K Number
K013837
Manufacturer
Date Cleared
2002-09-30

(315 days)

Product Code
Regulation Number
866.3780
Reference & Predicate Devices
N/A
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Platelia Toxo IgM TMB kit is an in-vitro diagnostic test kit for the qualitative and quantitative detection of anti-Toxoplasma gondii IgM in human serum or plasma (EDTA, Heparin, Citrate).

Note:

  • . Patient testing with the Platelia® Toxo IgM assay must be performed in conjunction with an anti-Toxoplasma gondii IgG antibody assay.
  • The Platelia® Toxo IgM assay is presumptive for the detection of anti-● Toxoplasma gondii IgM antibodies and presumptive for the diagnosis of acute, recent or reactivated Toxoplasma gondii infection.
  • The performance of the Platelia® Toxo IgM assay has not been established for ● neonate testing.
  • . The Platelia® Toxo IgM assay has not been cleared/approved by the FDA for blood/plasma donor screening.
Device Description

The Platelia® Toxo IgM TMB assay is a qualitative assay which utilizes an immunocnzymatic double sandwich method. Diluted samples and controls are placed into microplate wells coated with antibodies to human IgM. The IgM antibodies present in the samples are captured by the solid phase. Remaining antibodies (including any of the IgG class) and other serum proteins are removed by washing. A solution containing T. gondii antigen and conjugate (monoclonal antibody to T. gondii labeled with horseradish peroxidase) is placed into each well. T. gondii IgM antibodies in the test sample that are captured on the solid phase bind the T. gondii antigen-complex. Excess T. gondii antigen and conjugate are removed by washing. A peroxidase substrate and chromogen solution is added which reacts with the conjugate to initiate a color development reaction is stopped by the addition of an acid. The optical density readings for the test samples are obtained with a spectrophotometer set at a wavelength of 450 nm. The presence of T. gondii IgM antibodies in an individual sample is determined by comparing the optical density reading for the sample to the optical density reading of the cut-off control serum.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study used to demonstrate the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the document demonstrates substantial equivalence to a predicate device and provides performance metrics. Based on the comparison study, the implicit acceptance criteria would be very high agreement rates with a legally marketed predicate device.

Performance MetricAcceptance Criteria (Implied)Reported Device Performance (Platelia® Toxo IgM TMB)
Overall AgreementHigh agreement with predicate99.53% (95% CI: 98.76% - 100.00%)
Negative AgreementHigh agreement with predicate100.00% (95% CI: 99.82% - 100.00%)
Positive AgreementHigh agreement with predicate98.72% (95% CI: 96.61% - 100.00%)
Sensitivity (CDC Panel)100% agreement for positives100% agreement with positive specimens
Specificity (CDC Panel)100% agreement for negatives100% agreement with negative specimens
Intra-assay CV (OD)Low CVRanges from 1.2% to 24.0%
Intra-assay CV (S/CO)Low CVRanges from 1.2% to 25.3%
Inter-assay CV (OD)Low CVRanges from 1.6% to 43.7%
Inter-assay CV (S/CO)Low CVRanges from 1.7% to 38.7%

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

  • Comparison Studies:
    • Test Set Sample Size: 348 patient samples and 97 specimens from 40 seroconversion panels, for a combined total of 445 specimens.
    • Data Provenance: The document states that 445 fresh and frozen serum samples were "obtained from pregnant women during routine laboratory activities in the area of Paris, France." It also mentions "comparative prospective and retrospective testing" but does not specify the origin or nature of the "patient samples" portion of the 348. The 97 seroconversion panel specimens are not given specific provenance beyond being "from 40 seroconversion panels."
  • CDC Test Panel:
    • Test Set Sample Size: 32 positive samples and 65 negative samples, for a total of 97 samples.
    • Data Provenance: "serum panel obtained from the CDC." (Country of origin implicitly USA).

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. For the "Comparison Studies," the reference for ground truth is "another commercially available enzyme immunoassay (EIA)", which implies that its results were taken as the standard. For the "CDC Test Panel," the samples are described as "masked, characterized serum panel," suggesting they have a pre-established ground truth, likely determined by experts or a reference method, but no details are provided.

4. Adjudication Method for the Test Set

The document does not mention any adjudication method for the test set. The comparison is made directly against a predicate EIA device or pre-characterized CDC panels. There is no indication of multiple readers or an adjudication process for discrepancies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic assay, not an AI imaging device involving human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the performance presented for the Platelia® Toxo IgM TMB assay is a standalone, algorithm-only performance. It refers to the kit's ability to detect antibodies based on optical density readings and comparison to a cut-off control, without human interpretation of ambiguous results (beyond following the kit's instructions for qualitative interpretation). The "Note" about physician interpretation in conjunction with an IgG assay refers to clinical utility, not the device's standalone analytical performance.

