(100 days)
The Sofia hCG FIA is an immunofluorescence-based lateral flow assay intended for the qualitative detection of human Chorionic Gonadotropin (hCG) in urine specimens and is designed to aid early detection of pregnancy. The test is intended for prescription use only, including use at point-of-care sites.
The test kit consists of individually packaged test Cassettes-each containing monoclonal murine antibodies for the capture and detection of hCG; disposable specimen transfer pipettes; and a package insert. The test is a qualitative immunofluorescence-based assay used to detect concentrations of 20 mIU/mL hCG or more in urine.
The Sofia hCG FIA is an immunofluorescence-based lateral flow assay intended for the qualitative detection of human Chorionic Gonadotropin (hCG) in urine specimens to aid early detection of pregnancy. The device is for prescription use only, including at point-of-care sites.
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating acceptance criteria for each performance metric as distinct pass/fail thresholds. However, the performance data presented can be interpreted as demonstrating the device meets the implied requirements for accuracy and reliability for its intended use.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Analytical Sensitivity: Detect hCG at 20 mIU/mL or lower. | Detection Limit: The positive/negative threshold at which 100% of the samples tested positive was confirmed at 20 mIU/mL hCG. |
| Reproducibility: Consistent results across sites and operators. | Reproducibility: Tested at 3 laboratories by 3 operators each, using contrived samples (5-25 mIU/mL hCG). Results at each site agreed 100% with expected results. No significant differences observed within run, between runs, or between sites. |
| Absence of High-Dose Hook Effect: Correctly identify high hCG concentrations. | High Dose Hook Effect: Positive results observed up to 500,000 mIU/mL hCG. No hook effect observed for urine samples with hCG concentrations up to 500,000 mIU/mL. |
| Analytical Specificity: No interference or cross-reactivity from common substances. | Analytical Specificity: No cross-reactivity or interference observed for extensive lists of chemical substances (e.g., Acetaminophen, Aspirin, Caffeine, Ethanol), urine analytes (e.g., Albumin, Glucose, Hemoglobin), hormones (e.g., hLH, hFSH, hTSH, Estriol), and microorganisms (e.g., Escherichia coli, Candida albicans) at specified concentrations. pH (5-9) and Specific Gravity (1.005-1.037) also showed no interference. |
| Clinical Performance: High agreement with a commercially available qualitative test. | Clinical Performance (compared to a commercially available qualitative test):- Positive Agreement: >99% (176/177) (95% Cl=97-100%)- Negative Agreement: >99% (795/797) (95% Cl=99-100%)- Overall Agreement: >99% (971/974) (95% Cl=99-100%) |
2. Sample Size and Data Provenance for the Test Set:
- Sample Size for Clinical Performance (Test Set): 974 fresh urine specimens.
- Data Provenance: The clinical study was multi-center, conducted by health care personnel at five (5) distinct sites in various geographical regions within the United States. The data is prospective, collected from patients presenting for pregnancy testing.
3. Number of Experts and Qualifications for Ground Truth (Test Set):
The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical test set. The clinical performance study compares the Sofia hCG FIA to "a commercially available qualitative test," implying that the result from this comparator test served as the reference or ground truth.
4. Adjudication Method for the Test Set:
The document does not describe an adjudication method for the clinical test set. The comparison is directly between the Sofia hCG FIA and a single "commercially available qualitative test."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
A MRMC comparative effectiveness study was not explicitly performed or described in the provided text. The clinical study compares the device's performance to another commercial test, not to human readers with or without AI assistance. The Sofia hCG FIA is a rapid immunoassay read by an instrument (Sofia Analyzer), not an imaging device typically associated with MRMC studies involving human readers.
6. Standalone Performance:
Yes, standalone performance was assessed. The entire document describes the performance of the Sofia hCG FIA algorithm (via the Sofia Analyzer) in various analytical and clinical studies, independent of human interpretation or intervention in the diagnostic process beyond specimen collection and loading the cassette. The Sofia Analyzer dictates the development time, scans the strip, and analyzes the fluorescent signal using method-specific algorithms to display the result (Positive, Negative, or Invalid).
