QUICKVUE ADVANCE PH AND AMINES GLL TEST
Device Facts
| Record ID | K040008 |
|---|---|
| Device Name | QUICKVUE ADVANCE PH AND AMINES GLL TEST |
| Applicant | Quidel Corp. |
| Product Code | CEN · Clinical Chemistry |
| Decision Date | Apr 29, 2004 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1550 |
| Device Class | Class 1 |
Indications for Use
The test contains two colorimetric qualitative tests for use in the characterization of vaginal fluid samples: 1) a pH test that differentiates vaginal fluid pH < 4.7 from vaginal fluid pH ≥ 4.7; and 2) a test that detects elevated levels of volatile amines (> 0.5 mM trimethylamine) in vaginal fluid. The QuickVue Advance pH and Amines gII 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 Story
QuickVue Advance pH and Amines gII test is a qualitative, colorimetric diagnostic tool for bacterial vaginosis. Input: vaginal fluid sample. Operation: pH test uses colorimetric indicator to differentiate pH < 4.7 vs ≥ 4.7; amines test uses BCG film with dried alkali (potassium hydroxide analog) to detect volatile amines > 0.5 mM. Output: visual color change (greenish-blue plus sign) against yellow background if positive; procedural control dot confirms valid test. Used in physician office laboratories or clinical settings by healthcare professionals. Results aid clinical diagnosis of bacterial vaginosis. Benefits: rapid, point-of-care assessment of vaginal fluid characteristics.
Clinical Evidence
Multi-center study of 464 post-pubertal women. Compared QuickVue Advance to Amsel criteria (gold standard) and Nugent Gram stain for reconciliation. Results: 92.0% sensitivity and 95.0% specificity (reconciled). Physician office laboratory study (n=352) showed 99% overall accuracy across negative, positive, and moderate positive samples.
Technological Characteristics
Hand-held card with colorimetric indicators. pH test: nitrazine yellow. Amine test: bromocresol green and sodium aluminate (alkali ink). Qualitative visual readout. No instrumentation required. Standalone device.
Indications for Use
Indicated for post-pubertal women as an aid in the diagnosis of bacterial vaginosis by detecting elevated vaginal pH (≥ 4.7) and volatile amines (> 0.5 mM). Intended for use by healthcare professionals in a clinical setting.
Regulatory Classification
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.
Predicate Devices
- FemExam TestCard test (K962718)
Related Devices
- K962718 — FEMEXAM TESTCARD · Litmus Concepts, Inc. · Feb 7, 1997
- K091287 — VS-SENSE TEST · Common Sense , Ltd. · Aug 31, 2009
Submission Summary (Full Text)
{0}
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE
A. 510(k) Number:
K040008
B. Purpose for Submission:
Modified product
C. Analyte:
pH and volatile amines
D. Type of Test:
Qualitative colorimetric assay
E. Applicant:
Quidel Corporation
F. Proprietary and Established Names:
QuickVue Advance pH and Amines gII Test
G. Regulatory Information:
1. Regulation section:
21 CFR §862.1550 Urinary pH (nonquantitative) test system
2. Classification:
Class 1
3. Product Code:
CEN
4. Panel:
Chemistry (75)
H. Intended Use:
1. Intended use(s):
The test contains two colorimetric qualitative tests for use in the characterization of vaginal fluid samples: 1) a pH test that differentiates vaginal fluid pH < 4.7 from vaginal fluid pH ≥ 4.7; and 2) a test that detects elevated levels of volatile amines (> 0.5 mM trimethylamine) in vaginal fluid.
2. Indication(s) for use:
"The QuickVue Advance pH and Amines gII 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."
3. Special condition for use statement(s):
The product is intended for use in a health-care setting.
4. Special instrument Requirements:
None.
I. Device Description:
The device is a hand-held card with two defined test areas that contain colorimetric indicators that change color when in contact with undiluted vaginal fluid. It detects
{1}
vaginal $\mathrm{pH} \geq 4.7$ and volatile amines at concentrations $>0.5\mathrm{mM}$ . The $\mathrm{pH}$ test is run by gently rubbing a sterile amine-controlled swab over the entire surface of the $\mathrm{pH}$ test area. The amine test is run second using the same swab, by gently rubbing from the outside of the test circle to the center. Results for both tests should be run after one minute.
# J. Substantial Equivalence Information:
1. Predicate device name(s): FemExam TestCard Test
2. Predicate K number(s): K962718
3. Comparison with predicate:
The device is similar to the predicate in the following ways: they have the same intended use and sensitivity, use the same test indicators, use the same test format, use the same clinical sample, and have the same number of steps in the procedure (two - one per test).
The differences between the tests are: the proposed test is read one minute after application of the sample while the predicate test is read two minutes after application, and the procedural controls and positive indicators are a different shape and color than the predicate.
