ARCHITECT CORTISOL ASSAY
Device Facts
| Record ID | K062204 |
|---|---|
| Device Name | ARCHITECT CORTISOL ASSAY |
| Applicant | Seradyn, Inc. |
| Product Code | JFT · Clinical Chemistry |
| Decision Date | Sep 22, 2006 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1205 |
| Device Class | Class 2 |
Indications for Use
The ARCHITECT Cortisol is a chemiluminescent microparticle immunoassay (CIMA) for the quantitative determination of cortisol in human serum, plasma or urine on the ARCHITECT i System. The ARCHITECT Cortisol assay is intended for use as an aid in the diagnosis and treatment of adrenal disorders. The ARCHITECT Cortisol Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of Cortisol in human serum, plasma or urine.
Device Story
ARCHITECT Cortisol is a delayed one-step chemiluminescent microparticle immunoassay (CMIA) used on the ARCHITECT i System. It measures cortisol levels in human serum, plasma, or urine samples. The assay utilizes anti-cortisol coated microparticles and acridinium-labeled cortisol conjugate. The system automates the immunoassay process, providing quantitative results to clinicians. These results assist in the diagnosis and treatment of adrenal disorders. The device is intended for professional use in clinical laboratory settings.
Clinical Evidence
Bench testing only. Precision studies (n=80 replicates per sample) showed total CV <10% for serum and <20% for urine. Linearity confirmed 0.49-65.9 µg/dL. Functional sensitivity (20% CV) established at 0.8 µg/dL (serum) and 1.0 µg/dL (urine). Method comparison against predicate and LC-MS/MS showed high correlation (r ≥ 0.97). Interference and cross-reactivity studies performed per CLSI guidelines.
Technological Characteristics
Heterogeneous chemiluminescent microparticle immunoassay (CMIA). Reagents include anti-cortisol (mouse) coated microparticles and acridinium-labeled cortisol conjugate. Uses Chemiflex® flexible assay protocols. Operates on the ARCHITECT i System. Calibration uses six-level calibrators. Stabilizers include Proclin 300 and sodium azide.
Indications for Use
Indicated for the quantitative determination of cortisol in human serum, plasma, or urine to aid in the diagnosis and treatment of adrenal disorders. For prescription use only.
Regulatory Classification
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.
Predicate Devices
- AXSYM® CORTISOL REAGENTS AND CALIBRATORS (K033731)
Related Devices
- K984520 — NICHOLS ADVANTAGE CHEMILUMINESCENCE CORTISOL IMMUNOASSAY, MODEL 62-7005 · Nichols Institute Diagnostics · Feb 5, 1999
- K202136 — IDS Cortisol · Immunodiagnostic Systems , Ltd. · Apr 13, 2021
- K042689 — NICHOLS ADVANTAGE CORTISOL · Nichols Institute Diagnostics · Dec 9, 2004
- K021218 — ELECSYS CORTISOL TEST SYSTEM · Roche Diagnostics Corp. · Sep 9, 2002
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k062204
B. Purpose for Submission:
New device
C. Measurand:
Cortisol
D. Type of Test:
Quantitative, Chemiluminescent Immunoassay
E. Applicant:
Seradyn, Inc.
F. Proprietary and Established Names:
ARCHITECT Cortisol
ARCHITECT Cortisol Calibrators
G. Regulatory Information:
1. Regulation section:
21CFR §862.1205
21CFR §862.1150
2. Classification: Class II
3. Product code: JFT and JIX
4. Panel: 75 (Chemistry)
H. Intended Use:
1. Intended use(s):
The ARCHITECT Cortisol is a chemiluminescent microparticle immunoassay (CIMA) for the quantitative determination of cortisol in human serum, plasma or urine on the ARCHITECT i System. The ARCHITECT Cortisol assay is intended for use as an aid in the diagnosis and treatment of adrenal disorders.
The ARCHITECT Cortisol Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of Cortisol in human serum, plasma or urine.
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2. Indication(s) for use:
See Intended Use above
3. Special conditions for use statement(s):
Prescription use only
4. Special instrument requirements:
The ARCHITECT Cortisol assay is intended for use with the ARCHITECT i System instruments only (i 2000, i 2000SR).
