(266 days)
Curian Campy, for use with the Curian Analyzer, is a rapid, qualitative fluorescent immunoassay for the detection of a Campylobacter-specific antigen in human fecal specimens. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in human stool from patients with signs and symptoms of gastroenteritis. The test is intended for use with unpreserved fecal specimens or preserved fecal specimens in transport media. Test results are to be used in conjunction with information available from the patient clinical evaluation and other diagnostic procedures. Curian Campy is intended to aid in the diagnosis of Campylobacter infection.
The Curian® Campy assay is a qualitative in vitro diagnostic test for the detection of Campylobacter-specific antigens in human stool samples collected from individuals with signs and symptoms of gastroenteritis. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in unpreserved or preserved stool in Cary-Blair or C&S transport media. The Curian® Campy assay utilizes fluorescence technology with the cleared Curian® Analyzer (K192817) to detect Campylobacter-specific antigens in human stool.
Here's a breakdown of the acceptance criteria and study details for the Curian Campy device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate section with predefined thresholds. However, based on the presentation of clinical performance data, the implicit acceptance criteria for sensitivity and specificity are demonstrated by the confidence intervals achieved in the clinical studies. For analytical performance, 100% agreement for certain categories and no observed interference/cross-reactivity are the implicit acceptance criteria.
| Category | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Clinical Performance (Prospective Study) | Sensitivity and Specificity with acceptable 95% Confidence Intervals (relative to predicate, implied) | Sensitivity: 85.7% (95% CI: 65.4% - 95.0%)Specificity: 98.1% (95% CI: 97.2% - 98.7%) |
| Clinical Performance (Archived Study) | Sensitivity and Specificity with acceptable 95% Confidence Intervals (relative to predicate, implied) | Sensitivity: 96.6% (95% CI: 82.8% - 99.4%)Specificity: 98.1% (95% CI: 95.6% - 99.2%) |
| Contrived Study (Positive Percent Agreement) | 100% PPA for expected positive results. | PPA: 100.0% (95% CI: 97.5% - 100.0%) |
| Contrived Study (Negative Percent Agreement) | 100% NPA for expected negative results. | NPA: 100.0% (95% CI: 94.0% - 100.0%) |
| Reproducibility | High percent agreement with expected results across different sites, operators, and kit lots. | Unpreserved Stool: 100% PA for true negative and moderate positive. High negative: 98.7% PA (95% CI: 95.2% - 99.6%). Low positive: 82.7% PA (95% CI: 75.8% - 87.9%) (lower than expected due to under-sampling issue).Preserved Stool (C&S): 100% PA for true negative and low positive. High negative: 95.3% PA (95% CI: 90.6% - 97.7%). |
| Prozone / Hook Effect | No prozone/hook effect observed. | Not observed with test concentrations ranging from 4xLoD to 430xLoD. |
| Cross-Reactivity/Microbial Interference | No cross-reactivity or interference (except for specified C. helveticus concentrations). | No cross-reactivity or interference with listed organisms, except for C. helveticus at concentrations > 3.75x10^6 CFU/mL (unpreserved) and > 7.50x10^6 CFU/mL (C&S preserved). |
| Interfering Substances | No interference observed with tested substances at specified concentrations. | No interference observed with any of the evaluated substances at their respective test concentrations. |
| Assay Reactivity/Inclusivity | All specified strains generate positive results. | All listed strains generated positive results, though some C. upsaliensis and C. lari strains exhibited elevated LoDs compared to reference strains. |
| Brush Bridging Study | 100% correlation with anticipated results for positive and negative samples. | All positive samples gave expected positive results, and all negative samples were negative. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Prospective Clinical Study:
- Sample Size: 1,474 specimens
- Data Provenance: Prospective, collected from July 2020 to December 2020 at five clinical study sites across geographically distinct regions throughout the United States.
- Archived Clinical Study:
- Sample Size: 290 archived samples
- Data Provenance: Retrospective. The samples had prior culture and speciation results and were retrospectively tested.
- Contrived Study:
- Sample Size: 210 specimens (150 positive, 60 negative).
