information for such use, including indications, effects, routes, methods, and frequency and duration of administration and any relevant hazards, contraindications, side effects, and precautions, under which practitioners licensed by law to employ the device can use the device safely and for the purposes for which it is intended, including all purposes for which it is advertised or represented. This information will not be required on so-called reminder-piece labeling which calls attention to the name of the device but does not include indications or other use information.
(4) All labeling, except labels and cartons, bearing information for use of the device also bears the date of the issuance or the date of the latest revision of such labeling.