(30 days)
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 direct nasal swabs and nasal or nasopharyngeal swabs eluted in viral transport media 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 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 and the 2014-2015 influenza seasons 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.
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 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 and nasal or nasopharyngeal swabs eluted in viral transport media from patients presenting with signs and symptoms of respiratory infection. The Alere™ i Influenza A & B system utilizes isothermal nucleic acid amplification technology and is 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 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.
Alere™ i Influenza A & B is 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 target amplification. Heating 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.
The document describes the Alere™ i Influenza A & B device, a rapid molecular in vitro diagnostic test. The acceptance criteria and the study proving the device meets these criteria are detailed in the provided text, particularly in the section regarding the modifications and comparison to the predicate device.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text focuses on demonstrating substantial equivalence to a predicate device rather than outright acceptance criteria with specific performance thresholds. However, the intent of the study was to show that the modified device performs similarly to the predicate. The "Device Comparison" table implicitly sets the "acceptance criteria" as matching the predicate device's performance for the listed parameters.
| Parameter | Acceptance Criteria (Implicit) | Reported Device Performance (Modified Device) |
|---|---|---|
| FDA Product Code | Same as K151464 (OCC, OZE, OOI) | OCC, OZE, OOI |
| Assay Target | Same as K151464 (Influenza A, Influenza B) | Influenza A, Influenza B |
| Intended Use | Same as K151464 (See detailed description) | Same as K151464 (Detailed description provided) |
| Intended Env for Use | Same as K151464 (Professional use, medical lab or point of care) | Professional use, in a medical laboratory or point of care |
| Instrumentation | Same as K151464 (Alere™ i Instrument) | Alere™ i Instrument |
| Self-Contained System | Same as K151464 (Integrated PC, Software, Touch Screen Display) | Integrated PC, Software, and Touch Screen Display |
| Automated Assay | Same as K151464 (Yes. Sample prep, amplification, detection, result interp.) | Yes. Sample preparation, amplification, detection, and result interpretation. |
| Sample Type | Same as K151464 (Nasal Swab and Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media) | Nasal Swab and Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media |
| Influenza A Viral Target | Same as K151464 (PB2 segment) | PB2 segment |
| Influenza B Viral Target | Same as K151464 (PA segment) | PA segment |
| Technology | Same as K151464 (Isothermal nucleic acid amplification) | Isothermal nucleic acid amplification for detecting the presence/absence of viral RNA in clinical specimens |
| Detection Method | Same as K151464 (Different reporter dyes for each target) | Assay uses different reporter dyes for each target |
| Internal Control | Same as K151464 (Yes) | Yes |
| Result Interpretation | Same as K151464 (Automated) | Automated |
| Assay Result | Same as K151464 (Qualitative) | Qualitative |
| Time to Result | Same as K151464 (< 15 minutes) | < 15 minutes |
2. Sample size used for the test set and the data provenance
The document explicitly states that the submission is a "Special 510(k) submission due to a modification" and that the "Alere™ i Influenza A & B incorporating the assay modifications (modified device) was compared to the legally marketed predicate device, the 510(k) cleared Alere™ i Influenza A & B test."
- Sample Size for Test Set: The document does not provide specific numbers for the sample size of clinical or simulated samples used in the comparison study. It only describes the nature of the comparison.
- Data Provenance: Not specified in the provided text. The study likely involved laboratory testing comparing the modified device to the predicate, but details on clinical data (e.g., country of origin, retrospective/prospective) are not available.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. As this is a molecular diagnostic test for viral RNA, the "ground truth" would typically be established by highly sensitive and specific laboratory methods (e.g., PCR, sequencing, or viral culture) rather than expert consensus on interpretation of images or clinical findings.
4. Adjudication method for the test set
Not applicable in the context of this document. Adjudication methods like 2+1 or 3+1 are typical for subjective interpretations (e.g., image reading by multiple radiologists). For a molecular diagnostic test, results are typically objective (positive/negative) and are validated against a gold standard method.
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
- MRMC Study: No, an MRMC comparative effectiveness study was not done.
- Effect Size of AI Assistance: Not applicable. This device is a standalone in vitro diagnostic (IVD) test, not an AI-assisted diagnostic tool for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the study implicitly evaluates the standalone performance of the modified device (an algorithm/assay). The "device description" and "technological characteristics" clearly indicate that the Alere™ i Influenza A & B system provides automated results (amplification, detection, and result interpretation) without human interpretation of the assay itself. The comparison is between the modified device's performance and the predicate device's performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The document does not explicitly state the type of ground truth used for the comparison study. However, for an in vitro diagnostic device like this, the ground truth would typically be established by a well-characterized reference method, such as:
- Real-time RT-PCR (often considered the molecular gold standard for viral detection)
- Viral culture (though the document mentions not attempting viral culture in certain cases unless a BSL 3+ facility is available, implying RT-PCR is the primary method for novel strains).
Given the context of comparing molecular assays, it is highly probable that a highly sensitive and specific molecular reference method (e.g., RT-PCR) was used to define the true positive/negative status of samples for both the predicate and modified device.
8. The sample size for the training set
The document describes a "Special 510(k) submission due to a modification" where "an additional molecular beacon was added to address an identified mismatch with certain Flu B strains and the sugar excipient was modified to enable more efficient lyophilization."
This implies that the design of the molecular assay was modified. Such modifications typically don't involve a "training set" in the machine learning sense. Instead, the assay's components (primers/probes/excipients) are designed based on known viral sequences and biochemical principles, and then validated through testing.
Therefore, information on a "training set" in the context of machine learning is not provided because this is a molecular assay with a predefined mechanism, not a learned algorithm.