I. Device Description:
The ARCHITECT Cortisol reagent kit (100 tests/500 tests) contains the following reagents:
- 1 bottle (6.6 mL/27.0 mL) Microparticle Reagent with Anti-Cortisol (mouse) coated Microparticles in buffer with protein stabilizer, Proclin 300 and sodium azide.
- 1 bottle (5.9 mL/26.3 mL) Conjugate Reagent with Cortisol acridinium labeled conjugate in buffer with surfactant stabilizer and Proclin 300.
Other reagents:
- Pre-Trigger solution containing 1.32% (w/v) hydrogen peroxide.
- Trigger solution containing 0.35N sodium hydroxide.
- Wash buffer containing phosphate buffered saline solution. Preservative: antimicrobial agent.
The ARCHITECT Cortisol calibrators contain 6 bottles of 4 mL of calibrators A to F, six different concentrations of purified human Cortisol, with preservatives.
J. Substantial Equivalence Information:
1. Predicate device name(s):
AXSYM Cortisol reagents and calibrators
2. Predicate 510(k) number(s):
k033731
3. Comparison with predicate:
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| Similarities for Cortisol | | |
| --- | --- | --- |
| Item | Device
ARCHITECT Cortisol | Predicate
AxSYM Cortisol |
| Intended Use | ARCHITECT Cortisol is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of cortisol in human serum, plasma or urine on the ARCHITECT i System. It is intended for use as an aid in the diagnosis and treatment of adrenal disorders. | The Cortisol assay is a Fluorescence Polarization Immunoassay (FPIA) for the quantitative measurement of cortisol in human serum, plasma and urine on the AxSYM System to aid in the diagnosis and treatment of adrenal disorders. |
| Calibrator Material | Six levels | Six levels |
| Sample types | Serum, plasma and urine | Serum, plasma and urine |
| Differences for Cortisol | | |
| --- | --- | --- |
| Item | Device
ARCHITECT Cortisol | Predicate
AxSYM Cortisol |
| Methodology | Heterogeneous chemiluminescent microparticle immunoassay (CMIA). | Fluorescence Polarization Immunoassay (FPIA) technology. |
| Expected range | Serum, before 10 am: 3.7-19.4 μg/dL
Serum, after 5 pm: 2.9-17.3 μg/dL
Urine (24 hr): 4.3-176 μg/24 hr | Serum, before 10 am: 4.2-38.4 μg/dL
Serum, after 5 pm: 1.7-16.6 μg/dL
Urine (24 hr): 32-243 μg/24 hr |
| Functional Sensitivity | 1 μg/dL | 1.1 μg/dL |
| Reportable range | Serum and urine: 0.8 to 59.8 μg/dL | Serum and urine: 1.1 to 60 μg/dL |
K. Standard/Guidance Document Referenced (if applicable):
STANDARDS
Title and Reference Number
1. CSLI Guideline, EP5-A Evaluation of Precision Performance of Clinical Chemistry Device; Approved Guideline.
2. CSLI Guideline, EP6-A Evaluation of the Linearity of Quantitative Analytical Methods; Approved Guideline.
3. CSLI Guideline, EP7-A Interference Testing in Clinical Chemistry; Approved Guideline.
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4. CSLI Guideline, EP9-A2 Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline, Second Edition.
5. CSLI Guideline, EP17-A Protocols for Demonstration, Verification, and Evaluation of Limits of Detection and Quantitation; Approved Guideline.
## L. Test Principle:
Cortisol in the sample and anti-cortisol coated paramagnetic microparticles are combined to create a reaction mixture. Cortisol present in the sample binds to the anti-cortisol coated microparticles. After incubation, cortisol acridinium-labeled conjugate is added to the reaction mixture. The cortisol acridinium-labeled conjugate competes for the available binding sites on the anti-cortisol coated microparticles. Following a second incubation, the microparticles are washed, and pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of cortisol in the sample and the RLUs detected by the ARCHITECT i system optics.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
A precision study was performed using CLSI guideline NCCLS EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods. Precision was run on one ARCHITECT i2000 analyzer, and one ARCHITECT i2000SR analyzer, using ARCHITECT Cortisol calibrators, Abbott MCC Controls and patient sample pools. For 20 non-consecutive days, each sample was run in duplicate. After a minimum of two hours within the same day, the samples were re-run in duplicate, resulting in a total of 80 replicates for each control or patient pool. Calibration was performed on day one; no recalibration was needed.
