(164 days)
Curian HpSA, for use with the Curian Analyzer, is a rapid, qualitative, fluorescent immunoassay for the detection of Helicobacter pylori antigen in human stool. Test results are intended to aid in the diagnosis of H, pylori infection and to demonstrate loss of H. pyloriantigen following treatment. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least following completion of therapy. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.
The Curian™ HpSA® assay is a qualitative in vitro diagnostic test for the detection of Helicobacter pylori in human stool. The Curian™ HpSA® assay utilizes fluorescence technology with the newly developed Curian™ Analyzer to detect H. pylori antigen. The Curian™ Analyzer has been designed to disposition sample results from lateral flow immunoassays.
Here's a breakdown of the acceptance criteria and study information for the Curian™ HpSA® and Curian™ Analyzer, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance study aiming for substantial equivalence to an FDA-cleared predicate device. The predicate device had a demonstrated sensitivity and specificity ≥ 95%, with a lower bound of the two-sided 95% confidence interval (CI) greater than 89% against a composite reference method. Therefore, the new device's agreement with this predicate is the key performance metric assessed.
| Performance Metric | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (with Comparator EIA) |
|---|---|---|
| Positive Percent Agreement (PPA) | Expected to be substantially equivalent to predicate | 96.1% (73/76) |
| 95% CI for PPA | Lower bound > 89% (from predicate criteria) | 89.0% - 98.6% |
| Negative Percent Agreement (NPA) | Expected to be substantially equivalent to predicate | 97.0% (452/466) |
| 95% CI for NPA | Lower bound > 89% (from predicate criteria) | 95.0% - 98.2% |
2. Sample Sizes and Data Provenance
- Test Set Sample Size: 542 evaluable specimens.
- Data Provenance: The specimens were from the intended use population, collected in a multi-center method comparison study conducted at three sites in the USA. The study appears to be prospective in nature, as it "evaluated" the device for detecting H. pylori stool antigen in human stool.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
This information is not explicitly provided in the document for the test set. The clinical study compares the new device to an "FDA-cleared H. pylori stool antigen EIA" which was itself previously evaluated against a composite reference method. The document does not describe the establishment of the ground truth for this specific study's test set, nor the number or qualifications of experts involved in that.
4. Adjudication Method (Test Set)
The primary comparison is between the new device and an FDA-cleared comparator EIA. However, in cases of discordance, PCR was used for adjudication:
- "2/3 Curian HpSA false negatives were dispositioned as negative by PCR"
- "8/14 Curian HpSA false positives were dispositioned as positive by PCR"
This suggests a form of supplementary adjudication using a molecular method for discordant results between the new device and the comparator EIA.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This document describes the performance of a diagnostic assay (Curian™ HpSA®) in a standalone clinical comparison against another assay, not the improvement of human readers with AI assistance.
6. Standalone Performance
Yes, a standalone performance study was done. The document explicitly describes the "Comparison of Curian™ HpSA® assay to an FDA-cleared H. pylori Stool Antigen EIA" focusing on the device's accuracy in detecting H. pylori antigen in human stool samples. The device itself (the Curian™ Analyzer) interprets the results from the lateral flow immunoassay.
7. Type of Ground Truth Used (Test Set)
The "ground truth" for the current study is effectively the results from an FDA-cleared H. pylori stool antigen EIA. This predicate EIA was, in turn, previously established against a "composite reference method (i.e., culture, histology, and RUT) for initial H. pylori diagnosis." So, indirectly, the ultimate ground truth is a composite reference method.
