The QuickVue Advance pH and Amines gll test contains two colorimetric tests intended for the qualitative detection of elevated vaginal fluid pH (pH ≥ 4.7) and the presence of volatile vaginal fluid amines. The test is intended for use by health care professionals as an aid in the diagnosis of bacterial vaginosis.

Device Description

The QuickVue Advance pH and Amines gll test contains two qualitative, colorimetric tests for use in the characterization of a vaginal fluid sample: (1) a pH test that differentiates vaqinal fluid pH < 4.7 from vaginal fluid pH > 4.7; and (2) a test that detects alkali volatilizable amines in vaginal fluid. The test is intended for use by health care professionals as an aid in the diagnosis of bacterial vaginosis.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the QuickVue® Advance pH and Amines gll test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
pH Test:
Differentiates vaginal fluid pH < 4.7 from vaginal fluid pH > 4.7	pH test produces a distinct greenish-blue plus sign against a yellow background and a greenish-blue procedural control dot for pH ≥ 4.7. For pH < 4.7, only a greenish-blue procedural control dot appears. (Visual, qualitative assessment)
Visual result within one minute	pH test produces a visual color change within one minute of sample application.
Invalid result for no procedural control dot	Any pH test that does not develop a procedural control dot is considered an invalid result.
Amines Test:
Detects alkali pre-mixed amines in vaginal fluid. It is designed to detect alkali volatilizable amines at concentrations above 0.5 mM.	Amines test produces a distinct greenish-blue plus sign against a yellow background and a greenish-blue procedural control dot within one minute when contacted with a vaginal fluid specimen containing volatile amines at concentrations above 0.5 mM. When volatile amines are not present, only a greenish-blue procedural control dot appears. (Visual, qualitative assessment)
Visual result within one minute	Amines test produces a visual color change within one minute of sample application.
Invalid result for no procedural control dot	Any amines test that does not develop a procedural control dot is considered an invalid result.
Overall Performance for BV Aid:
Aid in the diagnosis of bacterial vaginosis (BV)	Multi-center field clinical study: Sensitivity, specificity, and overall accuracy relative to the Amsel criteria with resolution by Gram stain were calculated. (Specific values for these metrics are not provided in the text, only that they were calculated.)
Excellent intra- and inter-assay precision	Demonstrated. (No quantitative data provided)
Reproducible manufacturability (lot-to-lot consistency)	Demonstrated. (No quantitative data provided)
No interference from potentially interfering substances	Demonstrated. (No specific substances or data provided)
Usability by physician office personnel	Physicians' Office Laboratory studies at three geographically distinct sites in the United States showed personnel could perform the test accurately and reproducibly. (No quantitative data provided)
Substantial equivalence to predicate devices	Demonstrated to be substantially equivalent to existing products, including the FemExam TestCard test (K962718) and the QuickVue Advance pH and Amines test.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: The exact number of patients/samples in the multi-center field clinical study is not explicitly stated in the provided text.
Data Provenance:
- Country of Origin: The Physicians' Office Laboratory studies were conducted at three geographically distinct sites in the United States. The country of origin for the multi-center field clinical study is not explicitly stated but is implicitly within the scope of a U.S. regulatory submission.
- Retrospective or Prospective: The text describes a "multi-center field clinical study" and "Physicians' Office Laboratory studies." This phrasing strongly suggests these were prospective studies, where the device was used on new samples/patients during the study period.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

Number of Experts: Not explicitly stated.
Qualifications of Experts: Not explicitly stated. The ground truth was established by "Amsel criteria with resolution by Gram stain." This implies that the interpretation of Amsel criteria and Gram stains would have been performed by qualified medical professionals (e.g., clinicians, laboratory technologists/microbiologists), but their specific number, roles, or years of experience are not mentioned.

4. Adjudication Method for the Test Set

The text mentions "resolution by Gram stain" in conjunction with Amsel criteria for establishing the ground truth. This indicates a form of adjudication, where Gram stain results were used to resolve or confirm diagnoses based on Amsel criteria. However, the specific method (e.g., 2+1, 3+1, etc., for multiple readers) is not detailed. It implies a reference standard (Gram stain) was used to confirm or adjudicate initial clinical assessments.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study is not explicitly mentioned or described. The studies focused on the standalone performance of the device and its usability by office personnel, rather than comparing human reader performance with and without AI assistance. The device itself is a qualitative rapid test, not an AI interpretation tool.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the primary clinical validation appears to be a standalone study of the device. The text describes the device's performance in diagnosing BV based on its pH and amines tests, with sensitivity, specificity, and accuracy calculated relative to the Amsel criteria and Gram stain. The Physicians' Office Laboratory studies assessed the ability of personnel to perform the test accurately, but the core performance metrics are for the device's results themselves. The device produces a visual color change which is then interpreted by a human user, meaning it's a "human-in-the-loop" device in terms of interpretation, but the "algorithm" is the biochemical reaction itself. The studies, however, evaluate the performance of this reaction and its subsequent visual readout.