K. Standard/Guidance Document Referenced (if applicable):
| Criteria | Reference: |
| --- | --- |
| Precision | NCCLS EP5-T2: Precision performance of clinical chemistry devices- second edition: tentative guideline (1992) |
| Amsel criteria for diagnosis of bacterial vaginosis | Amsel R, PA Totten, CA Spiegel, KC Chen, D Eschenbach, KK Holmes. 1983. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 74:14. |
| Nugent Gram Stain method and interpretation | Nugent R., MJ Krohn, SL Miller. 1991. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J. Clin. Microbiology 29:297 |
| Normal vaginal pH levels | Nyirjesy P. 2001. Chronic vulvovaginal candidiasis. Am. Fam. Physician 63:697 |
| Normal vaginal amine levels | Wolrath H, U Forsum, PG Larsson, H Borén. 2001. Analysis of bacterial vaginosis-related amines in vaginal fluid by gas chromatography and mass spectrometry. J. Clin. Microbiology 39:4026 |
# L. Test Principle:
Both the pH and amine test rely on colorimetric pH indicators that produce a visual color change within one minute of sample application. The pH test utilizes the indicator nitrazine yellow. When the pH test area comes in contact with a vaginal fluid sample with a $\mathrm{pH} \geq 4.7$ , a distinct greenish-blue plus sign appears against a
{2}
Page 3 of 8
yellow background, along with a greenish-blue procedural dot. When the vaginal fluid pH<4.7 only the procedural dot appears against the yellow background. Bromocresol green and an alkali ink containing sodium aluminate are utilized in the amine test. The test area produces a distinct greenish-blue plus sign and a greenish-blue procedural dot against a yellow background when vaginal fluids containing volatile amines at concentrations above 0.5 mM are present. Only the procedural dot appears when volatile amines are not present. In all cases, if the procedural dot does not appear the test is not valid.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
The analytical precision of the QuickVue Advance was established by a range of prepared solutions (listed in table) to represent samples. One operator used ten replicates of one lot of Advance reagents at each level. The test was interpreted at one minute and quantified using an internal color score chart where a score of 0.5 is the minimum color intensity for a clearly visible positive test and where 0 and 0.25 are negative. Inter-assay variation was tested as above over 4 days.
Intra-Assay Precision: QuickVue Advance pH Test
| pH Standards | Average Color Score | Standard Deviation | % CV | Minimum Test Score | Maximum Color Score |
| --- | --- | --- | --- | --- | --- |
| 4.0 | 0 | 0 | N/A | 0 | 0 |
| 4.4 | 0.15 | 0.13 | 86% | 0 | 0.25 |
| 4.8 | 1.08 | 0.24 | 22% | 0.75 | 1.5 |
| 5.5 | 4.10 | 0.32 | 8% | 4 | 5 |
Intra-Assay Precision: QuickVue Advance Amines Test
| Amine Standards | Average Color Score | Standard Deviation | % CV | Minimum Test Score | Maximum Color Score |
| --- | --- | --- | --- | --- | --- |
| 0 mM | 0.10 | 0.13 | 129% | 0 | 0.25 |
| 0.25 mM | 0.25 | 0.00 | 0% | 0.25 | 0.25 |
| 0.50 mM | 0.50 | 0.00 | 0% | 0.50 | 0.50 |
| 1.00 mM | 0.88 | 0.13 | 15% | 0.75 | 1.00 |
Inter-assay Precision: QuickVue Advance pH Test
| | Average Color Score (n=10) | | | | Precision | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| pH Standards | Day 1 | Day 2 | Day 3 | Day 4 | Mean | Std Dev | %CV |
| 4.0 | 0 | 0 | 0 | 0 | 0 | 0 | --- |
| 4.4 | 0.15 | 0.18 | 0.23 | 0.28 | 0.21 | 0.06 | 27% |
{3}
Page 4 of 8
| | Average Color Score (n=10) | | | | Precision | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| pH Standards | Day 1 | Day 2 | Day 3 | Day 4 | Mean | Std Dev | %CV |
| 4.8 | 1.08 | 1.65 | 1.55 | 1.45 | 1.43 | 0.25 | 18% |
| 5.5 | 4.10 | 4.30 | 4.00 | 4.00 | 4.10 | 0.14 | 3% |
| | | | | Inter-Assay Variation: 16.0% | | | |
Inter-assay Precision: QuickVue Advance Amines Test
| | Average Color Score (n=10) | | | | Precision | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Amines Standards | Day 1 | Day 2 | Day 3 | Day 4 | Mean | Std Dev | %CV |
| 0 mM | 0.10 | 0.13 | 0.05 | 0.03 | 0.08 | 0.05 | 61% |
| 0.25 mM | 0.25 | 0.25 | 0.23 | 0.23 | 0.24 | 0.01 | 6% |
| 0.50 mM | 0.50 | 0.50 | 0.50 | 0.50 | 0.50 | 0 | 0% |
| 1.00 mM | 0.88 | 0.88 | 0.90 | 0.93 | 0.89 | 0.02 | 3% |
| | | | | Inter-Assay Variation: 17.5% | | | |
b. Linearity/assay reportable range:
Not applicable, test as used clinically is qualitative.
