(99 days)
The Premier Platinum HpSA PLUS enzyme immunoassay (EIA) is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection and to monitor response during and post-therapy in patients. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least four weeks following completion of therapy.
Premier Platinum HpSA PLUS is an in vitro diagnostic, microwell-based, enzymelinked immunoassay for the detection of Helicobacter pylori antigen in human stool. The assay is intended for use in clinical laboratories to test for bacterial colonization to aid diagnosis, or monitor a patient's response during therapy to eradicate infection. The assay consists of Microwells coated with specific antibodies (solid phase/capture antibodies), Enzyme Conjugate (detector antibodies), Sample Diluent, Premier 20X Wash Buffer I, Premier Substrate Solution I, Premier Stop Solution I and Positive Control. Sample Diluent also functions as the Negative Control reagent.
No calibrators are needed to use this device.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Premier Platinum HpSA PLUS device:
Device Acceptance Criteria and Performance Study Analysis
The submission describes the Premier Platinum HpSA PLUS, an in vitro diagnostic enzyme immunoassay (EIA) for detecting H. pylori antigen in human stool. The primary goal of the submission is to demonstrate substantial equivalence to a predicate device, Premier Platinum HpSA.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as a separate section with predefined targets. Instead, the study aims to demonstrate that the new device performs "similarly" to the predicate, and that certain analytical performance characteristics are met. Based on the provided text, I've inferred the acceptance criteria from the reported performance and the comparisons made to the predicate or industry standards like EP12-A.
| Acceptance Criteria (Implied/Direct) | Reported Device Performance (Premier Platinum HpSA PLUS) |
|---|---|
| Clinical Performance (vs. Predicate) | |
| Overall Agreement with Predicate | 96.5% |
| Positive Agreement with Predicate | 100% |
| Negative Agreement with Predicate | 94.8% |
| Improvement over Predicate for Indeterminate Results | Clarified 7 out of 7 indeterminate results from predicate as definite positive using other tests (CLO/Histology/UBT) by HpSA PLUS, and 1 indeterminate result as definite negative. |
| Analytical Performance | |
| Precision/Reproducibility (intra-assay) | 97% (compared to predicate's 100% – this is for intra-assay, not overall reproducibility which is stated as 100%) |
| Overall Reproducibility | 100% (for samples above or below the limit of analytical sensitivity) |
| Performance of "High negative" samples at cutoff | Produced weakly positive results 42 out of 162 times (expected ~50% based on EP12-A) |
| Limit of Detection (H. pylori flagellar antigen in stool) | ≥ 4.67 ng/mL |
| Limit of Detection (H. pylori bacterial strain in stool) | ≥ 1.0 % organisms/mL (assuming the missing exponent is 10^?) |
| Assay Cutoff | 0.100 at OD450/630 |
| Absence of Indeterminate Range | All results definitive (no 0.100-0.120 OD range needed, unlike predicate) |
| Absence of Interference from Drugs/Nonmicrobial Substances | None had a significant effect on negative test results; positive results correlated closely with unspiked samples. |
| Absence of Interference from Microbial/Viral Organisms | None adversely affected final positive or negative test results. |
| Therapeutic Monitoring Performance | Eradication curves were substantively the same as predicate for strongly positive samples; differed at low positive states initially but identical by week four post-treatment. |
2. Sample Size Used for the Test Set and the Data Provenance
- Test Set (Clinical Comparison): 291 samples from symptomatic patients.
- Data Provenance: Not explicitly stated, but collected from "symptomatic patients" suggesting a clinical setting. It is retrospective as 33 of these samples were originally evaluated in an earlier trial for the predicate device.
- Test Set (Reproducibility): 2 high positive, 2 low negative, 1 low positive, and 1 high negative specimen in a reference panel, with 9 replicates each of the low positive and high negative samples, bringing the total cohort to 22 reference specimens.
- Data Provenance: Prepared from "archival specimens" and tested in "three different laboratories." This indicates a controlled, retrospective, and multi-site analytical study.
- Test Set (Interference Testing): 5 known H. pylori-positive and 5 known negative samples for drug interference; an unspecified number of samples for microbial/viral interference.
- Data Provenance: Laboratory-controlled spike-in experiments, prospective in nature for the study itself, using known positive/negative samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
There were no experts used to establish ground truth in the traditional sense for the clinical comparison. Instead, "other conventional tests such as CLO, Histology, or UBT" were used to arbitrate discordant results between the new device and the predicate. The qualifications of those performing these conventional tests are not specified.
4. Adjudication Method for the Test Set
For the clinical comparison, when results between Premier Platinum HpSA PLUS and the predicate were discordant, they were adjudicated against "test data from other conventional tests such as CLO, Histology, or UBT to determine the trueness of the results." This implies a form of external reference standard adjudication, rather than a consensus among human readers of the device output. It's not a 2+1 or 3+1 method directly related to human interpretation of the device results, but rather a comparison to established diagnostic methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
No MRMC study was done, nor is this an AI/human-in-the-loop device. It is a laboratory-based enzyme immunoassay. The comparison is between two similar lab tests.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, this is a standalone device. Its performance characteristics are reported as the output of the assay itself, interpreted quantitatively (OD readings) against a predefined cutoff. There is no human interpretation component in the sense of a radiologist reading an image or a pathologist reviewing a slide that would then be assisted by AI.
7. The Type of Ground Truth Used
- Clinical Comparison (for discordant results): A combination of other conventional diagnostic tests for H. pylori infection (CLO, Histology, UBT). These serve as the de facto "ground truth" to determine if the device's results are true positives/negatives.
- Analytical Sensitivity (Limit of Detection): Purified antigens and bacterial strains, where known concentrations were spiked, serving as a controlled, known standard.
