(88 days)
Not Found
Not Found
No
The device description and performance studies focus on a traditional immunofluorescence assay read by fluorescence microscopy. There is no mention of AI, ML, or automated image analysis.
No
This device is for in vitro diagnostic use, intended for detection and identification, not for treatment or therapy.
Yes
Explanation: The "Intended Use" section states that the kit is "intended for the detection and identification of human metapneumovirus (hMPV) in direct respiratory specimen cell preparations from nasopharyngeal swabs from patients with febrile respiratory illness." It also explicitly mentions "For In Vitro Diagnostic Use," indicating its purpose in diagnosing a condition. The performance study results (Sensitivity, Specificity, etc.) are also typical of a diagnostic device.
No
The device is a diagnostic kit that utilizes reagents and fluorescence microscopy to detect viral antigen. It is an in vitro diagnostic (IVD) device with physical components, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states "For In Vitro Diagnostic Use" in the Intended Use / Indications for Use section. This is the most direct confirmation.
Furthermore, the description of the device and its intended use aligns perfectly with the definition of an IVD:
- Intended Use: To detect and identify human metapneumovirus in respiratory specimens. This is a diagnostic purpose.
- Method: It uses a laboratory test (fluorescence microscopy with labeled antibodies) performed on biological samples (respiratory specimen cell preparations).
- Setting: It is intended for use in a clinical laboratory by trained personnel.
All these characteristics are consistent with an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Light Diagnostics™ Human Metapneumovirus DFA Kit is intended for the detection and identification of human metapneumovirus (hMPV) in direct respiratory specimen cell preparations from nasopharyngeal swabs from patients with febrile respiratory illness. This assay detects but is not intended to differentiate the four recognized genetic sub-lineages of hMPV.
Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. It is recommended that specimens found to be negative after examination of the direct specimen results be confirmed by FDA cleared hMPV molecular assay.
For In Vitro Diagnostic Use.
Product codes
OMG
Device Description
Light Diagnostics Human Metapneumovirus DFA Kit utilizes a single reagent for the detection and identification of human metapneumovirus. The fluorescein labeled monoclonal antibodies, specific for human metapneumovirus will bind to viral antigen in human metapneumovirus infected cells. - Unbound reagent is removed by rinsing with phosphate-buffered saline (PBS/Tween 20). Illumination allows visualization of the antigenantibody complex by fluorescence microscopy. When a FITC filter set is used, the human metapneumovirus antibody complex will exhibit an apple-green fluorescence. Uninfected cells stain a dull red due to the presence of Evans blue in the reagent.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Fluorescence microscopy
Anatomical Site
Respiratory specimen cell preparations from nasopharyngeal swabs
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical samples were submitted to each clinical laboratory in viral transport media, the cells were washed in PBS, dropped onto slides, and fixed in acetone. Slides were stained with the Light Diagnostics™ Human Metapneumovirus DFA Kit and examined using fluorescence microscopy. Clinical samples were also analyzed by a composite algorithm based on culture/RT-PCR/sequencing.
In the clinical study, nasopharyngeal swabs were the most prevalent specimen type. At Site One, 208 nasopharyngeal swab specimens were submitted to a regional medical center in southeastern Canada for hMPV testing. At Site Two, 199 nasopharyngeal swab specimens were submitted to a hospital laboratory in the northeastern United States for hMPV testing. At Site Three 200 specimens were submitted for testing, of which four were nasopharyngeal swabs. The total combined number of NPS specimens was 411. Sixty-Three specimens were found positive for hMPV by RT-PCR.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision/Reproducibility:
Studies were conducted using the Light Diagnostics™ hMPV DFA Reagent at three testing sites (one internal and two external) using multiple operators, multiple runs per day and multiple viral concentrations of a test panel. The test panel consisted of one true negative sample and samples at three levels of viral load including a high negative (sample with an analyte concentration below the LoD such that repeat testing of this sample should be negative at least 95% of the time), a low positive sample, and a moderate positive sample.
In internal testing, results were 100% in accordance with expected results (80/80 tests). In external testing, results were in accordance with expected results greater than 99% of the time (438/440 tests).
Analytical Sensitivity (Limit of Detection):
The Light Diagnostics™ hMPV DFA Reagent was tested with slides made from titrated quantitated virus culture. Four strains of hMPV were used, representing all four known subtypes of hMPV. Five ten-fold dilutions were made from viral seed stocks of known concentration for each strain. Samples of virus at each dilution were dropped on slides in duplicate, and four batches of slides were prepared from four cultures (eight replicates at each concentration).