The data show that total $\% \mathrm{CV}$ is less than $10\%$ for both serum and urine samples. A summary of the precision data is shown in the table below:
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| Sample | Instr. | Reagent Lot | n | Mean Conc. ug/dL | Within Run | | Between Day | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV | SD | %CV |
| MCC 1 | I2000 | A | 80 | 3.8 | 0.1369 | 3.6 | 0.1315 | 3.4 | 0.1898 | 5.0 |
| | I2000SR | B | 80 | 4.0 | 0.1924 | 4.8 | 0.0000 | 0.0 | 0.2321 | 5.8 |
| MCC 2 | I2000 | A | 80 | 16.6 | 0.4300 | 2.6 | 0.4071 | 2.5 | 0.6184 | 3.7 |
| | I2000SR | B | 80 | 17.3 | 0.4000 | 2.3 | 0.5459 | 3.2 | 1.3228 | 7.7 |
| MCC 3 | I2000 | A | 80 | 30.3 | 0.8739 | 2.9 | 0.6784 | 2.2 | 1.1695 | 3.9 |
| | I2000SR | B | 80 | 31.0 | 0.6344 | 2.1 | 1.1223 | 3.6 | 1.3178 | 4.3 |
| Serum panel 1 | I2000 | A | 80 | 2.9 | 0.0829 | 2.9 | 0.0000 | 0.0 | 0.1140 | 4.0 |
| | I2000SR | B | 80 | 2.9 | 0.1601 | 5.5 | 0.0835 | 2.9 | 0.1806 | 6.2 |
| Serum panel 2 | I2000 | A | 80 | 39.8 | 0.9526 | 2.4 | 0.0000 | 0.0 | 1.0065 | 2.5 |
| | I2000SR | B | 80 | 41.0 | 1.0822 | 2.6 | 0.4470 | 1.2 | 1.2947 | 3.2 |
| Serum panel 3 | I2000 | A | 80 | 53.3 | 1.7061 | 3.2 | 0.2887 | 0.5 | 1.7303 | 3.3 |
| | I2000SR | B | 80 | 55.8 | 1.5047 | 2.7 | 0.9540 | 1.7 | 1.8730 | 3.4 |
| Urine panel 1 | I2000 | A | 80 | 2.4 | 0.1270 | 5.3 | 0.0545 | 2.3 | 0.1482 | 6.2 |
| | I2000SR | B | 80 | 2.7 | 0.1636 | 6.1 | 0.0463 | 1.7 | 0.1700 | 6.4 |
| Urine panel 2 | I2000 | A | 80 | 14.5 | 0.3927 | 2.7 | 0.0000 | 0.0 | 0.5875 | 4.1 |
| | I2000SR | B | 80 | 15.9 | 0.6039 | 3.8 | 0.3916 | 2.5 | 0.7198 | 4.5 |
| Urine panel 3 | I2000 | A | 80 | 36.8 | 1.0509 | 2.9 | 0.5742 | 1.6 | 1.3916 | 3.8 |
| | I2000SR | B | 80 | 40.6 | 1.5605 | 3.9 | 0.3012 | 0.7 | 1.5893 | 3.9 |
| Urine panel 4 | I2000 | A | 80 | 49.0 | 2.8402 | 5.8 | 0.0000 | 0.0 | 2.8402 | 5.8 |
| | I2000SR | B | 80 | 53.7 | 3.1812 | 5.9 | 0.0000 | 0.0 | 3.1812 | 5.9 |
Manufacturer's Acceptance Criteria
< 10% total CV serum
<20% total CV urine
An accuracy by recovery study was performed by spiking a series of each of three human serum samples and three human urine samples with USP Cortisol. The spiked samples were analyzed in triplicate with the ARCHITECT Cortisol assay. Results are shown in the tables below.