- Interference Testing: Known H. pylori-positive and negative samples spiked with various substances/microbes, representing a known state (positive/negative for H. pylori, plus presence of interferent).
- Reproducibility: A reference panel with defined states (high positive, low positive, high negative, low negative), serving as a known standard.
8. The Sample Size for the Training Set
No specific training set is mentioned as this device is not an AI/machine learning algorithm that requires a training phase. It is a traditional immunoassay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device.
{0}------------------------------------------------
510(k) SUMMARY
510(k) number: K053335
Submitters name and address: Meridian Bioscience, Inc. 3471 River Hills Drive Cincinnati. OH 45244 513-271-3700 Contact: Susan Rolih
Date summary prepared: January 30, 2006
Name of the device: Premier Platinum HpSA PLUS Enzyme Immunoassay for the detection of H. pylori antigen in human stool specimens
Classification: LYR, CFR section 866.3110
Predicate device to which this device is being compared: Premier Platinum HpSA (Meridian Bioscience, Inc., Cincinnati, OH) (K980076, K983255)
Device description: Premier Platinum HpSA PLUS is an in vitro diagnostic, microwell-based, enzymelinked immunoassay for the detection of Helicobacter pylori antigen in human stool. The assay is intended for use in clinical laboratories to test for bacterial colonization to aid diagnosis, or monitor a patient's response during therapy to eradicate infection. The assay consists of Microwells coated with specific antibodies (solid phase/capture antibodies), Enzyme Conjugate (detector antibodies), Sample Diluent, Premier 20X Wash Buffer I, Premier Substrate Solution I, Premier Stop Solution I and Positive Control. Sample Diluent also functions as the Negative Control reagent.
No calibrators are needed to use this device.
Intended use: The Premier Platinum HpSA PLUS enzyme immunoassay (EIA) is an in vitro qualitative procedure for the detection of Helicobacter pylori antigens in human stool. Test results are intended to aid in the diagnosis of H. pylori infection and to monitor response during and post-therapy in patients. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least four weeks following completion of therapy.
There is no change to the intended use of this device from its predicate.
Comparison charts (Premier Platinum HpSA PLUS vs Predicate Device):
| Characteristics | Premier Platinum HpSAPLUS | Premier Platinum HSA(predicate) |
|---|---|---|
| Device Type | ||
| In vitro diagnostic device | Yes | Yes |
| Control | Includes external controlreagent | Includes external controlreagent |
| Calibrator | No | No |
| Intended Use | ||
| Detection of H. pylori antigen | Yes | Yes |
| Screening test | Yes | Yes |
| Diagnostic test | No | No |
| Monitoring therapy | Yes | Yes |
| Acceptable Sample | ||
| Stool | Yes | Yes |
{1}------------------------------------------------
| Laboratory Equivalence with (Predicate Device) | Premier Platinum HpSAPLUS | Predicate |
|---|---|---|
| Combined Totals | ||
| Agreement, positive tests | 100% | N/A |
| Agreeement, negative tests | 94.8% | N/A |
| Agreement, overall | 96.5% | N/A |
| Performance characteristics | ||
| Precision/Reproducibility (intra-assay) | 97% | 100% |
| Linearity/reportable range | N/A | N/A |
| Analytical limit of detection/sensitivity | ≥ 4.67 ng in stool | ≥ 184 ng in stool |
| Assay cutoff | 0.100 at OD450/630 | 0.120 at OD450/630 |
| Indeterminant range | None | 0.100 - 0.120 atOD450/630 |
Interpretation of test results
The results of bench tests were read using a standard laboratory dual wave length spectrophotometer. Results were interpreted according to the following scale:
Spectrophotometric dual wavelength (450/630 nm) Negative < 0.100 Positive ≥ 0.100
Results occurring in the 0.100 to 0.120 OD range were tracked to determine if a significant number of results were obtained such that would justify the inclusion of an equivocal range. The alsence of equivocal results in the studies showed that this criteria was not necessary.
Analytical sensitivity – limit of detection
Study design: Serial dilutions of purified H. pylori flagellar antigen and a H. pylori bacterial strain (ATCC 43504) were prepared in stool or Sample Diluent and used to determine the lowest concentration of antigen that would still yield a definitive positive result (Assoco ≥ 0.100 on Premier Platinum HpSA PLUS). Final concentrations were calculated from the data points using linear regression analysis. Conclusions to the study: The analytical limit for H. pylori flagellar antigen is 4.67 ng/mL in stool and 0.69 ng/mL in sample diluent. The limit for H. pylori bacterial strain is 1.0 % organisms/mL in stool and 4.0 1 10111 organisms/mL in Sample Diluent. The limits are lower than those reported for the Predicate Device,
Linearitv
Linearity does not apply to the endpoint produced by this device.
Interfering substance testing
Drugs, Nonmicrobial Substances
Study design: Selected drugs and other nonmicrobial substances that might be present in stool specimens were added to five known H. pylori-positive and five known negative samples. The final concentrations of the additives per 500 ul. of human stool are as follows: TUMS - 10 mg, Pepto Bismoluna of the Tagamet - 1 mg, Prilosec OTC - 1 mg, barium suifate - 10 mg, whole blood - 100 mucin - 6.7 mg, human hemoglobin (to make dark stool) – 15 mg, steric + palmitic acids (to make fatty stool) – 7.9 mg. The spiried samples were tested in triplicate and in parallel with an unspiked control. Acceptance criteria required the values within replicates be similar to each other and to the value obtained with the unspiked specmers. None of the potentially interfering substances had a significant effect on negative test results. Notes correlated closely with unspiked samples. Conclusions to the study. Trues or nonmicrobial substances that might be present as co-contaminants of stool samples do not adversely affect results obtained with Premier Platinum HpSA PLUS. These data correlate with data published for the predicate device.
