(67 days)
No
The summary describes a standard RT-PCR test with melt analysis and a simple calling scheme based on the detection of specific nucleic acid sequences. There is no mention of AI or ML in the device description, intended use, or performance studies. The changes described relate to unmasking existing assays, not implementing new analytical methods.
No.
This device is an in vitro diagnostic test designed to detect SARS-CoV-2 nucleic acids for diagnostic purposes, not to treat or therapeutically benefit patients.
Yes
The "Intended Use / Indications for Use" section explicitly states that the "BioFire® COVID-19 Test 2 is a qualitative nested multiplexed RT-PCR in vitro diagnostic test." It also describes its purpose as detecting nucleic acids from SARS-CoV-2 and providing results for the identification of SARS-CoV-2 RNA.
No
The device is an in vitro diagnostic test that requires specific hardware (BioFire FilmArray 2.0 and BioFire FilmArray Torch Systems) to perform the testing process, including nucleic acid extraction, reverse-transcription, and nested PCR. While the submission involves a software change to unmask additional assays, the core device is not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The BioFire® COVID-19 Test 2 is a qualitative nested multiplexed RT-PCR in vitro diagnostic test intended for use with the BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems."
Furthermore, the document includes the statement "For In Vitro Diagnostic Use."
N/A
Intended Use / Indications for Use
The BioFire® COVID-19 Test 2 is a qualitative nested multiplexed RT-PCR in vitro diagnostic test intended for use with the BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire COVID-19 Test 2 detects nucleic acids from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs (NPS) from symptomatic individuals suspected of COVID-19 by their healthcare provider.
Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in NPS specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out co-infection with other pathogens.
Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the relevant public health authorities. The BioFire COVID-19 Test 2 is intended for use by trained medical and laboratory professionals in a laboratory setting or under the supervision of a trained laboratory professional.
For In Vitro Diagnostic Use.
Product codes
OOX
Device Description
The BioFire COVID-19 Test 2 is a multiplexed nucleic acid-based test for the detection of SARS-CoV-2 RNA from nasopharyngeal swabs (NPS) eluted in either transport medium or saline. The test was originally described and cleared in K211079. The BioFire COVID-19 Test 2 uses BioFire FilmArray technology and is for use with BioFire FilmArray 2.0 and BioFire FilmArray Torch instruments. Once the sample is injected into the FilmArray pouch is loaded into the Film Array instrument which performs all aspects of testing including nucleic acid extraction, reverse-transcription, and nested PCR with melt analysis. The currently cleared version of the test uses three SARS-CoV-2 assays and returns a 'SARS-CoV-2 Detected' call if one or more of the SARS-CoV-2 assays are positive.
The purpose of this submission is to display results for four additional SARS-CoV-2 assays which are currently present on the test, but for which results are masked through software. The assays are being unmasked as a mitigation against the risk of future SARS-CoV-2 variants affecting the sensitivity of the BioFire COVID-19 Test 2 due to mutations in assay primer regions. Note that to date BioFire Defense has not identified any variants that are predicted to affect the performance of the three-assay version of BioFire COVID-19 Test 2 described in K211079. These changes are being requested preemptively. The calling scheme when using the seven total SARS-CoV-2 assays will remain unchanged: one or more positive SARS-CoV-2 assay results will return an overall 'SARS-CoV-2 Detected' result.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal swabs (NPS)
Indicated Patient Age Range
symptomatic individuals
Intended User / Care Setting
trained medical and laboratory professionals in a laboratory setting or under the supervision of a trained laboratory professional.
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)
Although the FDA-cleared version of the BioFire COVID-19 Test 2 described in K211079 only uses three SARS-CoV-2 assays for result interpretation, all seven assays were present on the test during the V&V study execution. Therefore, no additional testing was performed for this submission. Instead, all study data previously submitted in K211079 were re-analyzed using the updated BioFire COVID-19 Test 2 Pouch Module (Build 2.1.1.2C) to include results for the four previously masked assays in the study reports.
