(587 days)
For the in-vitro diagnostic quantitative determination of free and protein bound salivary cortisol in human saliva as an aid in the assessment of Cushing Syndrome and Addison's Disease. Measurements of cortisol in saliva are used in the diagnosis and treatment of disorders of the adrenal gland.
The kit consists of a 96 well GARGG (Goat Anti-Rabbit Gamma Globulin) coated microplate (12x8 breakable strip wells), seven ready-to-use calibrators (range 0.1-30 ng/ml) of gravimetrically prepared cortisol from a commercial source (Steraloids) and compared and traced to NIST cortisol, low and high controls, anti-Cortisol (rabbit), 10X concentrated Cortisol (analog)-peroxidase, substrate solution, stop reaction solution and 10X concentrated wash solution.
Here's a breakdown of the acceptance criteria and study information for the Pantex AM/PM Salivary Cortisol EIA Kit, based on the provided text:
The provided text focuses on the analytical performance of the Pantex AM/PM Salivary Cortisol EIA Kit and its equivalence to a predicate device. It demonstrates the device's ability to accurately and reliably measure salivary cortisol levels.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied / Contextual) | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | %CV ≤ 10% (for intra-assay, inter-assay, inter-lot) | Intra-assay: Low (5.4%), Medium (6.7%), High (6.3%) %CVInter-assay: Low (6.3%), Medium (7.2%), High (2.8%) %CVInter-lot: %CV range of 0.9% to 7.4% for various samples and controls. |
| Linearity | Desired Recovery % (Typically 90-110%) | Recovery ranging from 93.0% to 101.4% across 10 concentrations |
| Recovery | Desired Recovery % (Typically 90-110%) | Recovery ranging from 93.7% to 103.9% across 10 spiked samples |
| Reagent Stability | Demonstrated shelf life | 9 months when stored at 2-8°C |
| Sample Stability | Demonstrated stability under various conditions | Room Temperature (20-30°C): Up to 7 days37°C: Up to 7 days2-8°C: Up to 7 days<-15°C (7 freeze/thaw cycles): Up to 7 days<-15°C (Long term): Up to 180 days |
| Open Vial Reagent Stability | Demonstrated open vial stability | 31 days at 2-8°C for reagents and working HRP conjugate solution |
| Limit of Blank (LoB) | (Not explicitly stated acceptance criteria, but a measured value) | 0.0392 ng/mL |
| Limit of Detection (LoD) | (Not explicitly stated acceptance criteria, but a measured value) | 0.0519 ng/mL |
| Limit of Quantitation (LoQ) | (Not explicitly stated acceptance criteria, but a measured value) | 0.0519 ng/mL |
| Method Comparison (vs. Predicate) | High correlation and acceptable regression statistics | Linear Regression Equation: Y = 1.0269x + 0.0994Correlation (r²): 0.9797 |
| Interferences | No significant interference (recovery near 100%) | Caffeine, Food, Nicotine, Gum, Ethanol: Recoveries generally within 90-110% of control values, indicating no significant interference. |
| Analytical Specificity (Cross-Reactivity) | Low cross-reactivity for other steroids (except structurally similar ones) | Most C-21, C-19, and C-18 steroids showed <1% cross-reactivity. Notable exceptions: 11-Desoxycortisol (1.8133%), Corticosterone (1.0847%), 6β Hydroxycortisol (1.7177%), Prednisone (1.0874%), Prednisolone (25.9001%). (The document highlights Prednisolone as a "potential interfering substance"). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility:
- Intra-assay: 20 replicates for low, medium, and high samples.
- Inter-assay: Mean of average duplicates for 12 separate assays.
- Inter-lot: Duplicate measurements of 5 saliva pools and 3 saliva controls using 3 different lots.
- Repeatability: 3 saliva pools tested over 20 days (2 assays/day).
- Linearity: 10 sample concentrations (dilutions).
- Recovery: 10 saliva samples.
- Expected Reference Values (for establishing normal range): 152 male saliva samples and 152 female saliva samples (Total 304 samples).
- Detection Limits (LoB, LoD, LoQ): 120 measurements of "cortisol free free salvia" (clarified as cortisol-free saliva) and low-level cortisol samples.
- Analytical Specificity/Cross Reactivity: Each compound tested at 10,000 ng/mL (or 1000 ng/mL for some) in an unspecified number of samples.