8. Sample Size for Training Set
The document does not provide information on the sample size used for the training set. This is an in vitro diagnostic device, and details about its internal algorithm training (if any is applicable beyond general assay development) are not disclosed in this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for the training set was established, as details about training sets are not included in this summary.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 13, 2020
Meridian Bioscience, Inc. Cathlena Martinez Senior Specialist, Regulatory Affairs 3471 River Hills Drive Cincinnati, Ohio 45244
Re: K192817
Trade/Device Name: Curian HpSA, Curian Analyzer Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus Serological Reagents Regulatory Class: Class I. reserved Product Code: LYR Dated: September 30, 2019 Received: October 1, 2019
Dear Cathlena Martinez:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar, Ph.D. (ABMM) Chief. General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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510(k) Summary
510(k) number: K192817
Date of Preparation: September 30, 2019
| Owner: | Meridian Bioscience, Inc.3471 River Hills DriveCincinnati, Ohio 45244 USAPhone: (513) 271-3700Fax: (513) 272-5213 |
|---|---|
| Contact: | Primary Contact:Cathlena MartinezSenior Regulatory Affairs Specialist |
| Secondary Contact:Jack RogersDirector, Regulatory Affairs and Design Assurance | |
| Trade Name: | Curian™ HpSA® |
| Common Name: | Helicobacter pylori |
| Classification Name: | Campylobacter fetus serological reagents(21 CFR 866.3110, Product Code LYR) |
| Predicate Device: | PREMIER Platinum HpSA® PLUSK182559 |
Device Description
The Curian™ HpSA® assay is a qualitative in vitro diagnostic test for the detection of Helicobacter pylori in human stool. The Curian™ HpSA® assay utilizes fluorescence technology with the newly developed Curian™ Analyzer to detect H. pylori antigen. The Curian™ Analyzer has been designed to disposition sample results from lateral flow immunoassays.
Intended Use / Indications for Use
Curian HpSA, for use with the Curian Analyzer, is a rapid, qualitative, fluorescent immunoassay for the detection of Helicobacter pylori antigen in human stool. Test results are intended to aid in the diagnosis of H, pylori infection and to demonstrate loss of H. pyloriantigen following treatment. Accepted medical practice recommends that testing by any current method, to confirm eradication, be done at least following completion of therapy. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.
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| Similarities Between the New Device and the Predicate Device | ||
|---|---|---|
| NEW DEVICECurian™ HpSA®K192817 | PREDICATE DEVICEPREMIER Platinum HpSA® PLUSK182559 | |
| Product Code | Same as predicate | LYR |
| Intended Use /Indications for Use | Curian HpSA, for use with the CurianAnalyzer, is a rapid, qualitative, fluorescentimmunoassay for the detection ofHelicobacter pylori antigen in human stool.Test results are intended to aid in thediagnosis of H. pylori infection and todemonstrate loss of H. pylori antigenfollowing treatment. Accepted medicalpractice recommends that testing by anycurrent method, to confirm eradication, bedone at least four weeks followingcompletion of therapy. Test results shouldbe taken into consideration by thephysician in conjunction with the patienthistory and symptoms. | The Premier Platinum HpSA PLUS enzymeimmunoassay (EIA) is an in vitro qualitativeprocedure for the detection of Helicobacterpylori antigens in human stool. Test resultsare intended to aid in the diagnosis of H.pylori infection and to monitor responseduring and post-therapy in patients.Accepted medical practice recommends thattesting by any current method, to confirmeradication, be done at least four weeksfollowing completion of therapy. |
| Measurand | Same as predicate | H. pylori stool antigen |
| Target Population | Same as predicate | Persons suspected of having H. pyloriinfection |
| Specimen Type | Same as predicate | Unpreserved human Stool |
| Type of Test | Same as predicate | Qualitative |
| Quality Control | Same as predicate | Positive and Negative Controls are providedin kit |
| Kit Storage | Same as predicate | Refrigerated (2 to 8 °C) |
| Differences Between the New Device and the Predicate Device | ||
|---|---|---|
| NEW DEVICECurian™ HpSA®K192817 | PREDICATE DEVICEPREMIER Platinum HpSA® PLUSK182559 | |
| Technology | Fluorescent immunoassay | Enzyme immunoassay (EIA) |
| Format | Single use lateral flow cassette | Microwell plate |
| Result Interpretation | Instrument report | Visual or Spectrophotometric |
| Time to Result | 20 minutes | 15 minutes |
NON-CLINICAL PERFORMANCE DATA
Analytical Performance
Precision/Reproducibility
Reproducibility of the Curian™ HpSA® assay was evaluated by testing contrived sample panels at three investigational sites over a period of five days. Contrived panel members were prepared by spiking H. pylori purified flagellar antigen into negative diluted natural stool/ 30% physiological saline) at antigen concentrations above, near and below the assay limit of detection. The sample panel consisted of a low positive
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(1.5x LoD), moderate positive (3x LoD), high negative (0.5x LoD), and true negative samples. Diluted natural stool was used because of difficulties preparing dilutions with neat stool for analytical testing. The moderate positive and low positive panel members were positive 99.3% (149/150) and 98.0% (147/150) of the time. The high negative and true neqative panel members were negative 88.7% (133/150) of the time. These results are acceptable.