7. Type of Ground Truth Used:
- Analytical Performance Studies (Reproducibility, Detection Limit, High-Dose Hook Effect, Analytical Specificity): The ground truth was established using known, contrived samples prepared by spiking negative urine with specific, traceable concentrations of hCG (WHO International 4th Standard) or other substances.
- Clinical Performance Study: The ground truth was based on the results obtained from another commercially available qualitative test when evaluating clinical patient samples.
8. Sample Size for the Training Set:
The document does not explicitly state a separate "training set" for the Sofia hCG FIA. As a lateral flow immunoassay read by an analyzer with method-specific algorithms, the "training" would likely refer to the data used during the development and optimization of the instrument's algorithm and the assay reagents themselves. This information is not provided in detail, as the focus is on the validation performance of the finished product.
9. How Ground Truth for Training Set was Established:
As mentioned above, a "training set" is not explicitly described. However, during the development of such a device, a vast number of samples with known hCG concentrations (established through analytical methods, often traceable to international standards) would be used to develop and refine the detection algorithms and thresholds for the Sofia Analyzer. This would involve rigorous calibration and optimization to correctly identify positive and negative results across the intended range of hCG concentrations and ensure specificity. The performance studies detailed in the submission serve as the validation of this developed system.
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AUG 2 2013
510(k) SUMMARY
Date Prepared:
Type of Test: Qualitative fluorescent hCG immunoassay
July 29, 2013
Applicant: Quide! Corporation 10165 McKellar Court San Diego, California 92121 Telephone: 858-552-7908 Fax: 858-646-8045
Submission Contact: John D. Tamerius, Ph.D.
Sofia® hCG FIA Proprietary and Established Names:
Device Classification:
| Product Code: | JHI |
|---|---|
| Classification: | Class II |
| Regulatory Section: | 21 CFR 862.1155(a), HumanChorionic Gonadotropin (HCG)test system intended for the earlydetection of pregnancy |
| Panel: | Clinical Chemistry (75) |
Intended Use: The Sofia hCG FIA is an immunofluorescence-based lateral flow assay intended for the qualitative detection of human Chorionic Gonadotropin (hCG) in urine specimens and is designed to aid early detection of pregnancy.
The test is intended for prescription use only, including use at point-of-care sites.
Device Description: The test kit consists of individually packaged test Cassettes-each containing monoclonal murine antibodies for the capture and detection of hCG; disposable specimen transfer pipettes; and a package The test is a qualitative immunofluorescenceinsert. based assay used to detect concentrations of 20 mIU/mL hCG or more in urine.
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Comparison with Predicate:
| Item | Proposed Device | Predicate Device |
|---|---|---|
| Features | Sofia hCG FIA | QuickVue+ One-Step hCGCombo test (K973858) |
| Intended Use | The Sofia hCG FIA is animmunofluorescence-basedlateral flow assay intended forthe qualitative detection ofhuman ChorionicGonadotropin (hCG) in urinespecimens and is designed toaid early detection ofpregnancy.The test is intended forprescription use only,including use at point-of-caresites. | The QuickVue+ One-Step hCGCombo test is a one-stepimmunoassay intended for thequalitative detection of humanChorionic Gonadotropin (hCG)in serum or urine for the earlydetection of pregnancy. Thetest is intended for use byhealthcare professionals. |
| Specimen Type | Urine | Urine/Serum |
| Format | Cassette | Cassette |
| Test Principle | Immunofluorescence-basedlateral flow assay | Lateral flow immunoassay |
| Instrument | Sofia Analyzer | No instrument; visually-readassay |
| Read Result Time | Approximately 3 minutes | 3 minutes for urine |
| Analytical Sensitivity | 20 mIU/mL for urine | 20 mIU/mL for urine |
| Traceability | WHO International Standard4th Edition 75/589 | WHO International Standard 3rdEdition 75/537 |
| Storage | 15 to 30°C | 15 to 30°C |
.