7. Type of Ground Truth Used

Expert Consensus + Pathology (or a related clinical standard): The ground truth was established based on "Amsel criteria with resolution by Gram stain."
- Amsel Criteria: These are clinical criteria for diagnosing bacterial vaginosis, which are based on clinical signs and symptoms. This could be considered a form of clinical expert consensus in a diagnostic setting.
- Gram Stain: This is a laboratory diagnostic method that involves microscopic examination of a vaginal fluid smear, often considered a "gold standard" or a very strong reference standard for BV diagnosis in many contexts. It's a form of pathology/microbiology result.
- Therefore, the ground truth is a combination of established clinical criteria and a robust laboratory reference method, with the Gram stain serving to "resolve" or confirm diagnoses.

8. Sample Size for the Training Set

Not specified. The provided text describes validation and clinical studies but does not mention any "training set" or explicit machine learning model development. This device is a rapid diagnostic test based on chemical reactions and visual color changes, not a software-based AI algorithm that would typically require a training set in the modern sense.

9. How the Ground Truth for the Training Set Was Established

N/A. As this is not an AI/machine learning device with an explicit "training set," this question is not applicable. The device's underlying principles are chemical indicators. Performance parameters were validated through the clinical studies described, not by training a model.

Summary

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APR 2 9 2004

K040008

SUMMARY OF SAFETY AND EFFECTIVENESS XI.

Product:

QuickVue® Advance pH and Amines gll test

Manufacturer:

QUIDEL Corporation 10165 McKellar Court San Diego, California 92121 U.S.A.

Device Classification:

Urinary pH (nonquantitative) test system 21 CFR 862.1550 Class I

Intended Use:

The QuickVue Advance pH and Amines all test contains two qualitative, colorimetric tests for use in the characterization of a vaginal fluid sample: (1) a pH test that differentiates vaqinal fluid pH < 4.7 from vaginal fluid pH > 4.7; and (2) a test that detects alkali volatilizable amines in vaginal fluid. The test is intended for use by health care professionals as an aid in the diagnosis of bacterial vaginosis.

Principles of the Test:

pH Test: The pH test contains a colorimetric pH indicator, which produces a visual color change within one minute of sample application. When contacted with a vaginal fluid sample at or above pH 4.7, the pH test area produces a distinct greenish-blue plus sign against a vellow background and a greenish-blue procedural control dot in the test area. When contacted with a vaginal fluid sample lower than pH 4.7, the pH test produces only a greenish-blue procedural control dot, within one minute, against a yellow background in the test area. Any test that does not develop a procedural control dot is considered an invalid result.

Amines Test: The QuickVue Advance Amines gll test contains a colorimetric pH indicator, which produces a visual color change within one minute of sample application. The test employs a film of BCG in the yellow test area that is surrounded by a thick black ring covered with a dried alkali analogous to the potassium hydroxide (KOH) used to perform the whiff test. The amines test area produces a distinct greenish-blue plus sign against a yellow background within one minute and a greenish-blue procedural control dot in the test area when contacted with a vaginal fluid specimen containing volatile amines at concentrations above 0.5 mM. When contacted with a vaginal fluid specimen that does not contain alkali volatilizable amines test produces a greenishblue procedural control dot against a yellow background in the test area (within one minute). Any test that does not develop a procedural control dot is considered an invalid result.

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Safety and Effectiveness:

Numerous studies were undertaken to validate the performance characteristics and the substantial equivalence of the QuickVue Advance pH and Amines gll test. These studies included the following:

The test was shown to have excellent intra- and inter-assay precision. 1.
Lot-to-lot consistency analyses showed the test to be reproducibly manufacturable. 2.
Potentially interfering substances were shown not to interfere. ന്
A multi-center field clinical study was conducted. Sensitivity, specificity and overall 4. accuracy relative to the Amsel criteria with resolution by Gram stain were calculated.
ம் Physicians' Office Laboratory studies were conducted to show that physician office personnel could perform the test accurately and reproducibly. Testing was performed at three geographically distinct sites in the United States.

Conclusion:

These studies demonstrated the substantial equivalence of the QuickVue Advance pH and Amines gll test to existing products already marketed, including the FemExam TestCard test [510(k) K962718], also sold under the brand name QuickVue Advance pH and Amines test. They further demonstrated the suitability of the product for laboratory and professional 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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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/2/Picture/2 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with three lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 2 9 2004

Ms. Jennifer S. Hankard Regulatory Affairs Manager Quidel Corp. 10165 McKellar Ct. San Diego, CA 92121

Rc: K040008

Trade/Device Name: QuickVue® Advanced pH and Amines gII test Regulation Number: 21 CFR 862.1550 Regulation Name: Urinary pH (nonquantitative) test system Regulatory Class: Class I Product Code: CEN Dated: March 24, 2004 Received: March 30, 2004

Dear Ms. Hankard:

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 (OS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed 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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours.

Jean M. Cooper, MS, DVM.

Tean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): __ K040008

QuickVue® Advance pH and Amines gll test Device Name:

Indications For Use:

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

ielb. Sarl

Division Sign Off

Page 1 of

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) 040008

Regulation Number and Section

§ 862.1550 Urinary pH (nonquantitative) test system.

(a)
Identification. A urinary pH (nonquantitative) test system is a device intended to estimate the pH of urine. Estimations of pH are used to evaluate the acidity or alkalinity of urine as it relates to numerous renal and metabolic disorders and in the monitoring of patients with certain diets.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.