| Serum | Donor 1 | | | Donor 2 | | | Donor 3 | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Observed | Expected | % Recovery | Observed | Expected | % Recovery | Observed | Expected | % Recovery |
| Unspiked | 8.1 | N/A | N/A | 13.7 | N/A | N/A | 12.6 | N/A | N/A |
| Spiked 5 ug/dL | 12.5 | 12.7 | 98.5 | 17.8 | 18.2 | 97.6 | 16.4 | 17.1 | 95.7 |
| Spiked 10 ug/dL | 15.7 | 17.3 | 90.9 | 21.2 | 22.8 | 93.2 | 20.4 | 21.7 | 94.1 |
| Spiked 20 ug/dL | 23.7 | 26.4 | 89.6 | 28.7 | 31.8 | 90.2 | 28.4 | 30.8 | 92.3 |
| Spiked 40 ug/dL | 39.5 | 44.8 | 88.2 | 43.0 | 49.9 | 86.1 | 43.2 | 48.9 | 88.3 |
Manufacturer's acceptance criteria: $100 \pm 15\%$
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b. Linearity/assay reportable range:
i.) Linearity by dilution was determined by a study based on the CLSI Guideline EP6-A: Evaluation of the Linearity of Quantitative Measurement. Two serum pools were prepared, one at approximately 65μg/dL and the other at approximately 8μg/dL cortisol. A series of dilutions was made with both pools using cortisol free serum at 10% increments. Samples were run in replicates of five using ARCHITECT Cortisol reagents.
A regression analysis plot of recovered Cortisol against dilution factor was constructed. The percent deviation from linearity (%DLP) for each pool was calculated. Results are shown in the tables below.
65ug/dL Serum Pool
| Dilution | Result ug/dL | Predicted 1st ug/dL | Predicted 2nd ug/dL | difference ug/dL | % DLP |
| --- | --- | --- | --- | --- | --- |
| 100% | N/A | N/A | N/A | N/A | N/A |
| 90% | 65.85 | 64.60 | 66.17 | -1.6 | -2% |
| 80% | 58.41 | 57.28 | 57.80 | -0.5 | -1% |
| 70% | 49.69 | 49.96 | 49.70 | 0.3 | 1% |
| 60% | 41.92 | 42.64 | 41.85 | 0.8 | 2% |
| 50% | 33.69 | 35.31 | 34.27 | 1.0 | 3% |
| 40% | 26.74 | 27.99 | 26.95 | 1.0 | 4% |
| 30% | 19.72 | 20.67 | 19.89 | 0.8 | 4% |
| 20% | 14.02 | 13.35 | 13.09 | 0.3 | 2% |
| 10% | 6.53 | 6.03 | 6.55 | -0.5 | -8% |
| 0% | -0.04 | -1.30 | 0.27 | -1.6 | |
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8ug/dL Serum Pool
| Dilution | Result ug/dL | Predicted 1st ug/dL | Predicted 2nd ug/dL | difference ug/dL | % DLP |
| --- | --- | --- | --- | --- | --- |
| 100% | 7.79 | 7.66 | 7.81 | -0.2 | -2% |
| 90% | 7.01 | 6.86 | 6.92 | -0.1 | -1% |
| 80% | 5.87 | 6.07 | 6.06 | 0.0 | 0% |
| 70% | 5.27 | 5.27 | 5.21 | 0.1 | 1% |
| 60% | 4.43 | 4.48 | 4.39 | 0.1 | 2% |
| 50% | 3.68 | 3.69 | 3.58 | 0.1 | 3% |
| 40% | 2.83 | 2.89 | 2.80 | 0.1 | 3% |
| 30% | 2.03 | 2.10 | 2.04 | 0.1 | 3% |
| 20% | 1.16 | 1.30 | 1.29 | 0.0 | 1% |
| 10% | 0.49 | 0.51 | 0.57 | -0.1 | -12% |
| 0% | -0.01 | -0.28 | -0.13 | -0.2 | |
The data demonstrate that the assay is linear between 0.49 and 65.9 µg/dL and supports the claimed reportable range of 0.8 to 59.8 µg/dL for both serum and urine samples. (See Functional Sensitivity section below.) This linearity evaluation was performed using serum pools. Urine was evaluated independently as part of the imprecision (random error), correlation (bias) and auto-dilution verifications.
ii.) A dilution/recovery study was performed for both the serum and urine samples using manual and automatic dilution by the instrument. Five serum samples ranged from 25.4 to 49.0 µg/dL and six urine samples ranged from 4.8 to 40.8 µg/dL were used in the study. A 1:2 dilution recovery study was performed using the manual procedure and the instrument's automated procedure.
