← Product Code [PLO](/submissions/MI/subpart-d%E2%80%94serological-reagents/PLO) · K160462

# FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray Torch (K160462)

_Biofire Diagnostics, LLC · PLO · Mar 17, 2016 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PLO/K160462

## Device Facts

- **Applicant:** Biofire Diagnostics, LLC
- **Product Code:** [PLO](/submissions/MI/subpart-d%E2%80%94serological-reagents/PLO.md)
- **Decision Date:** Mar 17, 2016
- **Decision:** SESE
- **Submission Type:** Special
- **Regulation:** 21 CFR 866.3970
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The FilmArray Meningitis/Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray, FilmArray Torch systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae. Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus. Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system (CNS) infection. Not all agents of CNS infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling CNS medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing.

## Device Story

Multiplexed nucleic acid test; uses FilmArray Torch system. Input: CSF sample mixed with buffer; loaded into disposable pouch. Process: Automated mechanical/chemical lysis; magnetic bead purification; nested multiplex RT-PCR; high-resolution DNA melt analysis. Output: Automated identification of 14 CNS pathogens. Used in clinical labs; operated by technicians. Software guides user through loading/scanning; interprets melt curves; generates report. Results aid diagnosis in conjunction with clinical/lab data; supports clinical decision-making regarding meningitis/encephalitis management. Benefits: Rapid (approx. 1 hour) identification of pathogens compared to standard culture.

## Clinical Evidence

Bench testing only. Intra-laboratory precision study compared 9 FilmArray Torch modules against 9 FilmArray 2.0 instruments; all analytes detected at 1x LoD in ≥95% of samples. Method comparison studies (synthetic template, negative samples, representative organisms) showed ≥95% positive agreement and 100% negative agreement. Melting temperature variation was within ±0.5°C. WHO International Standard for CMV confirmed detection at established LoD.

## Technological Characteristics

Nested multiplex real-time PCR; high-resolution melting analysis; CMOS camera for fluorescent imaging. Integrated tower configuration with up to 12 modules. Software-driven kiosk-style touch-screen interface. Ethernet connectivity. Automated sample processing and edge-loading mechanism. Compliant with ISO 14971:2012 for risk management.

## Regulatory Identification

A device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid is a qualitative in vitro device intended for the detection and identification of microbial-associated nucleic acid sequences from patients suspected of meningitis or encephalitis. A device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid is intended to aid in the diagnosis of meningitis or encephalitis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.

## Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical studies: Analytical sensitivity (limit of detection), inclusivity, reproducibility, interference, cross reactivity, and specimen stability.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted comparator methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) The Intended Use statement in the device labeling must include a statement that the device is intended to be used in conjunction with standard of care culture.
(6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(7) The device labeling must include a limitation stating that the negative results do not preclude the possibility of central nervous system infection.
(8) The device labeling must include a limitation stating that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions.
(9) The device labeling must include a limitation stating that positive results do not mean that the organism detected is infectious or is the causative agent for clinical symptoms.
(10) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.

## Predicate Devices

- FilmArray Meningitis/Encephalitis (ME) Panel for use with the FilmArray and FilmArray 2.0 systems ([DEN150013](/device/DEN150013.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

{0}

SPECIAL 510(k): Device Modification OIR Decision Memorandum

To: BioFire Diagnostics, LLC

RE: K160462

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II device requiring 510(k). The following items are present and acceptable:

1. The name and de novo application number of the SUBMITTER'S previously cleared device.

Trade Name: FilmArray Meningitis/Encephalitis (ME) Panel for use with the FilmArray and FilmArray 2.0 systems
De Novo Application: DEN150013

2. Submitter's statement that the INDICATION/INTENDED USE of the modified device, called "FilmArray® Meningitis/Encephalitis Panel for use with FilmArray systems," as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling.

Submitter states in the 510(k) Summary and in the submission that the intended use of the modified device has not changed from its predicate. The intended use of the modified device remains the same in the labeling.