- Method Comparison: 160 samples compared between the new device and the predicate device.
- Interferences Studies: 3 levels of Cortisol (low, medium, high) spiked with high concentrations of 5 interfering substances (alcohol, caffeine, nicotine, food, gum extracts). The number of individual replicates per interferent is detailed in the tables (typically 4 levels of interferent tested with each of the 3 cortisol pools).
Data Provenance: The document does not explicitly state the country of origin of the data or whether the samples were retrospective or prospective, except for the "Expected Reference Values" study which collected 304 samples (presumably from individuals) to establish a new reference range. Given the context of a 510(k) submission, these studies are typically conducted internally or by contract research organizations (CROs) for the device manufacturer.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The device is an in-vitro diagnostic (IVD) assay for quantitative measurement of salivary cortisol. The "ground truth" for such devices is typically established through:
- Reference materials: Calibrators and controls are traced to NIST cortisol.
- Known concentrations: For linearity, recovery, and interference studies, known concentrations of cortisol or interferents are added to samples.
- Comparison to a legally marketed predicate device: This is a key method for demonstrating substantial equivalence.
Therefore, for the analytical performance studies, no external human experts were used to establish "ground truth" in the way a radiologist would read an image. The ground truth relies on laboratory standards, analytical methods, and comparison to an established device.
4. Adjudication Method for the Test Set
Not applicable. This is an in-vitro diagnostic test, not a subjective interpretation task requiring adjudication by human readers.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. The device is a quantitative immunoassay, not an AI-assisted diagnostic intended for human reader interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the studies presented are standalone performance evaluations of the assay itself. The Pantex AM/PM Salivary Cortisol EIA Kit is an automated/semi-automated laboratory test using an enzyme immunoassay principle; its performance is determined by the output of the instrument reading the optical density, not by human interpretation of individual cases. It functions as an "algorithm only" in the sense that it provides a quantitative result based on chemical reactions and optical measurement, without human clinical interpretation being part of the device's performance claim.
7. The Type of Ground Truth Used
The ground truth for the analytical performance studies primarily relied on:
- Known concentrations/reference standards: For precision, linearity, recovery, detection limits, and analytical specificity, the accuracy is determined against samples with known, carefully prepared concentrations or certified reference materials (e.g., NIST cortisol).
- Comparison to a predicate device: For method comparison, the reference is the performance of the legally marketed predicate device (Salimetrics HS Salivary Cortisol EIA Kit).
- Spiked samples: For recovery and interference studies, known amounts of analyte or interferents were spiked into samples.
8. The Sample Size for the Training Set
Not applicable in the context of an enzyme immunoassay kit. There is no machine learning algorithm that requires a "training set" in the conventional sense. The "training" of such a device refers to its development and optimization based on chemical and biological principles, using reagents, controls, and calibration curves as part of its design for accurate measurement.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained above, there isn't a "training set" for an EIA kit in the machine learning context. The "ground truth" during the development and optimization of the kit would be based on fundamental analytical chemistry principles, known concentrations of cortisol, and established practices for immunoassay development and validation.
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K102841 510(k) Summary
| Submitted By: | Pantex, Division of Bio-Analysis, Inc.1701 Berkeley StreetSanta Monica, CA 90404USA(310) 828-7423 |
|---|---|
| Company Contact: | Romulo Garza, Ph.D., President/Senior Scientist |
| Date Summary Prepared: | 4-3-12 |
| Trade Name: | Pantex AM/PM Salivary Cortisol EIA Kit |
| Common Name: | Enzyme immunoassay, cortisol, salivary |
| Regulation Number and Panel: | 862.1205-Clinical Chemistry |
| Classification Product Code: | NHG |
| Classification: | Class II |
| Substantially Equivalent Device: | K011323 Salimetrics HS Salivary Cortisol EIAKit Item No. 1-3102 (single) 96 well kit |
| Device Description: |
A. Test principle.
The basis of the Cortisol Enzyme Immunoassay (EIA) is the quantitative relation between ligand concentration and the proportion of Cortisol (analog) enzyme conjugate bound to the antiserum. For example: Cortisol in the calibrators and unknowns compete with Cortisol coupled to peroxidase for antibody binding sites. After incubation, unbound components are washed away. The reaction between Cortisol peroxidase with the substrate (TMB) produces a blue color. The pre-determined time of incubation the reaction is stopped and a yellow color is formed. The optical density (read at 450 nm) is inversely proportional to the cortisol of calibrators, saliva samples and saliva controls.