9. How the ground truth for the training set was established
As there is no mention of a "training set" in the machine learning sense, this information is not applicable and not provided. The development and optimization of the molecular assay's components (like the additional molecular beacon) would rely on existing knowledge of viral genomics and robust laboratory testing, rather than a "ground truth" derived from a training dataset.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an image of three human profiles facing to the right. The profiles are stacked on top of each other, with the first profile being the largest and the third profile being the smallest.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 21, 2016
ALERE SCARBOROUGH, INC. ANGELA DRYSDALE VP REGULATORY AFFAIRS - INFECTIOUS DISEASE 10 SOUTHGATE RD SCARBOROUGH ME 04074
Re: K163266
Trade/Device Name: Alere i Influenza A & B, Alere i Influenza A & B Control Swab Kit, Alere i Instrument Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OCC, OZE, OOI Dated: November 18, 2016 Received: November 21, 2016
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 (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
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/ResourcesforYou/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,
Himani Bisht -S 2016.12.21 14:36:55 -05'00'
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K163266
Device Name Alere™ i Influenza A & B
Indications for Use (Describe)
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 direct nasal swabs and nasal or nasopharyngeal swabs eluted in viral transport media 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 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 and the 2014-2015 influenza seasons 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.
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.
| 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}------------------------------------------------
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: K163266
SUBMITTER
Alere Scarborough, Inc. 10 Southgate Road Scarborough, ME 04074 Establishment Registration Number: 1221359
CONTACT PERSON
Angela Drysdale (207) 415-1393 (Office) (207) 730-5767 (FAX) angela.drysdale@alere.com (email)
DATE PREPARED
11/18/2016
TRADE NAME Alere™ i Influenza A & B
COMMON NAME Alere™ i flu, Alere™ i, Alere™ Influenza A & B
CLASSIFICATION NAME
Respiratory Viral Panel Multiplex Nucleic Acid Assay (per 21 CFR 866.3980) Instrumentation for Clinical Multiplex Test Systems (per 21 CFR 862.2570)
CLASSIFICATION Class II
PRODUCT CODE OCC, OZE, OOI
PANEL Microbiology (83)
PREDICATE DEVICES Alere™ i Influenza A & B, K151464
{4}------------------------------------------------
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 and nasal or nasopharyngeal swabs eluted in viral transport media from patients presenting with signs and symptoms of respiratory infection. The Alere™ i Influenza A & B system utilizes isothermal nucleic acid amplification technology and is 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 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.
Alere™ i Influenza A & B is 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 target amplification. Heating 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.
INTENDED USE
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 direct nasal or nasal or nasopharyngeal swabs eluted in viral transport media 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 and the 2014-2015 influenza seasons 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.
{5}------------------------------------------------
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.
TECHNOLOGICAL CHARACTERISTICS
Alere™ i Influenza A & B is an instrument-based, molecular in vitro diagnostic test utilizing isothermal nucleic acid amplification technology for the qualitative detection of influenza A and B viral RNA.
DEVICE COMPARISON
Alere Scarborough, Inc. is submitting this Special 510(k) submission due to a modification of Alere™ i Influenza A & B in which an additional molecular beacon was added to address an identified mismatch with certain Flu B strains and the sugar excipient was modified to enable more efficient lyophilization.
Alere™ i Influenza A & B incorporating the assay modifications (modified device) was compared to the legally marketed predicate device, the 510(k) cleared Alere™ i Influenza A & B test.
| Parameter | Alere™ i Influenza A & B(Modified Device) | Alere™ i Influenza A & B(K151464) |
|---|---|---|
| FDA Product Code | OCC,OZE, OOI | Same |
| Assay Target | Influenza A, Influenza B | Same |
| Intended Use | The Alere™ i Influenza A & B assay performed onthe Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermalnucleic acid amplification technology for thequalitative detection and discrimination ofinfluenza A and B viral RNA in direct nasal swabsand nasal or nasopharyngeal swabs eluted in viraltransport media from patients with signs andsymptoms of respiratory infection. It is intendedinfluenza A and B viral infections in humans inconjunction with clinical and epidemiological riskfactors. The assay is not intended to detect thepresence of influenza C virus.Negative results do not preclude influenza virusinfection and should not be used as the sole basisfor diagnosis, treatment or other patientmanagement decisions.Performance characteristics for influenza A wereestablished during the 2012-2013 and the 2014-2015 influenza seasons when influenza A/H3 andA/H1N1 pandemic were the predominantinfluenza A viruses in circulation. When otherinfluenza A viruses are emerging, performancecharacteristics may vary.If infection with a novel influenza A virus issuspected based on current clinical and | Same |
{6}------------------------------------------------
| Parameter | Alere™ i Influenza A & B(Modified Device) | Alere™ i Influenza A & B(K151464) |
|---|---|---|
| epidemiological screening criteria recommendedby public health authorities, specimens should becollected with appropriate infection controlprecautions for novel virulent Influenza virusesand sent to state or local health department fortesting. Viral culture should not be attempted inthese cases unless a BSL 3+ facility is available toreceive and culture specimens. | ||
| IntendedEnvironmentfor Use | Professional use, in a medical laboratory or pointof care | Same |
| Instrumentation | Alere™ i Instrument | Same |
| Self-Contained System | Integrated PC, Software, and Touch ScreenDisplay | Same |
| Automated Assay | Yes. Sample preparation, amplification, detection,and result interpretation. | Same |
| Assay Information | ||
| Sample Type | Nasal Swab and Nasal or Nasopharyngeal SwabsEluted in Viral Transport Media | 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 viral RNA inclinical specimens | Same |
| Detection Method | Assay uses different reporter dyes for each target | Same |
| Internal Control | Yes | Same |
| Result Interpretation | Automated | Same |
| Assay Result | Qualitative | Same |
| Time to Result | < 15 minutes | Same |
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.