The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

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 unless a BSL 3E facility is available to receive and culture specimens.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;
To provide epidemiologic information for surveillance of circulating influenza viruses.

Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the patient meets the most current U.S.Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

Device Description

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with the CDC device. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI) or from viral culture.

Oligonucleotide primers and probes for detection of influenza A, influenza B, and influenza A of swine origin were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses, avian influenza A(H5) viruses, and genetic lineages of influenza B were selected from highly conserved regions of their hemagglutinin (HA) genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

AI/ML Overview

The provided document, K243274: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, is an FDA 510(k) clearance letter. This document primarily describes the device, its intended use, and confirms its substantial equivalence to a previously cleared predicate device (K243931). Critically, it states that no analytical or clinical testing was performed for this specific modification, as the submission was to add a Predetermined Change Control Plan (PCCP).

Therefore, the document does not contain the detailed study results, acceptance criteria, sample sizes, ground truth establishment, or expert involvement for the original validation of the device's performance. It explicitly states that "The performance characteristics of the CDC Flu rRT-PCR Dx Panel... were previously established and remain the same as the predicate device (K243931)."

As such, I cannot provide the specific information requested in the prompt based on the provided text alone. The prompt asks for details of "the device" meeting acceptance criteria, and this document pertains to a modification that did not involve re-evaluating performance.

However, I can interpret what would typically be sought for such an analysis in the context of an in vitro diagnostic (IVD) PCR panel like the one described. I will outline what the acceptance criteria and the study that proves the device meets them would likely entail for an IVD, but with the explicit understanding that the provided document does not contain these details.

Based on the provided document, the device's performance characteristics were "previously established" for the predicate device (K243931) and are simply carried over here as "remaining the same." The current submission (K243274) is for adding a Predetermined Change Control Plan (PCCP) and states that "No analytical testing was performed for this modification" and "No clinical testing was performed for this modification."

Therefore, the detailed information regarding acceptance criteria, reported performance, sample sizes, expert involvement, and ground truth establishment for the original validation of this device is NOT present in the provided text. The tables and descriptions below represent what would typically be expected for an FDA cleared RT-PCR diagnostic panel, assuming the original studies were conducted to industry standards, but are not extracted directly from the given document.

Acceptance Criteria and Device Performance (Hypothetical for an RT-PCR IVD)

For a real-time RT-PCR diagnostic panel like the CDC Human Influenza Virus Panel, acceptance criteria and performance would typically focus on analytical sensitivity (Limit of Detection - LoD), analytical specificity (cross-reactivity, inclusivity), and clinical performance (sensitivity, specificity).

1. Table of Acceptance Criteria and Reported Device Performance (Hypothetical)

Performance Metric	Target Analyte(s)	Acceptance Criteria (Hypothetical)	Reported Device Performance (Hypothetical)
Analytical Sensitivity (LoD)	Influenza A	Detect 95% of replicates at a specified viral RNA concentration (e.g., < 500 copies/mL)	Achieved 100% detection for Influenza A (H1N1, H3N2, pdm09) at [X] copies/mL; 95% at [Y] copies/mL.
	Influenza B	Detect 95% of replicates at a specified viral RNA concentration (e.g., < 500 copies/mL)	Achieved 100% detection for Influenza B (Victoria, Yamagata) at [A] copies/mL; 95% at [B] copies/mL.
	H5 Subtype	Detect 95% of replicates for relevant H5 strains at a specified concentration (e.g., < 1000 copies/mL)	Achieved 100% detection for specified H5 strains at [C] copies/mL; 95% at [D] copies/mL.
Analytical Specificity (Inclusivity)	All targets	Detect 100% of tested strains/isolates representing known genetic diversity within each target (e.g., various clades/lineages).	100% detection across all 50 tested Influenza A strains (H1N1, H3N2, pdm09) and 30 Influenza B strains (Victoria, Yamagata); 5 specific H5 strains.
Analytical Specificity (Exclusivity/Cross-Reactivity)	All targets	No cross-reactivity with common respiratory pathogens or human nucleic acid (e.g., < 5% false positives/inhibitory effects).	No cross-reactivity observed with 30 non-influenza respiratory pathogens (e.g., RSV, HRV, Adenovirus) or human nucleic acid for any target.
Clinical Sensitivity	All targets	> 90% Positive Percent Agreement (PPA) compared to a gold standard (e.g., viral culture, sequencing).	Overall PPA: 95.8% (Influenza A), 94.2% (Influenza B), 97.1% (H5 presumptive). Ranges for specific kits within these bounds.
Clinical Specificity	All targets	> 95% Negative Percent Agreement (NPA) compared to a gold standard.	Overall NPA: 98.5% (Influenza A), 99.1% (Influenza B), 99.5% (H5 presumptive). Ranges for specific kits within these bounds.
Reproducibility/Precision	All targets	Coefficient of Variation (CV) < 10% for Cq values at low and high positive concentrations across different sites, lots, operators.	Inter-site CV < 5%, Inter-lot CV < 3%, Inter-operator CV < 4% for all targets at specified concentrations.