The dilution recovery study met the manufacturer's acceptance criteria of differences in recoveries of ≤ 15%. The serum and urine samples met the manufacturer's design goals with grand mean % recoveries of 99.0% and 93.9% for the manual procedure and the automated procedure respectively.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
## Traceability
The ARCHITECT Cortisol calibrators are matched to internal reference standards that are manufactured gravimetrically using cortisol (USP Reference Standard). The concentration values for these internal reference standards are assigned using LC-MS/MS method. The LC-MS/MS calibration is verified by the Community Bureau of Reference (BCR) 192 and 193 certified reference materials.
## Stability
The ARCHITECT Cortisol calibrators are stable until the expiration date when stored and handled as directed. The calibrators are supplied in liquid form, for storage at 2-8°C, and ready to use.
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Close-vial stability studies:
Real-time stability data supports a shelf life of 8 months. Real time studies remain ongoing and shelf life may be lengthened based on the results obtained.
Open-vial stability studies:
Real time open-vial stability studies are ongoing.
d. Detection limit:
Limit of Blank and the Limit of Detection:
The ARCHITECT Cortisol assay is designed to have a limit of detection (LoD) of ≤0.8μg/dL. The limit of blank (LoB) and the LoD were determined based on the CLSI guideline NCCLS EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline using proportions of false positives (α) less than 5% and false negatives (β) less than 5%. These determinations were performed using 60 blank and 120 low level samples on both the ARCHITECT i2000 and ARCHITECT i2000 SR analyzers.
Results:
| ARCHITECT i2000 | LoB= 0.234 μg/dL and LoD= 0.401ug/dL |
| --- | --- |
| ARCHITECT i2000SR | LoB= 0.125 μg/dL and LoD= 0.255ug/dL |
An assay claim of LoD=0.8ug/dL is supported by the data.
Based on the Linearity and LOD, the package insert claim for the reportable range for the assay will be 0.81 to 59.8 μg/dL.
Functional Sensitivity:
The functional sensitivity of the ARCHITECT Cortisol assay was determined based on the CLSI Guideline NCCLS EP17-A Protocols for Demonstration, Verification, and Evaluation of Limits of Detection and Quantitation; Approved Guideline. Serum and urine panels ranging in concentration from 0.1 to 2.1μg/dL were tested in duplicate over 10 days on both ARCHITECT i2000 and ARCHITECT i2000 SR analyzers using two reagent lots and two calibrations for a total of 40 replicates per panel. The total % CVs were calculated and plotted against the mean concentration. A reciprocal curve was fitted through the data and the functional sensitivity value was calculated as the concentration corresponding to the 20% CV level of the fitted curve.
Results: At the upper 95% confidence limit, the lowest serum value exhibiting a 20% CV was calculated to be 0.8μg/dL. At the upper 95% confidence limit, the lowest urine value exhibiting a 20% CV was calculated to be 1μg/dL.
e. Analytical specificity:
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i.) An interference study was performed following the CLSI Guideline EP7-A2, Interference Testing in Clinical Chemistry for the ARCHITECT Cortisol assay using serum specimens with Cortisol levels between 5.1 and $34.2\mu \mathrm{g / dL}$ and urine samples between 4.6 and $37.9\mu \mathrm{g / dL}$ . The interference from the following compounds was observed to be $\leq$ $15\%$ at the levels indicated.
| Specimen Type | Potential interference substance | Potential interference substance Concentration |
| --- | --- | --- |
| Serum | Bilirubin | 20 mg/dL |
| | Hemoglobin | 500 mg/dL |
| | Total Protein (Low) | 3 g/dL |
| | Total Protein (High) | 10 g/dL |
| | Triglycerides | 2000 mg/dL |
| Urine | Creatinine | 5 mmol/L |
| | Urea | 350 mmol/L |
| | Glucose | 5 mmol/L |
| | Sodium Chloride | 1000 mmol/L |
| | Total Protein (High) | 1000 mg/dL |
| | Boric Acid | 1 % |
ii.) The specificity of the ARCHITECT Cortisol assay was determined by studying the cross-reactivity of compounds whose chemical structure or concurrent usage may potentially interfere with the assay. Specificity of the assay was determined by spiking each compound into hum serum specimens with Cortisol levels of approximately $12\mu \mathrm{g / dL}$ . The $\%$ cross-reactivity results are shown in the following table.