Microbial/Viral organisms (potentially cross-reactive or interfering species)
Study design: The bacteria, yeast and viruses selected were that might be expected to be present in human stool samples either as part of normal flora or from a disease state. The final concentration of bracteria
{2}------------------------------------------------
or yeast in each sample was ≥ #4 McFarland Standard (1.2 X 10 organisms/mL). The final concentration of viruses in each sample was not determined. Unspiked samples were tested in parallel to provide a reference against which the reactions with spiked samples could be compared. Samples were tested in triplicate. Acceptance criteria required that the values within replicates be similar to each other and to the value obtained with the unspiked specimen. See data in Tables below. None of the potential co-contaminants adverselv affected the final positive or negative test results. Conclusions to the study: Microbial and viral organisms that might be present as co-contaminants of stool samples do not adversely affect results obtained with Premier Platinum HpSA PLUS. These data correlate with data published for the predicate device.
| Sample | 42 | 32 | ||||||
|---|---|---|---|---|---|---|---|---|
| Run 1 | Run 2 | Run 3 | Avg | Run 1 | Run 2 | Run 3 | Avg | |
| No Spike | 0.465 | 0.409 | 0.415 | 0.430 | 1.472 | 1.316 | 1.099 | 1.296 |
| No Spike | 0.536 | 0.553 | 0.494 | 0.528 | 1.861 | 1.979 | 1.900 | 1.913 |
| No Spike | 0.417 | 0.468 | 0.403 | 0.429 | 1.464 | 1.550 | 1.706 | 1.573 |
| No Spike | 0.445 | 0.460 | 0.478 | 0.472 | 1.308 | 1.345 | 1.562 | 1.405 |
| No Spike | NT | NT | NT | NT | 1.412 | 1.468 | 1.330 | 1.403 |
Effects of various microbial organisms on positive test results.
| NT = not tested | ||
|---|---|---|
| -- | -- | ----------------- |
| 42 | 32 | |||||||
|---|---|---|---|---|---|---|---|---|
| Sample | Run 1 | Run 2 | Run 3 | Avg | Run 1 | Run 2 | Run 3 | Avg |
| Adenovirus | 0.460 | 0.438 | 0.412 | 0.437 | 1.517 | 1.511 | 1.340 | 1.456 |
| Aeromonas hydrophila | 0.508 | 0.557 | 0.469 | 0.511 | 1.837 | 1.766 | 1.860 | 1.821 |
| Borrelia burgdorferi | 0.480 | 0.306 | 0.293 | 0.360 | 1.239 | 1.307 | 1.230 | 1.259 |
| Campylobacter lari | 0.421 | 0.522 | 0.410 | 0.451 | 1.721 | 1.733 | 1.848 | 1.767 |
| Campylobacter fetus | NT | NT | NT | NT | 1.505 | 1.633 | 1.623 | 1.587 |
| Campylobacter jejuni | NT | NT | NT | NT | 1.544 | 1.378 | 1.489 | 1.470 |
| Campylobacter jejuni 2 | NT | NT | NT | NT | 1.520 | 1.526 | 1.396 | 1.481 |
| Campylobacter jejuni solution | NT | NT | NT | NT | 1.402 | 1.661 | 1.612 | 1.558 |
| Campylobacter lari | NT | NT | NT | NT | 1.594 | 1.512 | 1.565 | 1.557 |
| Candida albicans | 0.452 | 0.436 | 0.423 | 0.437 | 1.682 | 1.642 | 1.839 | 1.721 |
| Citrobacter freundii | 0.563 | 0.557 | 0.527 | 0.549 | 2.264 | 2.264 | 2.181 | 2.236 |
| Clostridium difficile | 0.543 | 0.600 | 0.516 | 0.553 | 1.878 | 1.996 | 2.047 | 1.974 |
| Clostridium perfringens | 0.514 | 0.496 | 0.516 | 0.509 | 1.799 | 1.833 | 1.922 | 1.851 |
| Enterobacter cloacae | 0.428 | 0.572 | 0.553 | 0.518 | 2.373 | 2.374 | 2.469 | 2.405 |
| Enterococcus faecalis | 0.506 | 0.517 | 0.555 | 0.526 | 2.033 | 1.963 | 2.134 | 2.043 |
| Escherichia coli 0157:H7 | 0.569 | 0.534 | 0.527 | 0.543 | 2.177 | 2.228 | 2.243 | 2.216 |