- Data Provenance: Contrived samples (spiked with Campylobacter species).
- Reproducibility Study:
- Sample Size: 320 samples (160 unpreserved stool, 160 preserved stool in C&S media).
- Data Provenance: Contrived samples, tested across three sites (one internal, two external).
- Prozone / Hook Effect Study:
- Sample Size: 14 dilutions (n=7 for preserved, n=7 for unpreserved) tested in replicates of 5.
- Data Provenance: Contrived samples.
- Cross-Reactivity/Microbial Interference Study:
- Sample Size: Not explicitly stated as a number, but involves testing various bacteria, fungi, and viral strains (spiked into stool, some clinical Norovirus samples).
- Data Provenance: Primarily contrived samples, with 5 clinical Norovirus stool specimens.
- Interfering Substances Study:
- Sample Size: Not explicitly stated, but involves testing C. jejuni low positive contrived samples in the presence of 27 different chemical and biological substances.
- Data Provenance: Contrived samples.
- Assay Reactivity/Inclusivity Study:
- Sample Size: Not explicitly stated, but involves testing multiple strains of C. jejuni, C. coli, C. upsaliensis, and C. lari.
- Data Provenance: Laboratory strains.
- Brush Bridging Study:
- Sample Size: 53 non-pipettable clinical stool specimens (5 positive, 48 negative) from the prospective and archived clinical studies, plus a panel of contrived samples (25 at 3x LoD, 25 at 5x LoD, 25 negative).
- Data Provenance: Clinical (from prior studies) and contrived.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Ground Truth for Clinical Studies (Prospective and Archived): The ground truth was established by "standard of care Campylobacter culture and speciation" which is a laboratory method. There is no mention of human experts directly establishing the ground truth for classification of individual samples.
- Ground Truth for Contrived Studies (Reproducibility, Analytical Sensitivity, Prozone, Cross-Reactivity, Interfering Substances, Assay Reactivity): The ground truth was established by creating samples with known concentrations of organisms or by confirming the absence of organisms. This suggests laboratory verification rather than expert clinical assessment.
4. Adjudication Method for the Test Set
- Prospective Clinical Study: For specimens with discordant results between the Curian Campy assay and the reference method (culture and speciation), further evaluation was done using "FDA-cleared commercial nucleic acid amplification test (NAAT)". This acts as a form of adjudication for discordant results, though it's not a human consensus process.
- Archived Study, Contrived Studies, Analytical Performance Studies: No adjudication method is explicitly described for these studies other than the initial ground truth determination.
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 comparative effectiveness study was done.
- This device is an in-vitro diagnostic assay (Curian Campy) read by an automated analyzer (Curian Analyzer), not an AI assisting human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, the performance data presented for the Curian Campy assay is standalone. The device (Curian Campy assay with the Curian Analyzer) provides a qualitative result (positive/negative) automatically. The interpretation of results is "automated by Curian Analyzer," and the clinical studies directly evaluate this automated output against a reference standard.
7. The Type of Ground Truth Used
- Clinical Studies (Prospective and Archived): The primary ground truth was culture and speciation for Campylobacter. For discordant results in the prospective study, an FDA-cleared commercial nucleic acid amplification test (NAAT) was used for further evaluation.
- Analytical Performance Studies (Reproducibility, Analytical Sensitivity, Prozone, Cross-Reactivity, Interfering Substances, Assay Reactivity, Contrived Study): The ground truth was based on known concentrations of spiked organisms or known negative samples, verified by laboratory methods.
8. The Sample Size for the Training Set
- The document does not describe algorithmic training. This device appears to be a fluorescence immunoassay interpreted by an analyzer, not a machine learning or AI algorithm that requires a separate training set. The descriptions of "analytical performance" and "clinical performance" are for evaluating the performance of the device itself, not for training an AI model.
9. How the Ground Truth for the Training Set was Established
- As there is no mention of an AI algorithm requiring a training set, this question is not applicable to the information provided.
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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.