c. Traceability (controls, calibrators, or method):
Not applicable.
d. Detection limit:
Limits of detection were determined by prepared solutions spanning negative through borderline threshold through low positive; levels tested are in the tables below. Twenty-one (21) replicates of each level were evaluated using three different lots of QuickVue Advance tests. Relative color scores were determined using an internal color score chart where a score of 0.5 is the minimum color intensity for a clearly visible positive test. Data is represented here qualitatively.
Limits of Detection: QuickVue Advance pH Study
| | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- |
| pH Level | Correct Call | % Correct | Correct Call | % Correct | Correct Call | % Correct |
| 4.0 | Neg | 100 | Neg | 100 | Neg | 100 |
| 4.1 | Neg | 100 | Neg | 100 | Neg | 100 |
| 4.2 | Neg | 100 | Neg | 100 | Neg | 100 |
| 4.3 | Neg | 100 | Neg | 100 | Neg | 100 |
| 4.4 | Neg | 100 | Neg | 100 | Neg | 100 |
| 4.5 | Neg | 81 | Neg | 100 | Neg | 62 |
| 4.6 | Neg | 48 | Neg | 52 | Neg | 38 |
| 4.7 | Pos | 100 | Pos | 76 | Pos | 90 |
| 4.8 | Pos | 100 | Pos | 95 | Pos | 100 |
| 4.9 | Pos | 100 | Pos | 100 | Pos | 100 |
{4}
Page 5 of 8
| | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- |
| pH Level | Correct Call | % Correct | Correct Call | % Correct | Correct Call | % Correct |
| 5.0 | Pos | 100 | Pos | 100 | Pos | 100 |
| 5.5 | Pos | 100 | Pos | 100 | Pos | 100 |
## Limits of Detection: QuickVue Advance Amine Study
| | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- |
| Amines Level | Correct Call | % Correct | Correct Call | % Correct | Correct Call | % Correct |
| 0 mM | Neg | 100 | Neg | 100 | Neg | 100 |
| 0.25 mM | Neg | 86 | Neg | 86 | Neg | 95 |
| 0.35 mM | Neg | 43 | Neg | 71 | Neg | 91 |
| 0.50 mM | Pos | 100 | Pos | 100 | Pos | 95 |
| 0.75 mM | Pos | 100 | Pos | 100 | Pos | 100 |
| 1.0 mM | Pos | 100 | Pos | 100 | Pos | 100 |
| 2.0 mM | Pos | 100 | Pos | 100 | Pos | 100 |
| 5.0 mM | Pos | 100 | Pos | 100 | Pos | 100 |
Referencing NCCLS EP5-T2 guidelines, the sponsor established the limit of detection at pH4.7 and amines at 0.50 mM.
## e. Analytical specificity:
To test the specificity of the QuickVue Advance pH and amine test, a variety of over-the-counter vaginal-use products were tested for their ability to interfere with the tests. Negative and positive control solutions were spiked with various concentrations of product; none of the products tested at the concentrations indicated interfered with detection of positives or negative control sample:
## QuickVue Advance pH test Interference Study
| Substance | Negative Control | | | | Positive Control | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Highest Conc Tested w/ No Interference | Number Correct Calls | | | Highest Conc Tested w/ No Interference | Number Correct Calls | | |
| | | Call | n | % | | Call | N | % |
| None | N/A | Neg | 2/2 | 100% | N/A | Pos | 2/2 | 100% |
| K-Y Jelly | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Replens | 20% w/v | Neg | 2/2 | 100% | 4% w/v | Pos | 2/2 | 100% |
| Delfen | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Conceptrol | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Gyne-Lotrim-3 | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vagistat-1 | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Massengil | 2% w/v | Neg | 2/2 | 100% | 0.2% w/v | Pos | 2/2 | 100% |
{5}
Page 6 of 8
| Substance | Negative Control | | | | Positive Control | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Highest Conc Tested w/ No Interference | Number Correct Calls | | | Highest Conc Tested w/ No Interference | Number Correct Calls | | |
| | | Call | n | % | | Call | N | % |
| Summer's Eve | 20% w/v | Neg | 2/2 | 100% | 0.2% w/v | Pos | 2/2 | 100% |
| Vagisil | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vaginex | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vagisil Powder | 4% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
## QuickVue Advance Amine test Interference Study
| Substance | Negative Control | | | | Positive Control | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Highest Conc Tested w/ No Interference | Number Correct Calls | | | Highest Conc Tested w/ No Interference | Number Correct Calls | | |
| | | Call | n | % | | Call | N | % |
| None | N/A | Neg | 2/2 | 100% | N/A | Pos | 2/2 | 100% |
| K-Y Jelly | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Replens | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Delfen | 0.1% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Conceptrol | 0.4% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Gyne-Lotrim-3 | 4% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vagistat-1 | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Massengil | 0.2% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Summer's Eve | 0.02% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vagisil | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vaginex | 20% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
| Vagisil Powder | 4% w/v | Neg | 2/2 | 100% | 20% w/v | Pos | 2/2 | 100% |
## f. Assay cut-off:
The sponsor-identified levels of the assay are a pH 4.7 and an amine concentration of 0.50 mM. These levels correspond to two of the four Amsel criteria, a well-recognized method for diagnosing bacterial vaginosis (see reference above). The Amsel criterion for pH is ≥4.7 while the criterion for amines is the detection of a 'fishy' amines odor when a drop of 10% KOH is added to a sample of vaginal fluid (the "whiff test").
