FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The EUROIMMUN Anti-LKM-1 ELISA (IgG) test kit is intended for the qualitative detection of IgG class autoantibodies against LKM-1 (cytochrome P450 IID6 of liver-kidney-microsomes) in human serum and plasma. It is used as an aid in the diagnosis of autoimmune hepatitis, type 2, in conjunction with other laboratory and clinical findings.

Device Description

The EUROIMMUN Anti-LKM-1 ELISA (IgG) consists of a microwell ELISA plate coated with LKM-1 antigen, calibrator, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the EUROIMMUN Anti-LKM-1 ELISA (IgG) device, based on the provided text:

Acceptance Criteria and Device Performance

Parameter	Acceptance Criteria (Implicit)	Reported Device Performance
Intended Use	Qualitative detection of IgG class autoantibodies against LKM-1 as an aid in diagnosing autoimmune hepatitis, type 2.	Same as intended use.
Predicate Device	Substantial equivalence to Inova Quanta Lite LKM-1 ELISA (K000535).	The new device is substantially equivalent to the predicate device, sharing similar intended use, technology (ELISA), assay platform (96-well microtiter plates), assay format (qualitative), calibration (relative), antigen (recombinant cytochrome P450 IID6), substrate (TMB), reagent preparation, and procedure. Minor differences exist in conjugate, calibrators/controls, wash buffer concentration, stop solution concentration, sample types (plasma included for new device), reported results (ratio vs. units), and cut-off level. A method comparison study with the predicate device showed a negative agreement of 96.9% (95% C.I.: 92.9% - 99.0%), a positive agreement of 97.2% (95% C.I.: 85.5% - 99.9%), and overall agreement of 96.9% (95% C.I.: 93.5% - 98.9%).
Precision	Sufficient intra-assay and inter-assay reproducibility, with no positive samples found negative and vice-versa (with minor exceptions near cutoff).	Intra-Assay Reproducibility (n=20): Sample 1 (negative): 100% negative; Sample 2 (negative): 100% negative; Sample 3 (positive): 100% positive; Sample 4 (positive): 100% positive; Sample 5 (positive): 100% positive; Sample 6 (positive): 100% positive.
		Inter-Assay Reproducibility (n=24): Sample 1 (negative): 100% negative; Sample 2 (negative): 96% negative (4% positive, likely single determination near cutoff); Sample 3 (positive): 100% positive; Sample 4 (positive): 100% positive; Sample 5 (positive): 100% positive; Sample 6 (positive): 100% positive.
		Lot-to-Lot Reproducibility: Sufficient, with no positive sample found negative and vice versa. Examples shown for 11 samples over different 'n' values: positives remained 100% positive, negatives remained 100% negative.
Analytical Specificity	No significant cross-reactivity with antibodies against SLA/LP, and no significant interference from common substances (hemoglobin, triglycerides, bilirubin).	Cross-reactivity: 28 sera positive for SLA/LP were all negative in the Anti-LKM-1 ELISA (IgG). Interference: Recovery between 86-126% for samples spiked with hemoglobin (up to 1000 mg/dL), triglycerides (up to 2000 mg/dL), and bilirubin (up to 40 mg/dL). No significant interference observed.
Clinical Sensitivity	High sensitivity for AIH type 2.	For Autoimmune hepatitis type 2 (AIH-2): 95.6% (95% C.I.: 87.6 - 99.1%)
Clinical Specificity	High specificity against various control groups (AIH/PBC overlap, AIH-1, viral hepatitis, toxic liver damages, steatohepatitis, PBC, PSC, other autoimmune diseases).	For various control groups (AIH/PBC overlap, AIH-1, viral hepatitis, toxic liver damages, steatohepatitis, PBC, PSC, other autoimmune diseases): 100.0% (95% C.I.: 99.2 - 100.0% total specificity for these combined groups). Specificity for each individual control group was 100%.
Matrix Comparison	Equivalence of concentration between serum and corresponding plasma matrices (EDTA, Heparin, Citrate).	Passing-Bablok regression showed: EDTA plasma (y = 0.02 + 1.00 x, 95% C.I. of intercept: -0.04 to 0.06, 95% C.I. of slope: 0.98 to 1.02); Heparin plasma (y = -0.00 + 1.00 x, 95% C.I. of intercept: -0.03 to 0.06, 95% C.I. of slope: 0.97 to 1.01); Citrate plasma (y = 0.00 + 0.97 x, 95% C.I. of intercept: -0.06 to 0.05, 95% C.I. of slope: 0.95 to 1.00). All comparisons satisfied the condition for equivalence (95% C.I. of slope contains 1.0, and 95% C.I. of intercept contains 0). Coefficients of determination were >0.99 and %BIAS from serum was 87-109%.
Expected Values in Healthy Blood Donors	Characterization of results in a healthy population.	In a panel of 150 healthy blood donors, with a cut-off of ratio 1.0, only one was positive. Negatives: 149, Positives: 1. Mean value: Ratio 0.2.