December 23, 2021
Meridian Bioscience, Inc. Heather Planck Regulatory Affairs Specialist 3471 River Hills Drive Cincinnati, Ohio 45244
Re: K210976
Trade/Device Name: Curian Campy Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus Serological Reagents Regulatory Class: Class I, reserved Product Code: LQP Dated: March 31, 2021 Received: April 1, 2021
Dear Heather Planck:
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 mediation-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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Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) number: K210976
Date of Preparation: December 22, 2021
| Owner: | Meridian Bioscience, Inc.3471 River Hills DriveCincinnati, Ohio 45244 USAPhone: (513) 271-3700Fax: (513) 272-5213 |
|---|---|
| Contact: | Primary Contact:Heather PlanckRegulatory Affairs Specialist |
| Trade Name: | Curian® Campy |
| Common Name: | Campylobacter Spp. |
| Classification Name: | Campylobacter fetus serological reagents(21 CFR 866.3110, Product Code LQP) |
Device Description
The Curian® Campy assay is a qualitative in vitro diagnostic test for the detection of Campylobacter-specific antigens in human stool samples collected from individuals with signs and symptoms of gastroently. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in unpreserved or preserved stool in Cary-Blair or C&S transport media. The Curian® Campy assay utilizes fluorescence technology with the cleared Curian® Analyzer (K192817) to detect Campylobacter-specific antigens in human stool.
Intended Use / Indications for Use
Curian Campy, for use with the Curian Analyzer, is a rapid, qualitative fluorescent immunoassay for the detection of a Campylobacter-specific antigen in human fecal specimens. Curian Campy is intended to detect C. jejuni, C. coli, C. upsaliensis, and C. lari in human stool from patients with signs and symptoms of gastroenteritis. The test is intended for use with unpreserved fecal specimens or preserved fecal specimens in transport media. Test results are to be used in conjunction with information available from the patient clinical evaluation and other diagnostic procedures. Curian Campy is intended to aid in the diagnosis of Campylobacter infection.
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Predicate Device Comparison
| Similarities Between the New Device and the Predicate Device | ||
|---|---|---|
| NEW DEVICECurianTM Campy | PREDICATE DEVICECAMPYLOBACTER QUIK CHEKK191456 | |
| Intended Use/Indications for Use | Curian Campy, for use with the CurianAnalyzer, is a rapid, qualitative fluorescentimmunoassay for the detection of aCampylobacter-specific antigen in humanfecal specimens. Curian Campy is intendedto detect C. jejuni, C. coli, C. upsaliensis,and C. lari in human stool from patients withsigns and symptoms of gastroenteritis. Thetest is intended for use with unpreservedfecal specimens or preserved fecalspecimens in transport media. Test resultsare to be used in conjunction withinformation available from the patient clinicalevaluation and other diagnostic procedures.Curian Campy is intended to aid in thediagnosis of Campylobacter infection. | The CAMPYLOBACTER QUIK CHEK testis a rapid membrane enzyme-linkedimmunosorbent assay for the qualitativedetection of a Campylobacter -specificantigen in human fecal specimens. TheCAMPYLOBACTER QUIK CHEK test isdesigned to detect C. jejuni, C. coli, C. lari ,and C. upsaliensis from patients with signsand symptoms of gastroenteritis. The testis intended for use with preserved fecalspecimens in transport media andunpreserved fecal specimens. Test resultsshould be considered in conjunction withclinical findings and patient history. |
| Classification | Class I | Same |
| Product Code | LQP | Same |
| Regulation | 21 CFR 866.3110 | Same |
| Measured Analyte | Campylobacter -specific antigen | Same |
| Antibody Format | Monoclonal/Polyclonal | Same |
| Target Population | Individuals with signs and symptoms ofgastroenteritis | Same |
| Type of Test | Qualitative | Same |
| Sample Matrix | Human fecal specimen | Same |
| Specimen Type | Unpreserved fecal specimens and fecalspecimens in Cary-Blair and C&S TransportMedia | Same |
| Controls | Positive and negative control included in thekit. Internal Control line | Same |
| Species Detected | C. jejuni, C. coli, C. lari, and C. upsaliensis | Same |
| Read Result Time | < 30 minutes | Same |
| Format | Single Use Cassette | Same |