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Test Principle:
The Sofia hCG FIA is an immunofluorescence-based lateral flow test for use with the Sofia Analyzer. The test uses a pair of monoclonal murine antibodies specific to the beta subunit of hCG to capture and detect hCG. The beta subunit was chosen to ensure specificity as the alpha subunit is nearly identical to the alpha subunit found in LH, FSH and TSH.
To perform the test, a urine specimen is collected and dispensed into the Sample Well on the Test Cassette. The Cassette is placed inside of the Sofia Analyzer for an automatically defined development time. The Sofia Analyzer then scans the test strip and analyzes the fluorescent signal, using method-specific algorithms. The Sofia Analyzer then displays the test result (Positive, Negative, or Invalid) on the screen, and optionally prints the results on an integrated printer.
Summary of Performance Data:
Numerous studies were undertaken to document the performance characteristics and substantial equivalence of the test to the predicate device. These studies included the following:
- a. Analytical Performance
-
- Reproducibility
-
The reproducibility of the Sofia hCG FIA was evaluated at three (3) different laboratories. Three (3) different operators at each site tested a series of coded, contrived samples, prepared in negative urine, ranging from a low negative (5 mlU/mL) to a moderate positive (25 mlU/mL) hCG. For each level a total of 90 replicates were tested over five (5) different days at each site. The results at each site agreed 100% with the expected results for these levels. There were no significant differences observed within run, between runs, or between sites.
- High Dose Hook Effect
A high dose hook effect study was performed by spiking high levels of hCG concentrations 0 to 500,000 mlU/mL into negative urine and evaluating the test results. Positive results were observed up to 500,000 mlU/mL hCG. Therefore no hook effect was observed for urine samples with hCG concentrations up to 500,000 mIU/mL.
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-
- Detection Limit
The sensitivity of the device was tested by spiking pooled male urine with varying concentrations (0 to 100 mlU/mL) of hCG traceable to WHO International 4th Standard. The positive/negative threshold at which 100% of the samples tested positive was confirmed at 20 mIU/mL hCG.
- Detection Limit
-
- Analytical Specificity
Interference and cross-reactivity studies were performed by adding known amounts of chemical substances, urine analytes, hormones, and microorganisms to pooled negative urine. No cross-reactivity or interference was observed for the substances and microorganisms listed below:
- Analytical Specificity
| Item | Substance/Microorganism | Concentration | ||||
|---|---|---|---|---|---|---|
| Chemical Substances | ||||||
| 1 | Acetaminophen | 20 mg/dL | ||||
| 2 | Acetoacetic Acid | 1,600 mg/dL | ||||
| 3 | Acetylsalicylic Acid | 20 mg/dL | ||||
| 4 | Ampicillin | 2 mg/dL | ||||
| 5 | Ascorbic Acid | 20 mg/dL | ||||
| 6 | Atropine | 20 mg/dL | ||||
| 7 | β-Hydroxybutyrate | 2,000 mg/dL | ||||
| 8 | Benzoylecgonine | 8 mg/dL | ||||
| 9 | Bovine Serum | 10 mg/dL | ||||
| 10 | Caffeine | 20 mg/dL | ||||
| 11 | Cannabinol | 10 mg/dL | ||||
| 12 | Cellulose | 500 mg/dL | ||||
| 13 | Citric Acid | 500 mg/dL | ||||
| 14 | Clomiphene | 100 mg/dL | ||||
| 15 | Cow's Milk | 9 mg/dL | ||||
| 16 | DMSO | 0.90% | ||||
| 17 | EDTA | 80 mg/dL | ||||
| 18 | Ephedrine | 18 mg/dL | ||||
| 19 | Ethanol | 0.80% | ||||
| 20 | Gentisic Acid | 20 mg/dL | ||||
| 21 | Methanol | 0.90% | ||||
| 22 | Phenothiazine | 20 mg/dL | ||||
| 23 | Phenylpropanolamine | 20 mg/dL | ||||
| 24 | Salicylic Acid | 20 mg/dL | ||||
| 25 | Tetracycline | 20 mg/dL | ||||
| 26 | Theophylline | 20 mg/mL | ||||
| 27 | Uric Acid | 18 mg/dL | ||||
| Urine Substances | ||||||
| 28 | Albumin (serum) | 2,000 mg/dL | ||||
| 29 | Bilirubin | 1 mg/dL |