B. Kit Description.
The kit consists of a 96 well GARGG (Goat Anti-Rabbit Gamma Globulin) coated microplate (12x8 breakable strip wells), seven ready-to-use calibrators (range 0.1-30 ng/ml) of gravimetrically prepared cortisol from a commercial source (Steraloids) and compared and traced to NIST cortisol, low and high controls, anti-Cortisol (rabbit), 10X concentrated Cortisol (analog)-peroxidase, substrate solution, stop reaction solution and 10X concentrated wash solution.
C. Intended Use/Indications for Use:
For the in-vitro diagnostic quantitative determination of free and protein bound salivary cortisol in human saliva as an aid in the assessment of Cushing Syndrome and Addison's Disease. Measurements of cortisol in saliva are used in the diagnosis and treatment of disorders of the adrenal gland.
Predicate Device:
The predicate device for substantial equivalence in this submission is:
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| Device Name | Salimetrics Salivary Cortisol HS EIA Kit |
|---|---|
| Company | Salimetrics |
| 510(k) reference | K011323 |
Technology Comparison:
| Predicate Device: | New Device: | |
|---|---|---|
| Salimetrics Salivary Cortisol HSEIA Kit(K011323) | Pantex AM/PM SalivaryCortisol EIA Kit(K102841) pending | |
| Indications for use | For the in-vitro diagnosticquantitative determination of freeand protein bound salivarycortisol in human saliva as an aidin the assessment of CushingSyndrome and Addison's Disease.Measurement s of cortisol insaliva are used in the diagnosisand treatment of disorders of theadrenal gland. | For the in-vitro diagnosticquantitative determination offree and protein boundsalivary cortisol in humansaliva as an aid in theassessment of CushingSyndrome and Addison'sDisease.Measurement s of cortisol insaliva are used in the diagnosisand treatment of disorders ofthe adrenal gland. |
| Analyte | Free and Protein-boundCortisol | Free and Protein-boundCortisol |
| Sample Type | Saliva | Saliva |
| Method | Enzyme immunoassay | Enzyme immunoassay |
| Detection Method | Colormetric microplate reader | Colormetric microplate reader |
| Test Principle | Cortisol in the sample competeswith Cortisol-enzyme conjugatefor binding sites to antibodybound to a microwell. Unboundcomponents are washed away andenzyme is measured by a coloredreaction with the TMB substrate. | Cortisol in the samplecompetes with cortisol-enzyme conjugate for bindingsites to the antibody (rabbitanti cortisol) bound to aGARGG microplate.Unbound components arewashed away and enzyme ismeasured by a coloredreaction with the TMBsubstrate. |
| Calculations | Quantitative determinationwith standard curve | Quantitative determinationwith standard curve |
| Quality Control | Use of reference controls isrecommended | Use of reference controls isrecommended |
| Analytical MeasuringRange (AMR) | 0.12 ng/ml - 30.0 ng/ml | 0.1 ng/ml - 30.0 ng/ml |
| Expected Values(Normal range) | N=192Ages: 18-70AM range: 0.8 - 15.5 ng/mlPM range: <0.12 - 3.6 ng/ml | N=152Ages: 23 - 68AM range: 2.58 – 12.69 ng/mlPM range: 0.25 -2.96 ng/ml |
| Limits of Detection | Limit of Blank (LoB)not calculated | Limit of Blank (LoB)0.0392 ng/ml |
| Limit of Detection (LoD)not calculatedLimit of Quantitation (LoQ)not calculated | Limit of Detection (LoD)0.0519 ng/mlLimit of Quantitation (LoQ)0.0519 ng/ml | |
| Saliva Collection Device | Polypropylene vials andSalimetrics oral swab (SOS), Item# 5001.02 | VWR Sample Mailing TubeCat #16465-260 |
| Interferences | Information not available inSalimetric's package insert | An in-vitro spiking study withhigh doses of caffeine, food,nicotine, alcohol and chewinggum did not reveal significantinterference in themeasurement of cortisol insaliva using the PantexAM/PM Salivary Cortisol EIAKit Cat #631. |
| Stability and Storage ofKit Reagents (open vial) | Stated as stable at 2°-8°C until thekit's expiration date | The stability of the opened kitreagents were determined tobe 31 days when stored at 2°-8°C using Pantex AM/PMSalivary Cortisol EIA Kit Cat#631 |
{2}------------------------------------------------
Test Summary:
Performance Characteristics-
The performance characteristics of Pantex AM/PM Salivary Cortisol Enzyme Immunoassay were based on evaluations by the following analytical performance tests.