| Kit Storage | Refrigerated (2-8 °C) | Same |
| Differences Between the New Device and the Predicate Device | ||
| NEW DEVICECurian™ Campy | PREDICATE DEVICECAMPYLOBACTER QUIK CHEKK191456 | |
| Technology | Lateral flow fluorescentimmunoassay | Rapid membrane ELISA |
| Interpretation ofResults | Results interpretation automated byCurian Analyzer | Visual |
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NON-CLINICAL PERFORMANCE DATA
Analytical Performance
Precision/Reproducibility
The reproducibility of the Curian Campy assay was determined by testing contrived samples in both stool matrix types (i.e., unpreserved stool preserved in C&S transport media), across three sites (one internal and two external). Samples were created with the C. jejuni organism spiked into either preserved or unpreserved pooled negative stool matrix at the following concentrations: high negative (just below Cs), low positive (~Css), moderate positive (3x higher than the Css), and one true negative stool sample. Ten panels of blinded samples with 16 samples per panel were provided to each site per stool matrix type for a total of 320 samples (n=160 unpreserved stool and n=160 preserved stools in C&S media). Testing was conducted at each site twice a day over 5 nonconsecutive days by two operators per day per site and included three different kit lots (2 lots per site). In addition, positive controls were run daily.
The results were consistent among the different locations and exhibited 100% percent agreement (PA) with expected results for the true negative, low positive preserved stool samples in C&S media. The high negative samples exhibited a PA of 95.3% (95%C): 90.6% - 97.7%). For unpreserved stool samples, the results were consistent among the different locations and exhibited 100% PA for the true negative and moderate positive samples. The high negative unpreserved stool samples showed a PA of 98.7% (95%C): 95.2% - 99.6%) and the low positive stool samples showed PA of 82.7% (95%C1: 75.8% -87.9%), which was lower than expected; under-sampling with the Curian Campy transfer pipette was the cause.
Analytical Sensitivity
Analytical sensitivity studies were performed to determine the analytical limit of detection (LoD) of quantified Campylobacter whole cell stocks (C. jejuni, C. coli, C. upsaliensis, and C. lari) in human stool matrix for the Curian Campy assay. Three lots of the Curian Campy assay were evaluated. For each kit lot, an LoD was established and confirmed in separate studies for each target Campylobacter species across the three sample matrices. The concentrations were calculated in colony forming units per milliliter (CFU/mL) and their equivalent in CFU/test by factoring in the dilutions and the final volume used in the assay. The LoD values determined for the Curian Campy for each species detected by the assay in unpreserved and preserved (C&S and Carv-Blair) stool matrix are listed in the table below.
| C. jejuni | C. coli | C. upsaliensis | C. lari | ||||
|---|---|---|---|---|---|---|---|
| CFU/mL | CFU/test | CFU/mL | CFU/test | CFU/mL | CFU/test | CFU/mL | CFU/test |
| Unpreserved Stool Matrix | |||||||
| 4.00x105 | 1818 | 3.00x106 | 13636 | 1.62x106 | 7386 | 5.00x106 | 22727 |
| Preserved (C&S) Stool Matrix | |||||||
| 7.25x105 | 2266 | 1.57x107 | 49063 | 1.18x106 | 3681 | 1.16x107 | 36250 |
| Preserved (Cary-Blair) Stool Matrix | |||||||
| 7.25x105 | 2266 | 1.57x107 | 49063 | 2.36x106 | 7375 | 1.16x107 | 36250 |
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Prozone / Hook Effect
A study was performed to determine the potential for a high dose prozone/hook effect with the Curian Campy assay. Dilutions of quantified C. jejuni whole cell stock were prepared in negative sample matrix to create contrived positive samples containing known concentrations of the target antigen. Individual reactions were prepared such that the concentration in each replicate was that of a high positive specimen. approximately 4xLoD - 240xLoD for preserved samples (ranging from 2.70x10° to 1.73x10° CFU/mL) and 7xLoD - 430xLoD for unpreserved samples (ranging from 2.70x108 CFU/mL). A total of n=7 dilutions were prepared for both preserved and unpreserved specimen (n=14 total). Each sample dilution was tested in replicates of 5 to determine whether a hook/prozone effect was observed with the Curian Campy assay. A prozone/ hook effect was not observed with the Curian Campy assay when testing samples containing high concentrations of C. jejuni.