Bench Testing:
DF-SDY-029903 - BioFire COVID-19 Test Evaluation of Specificity: No unexpected reactivity was observed with any of the organisms/viruses. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-029904 - BioFire COVID-19 Test Evaluation of Sensitivity - LoD and Contrived Testing: Sensitivity of the modified BioFire COVID-19 Test 2 when using infectious SARS-CoV-2 virus is effectively equivalent to the predicate device: 3.3E+02 GC/mL.
DF-SDY-030331 - BioFire COVID-19 Test 2 Determination of Limit of Detection – Inactivated Virus: Sensitivity of the modified BioFire COVID-19 Test 2 when using inactivated SARS-CoV-2 is equivalent to the predicate device: 3.3E+02 GE/mL.
DF-SDY-030333 - BioFire COVID-19 Test 2 Evaluation of Specificity (Exclusivity): No unexpected reactivity was observed with any of the organisms/viruses. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030334 - BioFire COVID-19 Test 2 Evaluation of Potentially Interfering Substances: None of the substances tested were determined to be inhibitory to the BioFire COVID-19 Test 2. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030336 - BioFire COVID-19 Test 2 Evaluation of Specimen Storage and Transport: The detection rate for all evaluated samples and storage conditions was 100%. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030358 - Sensitivity/Proficiency Testing of the BioFire COVID-19 Test 2 with FDA-Provided SARS-CoV-2 Analytes: Overall results for testing the FDA Reference Panel with the modified BioFire COVID-19 Test 2 are comparable to the predicate device.
DF-SDY-030398 - BioFire COVID-19 Test 2 Multi-Site Reproducibility Evaluation: Percent agreement between observed and expected results were >95% for each sample and each site, except for negative samples at Site 2. Percent agreement at Site 2 for negative samples was 93.3%. The percent agreement was the same for the predicate device. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030404 - BioFire COVID-19 Test 2 Evaluation of Reactivity (Inclusivity): All four strains tested were detected at near LoD concentrations. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030666 - BioFire COVID-19 Test – Saline and PBS Validation: The detection rate for NPS in saline at 1x LoD was 20/20 (100%). Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
DF-SDY-030316 - COVID-19 Stability Study for COVID: The BioFire COVID-19 Test stability evaluation demonstrated 20 months of stability at 18-30°C.
Clinical Testing:
DF-SDY-030617 - BioFire COVID-19 Test 2 Prospective Clinical Evaluation: Performance of the modified BioFire COVID-19 Test 2 was 98.6% PPA (68/69), and 99.1% NPA (450/454). Whereas performance of the predicate device was 98.6% PPA (68/69) and 99.6% NPA (452/454). The overall performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device.
In Silico Analyses:
DF-SDY-030174 - COVID-19 Test In Silico Exclusivity Analyses: Only near-neighbor non-human coronavirus genomes showed significant homology to assay-specific sets of PCR2 primers and are predicted to be detected by the BioFire COVID-19 Test 2. It is unlikely that these isolates would be found in the human respiratory samples, however little is known about their potential to infect a human host. No other significant amplification of non-target sequences is predicted.
DF-OTH-030895 - BioFire COVID-19 Test In Silico Inclusivity Summary: No sequences submitted to GISAID before May 4, 2022, were identified with co-occurring mutations impacting the performance of all assays. As such, BFDf predicts all strains of SARS-CoV-2, including all current VOCs, VOIs, and VUMs, will be detected by the BioFire COVID-19 Test 2.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity of the modified BioFire COVID-19 Test 2 when using infectious SARS-CoV-2 virus is effectively equivalent to the predicate device: 3.3E+02 GC/mL.
Sensitivity of the modified BioFire COVID-19 Test 2 when using inactivated SARS-CoV-2 is equivalent to the predicate device: 3.3E+02 GE/mL.
Performance of the modified BioFire COVID-19 Test 2 was 98.6% PPA (68/69), and 99.1% NPA (450/454).
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.
(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.
(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 specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) 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 specimens;
(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;
(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (
e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (
e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;
(D) That positive and negative predictive values are highly dependent on prevalence;
(E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(F) When applicable (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.
