IMMULITE 2000 CMV IGM, IMMULITE CMV IGM CONTROLS, AND IMMULITE 200 CMV IGM ADJUSTOR MODEL L2KCM2, L2KCM6, LCMC1, LCMC2,

K100433 · Siemens Healthcare Diagnostics · LKQ · May 13, 2010 · Microbiology

Device Facts

• Record ID: K100433
• Device Name: IMMULITE 2000 CMV IGM, IMMULITE CMV IGM CONTROLS, AND IMMULITE 200 CMV IGM ADJUSTOR MODEL L2KCM2, L2KCM6, LCMC1, LCMC2,
• Applicant: Siemens Healthcare Diagnostics
• Product Code: LKQ · Microbiology
• Decision Date: May 13, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3175
• Device Class: Class 2

Intended Use

IMMULITE® 2000 CMV IgM is for in vitro diagnostic use with IMMULITE® 2000 Systems analyzers for the qualitative detection of IgM antibodies to cytomegalovirus (CMV) in human serum or plasma (EDTA or heparinized), as an aid in the diagnosis of current and recent CMV infection in individuals with signs and symptoms of CMV infection or clinical suspicion of CMV infection. This assay is not FDA cleared or approved for use in testing (screening) blood or plasma donors, neonatal screening, or for use at point-of-care facilities. Performance characteristics for this assay have not been established in immunocompromised, immunosuppressed or organ transplant individuals.

Device Story

IMMULITE 2000 CMV IgM is a solid-phase, enzyme-labeled chemiluminescent three-step immunoassay; utilizes beads coated with inactivated, purified CMV antigen (strain AD-169). Input: human serum or plasma. Process: 1) sample incubation with anti-human IgG to block IgG; 2) transfer to reaction tube where CMV IgM binds to bead-bound antigen; 3) addition of alkaline phosphatase-conjugated anti-human IgM; 4) chemiluminescent substrate addition. Output: qualitative result (reactive, nonreactive, indeterminate) and sample-to-cutoff ratio. Used in clinical laboratories on IMMULITE 2000 Systems analyzers. Results aid clinicians in diagnosing current or recent CMV infection. Benefits include automated, standardized detection of CMV-specific IgM antibodies.

Clinical Evidence

Performance evaluated via prospective and retrospective studies. Prospective study (n=527) showed 97.2% negative agreement. Retrospective study (n=109) of known positives showed 97.8% positive agreement. Analytical studies included precision (total CV 5.1-21.4%), cross-reactivity (potential RF interference noted), and interference testing (hemoglobin, triglycerides, bilirubin showed no effect).

Technological Characteristics

Solid-phase, enzyme-labeled chemiluminescent three-step immunoassay. Solid phase: beads coated with inactivated, purified CMV antigen (strain AD-169). Liquid phase: polyclonal goat anti-human IgG and alkaline phosphatase-conjugated polyclonal goat anti-human IgM. Automated on IMMULITE 2000 Systems. Qualitative output. No specific material standards cited.

Indications for Use

Indicated for qualitative detection of IgM antibodies to CMV in human serum or plasma to aid diagnosis of current/recent CMV infection in symptomatic individuals. Not for blood/plasma donor screening, neonatal screening, or point-of-care use. Performance not established in immunocompromised, immunosuppressed, or organ transplant patients.

Regulatory Classification

Identification

Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.

Predicate Devices

• VIDAS® CMV IgM assay (K933549)

Submission Summary (Full Text)

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K100433

## 510(k) Summary as Required by 21 CFR 807.92

| Submitter: | Siemens Healthcare Diagnostics Inc.<br>5210 Pacific Concourse Drive<br>Los Angeles, CA 90045-6900 |
|-----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Robert C. Eusebio<br>Director Regulatory Affairs<br>1584 Enterprise Blvd<br>West Sacramento, CA 95691<br>[phone] |
| Date Prepared: | May 10, 2010 |
| Device Trade Name: | IMMULITE® 2000 CMV IgM |
| Common Name: | Cytomegalovirus serological reagents<br>21 CFR 866.3175 |
| Substantial<br>Equivalence: | K933549<br>VIDAS® CMV IgM assay |
| Device Description: | IMMULITE 2000 CMV IgM is a solid-phase, enzyme<br>labeled chemiluminescent three-step immunoassay. The<br>solid phase (bead) is coated with inactivated, purified<br>CMV antigen (strain AD-169 from infected cell lysates).<br>The liquid phase consists of two reagents: 1) polyclonal<br>goat anti-human IgG antibody in buffer, and 2) alkaline<br>phosphatase (bovine calf intestine) conjugated to<br>polyclonal goat anti-human IgM antibody in buffer. |

MAY 13 2010
In the first cycle, the patient sample and polyclonal goat
anti-human IgG antibody are incubated together without
the bead for 30 minutes. During this time, anti-IgG
antibodies block IgG present in the patient's sample.