- I. Analytical Performance Precision/Repeatability Intra-assay Inter-assay Inter-lot variation Linearity Recovery Traceability, Reagent Stability, Sample Stability and Expected values Detection Limits Analytical Specificity/Cross Reactivity II.Method Comparison
- III. Interferences
- I. Analytical Performance
- a. Precision/Reproducibility
- (i) The intra-assay precision was determined from 20 replicates of low, medium and high samples.
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| Sample | N | Mean (ng/mL) | StandardDeviation (ng/mL) | %CV |
|---|---|---|---|---|
| Low | 20 | 0.627 | 0.034 | 5.4 |
| Medium | 20 | 3.995 | 0.266 | 6.7 |
| High | 20 | 25.232 | 1.579 | 6.3 |
- (ii) The inter-assay precision was determined from the mean of average duplicates for twelve (12) separate assays.
| Sample | N | Mean (ng/mL) | StandardDeviation (ng/mL) | %CV |
|---|---|---|---|---|
| Low | 12 | 0.587 | 0.037 | 6.3 |
| Medium | 12 | 4.163 | 0.301 | 7.2 |
| High | 12 | 25.126 | 0.712 | 2.8 |
- (iii) The inter-lot or between-lot variation was determined by duplicate measurements of five (5) pools of saliva samples and three (3) saliva controls using three (3) different lots. The results of intra-assay, inter-assay and inter-lot variation concluded a %CV of ≤10% for each sample tested.
| Salivasamples | Lot #012 | Lot #013 | Lot #014 | Inter-lot | Inter-lot | Inter-lot |
|---|---|---|---|---|---|---|
| ID | Mean(ng/ml) | Mean(ng/ml) | Mean(ng/ml) | Mean(ng/ml) | Std.Dev.(ng/ml) | CV(%) |
| 20 | 4.65 | 4.45 | 4.79 | 4.64 | 0.164 | 3.5 |
| 21 | 0.67 | 0.61 | 0.71 | 0.67 | 0.049 | 7.4 |
| 22 | 2.02 | 1.95 | 2.09 | 2.02 | 0.069 | 3.4 |
| 23 | 4.75 | 4.69 | 4.76 | 4.73 | 0.041 | 0.9 |
| 24 | 2.01 | 1.99 | 2.04 | 2.01 | 0.026 | 1.3 |
| 25 | 3.64 | 3.67 | 3.71 | 3.68 | 0.036 | 1.0 |
| LC | 0.98 | 0.94 | 1.01 | 0.98 | 0.036 | 3.7 |
| NC | 5.21 | 5.31 | 5.49 | 5.34 | 0.140 | 2.6 |
| HC | 10.79 | 10.13 | 10.52 | 10.48 | 0.329 | 3.1 |
- (iv) Repeatability
This study was conducted during 4 days of familiarization period and 20 days of testing. Two assays were performed daily with a minimum of 2 hours between assays. Three (3) different reagents lots and three (3) saliva pools were used for the study (Low, medium and high concentration). The pools were aliquoted and frozen until day of assay.
| Repeatability Low Concentration | |
|---|---|
| Concentration (ng/ml) | 0.600 |
| Standard Deviation | 0.0141 |
| (I) (User Variance/Claim Variance) x R | 62.695 |
| (II) Critical Chi-square | 65.171 |
| Claim Rejected (I>II) | No |
| Claim Accepted (I Yes |
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| Precision Low Concentration Pool | ||
|---|---|---|
| Standard Deviation, SD) | (% Coefficient of Variation CV) | |
| Within Run | 0.0224 | 3.79 |
| Between Run | 0.0462 | 7.80 |
| Repeatability | 0.0162 | 2.73 |
| Total Device Precision | 0.0538 | 9.09 |
.