Note: The actual quantitative values for LoD, PPA, and NPA would be specific to each kit and its validated performance.

Study Details (Hypothetical for an RT-PCR IVD)

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

Test Set Sample Size (Hypothetical):
- Analytical Validation: Typically involves a statistically significant number of replicates (e.g., 20-60 replicates per concentration level) for LoD, and a panel of 50-100 isolates/strains for inclusivity/exclusivity testing.
- Clinical Validation (Prospective/Retrospective): For an IVD like this, hundreds to thousands of clinical specimens would be evaluated. For example:
  - Influenza A/B Typing Kit: ~500-1000 positive specimens (e.g., 200-400 A, 100-200 B, remaining co-infections/untouched negatives) and ~500-1000 negative specimens.
  - Influenza A Subtyping Kit: ~300-500 Influenza A positive specimens, including a balanced representation of H1 and H3.
  - Influenza B Lineage Genotyping Kit: ~100-200 Influenza B positive specimens, balanced for Victoria and Yamagata lineages.
  - Influenza A/H5 Subtyping Kit: Could involve a smaller number of true H5 positives (often spiked or well-characterized rare clinical samples) and a larger set of other influenza A types and negatives.
Data Provenance (Hypothetical):
- Country of Origin: Likely multi-center studies within the United States given CDC's role and FDA clearance. Could also include international sites for broader strain diversity.
- Retrospective or Prospective: Clinical validation typically involves both.
  - Retrospective: Utilizing banked, well-characterized clinical specimens to ensure adequate representation of rare or specific targets/lineages.
  - Prospective: Collecting new clinical specimens as they arrive, processed independently to mimic real-world use conditions.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts (Hypothetical)

Number of Experts: For an RT-PCR assay, ground truth is usually established by highly reliable reference methods rather than human interpretation of images. However, if any interpretation or adjudication was needed (e.g., for discordant clinical results), it would involve a small panel.
- For PCR-based diagnostics, ground truth is typically established by:
  - Confirmatory PCR methods (e.g., an FDA-cleared reference assay, sequencing of the target region, or a highly sensitive lab-developed test).
  - Viral culture (particularly for original isolation and characterization of strains).
  - Next-generation sequencing (NGS) for comprehensive genetic characterization.
Qualifications of Experts (if applicable for discordant results/clinical adjudication):
- Senior Clinical Microbiologists, PhD-level or MD, with extensive experience (e.g., 10-20+ years) in diagnostic virology and molecular diagnostics in CLIA-certified laboratories.
- Researchers with expertise in influenza genomics and epidemiology (e.g., from CDC's influenza division).

4. Adjudication Method (Hypothetical)

For discordant results between the investigational device and the initial reference method in clinical studies, an adjudication method would be employed.
- Method: Often involves a third, more definitive method. For an RT-PCR assay, this would frequently be bi-directional Sanger sequencing of the viral target region detected, or a second, orthogonal PCR method run by an expert laboratory.
- Process: Results would be reviewed by a qualified laboratory director or team, and the definitive result (ground truth) would be assigned based on the adjudicating test.
- "None" is typically not an acceptable approach for discordant results in regulated clinical trials.

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

No, an MRMC study would generally not be applicable nor performed for this type of device. This device is a diagnostic kit (RT-PCR) that generates quantitative cycle threshold (Cq) values and qualitative (positive/negative/subtype) results. It does not involve "human readers" interpreting images or complex data in the same way an AI-assisted diagnostic imaging device would.
The "human-in-the-loop" aspect here is the laboratory technician performing the test and interpreting the Cq values based on predefined cut-offs. The device itself is not "AI-assisted."

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

Yes, a "standalone" or "algorithm only" performance is inherently measured for this device. An RT-PCR assay's performance (sensitivity, specificity, LoD) is determined by its analytical component (primers, probes, reagents, thermal cycling) and the software's ability to interpret raw fluorescence data into Cq values and apply predefined cut-offs for positive/negative calls.
This is the primary way the analytical performance is established and is the foundation for clinical performance. The "algorithm" here is the defined Cq cut-offs and interpretive logic built into the system.

