The Alere™ i Influenza A & B assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in nasal swabs from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2012-2013 influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

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 department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Alere™ i Strep A:

Alere™ i Strep A is a rapid, instrument-based, molecular in vitro diagnostic test utilizing isothermal nucleic acid amplification technology for the qualitative detection of Streptococcus pyogenes, Group A Streptococcus bacterial nucleic acid in throat swab specimens obtained from patients with signs and symptoms of pharyngitis. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections.

All negative test results should be confirmed by bacterial culture because negative results do not prection with Group A Streptococcus and should not be used as the sole basis for treatment.

Device Description

Alere™ i Influenza A & B is a rapid, instrument-based isothermal tests for the qualitative detection and differentiation of influenza A and influenza B from nasal swabs collected from patients presenting with signs and symptoms of respiratory infection. Alere™ i Strep A is a rapid, instrument-based isothermal test for the qualitative detection of Group A Strep from throat swab specimens. Both Alere™ i Influenza A & B and Alere™ i Strep A Systems utilize isothermal nucleic acid amplification technology and are comprised of:

. Sample Receiver – single use, disposable containing the elution buffer
. Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
Transfer Cartridge single use, disposable for transfer of the eluted sample to the Test Base, and ●
Alere™ i Instrument – repeat use reader

The reaction tubes in the Alere™ i Influenza A & B Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i Influenza A & B utilizes a pair of templates (similar to primers) for the specific amplification of RNA from influenza A and B and a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets.

The reaction tubes in the Alere™ i Strep A Test Base contain the reagents required for Group A Strep bacterial lysis and the subsequent amplification of the target nucleic acid and an internal control. Alere™ i Strep A utilizes a pair of templates (similar to primers) for the specific amplification of DNA from Group A Strep and a fluorescently labeled molecular beacon designed to specifically identify the amplified nucleic acid target.

Both assays are performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This reduces the risk of instrument contamination and sample carry-over between measurements.

To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, resuspending the lyophilized pellets contained within the Test Base and initiating bacterial lysis (for Alere™ i Strep A) and target amplification. Heating, mixing and detection by fluorescence is provided by the instrument, with results automatically reported.

Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.

AI/ML Overview

The provided document describes the Alere™ i Instrument, Alere™ i Influenza A & B, and Alere™ i Strep A devices. This submission focuses on a software modification to the Alere™ i Instrument to allow it to run both the Influenza A & B and Strep A assays, rather than changes to the assays themselves. Therefore, the "acceptance criteria" and "device performance" in this context refer to demonstrating that the software modification does not negatively impact the performance of the previously cleared assays.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Rationale for the Study: The primary goal of this 510(k) submission (K151690) is to demonstrate that a software modification to the Alere™ i Instrument, which enables it to run both the Alere™ i Influenza A & B and Alere™ i Strep A assays, does not alter the established safety and effectiveness of these assays. The previous versions of these tests (Alere™ i Influenza A & B, K141520 and Alere™ i Strep A, K141757) were already cleared. Therefore, the study focuses on validating the software modification.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of numerical "acceptance criteria" for clinical performance that needed to be met by a de novo study of the device. Instead, the acceptance criterion for this submission is implicitly that the software modification does not change the performance of the previously cleared assays. The reported "performance" for the modified device is that its functionality remains unchanged compared to the predicate devices.

Acceptance Criterion (Implicit)	Reported Device Performance (with software modification)
No change in the established assay functionality for Alere™ i Influenza A & B due to the software modification.	Alere™ i Influenza A & B assay functionality remains unchanged.
No change in the established assay functionality for Alere™ i Strep A due to the software modification.	Alere™ i Strep A assay functionality remains unchanged.
The Alere™ i Instrument with modified software performs equivalently to the predicate devices for both assays.	The Alere™ i Influenza A & B and Alere™ i Strep A tests performed on the Alere™ i Instrument containing modified software are substantially equivalent to the current legally marketed devices (Alere™ i Influenza A & B and Alere™ i Strep A performed on the Alere™ i Instrument).
All technological characteristics (e.g., FDA Product Code, Assay Target, Intended Use, Instrumentation, Sample Type, Technology, etc.) remain identical to the predicate device.	All listed technological characteristics are "Same" as the predicate devices, with the exception of the "Instrument software" which is the subject of the modification.