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| Item | Substance/Microorganism | Concentration |
|---|---|---|
| 30 | Glucose | 2,000 mg/dL |
| 31 | Haptoglobin | 1 mg/dL |
| 32 | Hemoglobin | 1 mg/dL |
| 33 | Human Anti-Mouse Antibodies | 2.85 ng/mL |
| 34 | Myoglobin | 1 mg/dL |
| 35 | Rheumatoid Factor | 1.08 IU/mL |
| 36 | Serum (negative human) | 1% |
| 37 | Urine Peroxide | 10 mg/dL |
| 38 | Urine pH | 5-9 |
| 39 | Urine Specific Gravity | 1.005-1.037 |
| Hormones | ||
| 40 | hLH | 450 mIU/mL |
| 41 | hFSH | 900 mIU/mL |
| 42 | hTSH | 1,000 mIU/mL |
| 43 | Estriol 17-beta | 28,000 $ μg $ /dL |
| 44 | Pregnanediol glucuronide | 45,000 $ μg $ /dL |
| 45 | β-core fragment, hCG | 5.1 x 105 pmol/L |
| Microorganisms | ||
| 46 | Escherichia coli | 2.61 x 108 CFU/mL |
| 47 | Streptococcus agalactiae (Group B) | 2.50 x 107 CFU/mL |
| 48 | Chlamydia trachomatis | 1 x 107 IFU/mL |
| 49 | Candida albicans | 1.07 x 107 CFU/mL |
b. Clinical Performance:
A multi-center clinical study was conducted to establish the performance of the Sofia hCG FIA compared to results obtained from another commercially available qualitative test. This study was conducted by health care personnel at five (5) distinct sites in various geographical regions within the United States. In this multi-center, point-of-care (POC) field trial, 974 fresh urine specimens, collected from patients presenting for pregnancy testing, were evaluated.
Sofia hCG FIA Performance Compared to a Commercially Available Qualitative Test
| Comparator Test | Positive Agreement = >99% (176/177) | |||
|---|---|---|---|---|
| Pos | Neg | (95% Cl=97-100%) | ||
| Sofia Pos | 176 | 2 | Negative Agreement = >99% (795/797) | |
| Sofia Neg | 795 | (95% Cl=99-100%) | ||
| Total | 177 | 797 | Overall Agreement = >99% (971/974) | (95% Cl=99-100%) |
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Image /page/5/Picture/0 description: The image shows the word "QUIDEL" in a bold, sans-serif font. The letters are all capitalized and black. A small registered trademark symbol is located to the right of the "L".
Conclusion:
These studies demonstrated the substantial equivalence of the Sofia hCG FIA for use with the Sofia Analyzer to the existing product already marketed, QuickVue+ One-Step hCG Combo test, K973858. They further demonstrated the suitability of the product for point-of-care use. Such studies are a critical element in establishing the fundamental safety and effectiveness of the product and its appropriateness for commercial distribution.
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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Quidel Corp. C/O John D. Tamerius 10165 McKellar Ct. SAN DIEGO CA 92121
August 2, 2013
Re: K131166
Trade/Device Name: Sofia® hCG FIA Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: II Product Code: JHI Dated: July 1, 2013 Received: July 3, 2013
Dear Dr. Tamerius:
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. 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 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for
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Page 2-Dr. Tamerius
the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For:
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K131166
Device Name: Sofia® hCG FIA
Indications for Use:
The Sofia hCG FIA is an immunofluorescence-based lateral flow assay intended for the qualitative detection of human Chorionic Gonadotropin (hCG) in urine specimens and is designed to aid early detection of pregnancy.
The test is intended for prescription use only, including use at point-of-care sites.
Prescription Use × (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Denise Johnson-lyles -S 2013.08.01 08:31:34 -04'00'
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
510(k)___k131166 _____________________________________________________________________________________________________________________________________________________________
Page 1 of 1
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.