7. The Type of Ground Truth Used

  • Comparison Studies: The ground truth for the comparison study was based on the results of "another commercially available enzyme immunoassay (EIA)"—specifically the Kallestad Diagnostics Platelia® Toxo IgM (K89498), which is the predicate device.
  • CDC Test Panel: The ground truth for the CDC test panel was based on a "masked, characterized serum panel," implying that the positivity or negativity of these samples was previously established by authoritative methods or reference labs (likely expert-driven characterization).

8. The Sample Size for the Training Set

The document does not provide information on a "training set" in the context of an algorithm or machine learning model. This is an immunoassay kit, where the "training" equivalent would be the development and optimization of the assay itself based on various biological samples, but specific sample sizes for such development are not listed as a "training set."

9. How the Ground Truth for the Training Set Was Established

As this is an immunoassay and not an AI/ML device, the concept of a "training set" with established ground truth, as typically understood in AI, does not directly apply. The design and optimization of the assay components (e.g., antigen, conjugate, chromogen) would have been based on extensive laboratory work and validation using known positive and negative samples, but these are not delineated as a formal "training set" with a separate ground truth establishment process in the context of this 510(k) summary.

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows a logo with the text "O+RAD" in bold, white letters against a black background. The logo has a rounded rectangular shape. The plus sign in "O+RAD" is slightly smaller than the other letters.

SEP 3 0 2002

ATTACHMENT I 510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K013837

DATE:September 10, 2002
APPLICANT:Bio-Rad3, Boulevard Raymond Poincaré92430 Marnes-la-Coquette, France
PHONE:33-1-47-95-6138
FAX:33-1-47-95-6242
OFFICIAL CORRESPONDENT:Sylvie Confida
PRODUCT TRADE NAME:Bio-Rad Platelia® Toxo IgM TMB
COMMON NAME:Toxoplasma IgM Enzyme Immunoassay (EIA)
CLASSIFICATION NAME:21 CFR 866.3780, Enzyme Linked Immunoabsorbent Assay,Toxoplasma Gondii
PREDICATE DEVICE:Kallestad Diagnostics Platelia® Toxo IgM (K89498)

DEVICE DESCRIPTION

The Platelia® Toxo IgM TMB assay is a qualitative assay which utilizes an immunocnzymatic double sandwich method. Diluted samples and controls are placed into microplate wells coated with antibodies to human IgM. The IgM antibodies present in the samples are captured by the solid phase. Remaining antibodies (including any of the IgG class) and other serum proteins are removed by washing. A solution containing T. gondii antigen and conjugate (monoclonal antibody to T. gondii labeled with horseradish peroxidase) is placed into each well. T. gondii IgM antibodies in the test sample that are captured on the solid phase bind the T. gondii antigen-complex. Excess T. gondii antigen and conjugate are removed by washing. A peroxidase substrate and chromogen solution is added which reacts with the conjugate to initiate a color development reaction is stopped by the addition of an acid. The optical density readings for the test samples are obtained with a spectrophotometer set at a wavelength of 450 nm. The presence of T. gondii IgM antibodies in an individual sample is determined by comparing the optical density reading for the sample to the optical density reading of the cut-off control serum.

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in black and white and features the company name in bold, sans-serif letters. The logo is enclosed in a rounded rectangle.

INTENDED USE

The Platelia® Toxo IgM TMB kit is an in vitro diagnostic test kit allowing the qualitative detection of anti-Toxoplasma gondii in human serum or plasma (EDTA, Heparin, Citrate).

Note:

  • Patient testing with the Platelia® Toxo IgM assay must be performed in conjunction with an anti-. Toxoplasma gondii IgG antibody assay.
  • . The Platelia® Toxo IgM assay is presumptive for the detection of anti-Toxoplasma gondii IgM antibodies and presumptive for the diagnosis of acute, recent, or reactivated Toxoplasma gondii infection.
  • . The performance of the Platelia® Toxo IgM assay has not been cleared/approved by the FDA for blood/plasma donor screening.

TECHNOLOGICAL CHARACTERISTICS

The Platelia® Toxo IgM TMB kit is a modified version of the Platelia® Toxo IgM kit and remains similar in form and function. The following comparison table indicates significant similarities and differences between the kits:

CharacteristicsPlatelia® Toxo IgM (Predicate)Platelia® Toxo IgM TMB
Format and Test Method96-well microplate EIA,non-breakaway wells96-well microplate EIA,breakaway wells
Intended UseAssay for the qualitativedetection of anti- Toxoplasmagondii IgM in human serumAssay for the qualitativedetection of anti- Toxoplasmagondii IgM in human serum orplasma
Positive and Negative ControlsPooled human serum, negativefor T. gondii , is used tomanufacture the negative controland to dilute the positive control.A synthetic matrix consisting ofTris-NaCl buffer, BSA, glycerol,and colorant is used tomanufacture the negative controland to dilute the positive control.
Chromogeno . phenylenediamine-2 HCL(OPD) tabletsTetramethylbenzidine (TMB)solution
WavelengthDual wavelength reading at492 nm and 620 nm.Dual wavelength reading at450 nm and 620 nm.