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

The document explicitly states: "Software verification and validation studies performed demonstrated that Alere™ i Influenza A & B and Alere™ i Strep A assay functionality remains unchanged due to this change."

However, no specific sample sizes for a "test set" (e.g., number of patient samples, artificial samples) used in these software validation studies are provided in the excerpt. The data provenance (country of origin, retrospective/prospective) is also not detailed for these specific software validation studies. Given that the submission asserts "no changes to the Alere™ i Influenza A & B or Alere™ i Strep A tests," it's highly probable that the software validation primarily involved testing with internal samples or simulated data to ensure proper functionality and integration, rather than a new full-scale clinical study with patient samples. The information indicates the tests themselves had established performance characteristics from previous submissions.

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

Since the study described here is focused on software validation and demonstrating unchanged functionality of existing assays, rather than determining the initial clinical accuracy of the assays against a clinical ground truth, there is no mention of experts establishing a ground truth for a test set in this context.

4. Adjudication Method for the Test Set

As there is no mention of a clinical test set requiring expert ground truth, no adjudication method is described.

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

No MRMC comparative effectiveness study was mentioned. The device is an in vitro diagnostic test, not an AI software intended to assist human readers in image interpretation or a similar task. It is a standalone instrument that provides qualitative diagnostic results.

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

Yes, the performance of the Alere™ i Instrument is inherently standalone. The device processes the sample and provides an automated qualitative result ("Influenza A Detect", "Influenza B Detect", "Strep A Detect", or "Not Detected"). The "Software verification and validation studies" described would have assessed this standalone performance with the modified software.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For the original clinical performance studies of the Alere™ i Influenza A & B (K141520) and Alere™ i Strep A (K141757) assays, the ground truth would typically involve:

For Influenza A & B: Viral culture as the gold standard, or potentially a highly multiplexed PCR reference method, on patient nasal swab samples.
For Strep A: Bacterial culture as the gold standard on patient throat swab samples.

However, for this specific submission (K151690), the "software validation" would likely use pre-characterized samples (e.g., positive and negative control samples, spiked samples with known concentrations of nucleic acid targets) or previously run clinical samples with known results from predicate studies, to verify that the software processes them identically and yields the same results. The document does not specify the ground truth for these software validation studies, but it would not be a new clinical ground truth establishment.

8. The Sample Size for the Training Set

No training set is mentioned in the context of this software modification. The assays themselves are isothermal nucleic acid amplification tests, not machine learning algorithms that require a training set in the typical sense. Any "training" would have been part of the initial development and optimization of the assays prior to the K141520 and K141757 submissions.

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

Not applicable, as no training set for a machine learning model is described.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 16, 2015

ALERE SCARBOROUGH, INC. ANGELA DRYSDALE VP REGULATORY & CLINICAL AFFAIRS-INFECTIOUS DISEASE 10 SOUTHGATE ROAD SCARBOROUGH ME 04074

Re: K151690 Trade/Device Name: Alere™ i Instrument. Alere™ i Influenza A & B, Alere™ i Strep A Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation for clinical multiplex test systems Regulatory Class: II Product Code: OOI, OCC, OZE, PGX Dated: June 22, 2015 Received: June 23, 2015

Dear Ms. Drysdale:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Ribhi Shawar-S 2015.07.16 13:25:50 -04'00' For

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K151690

Device Name Alere™ i Instrument, Alere™ i Influenza A & B, Alere™ i Strep A

Indications for Use (Describe)

Alere™ i Influenza A & B:

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Alere™ i Strep A:

All negative test results should be confirmed by bacterial culture because negative results do not prection with Group A Streptococcus and should not be used as the sole basis for treatment.

