BioFire RP2.1/RP2.1plus Control Panel M441 is intended for use as an external positive and negative assayed quality control to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H1-2009, Influenza A subtype H3, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza Virus, Respiratory Syncytial Virus, Severe Acute Respiratory Syndrome Coronavirus 2, Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae on the BioFire Respiratory Panel 2.1 (RP2.1), BioFire Respiratory Panel 2.1 plus) and BioFire Respiratory Panel 2.1-EZ (RP2.1-EZ) assay performed on the BioFire FilmArray systems. BioFire RP2.1/RP2.1plus Positive control is composed of synthetic RNA transcripts specifically designed for and intended to be used solely with the BioFire RP2.1phus and BioFire RP2.1-EZ assay. This product is not intended to replace manufacturer controls provided with the device.

Device Description

BioFire RP2.1/RP2.1plus Control Panel M441, P/N M441, is a quality control panel consisting of 2 ready-to-use, liquid controls, BioFire RP2.1/RP2.1plus Positive (Positive Control) and BioFire RP2.1/RP2.1plus Negative Control). The Positive Control contains noninfectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA carries segments of all respiratory pathogens detected by the BioFire® Respiratory Panel 2.1 (RP2.1), BioFire® Respiratory Panel 2.1plus (RP2.1plus), and BioFire® Respiratory Panel 2.1-EZ (RP2.1-EZ) assays (Table 1. below) on the BioFire® FilmArray systems, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). BioFire RP2.1/RP2.1plus Negative contains buffer and preservatives with no RNA. Each liquid control of BioFire RP2.1/RP2.1plus Control Panel M441 is processed separately according to BioFire RP2.1, RP2.1plus, and RP2.1-EZ assays manufacturer's Instructions for Use for patient samples (nasopharyngeal swabs) obtained from individuals suspected of respiratory tract infection and placed in Viral Transport Media (VTM)).

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Correct detection of Positive Control results	100% (86/86 correct positive control results in internal and external studies, excluding 1 invalid result. In external site testing, 26/26 positive controls were correct. In precision testing, all 60 positive controls were correct across 3 lots.)
Correct detection of Negative Control results	100% (85/85 correct negative control results in internal and external studies, excluding 1 invalid result. In external site testing, 25/25 negative controls were correct. In precision testing, all 60 negative controls were correct across 3 lots.)
Invalid Rate	1 out of 172 total tests (0.58%) across internal and external studies. In external site testing, 1 out of 52 tests (1.9%) was invalid. In precision testing, 0 out of 120 tests were invalid.
Robust and Reproducible performance across multiple control and reagent lots	Demonstrated through precision testing at MMQCI facility over 20 days using 3 pouch lots and 3 operators on two instruments, showing 100% correct results for all positive and negative controls. External study also demonstrated robust performance across 3 pouch lots, multiple instruments, and operators.

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

Total Test Set Sample Size: 172 tests (Internal and External studies combined).
- Internal Study: 120 tests (Precision testing).
- External Study: 52 tests.
Data Provenance:
- Internal Study: Performed at MMQCI's facility in Saco, Maine, USA.
- External Study: Performed at an independent U.S. facility.
Retrospective/Prospective: The studies appear to be prospective as they involved testing newly manufactured lots of the control panel on BioFire FilmArray systems under specified conditions.

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

This information is not provided in the document. For quality control materials like the BioFire RP2.1/RP2.1plus Control Panel M441, the "ground truth" is inherent to the composition of the control. The positive control is designed to contain synthetic RNA transcripts for specific pathogens, and the negative control is designed to not contain them. The "correctness" of results is determined by whether the BioFire FilmArray system detects the expected pathogens in the positive control and no pathogens in the negative control. It doesn't rely on human expert interpretation of results, but rather on the objective measurement by the instrument.

4. Adjudication Method for the Test Set

This information is not applicable as the "ground truth" for quality control materials is defined by their manufacturing composition and expected reaction, not by expert interpretation requiring adjudication. Results are either "correct" (matching the known composition) or "incorrect," or "invalid" by the instrument.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This device is an assayed quality control material for clinical microbiology assays, not an AI-powered diagnostic device that would assist human readers in interpreting clinical cases. Therefore, the concept of human readers improving with AI assistance is not applicable here.