and the comments of the comments of the comments of
| Repeatability Medium Concentration | |
|---|---|
| Concentration (ng/ml) | 4.0 ng/ml |
| Standard Deviation | 0.0894 |
| (I) (User Variance/Claim Variance) x R | 63.073 |
| (II) Critical Chi-square | 65.171 |
| Claim Rejected (I>II) | No |
| Claim Accepted (I Yes |
| Precision Medium Concentration Pool | ||
|---|---|---|
| Standard Deviation, SD) | (% Coefficient of Variation CV) | |
| Within Run | 0.1475 | 3.60 |
| Between Run | 0.0514 | 1.26 |
| Repeatability | 0.1025 | 2.50 |
| Total Device Precision | 0.1869 | 4.56 |
| Repeatability High Concentration | |
|---|---|
| Concentration (ng/ml) | 25 ng/ml |
| Standard Deviation | 0.5477 |
| (I) (User Variance/Claim Variance) x R | 62.035 |
| (II) Critical Chi-square | 65.171 |
| Claim Rejected (I>II) | No |
| Claim Accepted (I Yes |
| Precision High Concentration Pool | ||
|---|---|---|
| Standard Deviation, SD | (% Coefficient of Variation CV) | |
| Within Run | 0.4442 | 1.176 |
| Between Run | 0.2915 | 1.15 |
| Repeatability | 0.62276 | 2.46 |
| Total Device Precision | 0.8185 | 3.24 |
.
{5}------------------------------------------------
b. Linearity
Ten (10) sample concentrations that span the assay measuring range were performed Per EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures.
S=10 samples (dilutions) Concentration = (C1V1+C10V10)/(V1+V10)
| C1ng/ml | V1ng/ml | C10ng/ml | V10ng/ml | CalculatedConcentrationng/ml | ObtainedConcentrationng/ml | Recovery% | |
|---|---|---|---|---|---|---|---|
| 1 | 0.093 | * | 0.100 | 0.093 | 93.0 | ||
| 2 | 0.093 | 0.889 | 33.788 | 0.111 | 3.833 | 3.729 | 97.3 |
| 3 | 0.093 | 0.778 | 33.788 | 0.222 | 7.573 | 7.620 | 100.6 |
| 4 | 0.093 | 0.667 | 33.788 | 0.333 | 11.313 | 10.842 | 95.8 |
| 5 | 0.093 | 0.556 | 33.788 | 0.444 | 15.054 | 14.350 | 95.3 |
| 6 | 0.093 | 0.444 | 33.788 | 0.556 | 18.827 | 18.313 | 97.3 |
| 7 | 0.093 | 0.333 | 33.788 | 0.667 | 22.568 | 21.547 | 95.5 |
| 8 | 0.093 | 0.222 | 33.788 | 0.778 | 26.308 | 24.694 | 93.9 |
| 9 | 0.093 | 0.111 | 33.788 | 0.889 | 30.048 | 30.459 | 101.4 |
| 10 | * | 35.000 | 33.788 | 96.5 |
*Targets of low and high sample concentrations
c. Recovery:
Ten (10) saliva samples containing different levels of endogenous cortisol were spiked with known quantities of cortisol and assayed.
| Sample | Endogenous(ng/ml) | Added(ng/ml) | Expected(ng/ml) | Observed(ng/ml) | Recovery(%) |
|---|---|---|---|---|---|
| 1 | 0.493 | 0.250 | 0.743 | 0.739 | 99.5 |
| 2 | 0.878 | 0.500 | 1.378 | 1.291 | 93.7 |
| 3 | 1.551 | 1.000 | 2.551 | 2.641 | 103.5 |
| 4 | 1.850 | 2.000 | 3.850 | 3.958 | 102.8 |
| 5 | 0.936 | 4.000 | 4.936 | 4.951 | 100.3 |
| 6 | 1.042 | 8.000 | 9.042 | 9.394 | 103.9 |
| 7 | 0.691 | 16.000 | 16.691 | 17.165 | 102.8 |
| 8 | 0.622 | 20.000 | 20.622 | 19.997 | 97.0 |
| 9 | 2.057 | 24.000 | 26.057 | 24.938 | 95.7 |
| 10 | 0.348 | 28.000 | 28.348 | 28.943 | 102.1 |
d. Traceability/Reagent Stability/Sample Stability/Expected Values
The calibrators and controls are prepared from stock cortisol (Steraloids) and are gravimetrically weighed and prepared. Concentration of stock cortisol (Steraloids) concentrations were confirmed by comparison to NIST cortisol (y=1.029 x-0.2195. R20.9924)
{6}------------------------------------------------
Summary of the stability results
Real time stability studies are conducted to determine the reagent and kit shelf life (expiration date). Expiration date of the Pantex AM/PM Salivary Cortisol EIA Kit. Cat 631, is determined by results of shelf life studies and is based on the reagent that has the shorter assigned expiration day.