7. The Type of Ground Truth Used (Hypothetical)

Expert Consensus / Reference Methods:
- Confirmatory Molecular Methodologies: Often a consensus derived from an FDA-cleared reference RT-PCR assay, or an independently validated, highly sensitive laboratory-developed PCR test.
- Nucleotide Sequencing: Gold standard for definitive identification and subtyping (e.g., Sanger sequencing or Next-Generation Sequencing of key viral genes مثل Hemagglutinin (HA) or Neuraminidase (NA) for influenza).
- Viral Culture: Historically a gold standard for detecting viable virus, though less sensitive than PCR for direct clinical specimens. Often important for initial characterization of novel strains.
- Clinical Outcomes Data: While not the primary ground truth for the presence of the pathogen, clinical outcomes (e.g., patient recovery, severity of illness, epidemiological links) can provide supportive context for the clinical utility of the test.
For an influenza diagnostic, the molecular sequencing data and confirmed viral culture (for positive samples) along with a robust negative control (absence confirmed by multiple methods) would be the primary components of ground truth.

8. The Sample Size for the Training Set (Hypothetical)

Not applicable in the typical sense of machine learning/AI. This is a traditional RT-PCR assay kit. There isn't a "training set" for an AI model.
The "training" analogue would be the extensive research and development process to design primers and probes that are specific and sensitive to the target viruses, and to optimize the reaction conditions. This involves screening numerous viral strains and non-target organisms, but it's not a "training set" in the machine learning context.

9. How the Ground Truth for the Training Set Was Established (Hypothetical)

Not applicable due to the nature of the device. As mentioned, it's a traditional RT-PCR kit, not an AI/ML device that requires a training set and associated ground truth for model development. The design and optimization of such a kit rely on fundamental molecular biology principles, known genetic sequences of influenza viruses, and iterative laboratory testing.

Summary

U.S. Food & Drug Administration

10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

July 11, 2025

Centers for Disease Control and Prevention
Melissa Ivey
Regulatory Affairs Specialist
1600 Clifton Road
Atlanta, Georgia 30329

Re: K243274

Trade/Device Name: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 4)

Regulation Number: 21 CFR 866.3980
Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay
Regulatory Class: Class II
Product Code: OZE
Dated: October 16, 2024
Received: October 16, 2024

Dear Melissa Ivey:

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 (the 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 available 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.

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K243274 - Melissa Ivey
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FDA's substantial equivalence determination included the review and clearance of your Predetermined Change Control Plan (PCCP) titled "Pre-Determined Change Control Plan (PCCP) for modifications to the FDA-cleared CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel VER 01". See Section V.C. for the changes included in the PCCP. Under section 515C(b)(1) of the Act, a new premarket notification is not required for a change to a device cleared under section 510(k) of the Act, if such change is consistent with an established PCCP granted pursuant to section 515C(b)(2) of the Act. Under 21 CFR 807.81(a)(3), a new premarket notification is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Accordingly, if deviations from the established PCCP result in a major change or modification in the intended use of the device, or result in a change or modification in the device that could significantly affect the safety or effectiveness of the device, then a new premarket notification would be required consistent with section 515C(b)(1) of the Act and 21 CFR 807.81(a)(3). Failure to submit such a premarket submission would constitute adulteration and misbranding under sections 501(f)(1)(B) and 502(o) of the Act, respectively.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device

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K243274 - Melissa Ivey
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Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/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,

JOSEPH BRIGGS -S

Joseph Briggs, Ph.D.
Deputy Division Director
Division of Microbiology Devices
OHT7: Office of In Vitro Diagnostics
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known): K243274

Device Name: CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 4)

Indications for Use (Describe)

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2)

For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiological information for surveillance of circulating influenza viruses.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower

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respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

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For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;
To provide epidemiologic information for surveillance of circulating influenza viruses.

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.

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Traditional 510(k) CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel

510(k) Summary

I. GENERAL INFORMATION

Submitter
Centers for Disease Control and Prevention
1600 Clifton Road, NE
Atlanta, GA 30329

Contact Person
Marie Kirby
Lead, Genomics and Diagnostics Team
Virology, Surveillance and Diagnostic Branch, Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
mkirby@cdc.gov
(404)718-7689

Date Prepared: July 1, 2025

II. DEVICE INFORMATION

Proprietary Name: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 4)

Common Name: CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit

Regulation Section: 866.3980-Respiratory viral panel multiplex nucleic acid assay

Device Classification: Class II

Product Code: OZE

Panel: Microbiology

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III. PREDICATE DEVICE

K243931 - CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2), Influenza A Subtyping Kit (VER 4), Influenza B Lineage Genotyping Kit (VER 1.1 and 2), and Influenza A/H5 Subtyping Kit (VER 4)

IV. DEVICE DESCRIPTION

V. INTENDED USE

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/B Typing Kit (Ver2):

The Influenza A/B Typing Kit contains reagents and controls of the Centers for Disease Control and Prevention (CDC) Human Influenza Virus Real-Time reverse transcription polymerase chain reaction (RT-PCR) Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been U.S Food and Drug Administration (FDA)-cleared for use with this kit in conjunction with clinical and epidemiological information:

For qualitative detection of influenza virus type A or B viral ribonucleic acid (RNA) in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
To provide epidemiologic information for surveillance of circulating influenza viruses.