Cross-Reactivity/Microbial Interference
A cross-reactivity and microbial interference study was performed to determine if microorganisms found in human stool specimens) non-specifically react with the Curian Campy assay, or interfere with detection of Campylobacter-specific antigen when present at high concentrations. The specificity of Curian Campy was evaluated by testing bacteria, fungi, and viral strains spiked into unpreserved stool in C&S media. Each organism was tested with in the absence and presence of Campylobacter jejuni (at 2x LoD). Bacteria and fungi were testedat a minimum concentration of 1.0x107 CFU/mL (with the exception of C. helveticus) and viruses at minimum concentration of 1.0x105 TCIDso/mL). For Norovirus, 5 preserved clinical stool specimens were evaluated rather than contrived samples.
No cross-reactivity or microbial interference with the Curian Campy assay was observed except for C. helveticus (strain ATCC 51209), which was found to be positive at concentrations greater than 3.75x100 CFU/mL in unpreserved stool and 7.50x106 CFU/mL in preserved stool matrix. The organisms evaluated for cross-reactivity are listed below.
Acinetobacter baumannii Aeromonas hydrophila Bacillus cereus Bacillus subtilis Bacteroides fragilis Campvlobacter concisus Campylobacter fetus Campylobacter helveticus Campylobacter hyointestinalis Candida albicans Citrobacter freundii Clostridium bifermentans Clostridium difficile Clostridium perfringens Edwardsiella tarda Enterobacter cloacae Enterococcus faecalis Escherichia coli Escherichia coli EIEC Escherichia coli EPEC Escherichia coli ETEC Escherichia coli 0157:H7 (non-toxigenic) Escherichia coli 0157:H7 (toxigenic) Escherichia fergusonii Escherichia hermanii Helicobacter pylori
Adenovirus 1,2, 3, 5, 40, 41 Coxsackievirus B2, B3, B4, B5 Echovirus 9, 11, 18 Enterovirus 68, 69, 70, 71
Klebsiella pneumoniae Lactobacillus acidophilus Lactococcus lactis Listeria monocytogenes Peptostreptococcus anaerobius Plesiomonas shigelloides Porphyromonas asaccharolytica Prevotella melaninogenica Proteus vulgaris Pseudomonas aeruginosa Pseudomonas fluorescens Salmonella enterica susb. enterica serovar Hilversum Salmonella enterica susb. enterica serovar Typhimurium Salmonella enterica susb. enterica serovar Minnesota Serratia marcescens Shiqella boydii Shigella dysenteriae Shiqella flexneri Shigella sonnei Staphylococcus aureus Staphylococcus aureus (Cowan's) Staphylococcus epidermidis Streptococcus agalactiae Streptococcus dysgalactiae subsp. equisimilis Vibrio parahaemolvticus Yersinia enterocolitica Human Coronavirus Human Rotavirus Norovirus
Parechovirus 1 (formerly Echovirus 22)
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Interfering Substances
Interference testing was performed in the presence of chemical and biological substances introduced directly into contrived C. jejuni low positive unpreserved and preserved stool samples. Substances and their respective test concentrations evaluated are listed below. Interference was not observed with the Curian Campy assay for any of the substances evaluated at their respective test concentrations.