-
- The reagents stored at 2-8°C are stable for 9 months; therefore, the expiration date of the kit components is established at 9 months from the manufacturing date. We are basing the 9 month stability claim based on the results obtained with the real time stability study when stored at 2-8°C, supported by the reagents stored at room temperature (20 -28°C) and in reference to the stress chart that predicts reagents year stability at +5℃, by Kennon, L. "Use of models in determining chemical pharmaceutical stability".
Sample stability
| 1 ปี 1 ปี 2017 คนนิสเทคร กิน ที่ 11 ของแล้ว ค.ศ. 2017 ค.ศ. 2010 พ.ศ. 25 เมตร พ.ศ. 2010 พ.ศ. 25 | ||||||
|---|---|---|---|---|---|---|
| Storage | Room | 37 °C | 2-8 °C | <-15 °C | <- 15 ° C | |
| Temperature | (7 freeze / thaw | (Long term) | ||||
| 20 - 30 °C | cycles) | |||||
| Stability | Up to 7 days | Up to 7 | Up to 7 | Up to 7 days | Up to 180 days | |
| days | days |
Four (4) stress conditions on freshly collected saliva revealed the following:
Open vial and working Cortisol-HRP Conjugate solution stability determination.
| Condition | Stability | Storage Temperature |
|---|---|---|
| Reagents. Open vial stability | 31 days | 2-8 °C |
| Working Cortisol-HRP conjugate solution | 31 days | 2-8 °C |
Expected Reference Values:
The reference range was re-established by testing 152 male saliva samples and 152 female samples to have an equal number of male and female samples. The reference range and median were recalculated using CLSI C28-A3 as a guide. The following tables indicate the summary of the results
AM Expected Values:
| Subjects(Number) | Subjects(Gender) | Age(Years) | AM Median(ng/mL) | AM Range(ng/mL) |
|---|---|---|---|---|
| 152 | 76 Males76 Females | 23-68 | 6.70 | 2.58 - 12.69 |
PM Expected Values:
| Subjects(Number) | Subjects(Gender) | Age(Years) | PM Median(ng/mL) | PM Range(ng/mL) |
|---|---|---|---|---|
| 152 | 76 Males76 Females | 23-68 | 0.58 | 0.25 - 2.96 |
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e. Detection Limits
The LoB (limit of the blank), the LoD (limit of detection) and the LoO (limit of quantitation) were determined by generating one hundred and twenty (120) measurements each of "cortisol free free salvia and low level (<0.1 ng/ml) cortisol samples (Reference, CLSI EP17-A, protocols for Determination of Limits of Detection and Limits of Quantitation).
| Limits of Blank(LoB)ng/mL | Limits of Detection(LoD)ng/mL | Limits of Quantitation(LoQ)ng/mL |
|---|---|---|
| 0.0392 | 0.0519 | 0.0519 |
f. Analytical Specificity/Cross Reactivity
Cross-reactivity was determined by testing those compounds most like to interfere with the Pantex AM/PM Salivary Cortisol E1A Kit. The specificity of the antiserum was evaluated by evaluating the cross-reactivity expressed as ratios of concentration of unlabeled cortisol over the compound that displaces 50% of cortisol-enzyme conjugate from the antiserum.
