BIRAMED BIOTECH BORRELIA B31 IGM VIRABLOT

K051169 · Viramed Biotech AG · LSR · Aug 11, 2005 · Microbiology

Device Facts

• Record ID: K051169
• Device Name: BIRAMED BIOTECH BORRELIA B31 IGM VIRABLOT
• Applicant: Viramed Biotech AG
• Product Code: LSR · Microbiology
• Decision Date: Aug 11, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3830
• Device Class: Class 2

Indications for Use

The Viramed Biotech Borrelia B31 IgM ViraBlot® is an in vitro qualitative assay for the detection of IgM antibodies to Borrelia burgdorferi in human serum. It is intended for use in testing human serum samples which have been found positive or equivocal using an EIA or IFA test procedure for B. burgdorferi antibodies. Positive results from this Western Blot assay are supportive evidence of infection with B. burgdorferi, the causative agent of Lyme disease. The Viramed Biotech Borrelia B31 ViraBlot can be used during the acute phase (0-4 weeks of symptoms onset) of B. burgdorferi infection. After this early period, infected patients are usually found to be Western blot positive for IgG. A positive IgM test alone is not recommended for use in determining active disease in persons with illness of longer than one month.

Device Story

The Viramed Biotech Borrelia B31 IgM ViraBlot is an immunoblot assay for detecting IgM antibodies to Borrelia burgdorferi in human serum. The device utilizes electrophoretically isolated antigens bound to a nitrocellulose membrane. Patient serum is incubated with the strip; specific antibodies bind to antigens. After washing, an enzyme-labeled anti-human IgM conjugate is added, followed by a substrate that produces a color change at specific band locations upon reaction. The presence of colored precipitation indicates antibody presence. Results are interpreted by comparing band patterns to a lot-specific band locator. The test is performed in a laboratory setting by qualified technicians. It serves as a secondary test for samples previously screened by EIA or IFA. The output provides supportive evidence of B. burgdorferi infection, aiding clinicians in diagnosing Lyme disease during the acute phase.

Clinical Evidence

Performance evaluated using 100 clinically diagnosed Lyme borreliosis samples. Sensitivity: 70% (acute/erythema migrans), 95% (convalescent/erythema migrans), 95% (early disseminated neuroborreliosis), and 35% (late stage Lyme arthritis). Analytical specificity was 96% (194/200) in normal blood donors. Method comparison with predicate showed 62.5% to 85% agreement. Correlation with CDC Lyme Disease Panel was 86.4% (38/44). Reproducibility study across three sites and six readers demonstrated 100% concordance in 18 of 19 bands.

Technological Characteristics

In vitro qualitative Western Blot assay for IgM antibody detection. Utilizes human serum samples. Manual or semi-automated laboratory test format.

Indications for Use

Indicated for qualitative detection of IgM antibodies to Borrelia burgdorferi in human serum. Intended for patients with sensitive or equivocal EIA/IFA test results. Used during acute phase (0-4 weeks post-symptom onset) of B. burgdorferi infection. Not recommended for determining active disease in patients with illness >1 month.

Regulatory Classification

Identification

Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), the Treponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies to Treponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genus Treponema and provides epidemiological information on syphilis.

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K051169

B. Purpose for Submission:
New device

C. Measurand:
IgM antibodies to *Borrelia burgdorferi*

D. Type of Test:
Western blot test

E. Applicant:
Viramed Biotech AG

F. Proprietary and Established Names:
*Borrelia B31 IgM ViraBlot®*

G. Regulatory Information:

1. Regulation section: 21CFR 866. 3830, Treponema pallidum treponemal test reagents
2. Classification: Class: II
3. Product code: 83 LSR; Reagent, Borrelia Serological Reagent
4. Panel: 83 Microbiology

H. Intended Use:

1. Intended use(s):
The Viramed Biotech Borrelia B31 IgM ViraBlot® is an *in vitro* qualitative assay for the detection of IgM antibodies to *Borrelia burgdorferi* in human serum. It is

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intended for use in testing human serum samples which have been found positive or equivocal using an EIA or IFA test procedure for B. burgdorferi antibodies. Positive results from this Western Blot assay are supportive evidence of infection with B. burgdorferi, the causative agent of Lyme disease. The Viramed Biotech Borrelia B31 ViraBlot can be used during the acute phase (0-4 weeks of symptoms onset) of B. burgdorferi infection. After this early period, infected patients are usually found to be Western blot positive for IgG. A positive IgM test alone is not recommended for use in determining active disease in persons with illness of longer than one month.

2. Indication(s) for use:
The Viramed Biotech Borrelia B31 IgM ViraBlot® is an in vitro qualitative assay for the detection of IgM antibodies to Borrelia burgdorferi in human serum. It is intended for use in testing human serum samples which have been found positive or equivocal using an EIA or IFA test procedure for B. burgdorferi antibodies. Positive results from this Western Blot assay are supportive evidence of infection with B. burgdorferi, the causative agent of Lyme disease. The Viramed Biotech Borrelia B31 ViraBlot can be used during the acute phase (0-4 weeks of symptoms onset) of B. burgdorferi infection. After this early period, infected patients are usually found to be Western blot positive for IgG. A positive IgM test alone is not recommended for use in determining active disease in persons with illness of longer than one month.

