(143 days)
The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.
The Revogene was previously cleared under K170558. Meridian Biosciences, Inc. is submitting this 510(k) to implement a software modification to the Revogene that updates the current software with a PMT surveillance algorithm. The software monitors raw data fluorescence signal during assay testing and identifies issues due to a malfunction of the photomultiplier tube (the "PMT"), a key component in the Revogene instrument's optics system used in the management of fluorescence signals. Upon detection of a PMT malfunction, the PMT surveillance algorithm software produces a specific error code to the user labeled "Detection Error" and will lock the instrument thereby preventing further use.
The provided text describes a 510(k) submission for a software modification to the Revogene instrument, specifically the addition of a PMT (photomultiplier tube) surveillance algorithm. This modification is intended to monitor raw data fluorescence signals and identify issues due to a malfunction of the PMT, a key component in the instrument's optics system. Upon detection of a PMT malfunction, the algorithm produces an error code and locks the instrument, preventing further use.
The document states that this change does not affect the device's intended use nor alter the device's fundamental scientific technology. Therefore, the acceptance criteria and performance study details are focused on validating the new PMT surveillance algorithm's functionality and ensuring it does not negatively impact the previously cleared performance of the Revogene instrument.
Based on the provided text, a formal table of acceptance criteria and reported device performance, akin to what would be provided for a diagnostic or AI algorithm's clinical performance, is not explicitly present for the PMT surveillance algorithm itself. The document emphasizes that the modification is minor and focuses on the software's ability to detect and report PMT malfunctions.
However, we can infer the acceptance criteria and study proving the device meets them from the description of the software modification and the context of a 510(k) submission for a software update.
Here's a breakdown based on the provided information, addressing each point as much as possible:
Acceptance Criteria and Reported Device Performance
The core acceptance criterion for this software modification is that the PMT surveillance algorithm successfully detects and reports PMT malfunctions. The reported performance would be the successful implementation of this functionality.
Inferred Acceptance Criteria Table:
| Acceptance Criterion (Inferred) | Reported Device Performance (Inferred) |
|---|---|
| Functional Requirement 1: Accurate detection of PMT malfunctions | The PMT surveillance algorithm successfully monitors raw data fluorescence signals. |
| Functional Requirement 2: Generation of specific error code | Upon detection of a PMT malfunction, the software produces a specific error code labeled "Detection Error". |
| Functional Requirement 3: Instrument lock-out | Upon detection of a PMT malfunction, the instrument is locked, preventing further use. |
| Non-Functional Requirement 1: No impact on intended use | The software update does not affect the Revogene's intended use (in vitro diagnostic nucleic acid testing) as previously cleared. |
| Non-Functional Requirement 2: No alteration of fundamental scientific technology | The software update does not alter the fundamental scientific technology (fluorescence-based real-time PCR) of the Revogene instrument. |
Study Proving Acceptance Criteria:
The document implicitly indicates that a validation study was performed to demonstrate the functionality of the PMT surveillance algorithm. While details are scarce, the submission implies that the testing confirmed the algorithm's ability to detect PMT issues and trigger the appropriate error and lock-out mechanisms.
Detailed Study Information (Based on Inferences and General 510(k) Practices for Software Updates)
-
A table of acceptance criteria and the reported device performance:
(See above table for inferred criteria and performance, as direct explicit table is not provided in the document for the new software feature). The document stresses that the overall performance characteristics of the Revogene instrument remain as previously cleared (K170558, K170557, etc.), and this software update doesn't change those. -
Sample sizes used for the test set and the data provenance:
- Test Set Sample Size: Not explicitly stated for the PMT surveillance algorithm. For a software update of this nature (detecting a hardware malfunction), the "test set" would likely involve inducing PMT malfunctions (or simulating conditions that would lead to them) on multiple instruments to verify the algorithm's response. The general statement "The submitted information demonstrates that the modified Revogene instrument is safe, effective" implies a sufficient level of testing.