| Compound | Spiked Concentration | % Cross-reactivity |
|---|---|---|
| C-21 Steroids | ||
| Cortisol | 10,000 ng/ml | 100.0000 |
| 17-OH-Progesterone | 10,000 ng/ml | 0.0284 |
| Pregnenolone | 10,000 ng/ml | 0.0038 |
| 17-OH-Pregnenolone | 10,000 ng/ml | 0.0066 |
| Progesterone | 10,000 ng/ml | 0.0079 |
| Desoxycorticosterone | 10,000 ng/ml | 0.0517 |
| 11-Desoxycortisol | 10,000 ng/ml | 1.8133 |
| Dexamethasone | 10,000 ng/ml | 0.0164 |
| Cortisone | 10,000 ng/ml | 0.7600 |
| Corticosterone | 10,000 ng/ml | 1.0847 |
| Aldosterone | 10,000 ng/ml | 0.0070 |
| C-19 Steroids | ||
| Androstenedione | 10,000 ng/ml | 0.0038 |
| Testosterone | 10,000 ng/ml | 0.0042 |
| 5αDHT | 10,000 ng/ml | 0.0019 |
| DHEA-SO4 | 10,000 ng/ml | 0.0031 |
| Androstanedione | 10,000 ng/ml | 0.0028 |
| C-18 Steroids | ||
| Estradiol 17β | 10,000 ng/ml | 0.0024 |
| Estradiol 17α | 10,000 ng/ml | 0.0003 |
| Estrone | 10,000 ng/ml | 0.0010 |
| Estriol | 10,000 ng/ml | 0.0015 |
| Other structurally related steroids | ||
| Dehydroisoandrosterone | 1000 ng/ml | 0.0076 |
| 6αmethyl-17-Hydroxyprogesterone | 1000 ng/ml | 0.1427 |
| 6β Hydroxycortisol | 1000 ng/ml | 1.7177 |
| Prednisone | 1000 ng/ml | 1.0874 |
| Prednisolone | 1000 ng/ml | 25.9001 |
At >10% cross reaction prednisolone is a potential interfering substance.
{8}------------------------------------------------
- II. Method Comparison Studies
Tests were conducted for comparison between the Pantex AM/PM Salivary Cortisol EIA Kit, Cat and the predicate assay , Salimetrics HS Salivary Cortisol results of 160 samples were compared . Comparison of the Pantex AM/PM Salivary Cortisol EIA Kit (new device) and the Salimetrics HS Salivary Cortisol EIA (predicate) demonstrated acceptable regression and correlation statistics and appears to be substantially equivalent to the FDA cleared predicate device.
| Pantex AM/PM Salivary Cortisol EIA versus Salimetrics HS Salivary Cortisol EIA | |
|---|---|
| Linear Regression equation | $Y = 1.0269x + 0.0994$ |
| Correlation (r²) | 0.9797 |
III. Interferences Studies.
An in-vitro experiment was performed by spiking three (3) levels of Cortisol (low, medium and high) with high concentrations of five (5) potentially interfering substances: alcohol, coffee (as caffeine), cigarette (as nicotine) and food and gum extracts. The results obtained appear to demonstrate no significant interference of the substances tested in this study with the measurement of Cortisol in saliva using the Pantex AM/PM Salivary Cortisol EIA Kit, Cat #631.
In-vitro experiment results:
| Pools | Potential Interferent Caffeine Added (ug/mL) | Obtained Value (ng/mL) | Recovery from Control (%) |
|---|---|---|---|
| Low Pool | 0 | 1.420 | 100 |
| Low Pool | 800 | 1.444 | 101.7 |
| Low Pool | 400 | 1.438 | 101.3 |
| Low Pool | 200 | 1.477 | 104.0 |
| Middle Pool | 0 | 4.932 | 100 |
| Middle Pool | 800 | 5.143 | 104.3 |
| Middle Pool | 400 | 5.063 | 102.7 |
| Middle Pool | 200 | 4.539 | 92.0 |
| High Pool | 0 | 28.302 | 100 |
| High Pool | 800 | 26.010 | 91.9 |
| High Pool | 400 | 26.811 | 94.7 |
| High Pool | 200 | 27.563 | 97.4 |
{9}------------------------------------------------
| Pools | Potential InterferentFood Added(mg/mL) | Obtained Value(ng/mL) | Recovery fromControl(%) |
|---|---|---|---|
| Low Pool | 0.000 | 1.345 | 100 |
| 426 | 1.340 | 99.6 | |
| 213 | 1.332 | 99.0 | |
| 106.5 | 1.291 | 96.0 | |
| Middle Pool | 0.000 | 4.739 | 100 |
| 426 | 4.730 | 99.8 | |
| 213 | 4.834 | 102.0 | |
| 106.5 | 4.835 | 102.0 | |
| High Pool | 0.000 | 26.447 | 100 |
| 426 | 27.495 | 104.0 | |
| 213 | 26.283 | 99.4 | |
| 106.5 | 28.055 | 106.1 |
| Pools | Potential Interferent NicotineAdded (ug/mL) | Obtained Value (ng/mL) | Recovery from Control (%) |
|---|---|---|---|
| Low Pool | 0 | 1.362 | 100 |
| 800 | 1.436 | 101.7 | |
| 600 | 1.437 | 101.3 | |
| 400 | 1.4345 | 104.0 | |
| 200 | 1.317 | 96.7 | |
| Middle Pool | 0 | 4.871 | 100 |
| 800 | 5.243 | 107.6 | |
| 600 | 5.258 | 107.9 | |
| 400 | 5.087 | 104.4 | |
| 200 | 5.155 | 105.8 | |
| High Pool | 0 | 25.503 | 100 |
| 800 | 27.033 | 106.0 | |
| 600 | 26.397 | 103.5 | |
| 400 | 25.642 | 100.6 | |
| 200 | 24.928 | 97.8 |
.