| Escherichia coli 8739 | 0.500 | 0.263 | 0.499 | 0.421 | 1.882 | 1.890 | 1.952 | 1.908 |
| Escherichia coli 9637 | 0.493 | 0.536 | 0.498 | 0.509 | 1.850 | 1.782 | 1.864 | 1.832 |
| Escherichia fergusonii | 0.533 | 0.528 | 0.517 | 0.526 | 2.237 | 2.167 | 2.124 | 2.176 |
| Escherichia hermannii | 0.437 | 0.440 | 0.378 | 0.418 | 1.469 | 1.643 | 1.714 | 1.609 |
| Escherichia hermannii EMDI-64 | 0.488 | 0.436 | 0.443 | 0.456 | 1.838 | 1.530 | 1.748 | 1.705 |
| Helicobacter pylori | OUT* | OUT* | OUT* | OUT* | OUT | OUT | OUT | OUT |
| Klebsiella pneumoniae | 0.533 | 0.534 | 0.519 | 0.529 | 2.051 | 2.269 | 2.153 | 2.158 |
| Lactobacillus lactis | 0.474 | 0.456 | 0.420 | 0.450 | 1.486 | 1.642 | 1.684 | 1.604 |
| Listeria monocytogenes | 0.441 | 0.427 | 0.391 | 0.420 | 1.672 | 1.623 | 1.582 | 1.626 |
| Peptostreptococcus anaerobius | 0.422 | 0.341 | 0.381 | 0.381 | 1.559 | 1.481 | 1.516 | 1.519 |
| Proteus vulgaris | 0.509 | 0.487 | 0.476 | 0.491 | 1.880 | 1.950 | 1.962 | 1.931 |
{3}------------------------------------------------
| Sample | 42 | 32 | ||||||
|---|---|---|---|---|---|---|---|---|
| Run 1 | Run 2 | Run 3 | Avg | Run 1 | Run 2 | Run 3 | Avg | |
| Pseudomonas aeruginosa | 0.217 | 0.560 | 0.536 | 0.438 | 2.208 | 2.272 | 2.158 | 2.213 |
| Pseudomonas fluorescens | 0.448 | 0.427 | 0.460 | 0.445 | 1.620 | 1.785 | 1.749 | 1.718 |
| Rotavirus | 0.384 | 0.407 | 0.445 | 0.412 | 1.356 | 1.361 | 1.387 | 1.368 |
| Salmonella enterica serovar Hilversum | 0.441 | 0.433 | 0.429 | 0.434 | 1.290 | 1.661 | 1.617 | 1.523 |
| Salmonella enterica subsp. Enterica serovar Hilversum | 0.519 | 0.537 | 0.534 | 0.530 | 2.232 | 2.281 | 2.336 | 2.283 |
| Sample | 42 | 32 | ||||||
|---|---|---|---|---|---|---|---|---|
| Run 1 | Run 2 | Run 3 | Avg | Run 1 | Run 2 | Run 3 | Avg | |
| Salmonella enterica subsp. Enterica serovar Minnesota | 0.565 | 0.505 | 0.600 | 0.557 | 2.512 | 2.529 | 2.296 | 2.446 |
| Salmonella Group B | 0.413 | 0.431 | 0.388 | 0.411 | 1.632 | 1.597 | 1.784 | 1.671 |
| Salmonella typhimurium | 0.549 | 0.588 | 0.569 | 0.569 | 2.336 | 2.180 | 2.215 | 2.244 |
| Serratia liquefaciens | 0.445 | 0.429 | 0.457 | 0.444 | 1.508 | 1.610 | 1.653 | 1.590 |
| Serratia liquefaciens | 0.482 | 0.541 | 0.503 | 0.509 | 2.180 | 1.990 | 2.125 | 2.098 |
| Serratia marcescens | 0.393 | 0.470 | 0.329 | 0.397 | 1.019 | 1.411 | 1.617 | 1.349 |
| Shigella boydii | 0.540 | 0.552 | 0.520 | 0.537 | 2.171 | 2.091 | 2.235 | 2.166 |
| Shigella flexneri | 0.365 | 0.549 | 0.562 | 0.492 | 2.321 | 2.317 | 2.337 | 2.325 |
| Shigella dysenteriae | 0.536 | 0.534 | 0.535 | 0.535 | 2.294 | 2.241 | 2.275 | 2.270 |
| Shigella sonnei | 0.420 | 0.465 | 0.325 | 0.403 | 1.598 | 1.606 | 1.564 | 1.589 |
| Staphylococcus aureus | 0.618 | 0.526 | 0.527 | 0.557 | 2.243 | 2.255 | 2.189 | 2.229 |
| Staphylococcus aureus (Cowans 1) | 0.505 | 0.461 | 0.477 | 0.481 | 1.919 | 1.805 | 1.808 | 1.844 |
| Staphylococcus epidermidis | 0.587 | 0.518 | 0.570 | 0.558 | 2.294 | 2.200 | 2.121 | 2.205 |
| Streptococcus faecalis | 0.501 | 0.513 | 0.469 | 0.494 | 1.963 | 1.965 | 1.954 | 1.961 |
| Yersinia enterocolitica | 0.500 | 0.543 | 0.504 | 0.516 | 1.985 | 1.881 | 1.490 | 1.785 |
| Yersinia enterocolitica | 0.503 | 0.490 | 0.491 | 0.495 | 1.974 | 1.762 | 1.992 | 1.909 |
*Note: "> 3.000" signifies the signal exceeded the high limit of the plate reader used in the study was Auses 2.999.