In the second cycle, the pretreated sample and polyclonal
goat anti-human IgG antibody are transferred to the second
reaction tube. Anti-IgG antibodies block the remaining IgG
from the patient's sample from binding to the CMV
antigen on the bead. During this time, CMV IgM in the
patient sample binds to CMV antigen on the bead.
Unbound sample and reagent are then removed by
centrifugal washes.

In the third cycle, the enzyme conjugated polyclonal goat

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| | anti-human IgM antibody is added to the second reaction tube. The enzyme conjugate binds to immobilized IgM to form the antibody sandwich complex. The unbound enzyme conjugate is removed by centrifugal washes. Finally, chemiluminescent substrate is added to the reaction tube and the signal is generated in proportion to the bound enzyme. |
|------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use: | IMMULITE® 2000 CMV IgM is for in vitro diagnostic use with IMMULITE® 2000 Systems analyzers for the qualitative detection of IgM antibodies to cytomegalovirus (CMV) in human serum or plasma (EDTA or heparinized), as an aid in the diagnosis of current and recent CMV infection in individuals with signs and symptoms of CMV infection or clinical suspicion of CMV infection. This assay is not FDA cleared or approved for use in testing (screening) blood or plasma donors, neonatal screening, or for use at point-of-care facilities. |
| | Performance characteristics for this assay have not been established in immunocompromised, immunosuppressed or organ transplant individuals. |
| Technological Aspects: | A comparison of the device features, intended use, laboratory data and other information demonstrate that the IMMULITE® 2000 CMV IgM assay is substantially equivalent to the currently marketed bioMerieux Vitek VIDAS CMV IgM assay, as summarized in the following tables. |

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| | IMMULITE 2000 | VIDAS |
|---------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use with<br>IMMULITE® 2000 Systems<br>analyzers — for the qualitative<br>detection of IgM antibodies to<br>cytomegalovirus (CMV) in<br>human serum or plasma<br>(EDTA or heparinized), as an<br>aid in the diagnosis of current<br>and recent CMV infection in<br>individuals with signs and<br>symptoms of CMV infection or<br>clinical suspicion of CMV<br>infection. This assay is not<br>FDA cleared or approved for<br>use in testing (screening)<br>blood or plasma donors,<br>neonatal screening, or for use<br>at point-of-care facilities.<br>Performance characteristics<br>for this assay have not been<br>established in<br>immunocompromised,<br>immunosuppressed or organ<br>transplant individuals. | For in vitro diagnostic use<br>with a VIDAS instrument as<br>an automated enzyme-linked<br>fluorescent immunoassay<br>(ELFA) for the qualitative<br>detection of anti-CMV IgM<br>antibodies in human serum. It<br>is intended to be used as an<br>aid in the diagnosis of<br>cytomegalovirus infection. It<br>is not intended for use in<br>testing (screening) blood or<br>plasma donors. |
| Assay Type | Chemiluminescent enzyme<br>IgM antibody μ-capture<br>immunoassay | Enzyme-linked fluorescent<br>immunoassay (ELFA) |
| Capture/Detection<br>Antigen/Antibody | The solid phase is a bead<br>coated with inactivated,<br>purified CMV antigen (strain<br>AD-169 from infected cell<br>lysates). The conjugate is<br>polyclonal goat anti-human<br>IgM antibody conjugated to<br>alkaline phosphatase. | The Solid Phase Receptacle is<br>coated with CMV antigen<br>(strain AD169). The<br>conjugate is comprised of<br>mouse monoclonal anti-<br>human IgM antibodies<br>conjugated to alkaline<br>phosphatase. |
| Type of Assay | Qualitative Assay | Qualitative Assay |
| | IMMULITE 2000 | VIDAS |
| Cut-Offs | Test value = ratio of signal<br>from sample to that of signal<br>of adjustor curve parameter<br>P1. | Test Value Threshold = ratio<br>of signal from sample to set of<br>thresholds stored in the<br>computer |
| | ≥1.1 Reactive | ≥0.90 Positive |
| | 0.9 to < 1.1 Indeterminate | ≥0.70 to < 0.90 Equivocal |
| | <0.9 Non-reactive | <0.70 Negative |
| Sample Volume | 10 µL | 100 µL |
| Sample Type | Serum or plasma<br>(EDTA or heparinized) | Serum |
| Cross-Reactivity | Of 197 samples tested for<br>potential crossreactivity one<br>rheumatoid factor (RF) sample<br>tested reactive and one RF<br>sample tested indeterminate. | Of 62 samples tested for<br>potential crossreactivity, 6<br>yielded positive results. |
| Interference | Not effected by hemolysis,<br>lipemia or icterus at test<br>levels. | Potential hemolysis, icterus<br>and lipemia interferences<br>unknown as testing is not<br>reported in package insert. |