Type of Use ( Select one or both, as applicable )
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☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(K) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K151690

SUBMITTER

Alere Scarborough, Inc. 10 Southgate Road Scarborough, ME 04074 Establishment Registration Number: 1221359

CONTACT PERSON

Angela Drysdale (207) 730-5737 (Office) (207) 730-5767 (FAX) angela.drysdale@alere.com (email)

DATE PREPARED

7/14/2015

TRADE NAME

Alere™ i Instrument Alere™ i Influenza A & B Alere ™ i Strep A

COMMON NAME

Alere™ i flu, Alere™ i, Alere™ Influenza A & B Alere™ i Strep, Alere™ i, Alere™ Strep A

REGULATION NAME

Instrumentation for Clinical Multiplex Test Systems (per 21 CFR 862.2570) Respiratory Viral Panel Multiplex Nucleic Acid Assay (per 21 CFR 866.3980) Groups A, C and G Beta Hemolytic Streptococcus Nucleic acid Amplification System (per 21 CFR 866.2680)

CLASSIFICATION

Class II

PRODUCT CODES

001, OCC, OZE, PGX

PANEL Microbiology (83)

PREDICATE DEVICES

Alere™ i Influenza A & B, K141520 Alere ™ i Strep A, K141757

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DEVICE DESCRIPTION

. Sample Receiver – single use, disposable containing the elution buffer
. Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
Transfer Cartridge single use, disposable for transfer of the eluted sample to the Test Base, and ●
Alere™ i Instrument – repeat use reader

INTENDED USE

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

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Performance characteristics for influenza A were established during the 2012-2013 influenza season when influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

Alere™ i Strep A is a rapid, instrument-based, molecular in vitro diagnostic test utilizing isothermal nucleic acid amplification technology for the qualitative detection of Streptococcus pyogenes, Group A Streptococcus bacterial nucleic acid in throat swab specimed from patients with signs and symptoms of pharyngitis. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections.

All negative test results should be confirmed by bacterial culture because negative results do not preclude infection with Group A Streptococcus and should not be used as the sole basis for treatment.

TECHNOLOGICAL CHARACTERISTICS

Both assays are rapid, instrument-based, molecular in vitro diagnostic tests utilizing isothermal nucleic acid amplification technology for the qualitative detection of influenza A and B viral RNA or Streptococcus pyogenes, Group A Streptococcus bacterial nucleic acid.

DEVICE COMPARISON

The purpose of this submission is due to a modification of the software contained on the Alere™ i Instrument, there have been no changes to the Alere™ i Influenza A & B or Alere™ i Strep A tests. To enable launch of the Alere™ i Strep A test on the Alere™ i platform, a modification to the software was required to allow the user to run both the Alere™ i Influenza A & B and Alere™ i Strep A assays on the same instrument.

Alere™ i Influenza A & B incorporating the software modification was compared to the legally marketed predicate device, the 510(k) cleared Alere™ i Influenza A & B test.

Parameter	Alere™ i Influenza A & B(with software modification)	Alere™ i Influenza A & B (K141520)
FDA Product Code	OCC,OZE, OOI	Same
Assay Target	Influenza A, Influenza B	Same
Intended Use	The Alere™ i Influenza A & B assayperformed on the Alere™ i Instrument isa rapid molecular in vitro diagnostic testutilizing an isothermal nucleic acidamplification technology for thequalitative detection and discriminationof influenza A and B viral RNA in nasalswabs from patients with signs andsymptoms of respiratory infection. It isintended for use as an aid in thedifferential diagnosis of influenza A andB viral infections in humans inconjunction with clinical andepidemiological risk factors. The assay isnot intended to detect the presence of	Same