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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.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit (Ver4):

For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW], and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

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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.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit (Ver4):

For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW], and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

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To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

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 influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facility is available to receive and culture specimens.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Kit (Ver4):

The Influenza A/H5 Subtyping Kit contains reagents and controls of the Centers for Disease Control and Prevention (CDC) Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs and viral culture in conjunction with clinical and epidemiological risk factors;
To provide epidemiologic information for surveillance of circulating influenza viruses.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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To provide epidemiologic information for surveillance of circulating influenza viruses.

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 influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facility is available to receive and culture specimens.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Kit (Ver4):

For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs and viral culture in conjunction with clinical and epidemiological risk factors;
To provide epidemiologic information for surveillance of circulating influenza viruses.

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Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza B Lineage Genotyping Kit (Ver1.1 and 2):

For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza B Lineage Genotyping Kit (Ver1.1 and 2):

For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal

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aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

VI. TECHNOLOGICAL CHARACTERISTICS

The technological characteristics of the CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit remains the same as the predicate device (K243931). This modification was made to add the Predetermined Change Control Plan (PCCP) for Modifications to the FDA-cleared CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel VER 01 only. No technological characteristics were changed.

VII. SUBSTANTIAL EQUIVALENCE COMPARISON

There were no technical modifications to CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit. The intended use is the same as the predicate device (K243931). The instructions for use and other labeling are identical to the predicate device. This modification was made to add the Predetermined Change Control Plan (PCCP) for Modifications to the FDA-cleared CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel VER 01 only. This PCCP describes the following modifications:

Addition of a real-time PCR Instrument that is IVD-labeled and used in accordance with its instructions for use: Requires validation of limit of detection, a clinical evaluation, carry-over contamination studies and reproducibility. Specific procedures and acceptance criteria are defined in the PCCP. Addition of a real-time PCR instrument will require updates to the instructions for use (IFU) for the equipment listed, test procedure and interpretation, as necessary, and the performance data

All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

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sections.

Addition of PCR Master Mix that is IVD-labeled and used in accordance with its instructions for use: Requires validation of limit of detection and a clinical evaluation. Specific procedures and acceptance criteria are defined in the PCCP. Addition of a PCR master mix will require updates to the instructions for use (IFU) for the materials listed, test procedure and interpretation, as necessary, and the performance data sections.
Addition of Nucleic Acid Extraction - Manual Extraction or Reagent Only that is IVD-labeled and used in accordance with its instructions for use: Requires validation of limit of detection and a clinical evaluation. Specific procedures and acceptance criteria are defined in the PCCP. Addition of a manual nucleic acid extraction method or reagent will require updates to the instructions for use (IFU) for the equipment and materials listed, test procedure and interpretation, as necessary, and the performance data sections.
Addition of IVD Nucleic Acid Extraction - Instrument that is IVD-labeled and used in accordance with its instructions for use: Requires validation of limit of detection, a clinical evaluation, carry over contamination studies, and reproducibility. Specific procedures and acceptance criteria are defined in the PCCP. Addition of a nucleic acid extraction instrument will require updates to the instructions for use (IFU) for the equipment and materials listed, test procedure and interpretation, as necessary, and the performance data sections.
Modification of quencher on the oligonucleotide probes that are manufactured under good manufacturing practices (GMP): Requires validation of limit of detection and a clinical evaluation. Specific procedures and acceptance criteria are defined in the PCCP. Addition of a quencher chemistry will require updates to the instructions for use (IFU) for the materials listed, and the performance data sections.

VIII. ANALYTICAL PERFORMANCE EVALUATION

No analytical testing was performed for this modification. The performance characteristics of the CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit were previously established and remain the same as the predicate device (K243931). This modification was made to add the Predetermined Change Control Plan (PCCP) for Modifications to the FDA-cleared CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel VER 01 only.

IX. CLINICAL PERFORMANCE EVALUATION

No clinical testing was performed for this modification. The performance characteristics of the CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit were previously established and remain the same as the predicate device (K243931). This modification was made to add the Predetermined Change Control Plan (PCCP) for Modifications to the FDA-cleared CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel VER 01 only.

X. CONCLUSION

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The modification of the CDC Flu rRT-PCR Dx Panel: Influenza A/B Typing Kit, Influenza A Subtyping Kit, Influenza B Lineage Genotyping Kit, and Influenza A/H5 Subtyping Kit, to add the Predetermined Change Control Plan (PCCP) for Modifications to the FDA-cleared CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel VER 01 supports a substantial equivalence determination to the predicate and the indications for use remain the same.

Regulation Number and Section

§ 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.