3. Special conditions for use statement(s):
For prescription use

4. Special instrument requirements:
None

I. Device Description:
Electrophoretically isolated antigens are bound to a solid phase nitrocellulose support membrane called an immunoblot strip. For each test to be performed, the immunoblot strip and diluted test sera are placed in a well to react. If specific antibodies that recognize an antigen are present, they will bind to the specific antigens on the strip. After incubation the immunoblot strip is washed to remove unbound antibody. An enzyme labeled anti-human IgM is then added to each strip and incubated. If antibody is present, the conjugate will bind to the antibody attached to the specific antigens. The strip is washed to remove unbound conjugate and a substrate solution is added. If the enzyme/antibody complex is present, the substrate will undergo a precipitation and color change. After an incubation period, the reaction is stopped and the presence of precipitated substrate is visualized at specific locations on the strip. The presence of a colored precipitation at various locations on the Virastripe strip is an indirect measurement of Borrelia burgdorferi specific antibody in the patient specimen. A lot specific band locator (reacted immunoblot strip) is supplied and used to locate and identify

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specific Borrelia burgdorferi B31 antibodies on the test strip.

Positivity: The criteria for a positive Western blot result defined by the CDC are followed. For B. burgdorferi IgM positivity, the blot should be positive for at least 2 of the 3 protein bands: p41, p39, p23kDa

## J. Substantial Equivalence Information:

1. Predicate device name(s):
B. burgdorferi (IgM) Marblot Strip Test System from MarDx

2. Predicate 510(k) number(s):
k951709

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Procedure | Qualitative; B. burgdorferi IgM antibodies to specific protein bands. | Qualitative; B. burgdorferi IgM antibodies to specific protein bands. |
| Assay | Western blot | Western blot |
| Specimen Type | Serum | Serum |
| Differences | | |
| Item | Device | Predicate |
| Not applicable | Not applicable | Not applicable |

## K. Standard/Guidance Document Referenced (if applicable):

Not applicable

## L. Test Principle:

Western blot

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

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a. Precision/Reproducibility:

As a measure of kit precision, 6 blind coded specimens (2 strongly positive, 2 weakly positive and 2 negative) and kit controls were tested at three laboratory sites using the same kit lot number. For this study, two different readers within the three different laboratories assessed the band identification for each sample on the same blot. Six qualified technicians at the three sites assessed the Western blot bands from the same master lot kit number of Western blot kit. All samples were correctly interpreted by the 3 laboratories and 6 readers with 100% concordance in 18 of 19 bands for IgM.

b. Linearity/assay reportable range:

Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Not applicable

d. Detection limit:

Not applicable

e. Analytical specificity:

For determination of specificity, two hundred sera from normal blood donor individuals representing endemic and non-endemic geographic regions of the United States were tested for IgM Borrelia burgdorferi antibodies by the Viramed Borrelia B31 IgM Virablot®.

Negativity = 96% (194/200)

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Western blot testing was compared to a predicate device at two sites on routinely submitted specimens. At site 1, of a total 132 specimen tested, 8 were found to be EIA positive. At site 2, of a total of 109 specimens tested, 40 were found to be EIA positive.

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| EIA Positive / IgM WB | | BBI Western Blot | | |
| --- | --- | --- | --- | --- |
| Prospective Site 1 | | Pos | Neg | Total |
| Viramed Biotech | Pos | 2 | 3 | |
| Virablot® | Neg | 0 | 3 | |
| | | | | 8 |
| Agreement (5/8) =62.5% | | | | |
| Prospective Site 2 | | Trinity/MarDx Western Blot | | |
| | | Pos | Neg | Total |
| Viramed Biotech | Pos | 13 | 5 | |
| Virablot® | Neg | 1 | 21 | |
| | | | | 40 |
| Agreement (34/40)=85% | | | | |

## Correlations to the CDC Lyme Disease Panel

A Lyme Disease Clinical panel containing 45 clinically defined positives and negative samples was obtained from the Center for Disease Control and Prevention, Fort Collins, Colorado.

| Viramed Borrelia B31
IgM Western blot | CDC National
Lyme Disease Panel |
| --- | --- |
| Positive | 15/19 |
| Negative | 2325 |
| | Correlation = 86.4%(38/44) |

## College of American Pathologists 2003 Tick-borne Disease Proficiency Panel

The CAP Tick-borne Proficiency samples for the year 2003 were tested.

Samples tested: Positive 2 Negative 13

Correlation to Published CAP results proficiency = 86.7% (13/15)

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Sensitivity:

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One hundred sera were obtained from patients that were clinically diagnosed with Lyme borreliosis. Of these 100 sera, forty were paired (20 acute and 20 convalescent) sera from patients diagnosed with erythema migrans, 20 with early-disseminated neuroborreliosis and 40 with late stage Lyme arthritis.

| Clinical Stage | Sensitivity |
| --- | --- |
| Acute/Erythema Migrans
(Sampled 8-10 days after onset) | 70% (14/20) |
| Convalescent/Erythema Migrans
(Sampled 4 weeks after onset) | 95% (19/20) |
| Early disseminated neuroborreliosis | 95% (19/20) |
| Late Stage Lyme Arthritis | 35% (14/40) |

b. Clinical specificity:
Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Not applicable

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.