Positive results were obtained with at least 95% of replicates using the Light Diagnostics™ hMPV DFA Reagent on hMPV Al infected cells down to 400 PFU/mL, 100 PFU/mL of hMPV A2 infected cells, 625 PFU/mL of hMPV B1 infected cells, and 275 PFU/mL of hMPV B2 infected cells.
Clinical Evaluation:
Sample Size: 411 nasopharyngeal swab specimens.
Results: Of 63 specimens found positive for hMPV by RT-PCR, the Light Diagnostics Direct Immunofluorescence Assay detected 58 hMPV positive specimens.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity: 92% (95% Confidence Interval: 83-97%)
Specificity: 99% (95% Confidence Interval: 98-100%)
Positive Predictive Value: 97% (95% Confidence Interval: 89-99%)
Negative Predictive Value: 99% (95% Confidence Interval: 97-99%)
Predicate Device(s)
Validated RT-PCR method followed by bi-directional sequencing for confirmation 1) and identification of Human Metapneumovirus
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
MAR 1 2 2010
llipor
510(k) Premarket Notification for Light Diagnostics™ Human Metapneumovirus DFA Kit
| 510(k) SUMMARY | |
|---|---|
| Submitter: | Millipore Corporation |
| 28820 Single Oak Drive | |
| Temecula, CA 92590 | |
| Tel: (951) 676-8080 | |
| Fax: (951) 514-4482 | |
| Contact Name: | Catherine Karaman |
| Date Prepared: | November 19, 2009 |
| Product Name | |
| Trade Name: | Light Diagnostics ™ Human Metapneumovirus DFA Kit |
| Common Name: | Immunofluorescence Assay |
| Classification Name: | Human Metapneumovirus - unclassified |
Intended Use
Light Diagnostics™ Human Metapneumovirus DFA Kit is intended for the detection and identification of human metapneumovirus (hMPV) in direct respiratory specimen cell preparations from nasopharyngeal swabs from patients with febrile respiratory illness. This assay detects but is not intended to differentiate the four recognized genetic sub-lineages of hMPV.
Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. It is recommended that specimens found to be negative after examination of the direct specimen results be confirmed by FDA cleared hMPV molecular assay.
For In Vitro Diagnostic Use.
Predicate Device
- Validated RT-PCR method followed by bi-directional sequencing for confirmation 1) and identification of Human Metapneumovirus
1 of 6
1
Image /page/1/Picture/0 description: The image shows a logo with a stylized letter "M" and the word "MILLIPORE" written vertically on the right side. The left part of the "M" is filled with black, while the right part is outlined. The logo has a simple and modern design.
Device Description
Light Diagnostics Human Metapneumovirus DFA Kit utilizes a single reagent for the detection and identification of human metapneumovirus. The fluorescein labeled monoclonal antibodies, specific for human metapneumovirus will bind to viral antigen in human metapneumovirus infected cells. - Unbound reagent is removed by rinsing with phosphate-buffered saline (PBS/Tween 20). Illumination allows visualization of the antigenantibody complex by fluorescence microscopy. When a FITC filter set is used, the human metapneumovirus antibody complex will exhibit an apple-green fluorescence. Uninfected cells stain a dull red due to the presence of Evans blue in the reagent.
Technological Comparison of Methods
Comparison with Predicate:
During this study no FDA cleared predicate device was available. The performance characteristics of the Light Diagnostics TM Human Metapneumovirus DFA Assay were established by direct evaluation of clinical specimens compared to a composite algorithm based on cell culture results and a validated RT-PCR method followed by bidirectional sequencing for confirmation and identification of human metapneumovirus.
The methods differ in that:
Light Diagnostics™ Human Metapneumovirus DFA Kit contains a single reagent which contains FITC-labeled monoclonal antibodies directed against hMPV. This reagent detects hMPV antigens present in the patient specimen. Slides are necessary to detect and identify the virus from sample and yield an apple-green fluorescence color if positive. The composite RT-PCR/sequencing method detects viral RNA isolated from patient specimens.
1) Analytical Performance:
Cross-reactivity against common viruses, bacteria, and cell lines
The monoclonal antibodies used in the Light Diagnostics™ hMPV Direct Immunofluorescence Assay hMPV Reagent were tested against a variety of viruses and bacteria found in the respiratory tract, and cell lines commonly used to isolate respiratory Bacteria were tested with 10° CFU and viruses with 10° PFU/ml. No crossviruses. reactivity was observed for the hMPV Reagent when tested with the specified viruses, bacteria, or cell lines. The results are indicated in the table below.