- Data Provenance: Not specified. Given it's a software update for a commercialized instrument, the testing would typically be performed internally by the manufacturer (Meridian Bioscience, Inc.). It's likely retrospective in that it's testing a new feature on existing hardware, but the testing itself would be prospective for evaluating the new software. Country of origin not specified, but the manufacturer is based in Ohio, USA.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is unlikely to involve a panel of "experts" in the same way an AI diagnostic algorithm's ground truth is established. The ground truth for a PMT malfunction would be a measurable hardware degradation or induced failure that clearly indicates the PMT is not functioning correctly. This would be established by engineers or instrument specialists, not clinical experts like radiologists.
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Adjudication method for the test set:
- Not applicable in the context of this software update. Adjudication methods like 2+1 or 3+1 are typically for establishing ground truth for subjective human interpretations (e.g., medical image reads). Here, the judgment is objective: either the PMT is malfunctioning or it's not, and the software either detects it or it doesn't.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done:
- No. An MRMC study is not relevant for this type of software modification. MRMC studies are used to evaluate the impact of an AI algorithm on human reader performance for tasks involving perception and interpretation (e.g., diagnosing disease from medical images). This software is performing an automated internal diagnostic check on the instrument itself, not assisting human clinical interpretation.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The PMT surveillance algorithm operates automatically as an internal check. Its performance is evaluated purely on its ability to detect PMT malfunctions and trigger the pre-defined error and lock-out, without human intervention in its real-time operation.
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The type of ground truth used:
- Instrumental/Hardware Ground Truth: The ground truth would be based on objective measurements and engineered conditions that reliably indicate a PMT malfunction within the Revogene instrument's optics system. This could involve simulating PMT degradation, intentionally causing component failures, or verifying against known hardware states.
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The sample size for the training set:
- Not specified. For a diagnostic algorithm like this, the "training set" would involve data collected from instrument operations, potentially including data from instruments with known good or failing PMT conditions, to develop and refine the detection algorithms. The complexity of the algorithm (e.g., rule-based vs. machine learning) would influence the need for and size of a specific "training set." Given the description, it sounds more like a rule-based or threshold-based detection system rather than a complex machine learning model that requires a large, annotated training set in the typical sense.
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How the ground truth for the training set was established:
- If a "training set" was used (e.g., for setting detection thresholds or developing rules), the ground truth would have been established by engineering teams through controlled experiments, measurements of PMT performance over time, and potentially by inducing known PMT issues on instruments. This would involve characterization of the instrument's optical signals under various conditions, including states indicative of PMT malfunction.
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July 11, 2022
Meridian Bioscience, Inc Jack Rogers Regulatory Affairs Principal 3471 River Hills Drive Cincinnati, Ohio 45244
Re: K220480
Trade/Device Name: Revogene Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation For Clinical Multiplex Test Systems Regulatory Class: Class II Product Code: OOI Dated: February 17, 2022 Received: February 18, 2022
Dear Jack Rogers:
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
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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,
Ribhi Shawar, Ph.D. (ABMM) Branch Chief, General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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) K220480
Device Name Revogene
Indications for Use (Describe)
The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.
| 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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510(k) SUMMARY INSTRUMENT ONLY
A. Applicant Information
| Submission Date: | February 17, 2022 |
|---|---|
| Submitter Information: | Meridian Bioscience, Inc.3471 River Hills DriveCincinnati, Ohio 45244 |
| Contact Person: | Jack RogersRegulatory Affairs PrincipalMeridian Bioscience, IncTel: 513-271-3700Email: Jack.Rogers@meridianbioscience.com |
B. Proprietary and Established Names
Revogene®
C. Regulatory Information
| Trade Name: | Revogene® |
|---|---|
| Common name: | Revogene instrument |
| Regulation Number: | 21 CFR 862.2570 |
| Regulation Name: | Instrumentation for clinical multiplex systems |
| Regulatory Classification: | Class II |
| Product Code: | OOI – Real-time nucleic acid amplification |
| Panel: | Clinical Chemistry |
D. Purpose of Submission
To update the current Revogene® software with a PMT surveillance algorithm that includes an improvement to the Revogene System Software's management of fluorescence results. This change does not affect the device's intended use nor alter the device's fundamental scientific technology.