0
Date: July 25, 2022
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BioFire Defense, LLC Cynthia Phillips VP of Regulatory, Quality, and Clinical Affairs 79 W 4500 S. Suite 14 Salt Lake City, Utah 84107
Re: K221460
Trade/Device Name: BioFire COVID-19 Test 2 Regulation Number: 21 CFR 866.3981 Regulation Name: Device To Detect And Identify Nucleic Acid Targets In Respiratory Specimens From Microbial Agents That Cause The SARS-Cov-2 Respiratory Infection And Other Microbial Agents When In A Multi-Target Test Regulatory Class: Class II Product Code: OOX Dated: May 18, 2022 Received: May 19, 2022
Dear Cynthia Phillips:
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
1
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 (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 (QS) 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,
Himani Bisht, Ph.D. Assistant Director Viral Respiratory and HPV 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
2
Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
| 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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3
Special 510(k) Summary
I. Submitter
BioFire Defense, LLC 79 West 4500 South, Suite 14 Salt Lake City, UT 84107 Phone: (801) 262-3592 Fax: (801) 447-6907
Contact Person: Cynthia L. Phillips, Ph.D. Date Prepared: 2022-05-18
II. Device
Name of Device: BioFire® COVID-19 Test 2 Common or Usual Name: Same Regulation: 21 CFR 866.3981 Classification Name: Respiratory Specimen Nucleic Acid Sars-CoV-2 Test Product Code: OOX Regulatory Class: Class II (Special Controls) Panel: Microbiology
III. Predicate Device
BioFire® COVID-19 Test 2 (BioFire Defense, LLC) (K211079) This predicate has not been subject to a design-related recall.
Device Description IV.
The BioFire COVID-19 Test 2 is a multiplexed nucleic acid-based test for the detection of SARS-CoV-2 RNA from nasopharyngeal swabs (NPS) eluted in either transport medium or saline. The test was originally described and cleared in K211079. The BioFire COVID-19 Test 2 uses BioFire FilmArray technology and is for use with BioFire FilmArray 2.0 and BioFire FilmArray Torch instruments. Once the sample is injected into the FilmArray pouch is loaded into the Film Array instrument which performs all aspects of testing including nucleic acid extraction, reverse-transcription, and nested PCR with melt analysis. The currently cleared version of the test uses three SARS-CoV-2 assays and returns a 'SARS-CoV-2 Detected' call if one or more of the SARS-CoV-2 assays are positive.
The purpose of this submission is to display results for four additional SARS-CoV-2 assays which are currently present on the test, but for which results are masked through software. The assays are being unmasked as a mitigation against the risk of future SARS-CoV-2 variants affecting the sensitivity of the BioFire COVID-19 Test 2 due to mutations in assay primer
4
regions. Note that to date BioFire Defense has not identified any variants that are predicted to affect the performance of the three-assay version of BioFire COVID-19 Test 2 described in K211079. These changes are being requested preemptively. The calling scheme when using the seven total SARS-CoV-2 assays will remain unchanged: one or more positive SARS-CoV-2 assay results will return an overall 'SARS-CoV-2 Detected' result.
V. Intended Use
The BioFire® COVID-19 Test 2 is a qualitative nested multiplexed RT-PCR in vitro diagnostic test intended for use with the BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire COVID-19 Test 2 detects nucleic acids from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs (NPS) from symptomatic individuals suspected of COVID-19 by their healthcare provider.
Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in NPS specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out co-infection with other pathogens.
Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the relevant public health authorities. The BioFire COVID-19 Test 2 is intended for use by trained medical and laboratory professionals in a laboratory setting or under the supervision of a trained laboratory professional.
For In Vitro Diagnostic Use.
Substantial Equivalence VI.
The modified BioFire COVID-19 Test 2 is substantially equivalent to its predicate. No changes to the chemistry or intended use of the BioFire COVID-19 Test 2 have been made. Only minor modifications to the BioFire COVID-19 Test 2 Pouch Module software have been made to include results for seven SARS-CoV-2 assays instead of three. Performance evaluation studies used to support K211079 were re-analyzed with no significant impact. Table 1 compares elements of the modified BioFire COVID-19 Test 2 to its predicate device and outlines their similarities and differences.