| Barium Sulfate (5% w/v) | Mylanta® (4.2 mg/mL) |
|---|---|
| Benzalkonium chloride (1% w/v) | Naproxen sodium (5% w/v) |
| Ciprofloxacin (0.25% w/v) | Nonoxynol-9 (1% w/v) |
| Ethanol (1% w/v) | Nystatin (1% w/v) |
| Hog gastric mucin (3.5% w/v) | Palmitic Acid/Fecal Fat (40% w/v) |
| Human blood (40% v/v) | Pepto-Bismol® (5% v/v) |
| Human hemoglobin (10.0% w/v) | Phenylephrine (1% w/v) |
| Human urine (5% v/v) | Polyethylene glycol 3350 (10% w/v |
| Hydrocortisone (1% w/v) | Prilosec OTC® (5 µg/mL) |
| Imodium® A-D (5% v/v) | Sennosides (1% w/v) |
| Kaopectate® (5% v/v) | Simethicone (10% w/v) |
| Leukocytes (0.05% v/v) | Stearic Acid/Fecal Fat (40% w/v) |
| Mesalazine (10% w/v) | Tagamet® (5 µg/mL) |
| Metronidazole (0.25% w/v) | TUMS® (50 µg/mL) |
| Mineral Oil (10% w/v) | Vancomycin (0.25% w/v) |
Assay Reactivity/ Inclusivity
Several strains of C. jejuni, C. coli, C. upsaliensis, and C. lari were used to evaluate the specificity of the Curian Campy assay using both unpreserved and preserved stool (in C&S).
| C. jejuni | C. coli | C. upsaliensis | C. lari |
|---|---|---|---|
| Zeptometrix Z086 | ATCC 43482 | ATCC BAA-1059 | ATCC BAA-1060 |
| ATCC 33292 | ATCC 43476 | ATCC 49815 | ATCC 35222* |
| ATCC 49350 | ATCC 43478 | 2017/0506H | ATCC 35223* |
| ATCC 43442 | ATCC 43485 | 2016/1950* | 2013/0823H* |
| ATCC 33560 | ATCC BAA-1061 | ATCC 43954 | 2015/0814* |
| ATCC 43953* | 2015/2983 | ||
| 2016/2697* | 2016/0235* | ||
| 2018/0319H* | 2015/0519 | ||
| 2016/1931 | 2015/1582 | ||
| ATCC 700558* | 2015/2189 |
All strains listed below generated positive results when tested.
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*The following C. upsaliensis and C. lari strains exhibited elevated LoDs in comparison to the reference strains (ATCC 49816 and ATCC 43675) that were used in the LoD determination:
| Species | Strain | Reactivity Level inUnpreserved Stool | Reactivity Level in StoolPreserved in C&S |
|---|---|---|---|
| C. upsaliensis | 2016/1950 | 4x | 8x |
| ATCC 43953 | 2x | 8x | |
| 2016/2697 | 56x | 78x | |
| 2018/0319H | 40x | 55x | |
| ATCC 700558 | 24x | 33x | |
| C. lari | 2013/0823H | 8x | 4x |
| 2015/0814 | 8x | 4x | |
| 2016/0235 | 8x | 10x | |
| ATCC 35222 | 8x | 10x | |
| ATCC 35223 | 24x | 10x |
Brush Bridging Study
The Curian Campy assay is for use with unpreserved human stool specimens and human stool specimens preserved in Cary-Blair and C&S transport media. Most specimens are easily sampled using the transfer pipette provided in the kit; however, some unpreserved stool specimens are non-pipettable and require use of a specific brush (i.e., Curian Campy Stool Collection Brush, sold separately by Meridian) to adequately collect the sample for analysis in the Curian Campy assay. Fifty-three non-pipettable stool specimens (5 Campylobacter positives and 48 negatives) were processed with the brush during the prospective and archived clinical studies, combined.
To further support use of the brush with the Curian Campy assay, an analytical bridging study was performed that evaluated a panel consisting of contrived positive and negative samples collected/processed with the brush. Contrived positive samples were generated by spiking C. jejuni (strain ATCC #BAA-1234) into negative, non-pipettable stool samples were prepared at 3x LoD and 25 samples were prepared at 5x LoD. Twenty-five negative samples were also tested. Three non-expert operators tested each sample at one internal site. All positive samples gave the expected positive results, and all negative samples were negative. These results indicate that non-pipettable stool specimens can be collected with the brush prior to testing with the Curian Campy assay.