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Parameter	Alere™ i Influenza A & B(with software modification)	Alere™ i Influenza A & B (K141520)
	influenza C virus.
	Negative results do not precludeinfluenza virus infection and should notbe used as the sole basis for diagnosis,treatment or other patient managementdecisions.
	Performance characteristics for influenzaA were established during the 2012-2013 influenza season when influenzaA/H3 and A/H1N1 pandemic were thepredominant influenza A viruses incirculation. When other influenza Aviruses are emerging, performancecharacteristics may vary.
	If infection with a novel influenza A virusis suspected based on current clinicaland epidemiological screening criteriarecommended by public healthauthorities, specimens should becollected with appropriate infectioncontrol precautions for novel virulentInfluenza viruses and sent to state orlocal health department for testing. Viralculture should not be attempted in thesecases unless a BSL 3+ facility is availableto receive and culture specimens.
Intended Environmentfor Use	Professional use, in a medical laboratoryor point of care	Same
Instrumentation	Alere™ i Instrument	Same
Self-Contained System	Integrated PC, Software, and TouchScreen Display	Same
Automated Assay	Yes. Sample preparation, amplification,detection, and result interpretation.	Same
Assay InformationSample Type	Nasal Swab	Same
Influenza A Viral Target	PB2 segment	Same
Influenza B Viral Target	PA segment	Same
Technology	Isothermal nucleic acid amplification fordetecting the presence/absence of viralRNA in clinical specimens	Same
Detection Method	Assay uses different reporter dyes foreach target	Same
Internal Control	Yes	Same
Result Interpretation	Automated	Same
Assay Result	Qualitative	Same
Time to Result	< 15 minutes	Same

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Parameter	Alere™ i Influenza A & B(with software modification)	Alere™ i Influenza A & B (K141520)
Instrument software	Allow the user to run both the Alere™ i Influenza A & B and Alere™ i Strep A assays on the same instrument.	Allow the user to run only the Alere™ i Influenza A & B assay

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Alere™ i Strep A incorporating the software modification was compared to the legally marketed predicate device, the 510(k) cleared Alere™ i Strep A test.

Parameter	Alere™ i Strep A(with software modification)	Alere™ i Strep A(K141757)
FDA Product Code	PGX, OOI	Same
Assay Target	Streptococcus pyogenes	Same
Intended Use	Alere™ i Strep A is a rapid, instrument-based, molecular in vitro diagnostic test utilizing isothermal nucleic acid amplification technology for the qualitative detection of Streptococcus pyogenes , Group A Streptococcus bacterial nucleic acid in throat swab specimens obtained from patients with signs and symptoms of pharyngitis. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections.All negative test results should be confirmed by bacterial culture because negative results do not preclude infection with Group A Streptococcus and should not be used as the sole basis for treatment,	Same
Instrumentation	Alere™ i Instrument	Same
Assay Information
Sample Type	Throat Swab	Same
Target Analyte	Group A Streptococcus ( Streptococcus pyogenes )	Same
Technology	Isothermal nucleic acid amplification	Same
Internal Control	Yes	Same
Result Interpretation	Automated	Same
Assay Result	Qualitative	Same
Time to Result	< 8 minutes	Same
Instrument software	Allow the user to run both the Alere™ i Influenza A & B and Alere™ i Strep A assays on the same instrument.	Allow the user to run only the Alere™ i Strep A assay

SOFTWARE VALIDATION

Software verification and validation studies performed demonstrated that Alere™ i Influenza A & B and Alere™ i Strep A assay functionality remains unchanged due to this change.

The results of the software validation studies performed with the Alere™ i Instrument, demonstrate the Alere™ i Influenza A & B and Alere™ i Strep A tests performed on the Alere™ i Instrument containing modified software is substantially equivalent to the current legally marketed device, Alere™ i Influenza A & B and Alere™ i Strep A performed on the Alere™ i Instrument.

Regulation Number and Section

§ 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.