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| Element | Subject Device:
BioFire COVID-19 Test 2 | Predicate Device:
BioFire COVID-19 Test 2
(K211079) |
|---------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The BioFire® COVID-19 Test 2 is a qualitative nested multiplexed
RT-PCR in vitro diagnostic test intended for use with the
BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems.
The BioFire COVID-19 Test 2 detects nucleic acids from severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in
nasopharyngeal swabs (NPS) from symptomatic individuals
suspected of COVID-19 by their healthcare provider.
Results are for the identification of SARS-CoV-2 RNA. The SARS-
CoV-2 RNA is generally detectable in NPS specimens during the
acute phase of infection. Positive results are indicative of the
presence of SARS-CoV-2 RNA; clinical correlation with patient
history and other diagnostic information is necessary to
determine patient infection status. Positive results do not rule
out co-infection with other pathogens.
Results are meant to be used in conjunction with other clinical,
epidemiologic, and laboratory data, in accordance with the
guidelines provided by the relevant public health authorities.
The BioFire COVID-19 Test 2 is intended for use by trained
medical and laboratory professionals in a laboratory setting or
under the supervision of a trained laboratory professional. | Same |
| Specimen Type | Nasopharyngeal swabs eluted in transport medium or saline | Same |
| Pathogens
Detected | SARS-CoV-2 | Same |
| Analyte | RNA | Same |
| Number of
Assays | 3 | 7 |
| Technological
Principles | Nested multiplex RT-PCR followed by high resolution melting
analysis to confirm identity of amplified product | Same |
| Instrumentation | FilmArray 2.0 or FilmArray Torch systems | Same |
| Time to Result | ~45 minutes | Same |
| Reagent
Storage | Room temperature | Same |
| Test
Interpretation | Automated test interpretation and report generation. User
cannot access raw data. Software uses results from 3 assays. | Automated test
interpretation and report
generation. User cannot
access raw data. Software
uses results from 7 assays. |
| Controls | Two controls are included in each reagent pouch to control for
sample processing and both stages of PCR and melt analysis | Same |
| Assayed
External
Controls | None | Same |
| User
Complexity | Moderate/Low | Same |
Table 1. Substantial Equivalence between the subject device and predicate device
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Summary of Performance Data VII.
Although the FDA-cleared version of the BioFire COVID-19 Test 2 described in K211079 only uses three SARS-CoV-2 assays for result interpretation, all seven assays were present on the test during the V&V study execution. Therefore, no additional testing was performed for this submission. Instead, all study data previously submitted in K211079 were re-analyzed using the updated BioFire COVID-19 Test 2 Pouch Module (Build 2.1.1.2C) to include results for the four previously masked assays in the study reports.
Table 2 summarizes the re-analyzed studies and any changes in the performance data. Note that in some cases, studies were leveraged to support both the BioFire COVID-19 Test 2 (K211079) and the BioFire COVID-19 Test v1.1 (EUA200044). The BioFire COVID-19 Test v1.1 and BioFire COVID-19 Test 2 have identical chemistry and manufacturing processes.