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

This question is not applicable as the device is a physical quality control material, not a software algorithm. The "performance" being evaluated is how reliably the BioFire FilmArray system detects the components of the control panel. The control panel itself does not operate as a standalone algorithm.

7. The Type of Ground Truth Used

The ground truth used is the known composition of the control material.

Positive Control: Contains synthetic RNA transcripts for all respiratory pathogens detected by the BioFire® Respiratory Panel 2.1 (RP2.1), BioFire® Respiratory Panel 2.1plus (RP2.1plus), and BioFire® Respiratory Panel 2.1-EZ (RP2.1-EZ) assays, including SARS-CoV-2.
Negative Control: Contains buffer and preservatives with no RNA.

8. The Sample Size for the Training Set

This information is not applicable/not provided in the context of this device. This device is a quality control material, not a machine learning model that requires a training set. The manufacturing process and formulation are based on established molecular biology principles, not on training data.

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

This information is not applicable as there is no "training set" for this quality control material.

Summary

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

Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Maine Molecular Quality Controls, Inc. Joan Gordon President 23 Mill Brook Road Saco, Maine 04072

June 24, 2021

Re: K202196

Trade/Device Name: BioFire RP2.1/RP2.1plus Control Panel M441 Regulation Number: 21 CFR 866.3920 Regulation Name: Assayed quality control material for clinical microbiology assays Regulatory Class: Class II Product Code: PMN Dated: July 30, 2020 Received: August 5, 2020

Dear Joan Gordon:

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 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

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

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.

Kristian Roth, Ph.D. Deputy Director (Acting) 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) K202196

Device Name BioFire RP2.1/RP2.1plus Control Panel M441

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Image /page/3/Picture/0 description: The image shows the logo for Maine Molecular Quality Controls, Inc. The logo features the acronym "MMQCI" in a stylized font, with "MM" in dark red and "QCI" in yellow. A yellow abstract design is to the left of the acronym. Below the acronym, the full name of the company, "MAINE MOLECULAR QUALITY CONTROLS, INC.", is written in a smaller, sans-serif font.

23 Mill Brook Road Mill Brook Business Park Saco, Maine 04072 www.mmaci.com Phone: 207-885-1072 Fax: 207-885-1079

Section 5: 510 (k) Summary

510(k) Number:

Purpose for submission: New product

Applicant Information:

Applicant:	Maine Molecular Quality Controls, Inc.
Address:	23 Mill Brook RoadSaco, Maine 04072

Contact Person:	Joan Gordon, President MMQCI
Phone:	207-885-1072 extension 201
Fax:	207-885-1079
Email Address:	jgordon@mmqci.com

Preparation Date: July 30, 2020

Device

Device Trade Name:	BioFire RP2.1/RP2.1plus Control Panel M441
Device Common Name:	Quality Control Material for Microbiology Assays
Device Type:	Assayed quality control material for clinical microbiology assays
Class:	Class II (Special controls)
Regulation:	21 CFR 866.3920
Panel:	Microbiology - 83
Product code:	PMN

Predicate Device

K173171; FilmArray RP2/RP2plus Control Panel, P/N 315

Device Description

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

Image /page/4/Picture/0 description: The image shows the logo for MMQCI, which stands for Maine Molecular Quality Controls, Inc. The logo features the letters "MM" in a dark red color, with the letters "QCI" in yellow. A yellow swirl design is to the left of the letters. The full name of the company is written in smaller font below the letters.

Control Panel M441 is processed separately according to BioFire RP2.1, RP2.1plus, and RP2.1-EZ assays manufacturer's Instructions for Use for patient samples (nasopharyngeal swabs) obtained from individuals suspected of respiratory tract infection and placed in Viral Transport Media (VTM)).

Table 1. Respiratory pathogens detected by BioFire RP2.1, RP2.1plus, and RP2.1-EZassays.
Respiratory Pathogens
Adenovirus	Influenza B
Coronavirus 229E	Parainfluenza Virus 1
Coronavirus HKU1	Parainfluenza Virus 2
Coronavirus NL63	Parainfluenza Virus 3
Coronavirus OC43	Parainfluenza Virus 4
Middle East Respiratory Syndrome Coronavirus*	Respiratory Syncytial Virus
Severe Acute Respiratory Syndrome Coronavirus 2	Bordetella parapertussis (IS001)
Human Metapneumovirus	Bordetella pertussis (ptxP)
Human Rhinovirus/ Enterovirus	Chlamydia pneumoniae
Influenza A, subtypes H1, H1-2009, H3	Mycoplasma pneumoniae

*Detected by BioFire RP2.1plus assay only.