Analytical Sensitivity
Analytical sensitivity studies were performed to determine the analytical limit of detection (LoD) of purified Helicobacter pylori stool antigens (HpSA) in human stool matrix for the Curian HpSA assay. For this study, HpSA antigen was diluted at varying concentrations into diluted natural stool matrix. Three lots of the Curian HpSA assay were evaluated. The LoD is defined as the lowest concentration of the target analyte that produces positive results ≥ 95% of the time.
The LoD for the Curian HpSA assay was determined to be 2.0 ng/mL.
Prozone / Hook Effect
A study was performed to determine the potential for a high-dose prozone/hook effect with the Curian HpSA assay. A prozone/ hook effect can occur when very high levels of farget antigen are present in the test sample, leading to a false negative result.
Dilutions of H. pylori stool antigens (HpSA) were prepared in diluted natural negative sample matrix to create contrived HpSA positive samples containing known concentrations of antigen. Individual reactions were prepared such that the concentration in each replicate was that of a high positive specimen approximately 25X to 6250X LoD; ranging from 51 to 12,500 ng/mL. Each sample was tested to determine whether a prozone/ hook effect is observed with the Curian HpSA assay.
Results confirmed that prozone/ hook effect was not observed with the Curian HpSA assay when testing samples containing high concentrations of Helicobacter pylori stool antigens.
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Analytical Specificity
Cross-Reactivity:
The specificity of Curian HpSA was tested utilizing the following bacterial, fungal and viral strains. Each potentially cross-reactive microorganism was added at minimum concentrations of 1.0 x 107 CFU/mL (bacteria/fungi) or 1.0 x 105 TCIDso/mL (for viruses) to a diluted natural negative matrix and a contrived positive matrix sample. No crossreactivity or microbial interference with the Curian HpSA assay was observed.
| Organism Name | Strain ID | Organism Name | Strain ID |
|---|---|---|---|
| Adenovirus 40 | Dugan | Klebsiella pneumoniae | ATCC 13883 |
| Aeromonas hydrophila | ATCC 35654 | Proteus vulgaris | CCUG 6380 |
| Bacillus cereus | CCUG52704 | Pseudomonas aeruginosa | ATCC 39324 |
| Borrelia burgdorferi | B31.5A19 | Rotavirus | WA |
| Campylobacter coli | ATCC 10956 | Salmonella spp. Dublin | ATCC 15480 |
| Campylobacter jejuni | ATCC 29411 | Salmonella spp. Hilversum | ATCC 15784 |
| Candida albicans | ATCC 18804 | Salmonella spp. Minnesota | ATCC 9700 |
| Citrobacter freundii | ATCC 8090 | Salmonella typhimurium Group B | ATCC 14028 |
| Clostridium difficile | ATCC 43255 | Shigella boydii | ATCC 9207 |
| Clostridium perfringens | ATCC 12915 | Shigella dysenteriae | ATCC 9361 |
| Enterobacter cloacae | ATCC 15337 | Shigella flexneri | ATCC 12022 |
| Enterococcus faecalis | ATCC 49532 | Shigella sonnei | ATCC 25931 |
| E. coli O157:H7 | ATCC 43895 | Staphylococcus aureus | ATCC 6538 |
| E. coli | ATCC 9637 | Staphylococcus aureus Cowan I | ATCC 12598 |
| Escherichia fergusonii | ATCC 35469 | Staphylococcus epidermidis | ATCC 51625 |
| Haemophilus influenzae | ATCC 9006 | Yersinia enterocolitica | ATCC 23715 |
Organisms evaluated for cross-reactivity are listed below.
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Interfering Substances:
Interference testing was performed in the presence of chemical and biological substances introduced directly into contrived HpSA low positive and negative samples generated using diluted natural stool matrix. No interference was observed with the Curian HpSA assay for any of the substances tested. Substances tested and concentrations evaluated are listed below.