| Sample | 2-128 | |||
|---|---|---|---|---|
| Run 1 | Run 2 | Run 3 | Avg | |
| Unspiked Sample | 0.386 | 0.382 | 0.323 | 0.364 |
| Campylobacter lari | 0.399 | 0.398 | 0.390 | 0.396 |
| Campylobacter jejuni | 0.468 | 0.442 | 0.456 | 0.455 |
| Campylobacter jejuni solution | 0.432 | 0.427 | 0.409 | 0.423 |
| Campylobacter jejuni 2 | 0.414 | 0.410 | 0.393 | 0.406 |
| Campylobacter fetus | 0.398 | 0.427 | 0.383 | 0.403 |
{4}------------------------------------------------
| Sample | 2-42 | |||
|---|---|---|---|---|
| Run 1 | Run 2 | Run 3 | Avg | |
| No Spike | 0.011 | 0.009 | 0.014 | 0.011 |
| No Spike | 0.006 | 0.005 | 0.008 | 0.006 |
| No Spike | 0.006 | 0.007 | 0.014 | 0.009 |
| No Spike | 0.005 | 0.007 | 0.007 | 0.006 |
| No Spike | 0.006 | 0.008 | 0.006 | 0.007 |
| 2-42 | ||||
|---|---|---|---|---|
| Sample | Run 1 | Run 2 | Run 3 | Avg |
| Adenovirus | 0.007 | 0.007 | 0.006 | 0.007 |
| Aeromonas hydrophila | 0.004 | 0.006 | 0.006 | 0.005 |
| Borrelia bergdorferi | 0.012 | 0.006 | 0.007 | 0.008 |
| Campylobacter lari | 0.008 | 0.007 | 0.004 | 0.006 |
| Campylobacter fetus | 0.007 | 0.008 | 0.004 | 0.006 |
| Campylobacter jejuni | 0.016 | 0.006 | 0.008 | 0.010 |
| Campylobacter jejuni 2 | 0.000 | 0.006 | 0.007 | 0.004 |
| Campylobacter jejuni solution | 0.004 | 0.009 | 0.007 | 0.007 |
| Campylobacter lari | 0.005 | 0.007 | 0.006 | 0.006 |
| Candida albicans | 0.006 | 0.008 | 0.008 | 0.007 |
| Citrobacter freundii | 0.005 | 0.016 | 0.006 | 0.009 |
| Clostridium difficile | 0.010 | 0.011 | 0.009 | 0.010 |
| Clostridium perfringens | 0.010 | 0.008 | 0.008 | 0.009 |
| Enterobacter cloacae | 0.003 | 0.003 | 0.004 | 0.003 |
| Enterococcus faecalis | 0.002 | 0.002 | 0.007 | 0.004 |
| Escherichia coli 0157:H7 | 0.005 | 0.034 | 0.064 | 0.034 |
| Escherichia coli 8739 | 0.005 | 0.005 | 0.007 | 0.006 |
| Escherichia coli 9637 | 0.003 | 0.007 | 0.006 | 0.005 |
| Escherichia fergusonii | 0.004 | 0.002 | 0.007 | 0.004 |
| Escherichia hermannii | 0.008 | 0.007 | 0.008 | 0.008 |
| Escherichia hermannii EMDI-64 | 0.006 | 0.008 | 0.007 | 0.007 |
| Helicobacter pylori | > 3.000 | > 3.000 | > 3.000 | > 3.000 |
| Klebsiella pneumoniae | 0.004 | 0.004 | 0.007 | 0.005 |
| Lactobacillus lactis | 0.007 | 0.007 | 0.017 | 0.010 |
| Listeria monocytogenes | 0.008 | 0.005 | 0.009 | 0.007 |
| Peptostreptococcus anaerobius | 0.008 | 0.008 | 0.009 | 0.008 |
| Proteus vulgaris | 0.004 | 0.000 | 0.007 | 0.004 |
| Pseudomonas aeruginosa | 0.011 | 0.026 | 0.021 | 0.019 |
| Pseudomonas fluorescens | 0.006 | 0.007 | 0.007 | 0.007 |
| Rotavirus | 0.006 | 0.005 | 0.005 | 0.005 |
| Salmonella enterica serovar Hilversum | 0.008 | 0.007 | 0.009 | 0.008 |
| Salmonella enterica subsp. Enterica serovar Hilversum | 0.002 | 0.010 | 0.045 | 0.019 |
| Salmonella enterica subsp. Enterica serovar Minnesota | 0.005 | 0.008 | 0.005 | 0.006 |
| Salmonella Group B | 0.007 | 0.006 | 0.007 | 0.007 |
{5}------------------------------------------------
| Sample | Run 1 | Run 2 | Run 3 | Avg |
|---|---|---|---|---|
| Salmonella typhimurium | 0.003 | 0.007 | 0.005 | 0.005 |
| Serratia liquefaciens | 0.007 | 0.007 | 0.007 | 0.007 |
| Serratia liquefaciens | 0.000 | 0.003 | 0.004 | 0.002 |
| Serratia marcescens | 0.007 | 0.008 | 0.008 | 0.008 |
| Shigella boydii | 0.006 | 0.000 | 0.003 | 0.003 |
| Shigella flexneri | 0.004 | 0.027 | 0.004 | 0.012 |
| Shigella dysenteriae | 0.006 | 0.005 | 0.050 | 0.020 |
| Shigella sonnei | 0.007 | 0.002 | 0.009 | 0.006 |
| Staphylococcus aureus | 0.008 | 0.004 | 0.008 | 0.007 |
| Staphylococcus aureus (Cowans 1) | 0.007 | 0.009 | 0.007 | 0.008 |
| Staphylococcus epidermidis | 0.008 | 0.003 | 0.007 | 0.006 |
| Streptococcus faecalis | 0.006 | 0.005 | 0.007 | 0.006 |
| Yersinia enterocolitica | 0.005 | 0.004 | 0.008 | 0.006 |
| Yersinia enterocolitica | 0.004 | 0.003 | 0.006 | 0.004 |
Performance Evaluation Data Summarized
Comparison of Premier Platinum HpSA PLUS to Premier Platinum HpSA: Tests with 291 samples from symptomatic patients collected either prior to or following treatment were used to demonstrate that Premier Platinum HpSA PLUS performed similarly to Premier Platinum HpSA. Thirty three of these samples were originally evaluated in an earlier trial to demonstrate the effectiveness of Premier Platinum HpSA. Test performance including 95% confidence intervals is detailed in the following table.
| PP HpSA | ||||
|---|---|---|---|---|
| PP HpSA PLUS | Positive | Negative | Indeterminate | |
| Positive | 94 | 10 | 3 | |
| Negative | 0 | 183 | 1 | |
| Correlation | 277/287 (96.5%) | 93.7% - 98.3% | ||
| 95% CI | ||||
| Agreement | Positive test | 94/94 = 100% | ||
| Negative test | 183/193 = 94.8% |
Eight of the ten samples that were positive by Premier Platinum HpSA PLUS, but negative by Premier Platinum HpSA, were positive by CLO, histology or UBT testing. The three samples that were positive by Premier Platinum HpSA PLUS but indeterminate by Premier Platinum HpSA were positive by CLO, histology or UBT testing. The one sample that was negative by Premier Platinum HpSA PLUS but indeterminate by Premier Platinum HpSA was negative by CLO, histology or UBT testing.