Device Intended Use

BioFire RP2.1/RP2.1plus Control Panel M441 is intended for use as an external positive and negative assayed quality control to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/ Enterovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H1-2009, Influenza A subtype H3, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza Virus, Respiratory Syncytial Virus, Severe Acute Respiratory Syndrome Coronavirus 2, Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae on the BioFire® Respiratory Panel 2.1 (RP2.1), BioFire® Respiratory Panel 2.1 plus) and BioFire® Respiratory Panel 2.1-EZ (RP2.1-EZ) assays performed on BioFire FilmArray® systems. BioFire RP2.1/RP2.1plus Positive control is composed of synthetic RNA transcripts specifically designed for and intended to be used solely with the BioFire RP2.1, BioFire RP2.1plus and BioFire RP2.1-EZ assays. This product is not intended to replace manufacturer controls provided with the device.

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

Image /page/5/Picture/0 description: The image shows the logo for MMQCI, which stands for Maine Molecular Quality Controls, Inc. The logo features the letters "MMQCI" in a combination of maroon and yellow. The words "MAINE MOLECULAR QUALITY CONTROLS, INC." are written in a smaller font below the letters. A yellow graphic is on the left side of the logo.

Substantial Equivalence

BioFire RP2.1/RP2.1plus Control Panel M441 is manufactured using processes and a formula identical to those for MMQCI's quality control FilmArray RP2/RP2plus Control Panel (K173171), except for the addition of SARS-CoV-2 synthetic RNA. The Intended Use of the 2 control panels is the same.

Characteristic	Candidate Device: BioFireRP2.1/RP2.1plus Control PanelM441	Predicate Device:FilmArrayRP2/RP2plus ControlPanel (K173171)
Intended Use	External assayed quality control tomonitor in vitro lab nucleic acid test	Same
Physical format	Ready-to-Use Liquid	Same
Directions for Use	Process like patient sample	Same
Composition	Synthetic RNA transcripts	Same
Assay steps monitored	Reverse transcription, amplification,detection, identification	Same
Number of targetsmonitored in one assay	Multiple	Same
Pathogens contained inthe control panel	Respiratory, including SARS-CoV-2	Same, not SARS-CoV-2

Summary Performance Data

Three lots of BioFire RP2.1/RP2.1plus Control Panel M441. BioFire RP2.1/RP2.1plus Positive (Positive Control), P/N M44321, and BioFire RP2.1/RP2.1plus Negative Control), P/N M44221, were manufactured by MMQCI. Internal studies were performed by testing the 3 lots with the BioFire® RP2.1/RP2.1plus assay on BioFire FilmArray Systems.

The internal study was performed by testing the 3 lots at MMQCI (Saco, Maine) over 2.5 weeks with 3 pouch lots by 3 operators. An external study was performed at an independent U.S. facility to assess performance of the BioFire RP2.1/RP2.1plus Control Panel M441 by independent operators on a large number of BioFire FilmArray instruments. The external performance study tested the 3 lots of BioFire RP2.1/RP2.1plus Control Panel M441 over a period of 8 days using 3 BioFire FilmArray pouch lots, incorporating multiple operators and instruments. Two of the BioFire pouch lots used at MMQCI were also used for testing at the external site, for a total of 4 pouch lots used across the 2 sites.

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

Image /page/6/Picture/0 description: The image shows the logo for Maine Molecular Quality Controls, Inc. (MMQCI). The logo features the letters "MMQCI" in a combination of maroon and yellow colors. To the left of the letters, there is a stylized, abstract design in yellow, resembling a brushstroke or a flowing ribbon. Below the letters, the full name of the company, "MAINE MOLECULAR QUALITY CONTROLS, INC.," is written in smaller, maroon font.

Results and Conclusion:

All BioFire RP2.1/RP2.1plus Control Panel M441 controls were correctly detected in the internal and external studies. There was one Invalid result.

Table 2. Summary of All Test Results: Internal and External Sites
Numberof Sites	TotalTests	Invalid	CorrectPositiveControlResult	IncorrectPositiveControlResult	PercentCorrectPositiveControl	CorrectNegativeControlResult	IncorrectNegativeControlResult	PercentCorrectNegativeControl
2	172	1*	86	0	100%	85	0	100%

*The Invalid result was not included in percent correct.