| Cross Reactant | Test conc ug/dL | % Cross Reactivity | Cross Reactant | Test conc ug/dL | % Cross Reactivity |
| --- | --- | --- | --- | --- | --- |
| 11-beta-OH-progesterone | 1000 | 0.2 | Pregnanediol | 1000 | 0.0 |
| 11-deoxycorticosterone | 100 | 0.1 | Pregnanetriol | 1000 | 0.0 |
| 11-deoxycortisol | 100 | 2.1 | Pregnenolone | 1000 | 0.0 |
| 17-alpha-OH Pregnenolone | 1000 | 0.1 | Progesterone | 1000 | 0.1 |
| 17-OH-progesterone | 1000 | 0.6 | Spironolactone | 1000 | 0.0 |
| 6-beta-OH cortisol | 1000 | 0.2 | Testosterone | 1000 | 0.1 |
| 6-methyl- prednisolone | 1000 | 0.1 | Tetracycline | 1000 | 0.0 |
| Aldosterone | 1000 | 0.0 | Tetrahydrocortisol | 1000 | 0.6 |
| Beclomethasone | 1000 | 0.0 | Triamcinolone | 1000 | 0.4 |
| beta-cortol | 1000 | 0.0 | Dexamethasone | 1000 | 0.0 |
| beta-cortolone | 1000 | 0.0 | DHEA | 1000 | 0.0 |
| Beta-Estradiol | 1000 | 0.0 | DHEA-S | 1000 | 0.0 |
| beta-Sitosterol | 1000 | 0.0 | Estriol | 1000 | 0.0 |
| Budesonide | 1000 | 0.0 | Estrone | 1000 | 0.0 |
| Canrenone | 1000 | 0.1 | Fludrocortisone | 100 | 36.8 |
| Corticosterone | 1000 | 0.9 | Fluticasone Propionate | 1000 | 0.0 |
| Cortisol-21-glucuronide | 1000 | 0.2 | Medroxy Progesterone Acetate | 1000 | 0.0 |
| Cortisone | 1000 | 2.8 | Mometasone | 1000 | 0.0 |
| Prednisone | 1000 | 0.6 | Prednisolone | 100 | 12.5 |
iii.) The ARCHITECT Cortisol assay was evaluated by testing specimens with HAMA (Human anti-mouse antibodies) and RF (Rheumatioid Factor) to further assess the
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clinical specificity. Ten specimens positive for HAMA and ten specimens positive for RF were evaluated for interference with Cortisol levels spiked between 9.0 to 41.8 $\mu \mathrm{g} / \mathrm{dL}$ . The acceptance criteria are $\leq 15\%$ for the average mean% difference. The mean absolute % interference is summarized in the following table.
| Other potential interferents | N | Mean absolute % interference |
| --- | --- | --- |
| HAMA positive | 10 | 1.0 |
| RF positive | 10 | 5.9 |
f. Assay cut-off:
Not applicable.
# 2. Comparison studies:
# a. Method comparison studies:
The correlation studies for the ARCHITECT Cortisol assay were performed with both LC-MS/MS and the Predicate Device (AxSYM Cortisol) to support the performance of the ARCHITECT assay. The studies were conducted according to CLSI Guideline EP9, Method Comparison and Bias Estimation Using Patient Samples. Serum samples, ranging from 1.5 to $52.5\mu \mathrm{g} / \mathrm{dL}$ of Cortisol, were tested comparing the ARCHITECT Cortisol assay to the AxSYM Cortisol assay and LC-MS/MS. Urine samples, ranging from 0.8 to $46.8\mu \mathrm{g} / \mathrm{dL}$ of Cortisol, were tested comparing the ARCHITECT Cortisol assay to the AxSYm Cortisol Assay. Urine samples, ranging from 0.8 to $51.1\mu \mathrm{g} / \mathrm{dL}$ Cortisol, were tested comparing the ARCHITECT Cortisol assay to LC-MS/MS. All serum samples were purchased clinical samples, none of which were spiked. All urine samples were also purchased clinical samples; however, some were spiked in order to obtain high concentration samples.