| Substance (active ingredient(s)) | Test Concentration |
|---|---|
| Barium Sulfate | 5% w/v (50 mg/mL) |
| Benzalkonium chloride | 1% v/v |
| Ciprofloxacin | 0.25% w/v (2.5 mg/mL) |
| Ethanol | 1% v/v |
| Hog gastric mucin | 3.5% w/v (35 mg/mL) |
| Human blood (whole) | 40% v/v |
| Human hemoglobin | 12.5% w/v (125 mg/mL) |
| Human urine | 5% v/v |
| Hydrocortisone | 1% w/v (10 mg/mL) |
| Imodium® (Loperamide HCl, 1 mg/7.5 mL) | 5% v/v |
| Kaopectate® (Bismuth subsalicylate 262 mg/15 mL) | 5% v/v |
| Leukocytes | 0.05% v/v |
| Mesalazine (5-Aminosalicylic acid) | 10% w/v (100 mg/mL) |
| Metronidazole | 0.25% w/v (2.5 mg/mL) |
| MiraLAX® (Polyethylene Glycol 3350, 17 g/dose) | 7% w/v (70 mg/mL) |
| Mineral Oil | 10% v/v |
| Mylanta® (per 10 mL: (Aluminum hydroxide 800 mg, Magnesium hydroxide 800 mg, Simethicone 80 mg) | 4.2 mg/mL (2.5% v/v) |
| Naproxen Sodium | 5% w/v (50 mg/mL) |
| Nonoxynol-9 | 1% v/v |
| Nystatin | 1% w/v (10 mg/mL) |
| Palmitic acid (fecal fat) | 20% w/v (200 mg/mL) |
| Pepto-Bismol® (Bismuth subsalicylate 525 mg/30 mL) | 5% v/v |
| Phenylephrine | 1% w/v (10 mg/mL) |
| Prilosec OTC® (Omeprazole 20 mg/tablet) | 5 mg/mL |
| Sennosides | 1% w/v (10 mg/mL) |
| Simethicone | 10% v/v |
| Stearic acid (fecal fat) | 20% w/v (200 mg/mL) |
| Tagamet HB 200® (Cimetidine 200 mg/tablet) | 5 mg/mL |
| TUMS® | 5 mg/mL |
| Vancomycin | 0.25% w/v (2.5 mg/mL) |
Assay Reactivity/ Inclusivity
A total of five strains of H. pylori were evaluated for reactivity with the Curian HpSA assay. The final reactive concentrations observed for each strain are listed below.
| H. pylori straintested | Geographic origin &other information | ReactiveConcentration |
|---|---|---|
| ATCC 43504 | Australia | $1.0 x 10^5$ CFU/mL |
| CCUG 38771 | Unknown | $3.0 x 10^5$ CFU/mL |
| CCUG 19087 | South Africa | $3.0 x 10^5$ CFU/mL |
| ATCC 700392 | UK; clade hpEurope | $6.0 x 10^5$ CFU/mL |
| ATCC 700824 | US; clade hpAfrica1 | $3.0 x 10^5$ CFU/mL |
CLINICAL PERFORMANCE DATA
Comparison of Curian™ HpSA® assay to an FDA-cleared H. pylori Stool Antigen ElA
A multi-center Method Comparison Study was conducted at three sites in the USA to evaluate of the Curian HpSA for detecting H. pylori stool antigen in human stool from patients suspected of H. pylori infection. Test results were compared to results from an FDA-cleared H. pylori stool antigen EIA that was previously evaluated
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relative to the endoscopy biopsy composite reference method (i.e., culture, histology, and RUT) for initial H. pylori diagnosis with a demonstrated sensitivity and specificity greater than or equal to 95% and a lower bound of the twosided 95% confidence interval (CI) greater than 89%.
Five hundred forty-two (542) evaluable specimens from the intended use population were enrolled in the study.
Positive and negative percent agreement were determined between the Curian HpSA and comparator ElA in detecting HpSA antigens in human stool. The Curian HpSA demonstrated a positive percent agreement of 96.05% (95% Cl: 89.03%, 98.65%) and a negative percent agreement of 97.00% (95% Cl: 95.02%, with the comparator EIA
Performance:
| Positive and Negative Curian HpSA Results vs. FDA-cleared H. pylori stoolantigen EIA | ||||
|---|---|---|---|---|
| FDA-cleared H. pylori stool antigen EIA | ||||
| Positive | Negative | Total | ||
| Curian HpSA Assay | Positive | 73 | 14b | 87 |
| Negative | 3a | 452 | 455 | |
| Total | 76 | 466 | 542 | |
| Agreement | 95% CI (%) | |||
| PPA | 96.1% | (73/76) | 89.0%, 98.6% | |
| NPA | 97.0% | (452/466) | 95.0%, 98.2% |
ª 2/3 Curian HpSA false negatives were dispositioned as negative by PCR
b 8/14 Curian HpSA false positives were dispositioned as positive by PCR
CONCLUSION
The Curian™ HpSA® assay, as supported by the information submitted in this premarket submission, is substantially equivalent to the predicate device.
§ 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).