## 2. Comparison studies:
a. Method comparison with predicate device:
Not performed; device was compared to clinically based standard criteria (see below).
b. Matrix comparison:
Not applicable.
## 3. Clinical studies:
A multi-center study established the clinical performance of the device. A total of 464 vaginal fluid samples were collected from post-pubertal women. Approximately 43% of the women had signs or symptoms associated with
{6}
Page 7 of 8
altered vaginal pH and elevated amines. Vaginal fluid was first sampled for the QuickVue Advance tests then sampled for Amsel analysis and Nugent Gram stain assessment.
For a given patient to be considered positive by the Amsel criteria, she had to have 3 of 4 clinical criteria present: elevated pH, detectable volatile amines, 'clue' cells present on microscopic evaluation, and appearance (color, consistency, and amount) of vaginal discharge. To be considered 'positive' by QuickVue Advance in the clinical studies described below, the patient had to have a positive pH test and a positive amines test.
Of the 464 specimens, 302 patients were negative and 162 were positive by the Amsel criteria. The table below presents a comparison of the QuickVue Advance test to the Amsel criteria:
QuickVue Advance Clinical Performance Comparison to Amsel Criteria
| Comparative Method | | Amsel Reference Criteria | |
| --- | --- | --- | --- |
| | Outcome | Positive | Negative |
| Quidel Advance pH and Amines | Positive | 140 | 24 |
| | Negative | 13 | 287 |
Discordant results were reconciled using Nugent Gram Stain method; a score of 7 or more was considered positive for bacterial vaginosis:
QuickVue Advance Clinical Performance Comparison to Amsel Criteria Reconciled by Nugent Gram Stain
| Comparative Method | | Amsel Reference Criteria | |
| --- | --- | --- | --- |
| | Outcome | Positive | Negative |
| Quidel Advance pH and Amines | Positive | 149 | 15 |
| | Negative | 13 | 287 |
Clinical sensitivity and specificity are shown below:
QuickVue Advance Clinical Performance
| | Result | Unreconciled Clinical Criteria | Reconciled Clinical Criteria |
| --- | --- | --- | --- |
| QuickVue Advance Clinical Criteria | Sensitivity | 91.5% | 92.0% |
| | Specificity | 92.3% | 95.0% |
| | Overall | 92.0% | 94.0% |
{7}
Page 8 of 8
In an evaluation of the test in three physician's office laboratories, various operators assessed coded, known specimens over three days with the following results:
Summary of Physician's Office Laboratory Studies
| Sample | % Correct | n |
| --- | --- | --- |
| Negative | 97% | 107/110 |
| Positive | 99% | 117/118 |
| Moderate Pos | 100 % | 120/120 |
| Invalid Result | 100 % | 4/4 |
| Overall | 99 % | 348/352 |
According to the Flesh-Kincaid Grade-Level index, readability of the package insert was Grade 7.6.
4. Clinical cut-off:
The sponsor's determination of a vaginal pH cut-off is based on the Amsel criteria (reference above). The cut-off level for amines is based on studies done to support the predicate device. Vaginal fluid samples from 'whiff test' positive women were tested, and around 90% had amine levels above 0.5 mM.
5. Expected values/Reference range:
Normal vaginal fluid pH is typically 3.8 to 4.5 from although there is individual variation even in healthy women. Pregnancy, menopause, and other health conditions may change vaginal pH. Amines are usually not detectable, or are present at very low concentrations.
N. Conclusion:
The submitted information in this pre-market notification is complete and supports a substantial equivalence decision.