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E. Intended Use
| Intended Use: | The Revogene® instrument is intended for in vitro diagnostic(IVD) use in performing nucleic acid testing of specific IVDassays in clinical laboratories. Revogene is capable of automatedlysis and dilution of samples originating from various clinicalspecimen types. Revogene performs automated amplification anddetection of target nucleic acid sequences by fluorescence-basedreal-time PCR. |
|---|---|
| Indications for Use: | See Intended Use statement. |
| Special Conditions forUse Statement: | For prescription use onlyFor in vitro diagnostic use only |
| Special InstrumentRequirements: | MOCK PIE (use if less than 8 samples processed in a single run) |
F. Device Modification Description
The Revogene was previously cleared under K170558. Meridian Biosciences, Inc. is submitting this 510(k) to implement a software modification to the Revogene that updates the current software with a PMT surveillance algorithm. The software monitors raw data fluorescence signal during assay testing and identifies issues due to a malfunction of the photomultiplier tube (the "PMT"), a key component in the Revogene instrument's optics system used in the management of fluorescence signals. Upon detection of a PMT malfunction, the PMT surveillance algorithm software produces a specific error code to the user labeled "Detection Error" and will lock the instrument thereby preventing further use.
G. Substantial Equivalence Information
| Predicate device: | Revogene® |
|---|---|
| Predicate Device Number: | K170558 |
Comparison with Predicate:
| Modified Device | Predicate Device | |
|---|---|---|
| Item | Revogene®(Subject of 510(k)) | Revogene® (K170558) |
| Classification | Class II | Same |
| Intended Use | The Revogene® instrument is intended for invitro diagnostic (IVD) use in performing nucleicacid testing of specific IVD assays in clinicallaboratories. Revogene is capable of automatedlysis and dilution of samples originating fromvarious clinical specimen types. Revogeneperforms automated amplification and detectionof target nucleic acid sequences by fluorescence-based real-time PCR. | Same |
| Sample PreparationMethod | Automated cell lysis, DNA amplification andDNA detection | Same |
| Item | Modified DeviceRevogene®(Subject of 510(k)) | Predicate DeviceRevogene® (K170558) |
| Mode of Operation | Real-time Polymerase chain reaction withfluorogenic detection of amplified DNA | Same |
| Sample analysis andresult determination | Combination of software, instrument controlprotocols and assay definition files developedand determined by Meridian | Same |
| Level of Concern | Moderate | Same |
| Automatic Assay | Yes-result interpretation | Same |
| Sampleidentification | The instrument has two barcode readers toidentify reagents and patient specimens. Itprovides traceability of the sample ID to the PIEID, SBT ID, and assay ID. | Same |
| Internal ProcessControlDNA assays | Each PIE contains an internal process control(PrC) that controls for amplification inhibition,assay reagents, and sample processingeffectiveness. | Same |
| Internal ProcessControlRNA assays | Each PIE contains an Internal Control (IC) thatcontrols for amplification inhibition, and assayreagents effectiveness.Sample processing is monitored by aMicrofluidic Control (MFC). | Same |
| External Control | Materials available commercially but notrequired to run the test | Same |
| DNA Extraction | Cell lysis | Same |
| Specimens per run | Processes and analyzes up to 8 specimens perrun (8 PIEs) | Same |
| Assay Cartridge | One sample per PIE | Same |
| Single Use | PIE can be used only once | Same |
| Instrument OpticalChannels | Contains 4 optical channels | Same |
| InstrumentCalibration | The system is factory calibrated by themanufacturer and will undergo performancequalification testing on-site during annualpreventive maintenance. If qualification testingresults determine significant drift, the instrumentwill be returned to the manufacturer for re-calibration. | Same |
| Software Change | Update of the current software with a PMTsurveillance algorithm | - |
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H. Performance Characteristics
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2. Clinical Performance
See K170558 (Revogene Instrument), K140557 (Revogene GBS LB), K172569 (Revogene C. difficile), K183366 (Revogene Strep A), K190275 (Revogene Carba C)
I. Conclusion
The submitted information demonstrates that the modified Revogene instrument is safe, effective, and substantially equivalent to the legally marketed device.
§ 862.2570 Instrumentation for clinical multiplex test systems.
(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.