### Table 1: Comparison of IMMULITE® with VIDAS® Assay

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As part of the clinical study, samples from various patient populations were tested with both the IMMULITE® 2000 CMV IgM assay and the VIDAS® CMV IgM assay. A total of 636 serum samples were collected at four U.S. sites and three commercial suppliers and were tested at three U.S. sites. There were 109 retrospective samples tested where the CMV IgM + status was known. The remaining 527 samples from target enrollment groups were collected prospectively. Each sample was tested with the IMMULITE 2000 CMV IgM assay and with a commercially available CMV IgM assay (Kit A).

#### Comparison for Prospective Subjects*

| Kit A | IMMULITE 2000<br>CMV IgM | | |
|-----------|--------------------------|---------------|-------------|
| | Reactive | Indeterminate | Nonreactive |
| Positive | 8 | 0 | 2 |
| Equivocal | 2 | 1 | 7 |
| Negative | 6 | 6 | 495 |

Positive Agreement: 47.1% (8/17, 95% CI: 23.0% - 72.2%) Negative Agreement: 97.2 % (495/509, 95% CI: 95.4% - 98.5%

* Note: The terms "reactive", "nonreactive" and "indeterminate" (Ind) used for IMMULITE 2000 results correspond to "positive", "negative" and "equivocal" as used by other manufacturers in this context.

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#### Comparison for Retrospective Subjects

| | IMMULITE 2000<br>CMV IgM | | |
|-----------|--------------------------|---------------|-------------|
| Kit A | Reactive | Indeterminate | Nonreactive |
| Positive | 90 | 0 | 1 |
| Equivocal | 5 | 1 | 1 |
| Negative | 2 | 0 | 9 |

Positive Agreement: 97.8% (90/92, 95% CI: 92.4% - 99.7%) Negative Agreement: 56.3% (9/16, 95% CI: 29.9% - 80.2%

Precision information in the product insert for the predicate CMV IgM assay shows interassay coefficients of variation (CV) ranging from 4.0% to 6.5% for the two controls reported. The precision of the IMMULITE 2000 CMV assay as measured by total CV ranged from 5.1% to 21.4% for the 8 samples tested.

A comparison of the device features, intended use, laboratory data and other information demonstrates that the IMMULITE® 2000 CMV IgM is substantially equivalent to the currently marketed bioMerieux Vitek VIDAS CMV IgM assay.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Public Health Service

Siemens Healthcare Diagnostics c/o Mr. Robert C. Eusebio Director Regulatory Affairs 1584 Enterprise Blvd. West Sacramento, CA 95691

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Image /page/5/Picture/5 description: The image shows the date "MAY 13 2001". The text is in bold and appears to be from a document. The date is likely a reference to a specific event or record within the document.

Rc: K100433

Trade/Device Name: IMMULITE® 2000 CMV IgM Regulation Number: 21 CFR 866.3175 Regulation Name: Cytomegalovirus serological reagents. Regulatory Class: Class II Product Code: LKQ, JIT, JJX Dated: February 09, 2010 Received: February 16, 2010

Dear Mr. Eusebio:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

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

Enclosure

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# Indications for Use Form

510(k) Number (if known): K100433

Device Name: 1MMULITE® 2000 CMV IgM

Indications for Use:

IMMULITE® 2000 CMV IgM is for in vitro diagnostic use with IMMULITE® 2000 Systems analyzers for the qualitative detection of IgM antibodies to cytomegalovirus (CMV) in human serum or plasma (EDTA or heparinized), as an aid in the diagnosis of current and recent CMV infection in individuals with signs and symptoms of CMV infection or clinical suspicion of CMV infection. This assay is not FDA cleared or approved for use in testing (screening) blood or plasma donors, neonatal screening, or for use at point-of-care facilities.

Performance characteristics for this assay have not been established in immunocompromised, immunosuppressed or organ transplant individuals.

CMV IgM Controls are assayed, bi-level controls intended for use with the IMMULITE 2000 CMV IgM assay. They are intended as an aid in monitoring day-today assay performance.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off Office of In Vitro Diagnostic

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| 510(k) | The Scif |

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