3. A description of the device MODIFICATION(S), including clearly labeled diagrams, engineering drawings, photographs, user's and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

The modifications made to the FilmArray 2.0 system to configure the FilmArray Torch aimed to increase throughput capacity and benchtop workspace through single tower housing. Changes include:

- a reconfigured base instrument tower with optional, stacked, individual instrument modules,
- workflow altered for a manual read of the assay pouch's bar-code by the operator instead of automatic read within instrument,
- automatic edge-loading mechanism is used to load hydration reagents and clinical samples instead of a manual top-loading technique,
- automatic partial ejection of the assay pouch following conclusion of a run rather than manual removal of the pouch,
- printer is optional instead of included with the system,
- computer, barcode scanner, and touch screen interface integrated into the base of the tower configuration instead of a separate computer set-up,
- operation with kiosk-style (touch-screen) software,
- labeling appended with an additional operational procedure and with statements describing the validation/verification studies (i.e. LoD and reproducibility); these studies included an intra-laboratory precision study for the modified device.

4. Comparison Information (similarities and differences) to applicant's legally marketed predicate device including, labeling, intended use, physical characteristics, and software is shown in the table below.

{1}

Page 2 of 5

SIMILARITIES

|  ITEM | PREDICATE
FilmArray Meningitis/Encephalitis (ME)
Panel for use with FilmArray System
(FilmArray 2.0)
(DEN150013) | MODIFIED DEVICE
FilmArray Meningitis/Encephalitis (ME)
Panel for use with FilmArray Torch
(K160462)  |
| --- | --- | --- |
|  Organisms Detected | Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae, Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, and Cryptococcus neoformans/gattii | SAME  |
|  Analyte | DNA/RNA | SAME  |
|  Specimen Types | Cerebrospinal fluid (CSF) from lumbar puncture | SAME  |
|  Required Accessories and Reagents | FilmArray reagent kit stored at room temperature | SAME  |
|  Sample Loading | Syringe-based loading | SAME  |
|  Sample Preparation Protocol and Processing Steps | Automated sample processing occurs in the FilmArray ME pouch | SAME  |
|  Technological Principles | Nested multiplex real-time PCR with post-amplification analysis by high resolution melting that confirms the identity of each amplified product | SAME  |
|  Instrumentation-Software Communication | Communication from multiple FilmArray Torch modules travels via Ethernet cable/port | SAME (multiple FilmArray instruments)  |
|  Instrumentation-Core Software Functions | Step-by-step on-screen instructions that guide the operator through performing a run by utilizing a kiosk-style interaction (touch-screen interface) | SAME (operator must use the computer's mouse to navigate through protocols and instructions on-screen)  |
|  Instrumentation Optics | Complimentary metal-oxide semiconductor (CMOS) camera used for capturing fluorescent images of the PCR2 reactions | SAME  |

{2}

Page 3 of 5

|  Time to Result | Approximately 1 hour | SAME  |
| --- | --- | --- |
|  Test Interpretation and Results Reporting | Automated test interpretation and results reporting; user cannot access raw data; test report can be printed at the end of the run | SAME  |
|  Controls | Two internal controls (RNA processing control and PCR2 control) are stored in each reagent pouch to ensure all steps carried out in the pouch were successful | SAME  |
|  User Complexity | Moderate/Low | SAME  |

## DIFFERENCES

|  ITEM | PREDICATE
FilmArray Meningitis/Encephalitis (ME)
Panel for use with FilmArray System
(FilmArray 2.0)
(DEN150013) | MODIFIED DEVICE
FilmArray Meningitis/Encephalitis (ME)
Panel for use with FilmArray Torch
(K160462)  |
| --- | --- | --- |
|  Instrumentation and Set-Up | FilmArray 2.0 system that can include up to 8 separate instruments (8 pouch testing capability) connected to a single, stand-alone computer, barcode scanner, keyboard, and mouse | FilmArray Torch containing up to 12 FilmArray Torch modules (12-pouch testing capability) with a computer, barcode scanner, and touch-screen user interface incorporated in the system's base  |
|  Pouch Loading and Ejection | Manual top-loading mechanism; manual ejection after completion of run | Automated edge-loading mechanism; automatic partial ejection after completion of run  |
|  Workflow for Pouch Insertion | Pouch is automatically scanned within instrument | User must manually scan pouch prior to loading  |
|  Additional System Configuration | Printer is included with system | Printer is an optional component of the system  |

The indications for use provided below are identical for both devices.

