(30 days)
Not Found
No
The device description details a standard real-time PCR assay based on enzymatic activity and fluorescence detection. There is no mention of AI or ML in the intended use, device description, or the specific sections for AI/ML mentions. The interpretation of results is based on the presence of signals from specific primer/probe sets, not on complex algorithmic analysis typically associated with AI/ML in diagnostics.
No
This device is an in vitro diagnostic test for detecting B. anthracis DNA, which is used for diagnosis and detection, not for treating a condition or disease.
Yes.
The "Intended Use / Indications for Use" section explicitly states "The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis." and "The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens." This indicates its use in the diagnostic process.
No
The device description clearly outlines a physical assay involving primers, probes, and Taq polymerase, which are chemical and biological components, not software. It describes a laboratory test process, not a software application.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states: "The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis." This is the most direct indicator.
- Testing of Human Samples: The intended use specifies testing "human respiratory samples, whole blood, serum, plasma, swabs from lesions, cerebrospinal fluid, and bacterial culture isolates from individuals suspected of having anthrax." Testing human specimens for diagnostic purposes is a core function of IVDs.
- Contribution to Diagnosis: The text states that the results "should be used in conventional methods for identification of Bacillus anthracis isolates as part of the LRN Bacillus anthracis Testing Algorithm" and that the "diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens." While not the sole basis for diagnosis, the assay provides laboratory evidence used in the diagnostic process.
- Device Description: The description details a laboratory test method (PCR) that analyzes biological samples (DNA extracted from specimens).
The mention of environmental specimen testing is noted as not evaluated by the FDA for IVD purposes, but the primary intended use on human samples for diagnostic purposes clearly classifies it as an IVD.
N/A
Intended Use / Indications for Use
The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis. The assay can be used to test human respiratory samples, whole blood, serum, plasma, swabs from lesions, cerebrospinal fluid, and bacterial culture isolates from individuals suspected of having anthrax.
Results generated from direct specimentesting are presumptive for the identification of B. anthracis. Results generated from culture isolate testing should be used in conventional methods for identification of Bacillus anthracis isolates as part of the LRN Bacillus anthracis Testing Algorithm. The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
The B. anthracis Real-time PCR Assay is also intended for environmental specimen testing for biothreat detection and response. FDA has not evaluated claims related to the use of this assay on environmental specimens.
Product codes (comma separated list FDA assigned to the subject device)
NHT
Device Description
The B. anthracis Real-time PCR Assay uses a fluorogenic probe, consisting of an oligonucleotide with a reporter dve (FAM) attached to the 5' end and a quencher dye (BHQ1) attached at or near the 3′ end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5′ nuclease activity of Taq polymerase degrades the probe causing the reporter dye to separate from the quencher dye and a fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR. The Tag polymerase used in this assay is inactive at room temperature. It must be activated by incubation at 95°C, which also minimizes the production of nonspecific amplification products.
Each extracted DNA sample is tested with three B. anthracis primer and probe sets run as individual reactions. The primer and probe sets target genes encoding virulence factors as well as conserved regions of DNA from the B. anthracis chromosome. All primer and probe sets must be positive for the overall result of the B. anthracis Real-time PCR Assay to be interpreted as positive. Any result that is positive for some, but not all target regions, is still considered equivocal and follow-up laboratory investigation should be performed per the LRN Bacillus anthracis testing algorithm.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Respiratory, Lesions, Blood, CSF, Pleural, Bacterial Culture Isolates
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory Response Network (LRN) designated laboratories.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Not Found
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 7, 2019
Centers for Disease Control and Prevention Julie Villanueva Chief, Laboratory Preparedness and Response Branch 1600 Clifton Road NE, MS: H24-11 Atlanta, Georgia 30329
Re: K192871
Trade/Device Name: B. anthracis Real-time PCR Assay Regulation Number: 21 CFR 866.3045 Regulation Name: In vitro diagnostic device for Bacillus spp. detection Regulatory Class: Class II Product Code: NHT Dated: October 7, 2019 Received: October 8, 2019
Dear Julie Villanueva:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kristian Roth, Ph.D. Branch Chief Bacterial Multiplex and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K192871
Device Name B. anthracis Real-time PCR Assay
Indications for Use (Describe)
The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis. The assay can be used to test human respiratory samples, whole blood, serum, plasma, swabs from lesions, cerebrospinal fluid, and bacterial culture isolates from individuals suspected of having anthrax.