Analysis of samples producing discordant results
Samples producing discordant results between Premier Platinum HpSA PLUS and the predicate were evaluated against test data from other conventional tests such as CLO, Histology, or UBT to determine the trueness of the results. The results of that evaluation are provided shown in the Table below.
{6}------------------------------------------------
| SampleNumber | PP HpSA PLUS Results | CLO/Histology/UBTResults | PP HpSA Results(Predicate) | Interpretation usingCLO/Hist/UBT |
|---|---|---|---|---|
| UC82 | Positive | Negative | Negative | FP--PPHpSAPLUS |
| 2 | Positive | Positive | Indeterminate | TP--PPHpSAPLUS |
| 3-44 | Negative | Negative | Indeterminate | TN--PPHpSAPLUS |
| U082 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| U004 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| U120 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| U159 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| U056 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| U137 | Positive | Positive | Indeterminate | TP--PPHpSAPLUS |
| U161 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| P026 | Positive | Positive | Negative | TP--PPHpSAPLUS |
| P040 | Positive | Negative | Negative | FP--PPHpSAPLUS |
| P172 | Positive | Positive | Indeterminate | TP--PPHpSAPLUS |
| P173 | Positive | Positive | Negative | TP--PPHpSAPLUS |
Legend: FP = false positive, TP = true positive, TN = true negative
Performance Comparison Table
| Performance Characteristics (rounded) in Direct Comparison to | Premier Platinum HpSA | Premier Platinum HpSA |
|---|---|---|
| Clinical Status or Condition | PLUS | (Predicate) |
| Estimated Clinical Sensitivity | N/A | 96.1% |
| Estimated Clinical Specificity | N/A | 95.7% |
| Predictive Value of a Positive Test | N/A | 96.1% |
| Predictive Value of a Negative Test | N/A | 95.7% |
| Laboratory Equivalence with (Predicate Device) Combined Totals | ||
| Agreement, positive tests | 100% | N/A |
| Agreement, negative tests | 94.8% | N/A |
| Correlation | 96.5% | 95.9% |
| Performance characteristics | ||
| Precision/Reproducibility | 100% | 100% |
| Linearity/reportable range | N/A | N/A |
| Limit of detection | ≥ 4.67 ng in stool | ≥ 184 ng in stool |
| Assay cutoff | 0.100 at OD450/630 | 0.120 at OD450/630 |
Therapeutic Monitoring
Study design: A panel of frozen, archival specimens from four patients who were monitored during eradication therapy and tested using the predicate Premier Platinum HpSA (K980076 and K983255) were assessed using the Premier Platinum HpSA PLUS assay. One of the panels represented a low positive state with the predicate at the beginning of eradication therapy (See Figure 1.) The remaining three panels represented strongly positive states. (See Figures 2-4.) That data obtained with Premier Platinum HpSA PLUS was compared to that originally obtained with the predicate. In the case of strongly positive samples, the eradication curves for the two tests are substantively the same. The eradication curve for Premier Platinum HpSA PLUS differs from that of the predicate with low positive samples at the beginning of therapy since it produces stronger test results. However, by week four following treatment, the curves are identical. Conclusions to the study: Premier Platinum HpSA performs similarly to the predicate when used to monitor the effectiveness of eradication therapy.
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Image /page/7/Figure/2 description: Figure 1 shows a graph of the absorbance of two different substances, Predicate 450/630 and PLUS 450/630, for Patient 41. The x-axis represents the specimen number, ranging from 1 to 7, while the y-axis represents the absorbance. The absorbance of Predicate 450/630 is relatively low, ranging from 0.02 to 0.27, while the absorbance of PLUS 450/630 is higher, ranging from 0.00 to 3.00.
Image /page/7/Figure/3 description: The image contains the text "Figure 2.". The text is in a simple sans-serif font. The figure number is likely a reference to a larger document or publication.
Image /page/7/Figure/4 description: This image shows a graph titled "Patient 51" with "Absorbance" on the y-axis and "Specimen" on the x-axis. There are two lines on the graph, one labeled "Predicate 450/630" and the other labeled "PLUS 450/630". The graph shows the absorbance values for each specimen, with the values for "Predicate 450/630" being 3.000, 1.945, 0.034, 0.026, and 0.025, and the values for "PLUS 450/630" being 3.000, 2.868, 0.041, 0.007, and 0.006.
Figure 3.
Image /page/7/Figure/6 description: This image is a graph for patient 71 showing absorbance versus specimen number. There are two lines on the graph, one for predicate 450/630 and one for PLUS 450/630. Both lines start at 3.000 for specimens 1 and 2, but then drop to around 0.030 for specimens 3-9.
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Image /page/8/Figure/2 description: The image shows a graph and table for Patient 87. The graph plots absorbance on the y-axis versus specimen number on the x-axis for two different predicates, 450/630 and PLUS 450/630. Both predicates start with an absorbance of 3.000 for specimens 1 and 2, but then drop to 0.030 and 0.009 respectively for specimen 3. The absorbance values for specimens 4 through 7 are all below 0.033.
Figure 4.