2
Image /page/2/Picture/0 description: The image shows a logo with a large, stylized letter "M". The left half of the "M" is solid black, while the right half is white with a rough, textured appearance. To the right of the "M", the word "MILLIPORE" is printed vertically in a simple, sans-serif font. The letters are stacked on top of each other, reading from bottom to top.
| Organism or | hMPV Reagent |
|---|---|
| Adenovirus | Negative |
| Cytomegalovirus (CMV) | Negative |
| Herpes simplex virus, type 1 | |
| (HSV-1) | Negative |
| Herpes simplex virus, type 2 | |
| (HSV-2) | Negative |
| Influenza A virus | Negative |
| Influenza B virus | Negative |
| Parainfluenza virus type 1 | Negative |
| Parainfluenza virus type 2 | Negative |
| Parainfluenza virus type 3 | Negative |
| Respiratory syncytial virus | |
| (RSV) | Negative |
| Varicella-zoster virus (VZV) | Negative |
| Escherichia coli | Negative |
| Hemophilus influenzae | Negative |
| Moraxella catarrhalis | Negative |
| Pseudomonas aeruginosa | Negative |
| Staphylococcus aureus | Negative |
| Staphylococcus epidermis | Negative |
| Streptococcus pyogenes | Negative |
| Streptococcus salivarius | Negative |
| Cell Lines | Negative |
| A549 | Negative |
| BGMK | Negative |
| Hep-2 | Negative |
| LLCMK2 | Negative |
| MDCK | Negative |
| MRC-5 | Negative |
| RD | Negative |
| Vero | Negative |
Analytical Reactivity
In addition to the Analytical Sensitivity results (see below) a study was performed to demonstrate that the Light Diagnostics™ hMPV DFA Reagent detects virus isolates representing each of the four known genetic sublineages of hMPV (A1, A2, B1, B2). Positive specimens from the clinical study were genotyped to further support this study. The Light Diagnostics™ hMPV DFA Reagent detected hMPV in 21 clinical isolates from sublineage A2, 10 from sublineage B1, and 32 from sublineage B2 (including positive specimens from Site Three).
3 of 6 28820 Single Oak Drive, Temecula, CA 92590 Tel: (951)676-8080 Fax: (951)514-4482 Attachment 002
3
Image /page/3/Picture/0 description: The image shows the Millipore logo. The logo consists of a large letter 'M' with the left half filled in black and the right half outlined in black. To the right of the 'M' is the word 'MILLIPORE' in a vertical orientation.
| Virus subtypes | hMPV Reagent |
|---|---|
| hMPV A1 | + |
| hMPV A2 | + |
| hMPV B1 | + |
| hMPV B2 | + |
Precision/Reproducibility
Precision/reproducibility studies were conducted using the Light Diagnostics™ hMPV DFA Reagent at three testing sites (one internal and two external) using multiple operators, multiple runs per day and multiple viral concentrations of a test panel. The test panel consisted of one true negative sample and samples at three levels of viral load including a high negative (sample with an analyte concentration below the LoD such that repeat testing of this sample should be negative at least 95% of the time), a low positive sample, and a moderate positive sample. In internal testing, results were 100% in accordance with expected results (80/80 tests). In external testing, results were in accordance with expected results greater than 99% of the time (438/440 tests). The results of both external and internal testing are summarized below.
| Number of
Operators | Number
of Sites | Viral control level | Expected
Results | Results | %Accordance with
expected results |
|------------------------|--------------------|-----------------------------------------------------------------------|---------------------|---------------------------------------|--------------------------------------|
| 4 | 2 | Moderate | Positive | Positive
90/90 | 100% |
| 6 | 3 | Low | Positive | Positive
130/130 | 100% |
| 4 | 2 | High Negative
(viral concentration
below Limit of
Detection) | Negative | Negative
88/90
Positive
2/90 | 97% |
| 6 | 3 | Uninfected | Negative | Negative
130/130 | 100% |
| Overall | | | | 438/440 | 99% |
Analytical Sensitivity (Limit of Detection)
The Light Diagnostics™ hMPV DFA Reagent was tested with slides made from titrated quantitated virus culture. Four strains of hMPV were used, representing all four known subtypes of hMPV. Five ten-fold dilutions were made from viral seed stocks of known concentration for each strain. Samples of virus at each dilution were dropped on slides in
4
Image /page/4/Picture/0 description: The image shows a logo with a stylized letter "M" in black and white. The left side of the "M" is solid black, while the right side is white with a black outline. To the right of the "M", the word "MILLIPORE" is printed vertically in black, with the letters stacked on top of each other. The logo appears to be for a company or organization named Millipore.
duplicate, and four batches of slides were prepared from four cultures (eight replicates at each concentration). Positive results were obtained with at least 95% of replicates using the Light Diagnostics™ hMPV DFA Reagent on hMPV Al infected cells down to 400 PFU/mL, 100 PFU/mL of hMPV A2 infected cells, 625 PFU/mL of hMPV B1 infected cells, and 275 PFU/mL of hMPV B2 infected cells. Results are summarized below.