Comparison Table

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the logo for Bio-Rad. The logo is in white text on a black background. The text is bold and sans-serif.

PERFORMANCE SUMMARY

A. Precision Studies

Inter-assay and intra-assay reproducibility were determined by assaying two T. gondir IgM negative samples and four T. gondii IgM positive samples in triplicate, on three different days at three laboratory sites.

Site 1

Neg 1Neg 2Pos 1Pos 2Pos 3Pos 4
ODS/COODS/COODS/COODS/COODS/COODS/CO
N=999999999999
Mean=0.0270.0520.0220.0420.7421.4380.6601.2780.8251.5991.4772.862
Within Run
(intra-assay) sd=0.0010.0030.0020.0030.0110.0210.0110.0220.0160.0310.0170.034
%CV=5.2%5.1%7.5%7.6%1.5%1.4%1.7%1.7%1.9%1.9%1.2%1.2%
Total
(inter-assay) sd=0.0020.0050.0010.0030.0200.0410.0130.0380.0130.0480.0320.050
%CV=8.1%9.7%6.7%6.3%2.6%2.8%2.0%3.0%1.6%3.0%2.1%1.7%

Site 2

Neg 1Neg 2Pos 1Pos 2Pos 3Pos 4
ODS/COODS/COODS/COODS/COODS/COODS/CO
N=999999999999
Mean=0.0310.0500.0290.0480.7461.2060.6691.0830.7761.2551.5112.444
Within Run(intra-assay) sd=0.0070.0110.0070.0110.0250.0400.0150.0240.0090.0150.0510.082
%CV=22.5%23.0%22.6%23.2%3.3%3.3%2.3%2.3%1.2%1.2%3.4%3.4%
Total(inter-assay) sd=0.0090.0160.0070.0120.0240.0610.0150.0660.0120.0630.0460.151
%CV=29.9%32.8%22.3%24.4%3.2%5.0%2.2%6.1%1.5%5.0%3.0%6.2%

Site 3

Neg 1Neg 2Pos 1Pos 2Pos 3Pos 4
ODS/COODS/COODS/COODS/COODS/COODS/CO
N=999999999999
Mean=0.0320.0570.0240.0420.7691.3930.7051.2780.6841.2271.3462.426
Within Run
(intra-assay) sd=0.0040.0070.0060.0110.0550.1040.0230.0440.0110.0200.0610.107
%CV=11.6%12.1%24.0%25.3%7.1%7.5%3.3%3.5%1.6%1.6%4.5%4.4%
Total
(inter-assay) sd=0.0140.0220.0100.0160.0730.2030.0770.2120.1190.1500.0980.150
%CV=43.7%38.7%41.2%36.8%9.5%14.6%11.0%16.6%17.4%12.2%7.3%6.2%

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the logo for Bio-Rad Laboratories, a company that manufactures and distributes products for the life science research and clinical diagnostics markets. The logo is in white text on a black background. The text is bold and sans-serif.

In addition, inter-assay and intra-assay reproducibility with plasma samples were determined by assaying three additional samples (one T. gondii IgM negative sample and two T. gondii IgM positive samples) in triplicate, on three different days, at one laboratory site.

SerumNeg 1Pos 1Pos 2
ODS/COODS/COODS/CO
N =999999
Mean =0.0220.040.7101.261.0831.92
Within-Run(intra-assay) sd =0.0020.0030.0190.0340.0290.052
%CV =8.7%8.8%2.7%2.7%2.7%2.7%
Total(inter-assay) sd =0.0030.0060.0350.0770.0510.074
%CV =14.5%14.9%4.9%6.1%4.8%3.9%
EDTANeg 1Pos 1Pos 2
ODS/COODS/COODS/CO
N =999999
Mean =0.0240.040.7611.351.0631.88
Within-Run(intra-assay) sd =0.0020.0040.0190.0340.0190.033
%CV =8.3%8.3%2.5%2.6%1.7%1.8%
Total(inter-assay) sd =0.0020.0040.0360.0300.0560.076
%CV =8.5%9.4%4.7%2.2%5.2%4.0%
CitrateNeg 1Pos 1Pos 2
ODS/COODS/COODS/CO
N =999999
Mean =0.0220.040.6741.191.0751.91
Within-Run(intra-assay) sd =0.0010.0020.0170.0290.0200.036
%CV =5.0%5.0%2.5%2.5%1.9%1.9%
Total(inter-assay) sd =0.0020.0040.0310.0380.0430.091
%CV =9.9%10.6%4.5%3.2%4.0%4.8%
HeparinNeg 1Pos 1Pos 2
ODS/COODS/COODS/CO
N =999999
Mean =0.0220.040.7191.271.0341.83
Within-Run(intra-assay) sd =0.0010.0020.0120.0200.0220.039
%CV =4.4%4.4%1.6%1.6%2.1%2.1%
Total(inter-assay) sd =0.0020.0030.0240.0310.0590.115

{4}------------------------------------------------

Image /page/4/Picture/0 description: The image shows the logo for BIO-RAD. The logo is white text on a black rounded rectangle. The text is in all caps and bolded.