CLINICAL PERFORMANCE DATA
Clinical Performance
Prospective Study
The Curian Campy assay was evaluated from July 2020 to December 2020 at five clinical study sites representing geographically distinct regions throughout the United States. There were 1,474 specimens from patients with signs and symptoms of gastroenteritis for whom a diagnostic Campylobacter test had been ordered by a practicing physician, prospectively collected and enrolled into the study. All specimens were tested at the study sites with the Curian Campy assay and either had current standard of care Campylobacter culture and speciation performed and results available (reference method) or culture and speciation was performed as part of the study. The vast majority of specimens were pipettable and were processed with the Curian Campy pipette included in the kit. A small subset of specimens were nonpipettable and were processed with the Curian Campy Collection Brush (sold separately by Meridian). Clinical performance (sensitivity and specificity) for prospective specimens against the reference method (culture and speciation) are presented in the following table. There were no observable differences in
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performance of the Curian Campy assay with respect to study site, storage condition, kit lot, or patient gender or age. Prospective specimens with discordant results between the Curian Campy assay and the reference method were further evaluated of care (SoC) results obtained with an FDAcleared commercial nucleic acid amplification test (NAAT); results of discordant testing are footnoted below.
| Reference Method: Culture andSpeciation | |||||||
|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Parameter | Estimate | 95% CI | ||
| Positive | 18 | 28** | 46 | Sensitivity | 85.7% | [65.4% - 95.0%] | |
| Curian CampyAssay | Negative | 3* | 1425 | 1428 | Specificity | 98.1% | [97.2% - 98.7%] |
| Total | 21 | 1453 | 1474 |
| Curian Campy Overall Performance for Prospective Specimens versus Culture and Speciation | ||
|---|---|---|
- The Standard of Care (SoC) testing of two of the three false negative specimens by a high sensitivity, FDA-cleared nucleic acid amplification (NAAT) assay showed that one of the specimens produced a negative Campylobacter result, whereas one of the specimens produced a positive Campylobacter result; the third specimen was not subjected to NAAT testing as part of the SoC.
** Of the 28 false positive specimens, 10 were subjected to SoC testing by a high sensitivity, FDA-cleared NAAT assay. Two of these 10 specimens produced a positive Campylobacter result, whereas eight produced a negative Campylobacter result. Eighteen specimens were not subjected to NAAT testing as part of the SoC.
Archived Study
To further estimate sensitivity of the Curian Campy assay, 290 archived samples with culture and speciation results were retrospectively tested for Campylobacter antigen using the Curian Campy assay at all five study sites. The clinical performance (sensitivity and specificity) for archived samples against the reference method (culture and speciation) are presented in the table below.
| Reference Method: Culture andSpeciation | |||||||
|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Parameter | Estimate | 95% CI | ||
| Curian CampyAssay | Positive | 28 | 5 | 33 | Sensitivity | 96.6% | [82.8% - 99.4%] |
| Negative | 1 | 256 | 257 | Specificity | 98.1% | [95.6% - 99.2%] | |
| Total | 29 | 261 | 290 |
Curian Campy Overall Performance for Archived Samples versus Culture and Speciation
Contrived Study
Additional testing at each site was conducted with contrived samples at 2xLoD and 8xLoD for C. coli, C. upsaliensis, and C. lari and 3 reagent lots. All 210 specimens tested as expected with n=150 positive Campylobacter spp. specimen and n=60 negative specimen yielding 100% correlation with the anticipated results. Both sample matrices were represented with n=105 unpreserved stool specimens and n=105 stool specimens preserved in C&S transport media. The overall performance of the Curian Campy assay compared to the anticipated results is presented in the table below.
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Curian Campy Overall Performance for Contrived Specimens versus Contrived Anticipated Results
| Contrived: Anticipated Result | |||||||
|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | Parameter | Estimate | 95% CI | ||
| Curian CampyAssay | Positive | 150 | 0 | 150 | PPA | 100.0% | [97.5% - 100.0%] |
| Negative | 0 | 60 | 60 | NPA | 100.0% | [94.0% - 100.0%] | |
| Total | 150 | 60 | 210 |
CONCLUSION
The Curian® Campy assay, as supported by the information submitted in this premarket submission, is substantially equivalent to the predicate device (CAMPYLOBACTER QUIK CHEK; K191456).
§ 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).