External Site Testing

A total of 52 BioFire RP2.1/RP2.1plus Control Panel M441 samples were tested between April 29, 2020 and May 8, 2020 at an external test site, independent of MMQCI. Three lots of Positive Control (D24APR20, F28APR20 C29APR20) and three lots of Negative Control (D11MAR20, F09JUL19, L22JUL19) were tested on three BioFire pouch lots, incorporating multiple operators and BioFire FilmArray instruments. All 52 controls tested were successful on the first attempt except for 1 Invalid pouch.

Results and Conclusion:

All BioFire RP2.1/RP2.1plus Positive controls and all BioFire RP2.1/RP2.1plus Negative controls gave correct results, with 1 Invalid pouch. BioFire RP2.1/RP2.1plus Control Panel M441 performed robustly when tested at the external site across 3 pouch lots, on multiple BioFire FilmArray 2.0 and Torch instruments/ modules, incorporating multiple operators.

Table 3. Summary of External Results for 3 Control Lots
TotalTests	Invalid	CorrectPositiveControlResult	IncorrectPositiveControlResult	PercentCorrectPositiveControl	CorrectNegativeControlResult	IncorrectNegativeControlResult	PercentCorrectNegativeControl
52	1*	26	0	100%	25	0	100%

The Invalid sample was not included in the Percent Correct analysis.

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

Image /page/7/Picture/0 description: The image contains the logo for Maine Molecular Quality Controls, Inc. The logo features the acronym "MMQCI" in a stylized font, with "MM" in a dark red color and "QCI" in yellow. To the left of the acronym is a yellow graphic that resembles a stylized strand of DNA or a brushstroke. Below the acronym, the full name of the company, "MAINE MOLECULAR QUALITY CONTROLS, INC.," is written in a smaller, sans-serif font.

Precision Testing

Precision was demonstrated by testing 3 lots of BioFire RP2.1/RP2.1plus Positive control and 3 lots of BioFire RP2.1/RP2.1plus Negative control at MMQCI's facility in Saco, Maine over 20 days with 3 pouch lots by 3 operators using two FilmArray® 2.0 instruments. All BioFire RP2.1/RP2.1plus Control Panel M441 controls were correctly detected. No Invalid results were seen.

Results and Conclusion:

BioFire RP2.1/RP2.1plus Control Panel M441 is a robust and reproducible control panel across multiple control and reagent lots.

Table 4. Summary of Precision Testing for 3 Control Lots at MMQCI
Control	Control Lot #	No. of Tests	Invalid	Correct Results	Incorrect Results	Percent Correct
FilmArray RP2.1/RP2.1plus Positive	D24APR20	20	0	20	0	100%
FilmArray RP2.1/RP2.1plus Positive	F28APR20	20	0	20	0	100%
FilmArray RP2.1/RP2.1plus Positive	C29APR20	20	0	20	0	100%
FilmArray RP2.1/RP2.1plus Negative	D11MAR20	20	0	20	0	100%
FilmArray RP2.1/RP2.1plus Negative	F09JUL19	20	0	20	0	100%
FilmArray RP2.1/RP2.1plus Negative	L22JUL19	20	0	20	0	100%
	TOTAL	120	0	120	0	100%

Regulation Number and Section

§ 866.3920 Assayed quality control material for clinical microbiology assays.

(a)
Identification. An assayed quality control material for clinical microbiology assays is a device indicated for use in a test system to estimate test precision or to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. This type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
(i) Analyte concentration;
(ii) Expected values;
(iii) Analyte source;
(iv) Base matrix;
(v) Added components;
(vi) Safety and handling information; and
(vii) Detailed instructions for use.
(2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including:
(i) Description of the process for value assignment and validation.
(ii) Description of the protocol(s) used to establish stability.
(iii) Line data establishing precision/reproducibility.
(iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance.
(v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method.
(vi) Where applicable, detailed documentation related to studies for surrogate controls.
(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.
(4) Your 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:
(A) Assayed control material analyte(s);
(B) Whether the material is intended for quantitative or qualitative assays;
(C) Stating if the material is a surrogate control; and
(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.
(ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.”
(iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.”