B. Comparison Studies

Performance of the Platelia Toxo IgM TMB assay was evaluated against another commercially available enzyme immunoassay (EIA) by testing 348 patient samples and 97 specimens from 40 seroconversion panels. The combined results of the patient and seroconversion panel testing demonstrate an agreement of 99.53%.

1= 445TMB
NegEquivocal------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Pos
lgMNeg27
EIAEquivocal
Posાર્ય

Platelia Toxo IgM TMB vs IgM EIA Correlation Table (combined results)

Excluding equivocal samples / specimens, the combined results of comparative prospective and retrospective testing demonstrated the following:

Negative agreement : 100.00% (271/271). The 95% confidence intervaled is 99.82 - 100.00%. Positive agreement : 98.72% (154/156). The 95% confidence intervale is 96.61 - 100.00%. Overall agreement : 99.53% (425/427). The 95% confidence interval-6 is 98.76% - 100.00%.

C. Expected Values

A total of 445 fresh and frozen serum samples obtained from pregnant women during routine laboratory activities in the area of Paris, France were tested with the Platelia® Toxo IgM TMB assay. The distribution of serum / cut-off ratio values is shown in the following chart.

Image /page/4/Figure/9 description: The image is a bar chart titled "Platelia Toxo IgM TMB Expected Values". The x-axis is labeled "Ratio Serum / Cut-Off", and the y-axis is labeled "Frequency". The bar chart shows the frequency of different ratio serum/cut-off values. The bar chart shows that the most frequent ratio serum/cut-off value is less than 0.1, with a frequency of 214, and greater than or equal to 1.0, with a frequency of 154.

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for Bio-Rad. The logo is white text on a black rounded rectangle. The text reads "BIO-RAD" with a plus sign between "BIO" and "RAD".

D. CDC Test Panel

The following information is from a serum panel obtained from the CDC and tested by Bio-Rad Laboratories. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

The panel consists of 32 positive and 65 negative samples. The Platelia® Toxo IgM TMB assay demonstrated 100% agreement with the positive specimens and 100% agreement with the negative specimens.

Please Note: There should be no other statistical calculation or inferences drawn from the panel results.

{6}------------------------------------------------

Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized image of three human profiles facing right, stacked on top of each other. The profiles are drawn with thick, curved lines. The logo also includes the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular fashion around the image.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 3 0 2002

Mr. David Bhend Regulatory Affairs Associate Bio-Rad Laboratories Diagnostics Group 6565 18511 Avenue NE Redmond, WA 98052

Re: K013837

Trade/Device Name: Platelia® Toxo IgM TMB Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma gondii serological reagents Regulatory Class: Class II Product Code: LGD Dated: July 19, 2002 Received: July 23, 2002

Dear Mr. Bhend:

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 either class II (Special Controls) or class III (PMA), 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 comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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.

{7}------------------------------------------------

Page 2 -

This letter will allow you to begin marketing your device as described in your 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 : additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours.

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{8}------------------------------------------------

ATTACHMENT G INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K013837

Device Name: Platelia® Toxo IgM TMB

Indications for Use:

The Platelia Toxo IgM TMB kit is an in-vitro diagnostic test kit for the qualitative and quantitative detection of anti-Toxoplasma gondii IgM in human serum or plasma (EDTA, Heparin, Citrate).

Note:

  • . Patient testing with the Platelia® Toxo IgM assay must be performed in conjunction with an anti-Toxoplasma gondii IgG antibody assay.
  • The Platelia® Toxo IgM assay is presumptive for the detection of anti-● Toxoplasma gondii IgM antibodies and presumptive for the diagnosis of acute, recent or reactivated Toxoplasma gondii infection.
  • The performance of the Platelia® Toxo IgM assay has not been established for ● neonate testing.
  • . The Platelia® Toxo IgM assay has not been cleared/approved by the FDA for blood/plasma donor screening.

Woody Deubler

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K013837

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Professional Use: ___________

OR

Prescription Use: (Per 21 CFR 801.109

Over-The-Counter Use: (Optional Format 1-2-96)

§ 866.3780

Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).