| Study Number | Study Name | Summary of Results Following Reanalysis |
|---|---|---|
| Bench Testing | ||
| DF-SDY-029903 | BioFire COVID-19 Test Evaluation of | |
| Specificity | No unexpected reactivity was observed with any of the organisms/viruses. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device. | |
| DF-SDY-029904 | BioFire COVID-19 Test Evaluation of | |
| Sensitivity - LoD and Contrived | ||
| Testing | Sensitivity of the modified BioFire COVID-19 Test 2 when using infectious SARS-CoV-2 virus is effectively equivalent to the predicate device: 3.3E+02 GC/mL. | |
| DF-SDY-030331 | BioFire COVID-19 Test 2 | |
| Determination of Limit of Detection – | ||
| Inactivated Virus | Sensitivity of the modified BioFire COVID-19 Test 2 when using inactivated SARS-CoV-2 is equivalent to the predicate device: 3.3E+02 GE/mL. | |
| DF-SDY-030333 | BioFire COVID-19 Test 2 Evaluation of | |
| Specificity (Exclusivity) | No unexpected reactivity was observed with any of the organisms/viruses. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device. | |
| DF-SDY-030334 | BioFire COVID-19 Test 2 Evaluation of | |
| Potentially Interfering Substances | None of the substances tested were determined to be inhibitory to the BioFire COVID-19 Test 2. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device. | |
| DF-SDY-030336 | BioFire COVID-19 Test 2 Evaluation of | |
| Specimen Storage and Transport | The detection rate for all evaluated samples and storage conditions was 100%. Performance of the modified BioFire COVID-19 Test 2 is equivalent to the predicate device. | |
| DF-SDY-030358 | Sensitivity/Proficiency Testing of the | |
| BioFire COVID-19 Test 2 with FDA- | ||
| Provided SARS-CoV-2 Analytes | Overall results for testing the FDA Reference Panel with the modified BioFire COVID-19 Test 2 are comparable to the predicate device. | |
| DF-SDY-030398 | BioFire COVID-19 Test 2 Multi-Site | |
| Reproducibility Evaluation | Percent agreement between observed and expected results were >95% for each sample and each site, except for negative samples at Site 2. Percent agreement at Site 2 for negative samples | |
| Study Number | Study Name | Summary of Results Following Reanalysis |
| was 93.3%. The percent agreement was the same | ||
| for the predicate device. Performance of the | ||
| modified BioFire COVID-19 Test 2 is equivalent to | ||
| the predicate device. | ||
| DF-SDY-030404 | BioFire COVID-19 Test 2 Evaluation of | |
| Reactivity (Inclusivity) | All four strains tested were detected at near LoD | |
| concentrations. Performance of the modified | ||
| BioFire COVID-19 Test 2 is equivalent to the | ||
| predicate device. | ||
| DF-SDY-030666 | BioFire COVID-19 Test – Saline and | |
| PBS Validation | The detection rate for NPS in saline at 1× LoD was | |
| 20/20 (100%). Performance of the modified | ||
| BioFire COVID-19 Test 2 is equivalent to the | ||
| predicate device. | ||
| DF-SDY-030316 | COVID-19 Stability Study for COVID | The BioFire COVID-19 Test stability evaluation |
| demonstrated 20 months of stability at 18-30°C. | ||
| Clinical Testing | ||
| Performance of the modified BioFire COVID-19 | ||
| Test 2 was 98.6% PPA (68/69), and 99.1% NPA | ||
| (450/454). Whereas performance of the | ||
| DF-SDY-030617 | BioFire COVID-19 Test 2 Prospective | |
| Clinical Evaluation | predicate device was 98.6% PPA (68/69) and | |
| 99.6% NPA (452/454). The overall performance of | ||
| the modified BioFire COVID-19 Test 2 is | ||
| equivalent to the predicate device. | ||
| In Silico Analyses | ||
| DF-SDY-030174 | COVID-19 Test In Silico Exclusivity | |
| Analyses | Only near-neighbor non-human coronavirus | |
| genomes showed significant homology to assay- | ||
| specific sets of PCR2 primers and are predicted to | ||
| be detected by the BioFire COVID-19 Test 2. It is | ||
| unlikely that these isolates would be found in the | ||
| human respiratory samples, however little is known | ||
| about their potential to infect a human host. | ||
| No other significant amplification of non-target | ||
| sequences is predicted. | ||
| DF-OTH-030895 | BioFire COVID-19 Test In Silico | |
| Inclusivity Summary | No sequences submitted to GISAID before May 4, | |
| 2022, were identified with co-occurring | ||
| mutations impacting the performance of all | ||
| assays. As such, BFDf predicts all strains of SARS- | ||
| CoV-2, including all current VOCs, VOIs, and | ||
| VUMs, will be detected by the BioFire COVID-19 | ||
| Test 2 |
Table 2. Summary of Reanalyzed Performance Data
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