.
·
·
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| Pools | Potential InterferentGum Added(mg/mL) | Obtained Value(ng/mL) | Recovery fromControl(%) |
|---|---|---|---|
| Low Pool | 0 | 1.289 | 100 |
| 270 | 1.346 | 104.4 | |
| 135 | 1.286 | 99.8 | |
| 67.5 | 1.248 | 96.8 | |
| 33.75 | 1.280 | 99.3 | |
| Middle Pool | 0 | 4.843 | 100 |
| 270 | 4.957 | 102.4 | |
| 135 | 4.845 | 100 | |
| 67.5 | 4.712 | 97.3 | |
| 33.75 | 4.764 | 98.4 | |
| High Pool | 0 | 28.367 | 100 |
| 270 | 29.419 | 103.7 | |
| 135 | 29.247 | 103.1 | |
| 67.5 | 27.870 | 98.3 | |
| 33.75 | 28.216 | 99.5 |
| Pools | Potential InterferentEthanol Added(%) | Obtained Value(ng/mL) | Recovery fromControl(%) |
|---|---|---|---|
| Low Pool | 0 | 1.268 | 100 |
| 0.025 | 1.267 | 104.4 | |
| 0.050 | 1.230 | 99.8 | |
| 0.100 | 1.213 | 96.8 | |
| Middle Pool | 0 | 4.539 | 100 |
| 0.025 | 4.403 | 102.4 | |
| 0.050 | 4.320 | 100 | |
| 0.100 | 4.490 | 97.3 | |
| High Pool | 0 | 26.272 | 100 |
| 0.025 | 28.362 | 108.0 | |
| 0.050 | 28.744 | 109.4 | |
| 0.100 | 28.750 | 109.4 |
Concluding Statement:
Taken together, the performance characteristics, comparison studies with a predicate device and acceptable statistical performance studies in this 510(k) submission demonstrates that the Pantex AM/PM Salivary Cortisol EIA Kit, Cat #631, is safe and effective for its intended use and is substantially equivalent to the predicate device.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration
10903 New Hampshire Avenue Silver Spring, MD 20993
Pantex, Division of Bio-Analysis, Inc c/o Romulo Garza 1701 Berkeley Street Santa Monica, CA 90404
MAY - 8 2012
Re: K102841 ·
Trade Name: Pantex AM/PM Salivary Cortisol Enzyme Immunoassay Regulation Number: 21 CFR §862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Regulatory Class: Class II Product Codes: NHG Dated: April 3, 2012 Received: May 2, 2012
Dear Dr. Garza:
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 (1 wr 1), it 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please 11 Jou ability of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/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) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours,
N.
Steven H. Liao, Ph.D.
Courney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
K102841 510(k) Number (if known):
Device Name: Pantex AM/PM Salivary Cortisol Enzyme Immunoassay
Indications For Use:
For the in-vitto diagnostic quantitative determination of free and protein bound salivary cortisol in human saliva as an aid in the assessment of Cushing Syndrome and Addison's Disease. Measurements of cortisol in saliva are used in the diagnosis and treatment of disorders of the adrenal gland.
× Prescription Use (21 CFR Part 801 Subpart D) .
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Ruto Chem
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) 102841
Page 1 of 1
§ 862.1205 Cortisol (hydrocortisone and hydroxycorticosterone) test system.
(a)
Identification. A cortisol (hydrocortisone and hydroxycorticosterone) test system is a device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.(b)
Classification. Class II.