## FilmArray 2.0 (K160462) Indications for use (same as DEN150013):

The FilmArray Meningitis/Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based *in vitro* diagnostic test intended for use with FilmArray systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: *Escherichia coli K1*, *Haemophilus influenzae*, *Listeria monocytogenes*, *Neisseria meningitidis* (encapsulated), *Streptococcus agalactiae*, *Streptococcus pneumoniae*, Cytomegalovirus, Enterovirus, Herpes simplex virus 1,

{3}

Page 4 of 5

Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, and Cryptococcus neoformans/gatti.

The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system (CNS) infection. Not all agents of CNS infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert.

The FilmArray ME Panel is not intended for testing of specimens collected from indwelling CNS medical devices.

The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing.

5. A Design Control Activities Summary which includes:

a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis

A risk analysis of the modifications made to reconfigure the FilmArray 2.0 system into the integrated tower configuration of the FilmArray Torch was successfully completed in the context of 21 CFR 807.81 and the appropriate guidance. Reconfiguration of the platform did not alter the performance or capabilities of the device when run with the FilmArray ME Panel. Risk management of the FilmArray Torch Software and Firmware followed processes that were compliant with ISO 14971:2012.

b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied

In order to both validate and verify the FilmArray ME Panel for use on the FilmArray Torch, studies were completed to address risks associated with false negative, false positive, and delayed or no results. An intra-laboratory precision study was conducted between three FilmArray Torch systems (containing three Torch modules within each system for a total of 9 FilmArray Torch Modules per sample) and three sets of three FilmArray 2.0 instruments for a total of 9 FilmArray instruments. Results demonstrated that all analytes in the FilmArray ME Panel (at 1x LOD) were detected in at least 95% of the samples tested on both platforms. 100% of "Not Detected" results were observed for all analytes in the negative samples tested with the exception of H. influenzae that demonstrated a 98.3% agreement with the expected negative result. Additionally, melting temperature values were evaluated among the systems and results fell within the acceptance criteria of a standard deviation of ±0.5°C or less for each target (known system variation on the FilmArray).

Method comparison studies were conducted for the modified device (FilmArray Torch with ME Panel) and its predicate device (FilmArray 2.0 with ME Panel). These included a synthetic template method comparison study, a negative sample method comparison study, and a representative organism method comparison study. For all studies, the positive agreement was ≥95% and the negative agreement was 100%.

{4}

Page 5 of 5

An additional study was completed using the WHO International Standard for Human Cytomegalovirus (HCMV) for Nucleic Acid Amplification Techniques on the FilmArray and FilmArray 2.0 systems. The standard was tested at the previously established LoD concentration. When testing samples containing the WHO CMV standard, CMV was detected by the FilmArray ME Panel in 100% of the replicates tested at the confirmed LoD concentration on both FilmArray systems. This information was included in the revised package insert.

c) Declaration of Conformity with Design Controls

A “Declaration of Conformity” statement was submitted for the BioFire Diagnostics, LLC manufacturing facility. It was signed by the Vice President, Regulated Products and Clinical Affairs, and the Director of Quality Assurance. The statements indicate that:

i. “To the best of my knowledge, the verification activities, as required by the risk analysis, for the modification were performed by the designated individual(s) and the results demonstrated that the predetermined acceptance criteria were met.”

ii. “The manufacturing facility, BioFire Diagnostics, LLC, is in conformance with the design control requirements as specified in 21 CFR 820.30 and the records are available for review.”

6. Conclusion

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter’s description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared device.

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PLO/K160462](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PLO/K160462)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com