Study Details

Sample sizes used for the test set and the data provenance:
- Method Comparison with Predicate Device:
  - Sample Size: 196 total samples (167 initial samples + 29 additional samples created by mixing positive and negative samples).
  - Provenance: "A study was performed in cooperation with a university clinical hospital". Country of origin is not specified, but the context implies it's likely within the same regulatory region as the applicant (EUROIMMUN US INC.), possibly the US or Europe. The study type appears to be retrospective, using a pre-existing collection of samples from different patient groups.
  - Sample Breakdown: 58 from AIH patients, 66 from PBC patients, 15 from AIH/PBC overlap syndrome patients, and 28 from patients with viral hepatitis. 30 men and 137 women, age 1-87 years (average 50 years).
- Matrix Comparison:
  - Sample Size: 16 sample pairs (serum and corresponding plasma for EDTA, Heparin, and Citrate plasma).
  - Provenance: Not explicitly stated, but likely from a laboratory setting as part of an analytical validation. Retrospective.
- Clinical Studies (Sensitivity and Specificity):
  - Sample Size: 515 clinically characterized samples.
  - Provenance: "Performed in cooperation with several university, hospital and private laboratories". Country of origin not specified, but likely multi-center. Retrospective.
  - Sample Breakdown: 68 from AIH-2 patients, 65 from AIH-1 patients, 15 from AIH/PBC overlap syndrome patients, and 367 from other control groups (Viral hepatitis, Toxic liver damages, Steatohepatitis, PBC, PSC, Other autoimmune diseases: MCTD, celiac disease, Diabetes Type I, Hashimoto, Grave's disease, ulcerative colitis).
- Expected Values/Reference Range:
  - Sample Size: 150 apparently healthy blood donors.
  - Provenance: Not explicitly stated, but implies a collection from a healthy population. Retrospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications. The clinical samples were "clinically characterized" and categorized as originating "from AIH-2 patients," "AIH-1 patients," etc., suggesting diagnoses were established by medical professionals, but details about the consensus process or individual qualifications are not provided.
Adjudication method for the test set:
- No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for establishing the ground truth diagnoses. The samples were simply described as "clinically characterized," implying standard clinical diagnostic procedures were followed.
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 ELISA kit for detecting autoantibodies, not an imaging device or one that involves human interpretation of output that would typically be assessed in an MRMC study.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance data presented (precision, analytical specificity, clinical sensitivity, clinical specificity) represent the standalone performance of the ELISA kit itself. The output of the ELISA is a quantitative ratio, which is then interpreted against a fixed cut-off (Ratio 1.0) to yield a qualitative (positive/negative) result. This process does not involve a human "in-the-loop" for the interpretation of the direct output of the device beyond reading the final calculated ratio.
The type of ground truth used:
- Clinical Diagnosis: For the clinical sensitivity and specificity studies, the ground truth was established by "clinically characterized samples" from specific patient groups (e.g., "Autoimmune hepatitis type 2 (AIH-2) patients," "Viral hepatitis," "Primary biliary liver cirrhosis (PBC)"). This implies a ground truth based on established clinical diagnostic criteria, likely involving a combination of clinical findings, histology, and other laboratory tests.
- Predicate Device/Reference Method: For the method comparison study, the predicate device (Inova Quanta Lite LKM-1 ELISA) served as a reference method for comparison.
- Serological Status: For cross-reactivity, ground truth was based on samples "serologically positive for antibodies against SLA/LP."
The sample size for the training set:
- The document does not specify a separate "training set" for the ELISA device. ELISA assays are typically developed based on biochemical principles and optimized through analytical validation, rather than being "trained" in the same way machine learning algorithms are. The samples described in the performance characteristics section are for validation and verification of the device's analytical and clinical performance.
How the ground truth for the training set was established:
- As there's no explicitly defined "training set" in the context of machine learning for this ELISA device, this question is not directly applicable. The development and optimization of the ELISA kit would involve extensive laboratory work, antigen selection, and reagent formulation, with performance evaluated against characterized clinical samples as described in the "Test Set" details.

Summary

Regulation Number and Section

§ 866.5660 Multiple autoantibodies immunological test system.

(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).