| Virus strain | Limit of Detection |
|---|---|
| hMPV A1 | $4.0 x 10^2$ PFU/mL |
| hMPV A2 | $1.0 x 10^2$ PFU/mL |
| hMPV B1 | $6.25 x 10^2$ PFU/mL |
| hMPV B2 | $2.75 x 10^2$ PFU/mL |
2) Clinical Evaluation:
Clinical samples were submitted to each clinical laboratory in viral transport media, the cells were washed in PBS, dropped onto slides, and fixed in acetone. Slides were stained with the Light Diagnostics™ Human Metapneumovirus DFA Kit and examined using fluorescence microscopy. Clinical samples were also analyzed by a composite algorithm based on culture/RT-PCR/sequencing.
In the clinical study, nasopharyngeal swabs were the most prevalent specimen type. At Site One, 208 nasopharyngeal swab specimens were submitted to a regional medical center in southeastern Canada for hMPV testing. At Site Two, 199 nasopharyngeal swab specimens were submitted to a hospital laboratory in the northeastern United States for hMPV testing. At Site Three 200 specimens were submitted for testing, of which four were nasopharyngeal swabs. The total combined number of NPS specimens was 411. Sixty-Three specimens were found positive for hMPV by RT-PCR. Of these, the Light Diagnostics Direct Immunofluorescence Assay detected 58 hMPV positive specimens. Analysis for sensitivity, specificity, positive and negative predictive values are given below.
28820 Single Oak Drive, Temecula, CA 92590 - Tel: (951)676-8080 Fax: (951)514-4482 Attachment 002
5
Image /page/5/Picture/0 description: The image shows the logo for Millipore. The logo consists of a large letter "M" with the left half filled in with black and the right half is white. To the right of the "M" is the word "MILLIPORE" written vertically.
| DETECTING hMPV | RT-PCR | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| Light Diagnostics™ Human | ||||
| Metapneumovirus DFA Kit | ||||
| on direct specimens | Positive | 58 | 2 | 60 |
| Negative | 5 | 346 | 351 | |
| Total | 63 | 348 | 411 | |
| 95% Confidence Interval | ||||
| Sensitivity | 92% | 83-97% | ||
| Specificity | 99% | 98-100% | ||
| Positive Predictive Value | 97% | 89-99% | ||
| Negative Predictive Value | 99% | 97-99% |
Detection of hMPV in Direct Specimens using Light Diagnostics™ Human Metapneumovirus DFA Kit vs. RT-PCR
Conclusions Drawn from Evaluation:
Light Diagnostics™ Human Metapneumovirus DFA Kit uses a standard direct immunofluorescence assay procedure for the direct detection of hMPV in nasopharyngeal swab patient specimens. The monoclonal antibodies used in the reagent have been characterized to ensure specificity and reliability of the product. In clinical evaluations, the performance characteristics of the reagents were shown to be substantially equivalent to the predicate device.
The characterization and clinical evaluation of the Light Diagnostics™ Human Metapneumovirus DFA Kit demonstrates it is substantially equivalent to the predicate when used as intended as described in the product insert.
6
Image /page/6/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, consisting of a staff with two snakes coiled around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center-WO66-G609 Silver Spring, MD 20993-0002
MAR 1 2 2010
Millipore Corporation c/o Catherine Karaman Clinical and Regulatory Affairs Specialist 28820 Single Oak Drive Temecula, CA, 92590
| Re: | K093815 |
|---|---|
| Trade/Device Name: Light Diagnostics™ Human Metapneumovirus Direct | |
| Immunofluorescence Assay | |
| Regulation Number: 21CFR §866.3980 | |
| Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay | |
| Regulatory Class: Class II | |
| Product Code: OMG | |
| Dated: December 7, 2009 | |
| Received: December 14, 2009 |
Dear Ms. Karaman:
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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such 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
7
Page 2 - Catherine Karaman
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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jayaatm
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Indication
510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________
Device Name: Light Diagnostics™ Human Metapneumovirus DFA Kit
Indication for Use:
Light Diagnostics™ Human Metapneumovirus Direct Immunofluorescence Assay is intended for qualitative detection and identification of human metapneumovirus (hMPV) in direct respiratory specimen cell preparations from nasopharyngeal swab samples collected from patients with febrile respiratory illness. This assay detects but is not intended to differentiate the four recognized genetic sub-lineages of hMPV.
Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. It is recommended that specimens found to be negative after examination of the direct specimen results be confirmed by FDA cleared hMPV molecular assay.
For in vitro diagnostic use.
Prescription Use _ イ (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
............. ................................................................................................................................................................
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Ule Scif
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k): K093815
1 of 1