Results generated from direct specimentesting are presumptive for the identification of B. anthracis. Results generated from culture isolate testing should be used in conventional methods for identification of Bacillus anthracis isolates as part of the LRN Bacillus anthracis Testing Algorithm. The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
The B. anthracis Real-time PCR Assay is also intended for environmental specimen testing for biothreat detection and response. FDA has not evaluated claims related to the use of this assay on environmental specimens.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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5. 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Assigned 510(k) number: | K192871 |
|---|---|
| Submitted by: | Centers for Disease Control and Prevention |
| 1600 Clifton Road, MS: H24-11 | |
| Atlanta, GA 30329-4027 | |
| Contact Person: | Julie Villanueva, Ph.D. |
| Laboratory Preparedness and Response Branch Chief | |
| Division of Preparedness and Emerging Infections | |
| National Center for Emerging and Zoonotic Infectious Disease | |
| Centers for Disease Control and Prevention | |
| (Registration number: 1050190) | |
| 1600 Clifton Road, NE, MS: H24-11 | |
| Atlanta, GA 30329-4027 | |
| (404) 639-3851 (office) | |
| fkb8@cdc.gov | |
| Date prepared: | October 31, 2019 |
| Device trade name: | B. anthracis Real-time PCR Assay |
| Classification name and regulation: (if applicable) | In vitro diagnostic device for Bacillus spp. detection; 21 CFR 866.3045 |
| Predicate device(s): | B. anthracis Real-time PCR Assay |
| (K140426) |
Background
Anthrax is a zoonotic disease caused by B. anthracis that is transmissible to humans through handling or consumption of contaminated animal products. Infection can also occur through inhalation of B. anthracis spores from contaminated animal products such as wool or hides. Infection caused by human-to-human contact has been reported only rarely, and only via the cutaneous route (Versalovic, 2011). There have been 3 major presentations of anthrax in humans: cutaneous, ingestion, and inhalation. In cases of cutaneous anthrax, patients typically present with a painless blister or skin ulcer with a black area in the center. Inhalation anthrax is typically associated with cold or flu-like symptoms, cough, chest discomfort, shortness of breath, fatigue, and muscle aches. Symptoms of gastrointestinal anthrax typically include nausea, loss of appetite, bloody diarrhea, fever and severe stomach pain.
Prior to the development of the LRN B. anthracis Real-time PCR Assay, identification of B. anthracis was determined by using phenotypic differences between B. anthracis and the rest of the B. cereus group. (i.e. lack of motility and hemolysis, susceptibility to penicillin, colony morphology, susceptibility to
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lysis by gamma phage) (Hoffmaster, 2002). However, these methods require growth of the microorganism and can take at least 24 hours incubation to obtain a result. Due to the prevalence of B. anthracis in the environment, and its past use as a biological weapon, it has long been an organism of concern. The use of B. anthracis in the bioterrorism attacks of 2001 resulting in cases of inhalation and cutaneous anthrax increased public health concern and reinforced the worry that it would be used in the same way again. For these reasons, there was a need for rapid testing to aid in the identification of B. anthracis. The Laboratory Response Network (LRN) is part of a national bioterrorism preparedness initiative and one of the major goals of this initiative is the development and validation of rapid and specific assays for agents likely to be used in a bioterrorism event. Accordingly, scientists at the Centers for Disease Control and Prevention have developed several real-time PCR based assays to detect B. anthracis and other potential aqents of bioterrorism in an effort to meet the need for rapid detection.
Device Description
The B. anthracis Real-time PCR Assay uses a fluorogenic probe, consisting of an oligonucleotide with a reporter dve (FAM) attached to the 5' end and a quencher dye (BHQ1) attached at or near the 3′ end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5′ nuclease activity of Taq polymerase degrades the probe causing the reporter dye to separate from the quencher dye and a fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR. The Tag polymerase used in this assay is inactive at room temperature. It must be activated by incubation at 95°C, which also minimizes the production of nonspecific amplification products.
Each extracted DNA sample is tested with three B. anthracis primer and probe sets run as individual reactions. The primer and probe sets target genes encoding virulence factors as well as conserved regions of DNA from the B. anthracis chromosome. All primer and probe sets must be positive for the overall result of the B. anthracis Real-time PCR Assay to be interpreted as positive. Any result that is positive for some, but not all target regions, is still considered equivocal and follow-up laboratory investigation should be performed per the LRN Bacillus anthracis testing algorithm.