Reproducibility
Assay precision, intra-assay variability and inter-assay variability were assessed with a reference panel prepared from high positive samples (n = 2), low low negative samples (n = 2), and low positive and high neqative specimens (n = 1 each). The latter were diluted to near the assay limit of sensitivity. Nine replicates each of the low positive and high negative samples were included in the panel to bring the total cohort to 22 reference specimens. Each reference specimen was coded to prevent its identification during testing. Each was evaluated twice per day for three consecutive days by three different laboratories. In accordance with the IFU, values of < 0.100 are interpreted as negative when results are read at A450/630.
High negative samples (OD values just below 0.100) produced weakly positive results (OD values just above 0.100) in 42 out of 162 times tests. It is expected that high negative samples tested at the cut-off will produce weakly positive results 50% of the time. (See EP12-A, User protocol for evaluation of qualitative performance; approved guideline; NCCLS/CLSI, Vol. 22, no.14, 2002.) Low positive and low negative samples produced the correct results 100% of the time. Reproducibility was 100% with no intra-assay variability for samples prepared above or below the limit of analytical sensitivity.
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51し、, notification
Meridian Bioscience, Inc.
_US Premier Platinum HpS,
| esuits with reproducibility test par | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| sults at 450/630 nr | echnologist | echnologist | echnologist | ||||||||||||||||
| Sample II | Sample | l, keçi L keç | r und 7 Áseo | Day 3 | l unu l L fea | guna s Ligar Link | Day 2 | Day 2 | Day 3 | gung Esta g | t ung | grums Liked | Day 2 | Day 2 | l, ung | Day 3 Run 2 | |||
| Qual | g unst L. feet | und i z keq | Day 3 Run 1 | Run 2 | run 1 | run 2 | Run | run 1 | run 2 | ||||||||||
| Resul | |||||||||||||||||||
| HP # | 1.510 | 2.162 | 1.997 | 1.830 | 1.924 | 1.852 | 1 754 | 2.092 | .986 | 1.941 | 1.842 | .880 | 1.745 | 2.380 | 2.300 | 1.962 | 2.36 | 2.233 | 2.364 |
| 2 HP #2 | 1.06 | 1.445 | 1.436 | 1.283 | 1.217 | 1.244 | .537 | .406 | 1.302 | 1.307 | 293 | 1.154 | 1.858 | 1.743 | 1.400 | 1.698 | 1.689 | 1.614 | |
| Cut off LP # | 0.133 | 0.217 | 0.20€ | 0.176 | ତି ପ୍ରତିଶତ ସହ ପ୍ରତିଶତ | 0.188 | 0.162 | 0.274 | 0.234 | 0.192 | 0.203 | 0.186 | 0.175 | 0.292 | 0.290 | 0.294 | 0.289 | 0.290 | 0.301 |
| Cut off LP # | 0.133 | 0.206 | 0.197 | 0.171 | 0.214 | 0.166 | 0.165 | 0.271 | 0.237 | 0.213 | 0.189 | 0.173 | 0.185 | 0.310 | 0.294 | 0.268 | 0.273 | 0.299 | 0.299 |
| Cut off LP # | 0.133 | 0.179 | 0.195 | 0.195 | 0.207 | 0.176 | 0.179 | 0.197 | 0.234 | 0.199 | 0.185 | 0.158 | 0.178 | 0.318 | 0.311 | 0.305 | 0.298 | 0.299 | 0.290 |
| Cut off LP # | 0.133 | 0.185 | 0.215 | 0.187 | 0.210 | 0.182 | 0.149 | 0.265 | 0.219 | 0.219 | 0.175 | 0.163 | 0.167 | 0.295 | 0.312 | 0.279 | 0.308 | 0.295 | 0.336 |
| Cut off LP # | 0.133 | 0.180 | 0.211 | 0.179 | 0.210 | 0.176 | 0.172 | 0.243 | 0.185 | 0.214 | 0.164 | 0.149 | 0.167 | 0.286 | 0.275 | 0.288 | 0.318 | 0.296 | 0.316 |
| Cut off LP # | 0.133 | 0.20 | 0.219 | 0.22 | 0.220 | 0.188 | 0.178 | 0.239 | 0.215 | 0.214 | 0.146 | 0.137 | 0.156 | 0.300 | 0.292 | 0.287 | 0.315 | 0.305 | 0.318 |
| Cut off LP# | 0.133 | 0.207 | 0.187 | 0.206 | 0.203 | 0.189 | 0.131 | 0.217 | 0.220 | 0.203 | 0.140 | 0.133 | 0.158 | 0.293 | 0.29 | 0.30€ | 0.287 | 0.308 | 0.300 |
| 0 Cut off LP # | 0.133 | 0.186 | 0.187 | 0.202 | 0.223 | 0.179 | 0.163 | 0.233 | 0.201 | 0.211 | 0.118 | 0.097 | 0.140 | 0.309 | 0.307 | 0.267 | 0.298 | 0.290 | 0.299 |
| 1 Cut off LP # | 0.133 | 0.193 | 0.192 | 0.175 | 0.173 | 0.159 | 0.156 | 0.238 | 0.200 | 0.204 | 0.14( | 0.124 | 0.145 | 0.331 | 0.317 | 0.30 | 0.298 | 0.315 | 0.314 |
| 2 Cut off HN # | 0.075 | 0.094 | 0.104 | 0.074 | 0.12 | 0.076 | 0.078 | 0.131 | 0.097 | 0.098 | 0.059 | 0.060 | 0.066 | 0.096 | 0.094 | 0.09€ | 0.094 | 0.095 | 0.090 |
| 3 Cut off HN # | 0.075 | 0.10 | 0.103 | 0.069 | 0.105 | 0.074 | 0.074 | 0.152 | 0.112 | 0.083 | 0.090 | 0.097 | 0.105 | 0.08 | 0.093 | 0.095 | 0.093 | 0.085 | 0.094 |