Intended Use
The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis. The assay can be used to test human respiratory samples, whole blood, serum, plasma, swabs from lesions, CSF, pleural fluid, and bacterial culture isolates from individuals suspected of having anthrax.
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Results generated from direct specimen testing are presumptive for the identification of B. anthracis. Results generated from culture isolate testing should be used in conjunction with other conventional methods for identification of Bacillus anthracis isolates as part of the LRN Bacillus anthracis Testing Algorithm. The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
The B. anthracis Real-time PCR Assay is also intended for environmental specimen testing for biothreat detection and response. FDA has not evaluated claims related to the use of this assay on environmental specimens.
Device Comparison
The following table summarizes the similarities and differences between the cleared assay and the new submission for this device.
| | Predicate
B. anthracis Real-time
PCR Assay (K140426) | Device
B. anthracis Real-time
PCR Assay (new) |
|---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The B. anthracis Real-
Time PCR Assay is an in
vitro diagnostic test for
the qualitative detection
of plasmid and
chromosomal DNA
sequences from B.
anthracis . The assay can
be used to test human
respiratory samples,
whole blood, serum,
plasma, swabs from
lesions, CSF, pleural fluid,
and bacterial culture
isolates from individuals
suspected of having
anthrax.
Results generated from
direct specimen testing
are presumptive for the
identification of B.
anthracis . Results
generated from culture
isolate testing should be
used in conjunction with
other conventional
methods for identification
of Bacillus anthracis
isolates as part of the | Unchanged |
| | LRN Bacillus anthracis
Testing Algorithm. The
diagnosis of anthrax
infection must be made
based on history, signs,
symptoms, exposure
likelihood, and other
laboratory evidences, in
addition to the
identification of B.
anthracis from cultures or
detection directly in
clinical specimens. | |
| | Use is limited to
Laboratory
Response Network
(LRN) designated
laboratories. | |
| | The B. anthracis Real-
time PCR Assay is also
intended for
environmental specimen
testing for biothreat
detection and response.
FDA has not evaluated
claims related to the use
of this assay on
environmental
specimens. | |
| Principle of
Operation | Nucleic acid amplification
and fluorescent probe
detection | Unchanged |
| Targets | BA1 - pXO2 DNA
BA2 - pXO1 DNA
BA3 - B. anthracis
chromosomal region DNA | Unchanged |
| Sample Types | • Swabs from lesions
and vesicular material
• Whole Blood (EDTA or
sodium citrate)
• Serum/Plasma
• Respiratory specimens
(transtracheal
aspirates, bronchial
lavage, and sputum)
• Cerebrospinal fluid
• Pleural Fluid
• Bacterial culture
isolates
• Environmental samples
collected for
investigational or
surveillance use | Unchanged |
| Instrumentation | • Applied Biosystems
7500 Fast Dx Real-Time
PCR
• Cepheid SmartCycler I
• Cepheid SmartCycler II | • Applied Biosystems 7500
Fast Dx Real-Time PCR
Instrument
• Cepheid SmartCycler I
• Cepheid SmartCycler II
• QuantStudio Dx Real-Time
PCR Instrument |
| Software/
Hardware | Software/Hardware not
included as part of
device; may be run on
the manufacturer
installed and validated
software from the AB
7500 Fast Dx,
SmartCycler I, or
SmartCycler II | Software/Hardware not
included as part of device;
may be run on the
manufacturer installed and
validated software from the
AB 7500 Fast Dx,
SmartCycler I, SmartCycler
II, or QuantStudio Dx real-
time PCR instruments |
| Master mix | • Quanta PerfeCTa
MultiPlex qPCR
SuperMix, Low ROX
• Roche LightCycler
FastStart DNA Master
HybProbe | Unchanged |
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Establishment of Performance Characteristics
Inquiries regarding performance characteristics for the B. anthracis Real-time PCR Assay should be directed to the Centers for Disease Control and Prevention.
Analytical Limit of Detection (LoD)
The limit of detection for the B. anthracis Real-time PCR Assay was determined through an analytical sensitivity study.
Analytical Sensitivity and Specificity
Inquiries regarding performance characteristics for the B. anthracis Real-time PCR Assay should be directed to the Centers for Disease Control and Prevention.
Clinical Performance
Inquiries regarding clinical performance characteristics for the B. anthracis Real-time PCR Assay should be directed to the Centers for Disease Control and Prevention.