| 4 Cut off HN # | 0.075 | 0.073 | 0.104 | 0.088 | 0.092 | 0.082 | 0.07 * | 0.161 | 0.118 | 0.090 | 0.105 | 0.088 | 0.10 | 0.074 | 0.086 | 0.084 | 0.08 | 0.087 | 0.09 |
| Cut off HN # | 0.075 | 0.058 | 0.109 | 0.096 | 0.079 | 0.080 | 0.090 | 0.142 | 0.115 | 0.094 | 0.105 | 0.083 | 0.099 | 0.096 | 0.08 | 0.096 | 0.087 | 0.089 | 0.084 |
| Cut off HN # | 0.075 | 0.080 | 0.105 | 0.09 | 0.089 | 0.085 | 0.071 | 0.147 | 0.112 | 0.102 | 0.079 | 0.073 | 0.103 | 0.092 | 0.093 | 0.093 | 0.085 | 0.090 | 0.081 |
| 7 Cut off HN # | 0.075 | 0.083 | 0.116 | 0.096 | 0.101 | 0.098 | 0.087 | 0.137 | 0.111 | 0.107 | 0.085 | 0.073 | 0.09 | 0.090 | 0.098 | 0.093 | 0.09 | 0.093 | 0.082 |
| Cut off HN # | 0.075 | 0.088 | 0.113 | 0.089 | 0.113 | 0.088 | 0.097 | 0.128 | 0.101 | 0.113 | 0.064 | 0.068 | 0.083 | 0.082 | 0.08 | 0.094 | 0.080 | 0.089 | 0.08 |
| 9 Cut off HN # | 0.075 | 0.098 | 0.118 | 0.095 | 0.089 | 0.088 | 0.098 | 0.140 | 0.105 | 0.118 | 0.060 | 0.058 | 0.083 | 0.085 | 0.082 | 0.096 | 0.085 | 0.093 | 0.078 |
| 0 Cut off HN # | 0.075 | 0.090 | 0.103 | 0.083 | 0.112 | 0.092 | 0.091 | 0.126 | 0.104 | 0.109 | 0.046 | 0.053 | 0.069 | 0.085 | 0.086 | 0.09 | 0.093 | 0.092 | 0.088 |
| 21 LN # | 0.005 | 0.005 | 0.00€ | 0.006 | 0.005 | 0.005 | 0.007 | 0.001 | 0.002 | 0.004 | 0.00 | 0.00 | 0.002 | 0.003 | 0.004 | 0.003 | 0.004 | 0.004 | 0.003 |
| 2 LN #2 | 0.005 | 0.000 | 0.005 | 0.006 | 0.006 | 0.006 | 0.009 | 0.001 | 0.000 | 0.004 | 0.00 | 0.000 | 0.002 | 0.005 | 0.005 | 0.004 | 0.005 | 0.004 | 0.003 |
| rage high negative va | 0.085 | 0.109 | 0.14 | 0.108 | 0.087 | 0.088 | 0.086 | 0.100 | 0.102 | 0.077 | 0.093 | 0.088 | 0.085 | 0.084 | 0.073 | 0.089 | 0.090 | 0.085 | |
| rage low positive valu | 0.195 | 0.20 | 0.242 | 0.216 | 0.304 | 0.299 | 0.190 | 0.210 | 0.208 | 0.162 | 0.288 | 0.298 | 0.178 | 0.162 | 0.14 | 0.163 | 0.300 | 0.308 | |
| cent Correlatic | 00% | 100% | 100% | 95% | 100% | 100% | 20% | 00% | 100% | 95% | 95% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | |
| rrelation of cut off Specimen | 97% |
. . -+ -ﮯ۔ ducibility ith الله R Legend: LP = low positive, HP = High positive, LN = Low negative, HN = High negative,
{10}------------------------------------------------
CONCLUSIONS
Premier Platinum HpSA PLUS:
-
- Can be used reliably for the rapid detection of H. pylori in human stool specimens
{11}------------------------------------------------
Image /page/11/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like symbol with three overlapping, curved lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAR 1 0 2006
Ms. Susan Rolih Vice President, Regulatory Affairs and Quality Assurance Meridian Bioscience, Inc. 3471 River Hills Drive Cincinnati, OH 45244
K053335 Re:
Trade/Device Name: Premier Platinum HpSA PLUS Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter Fetus Serological Reagents Regulatory Class: Class I Product Code: LYR Dated: January 31, 2006 Received: February 1, 2006
Dear Ms. Rolih:
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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
{12}------------------------------------------------
Page 2 --
This letter will allow you to begin marketing your device as described in your Section 510(k) I mis lotel will and my your he FDA finding of substantial equivalence of your device to a legally premated predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
Sales, a Hogg
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
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Premier Platinum HpSA PLUS
510(k) Notification Meridian Bioscience, Inc.
INDICATIONS FOR USE STATEMENT Premier Platinum HpSA PLUS
510(K) Number: K053335
The Premier Platinum HpSA PLUS enzyme immunoassay (EIA) is an in vitro qualitative procedure for The Trention of Helicobacter pylor antigens in human stool. Test results are intended to aid in the the decodion of H. pylor infection and to monitor response during and post-therapy in patients. Accepted ulaginosis or i. pyron invocion that testing by any current method, to confirm eradication, be done at least four weeks following completion of therapy.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
freddie lu. loob
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
C1934) K05 3335
Section 4, Page 1 of 1
§ 866.3110
Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).