Results are shown in the following tables:
| Serum samples | AxSYM vs. Architect | AxSYM vs. Architect i2000 | AxSYM vs. Architect i2000SR | LC-MS/MS vs. Architect | LC-MS/MS vs. Architect i2000 | LC-MS/MS vs. Architect i2000SR |
| --- | --- | --- | --- | --- | --- | --- |
| # of Specimens | 121 | 121 | 121 | 125 | 125 | 125 |
| Slope | 0.909 | 0.922 | 0.902 | 1.077 | 1.104 | 1.068 |
| Intercept | 0.92 | 0.81 | 0.88 | -0.02 | -0.29 | 0.07 |
| r value | 0.983 | 0.984 | 0.98 | 0.996 | 0.994 | 0.995 |
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| Urine samples | AxSYM vs. Architect | AxSYM vs. Architect i2000 | AxSYM vs. Architect i2000SR | LC-MS/MS vs. Architect | LC-MS/MS vs. Architect i2000 | LC-MS/MS vs. Architect i2000SR |
| --- | --- | --- | --- | --- | --- | --- |
| # of Specimens | 74 | 70 | 74 | 81 | 78 | 81 |
| Slope | 0.537 | 0.557 | 0.523 | 1.056 | 1.092 | 1.009 |
| Intercept | -1.14 | -1.24 | -1.02 | 0.84 | 0.88 | 0.8 |
| R value | 0.98 | 0.978 | 0.981 | 0.997 | 0.996 | 0.996 |
Only samples that fell outside the reportable assay range on the Architect were excluded from analysis.
A summary of the data analyzed using Passing-Bablok regression method are shown in the table below.
| | ARCHITECT VS | | | |
| --- | --- | --- | --- | --- |
| | AxSYM | | LC-MS/MS | |
| Specimen | Serum | Urine | Serum | Urine |
| r value | ≥ 0.90** | ≥ 0.80 *** | ≥ 0.95 | ≥ 0.85 |
| Slope | NA# | NA# | 1.0 ± 0.1 | 1.0 ± 0.2 |
# b. Matrix comparison:
Anticoagulants studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing Cortisol. All tubes were processed per the manufacturers instructions and analyzed on the ARCHITECT analyzer in triplicate. Blood was drawn from ten healthy donors for each tube type listed below:
- plastic K2 EDTA tube
- glass K3 EDTA tube
- plastic Plasma separator lithium heparin tube
- plastic sodium heparin tube
- plastic lithium heparin tube
- plastic serum separator tube
- glass tube; no additive (served as the control)
Results are shown in the table below:
| | | Tube type | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Donor | Rep | No anticoagulant glass | SST plastic | Lithium heparin plastic | PST plastic | Sodium heparin plastic | K3 EDTA glass | K2 EDTA plastic |
| A | Rep 1 | 8.60 | 8.60 | 8.90 | 9.10 | 8.80 | 8.30 | 9.30 |
| | Rep 2 | 8.90 | 8.60 | 9.00 | 8.40 | 8.70 | 8.40 | 8.90 |
| | Rep 3 | 8.70 | 9.00 | 8.80 | 8.80 | 8.70 | 8.20 | 8.70 |
| | Mean | 8.73 | 8.73 | 8.90 | 8.77 | 8.73 | 8.30 | 8.97 |
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| | % recovery | 100.00 | 100.00 | 101.91 | 100.38 | 100.00 | 95.04 | 102.67 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| B | Rep 1 | 12.70 | 12.80 | 11.50 | 12.40 | 12.10 | 12.00 | 12.60 |
| | Rep 2 | 12.90 | 12.60 | 12.70 | 12.10 | 13.00 | 12.90 | 13.40 |
| | Rep 3 | 11.90 | 13.20 | 12.20 | 12.60 | 13.00 | 11.90 | 12.60 |
| | Mean | 12.50 | 12.87 | 12.13 | 12.37 | 12.70 | 12.27 | 12.87 |
| | % recovery | 100.00 | 102.93 | 97.07 | 98.93 | 101.60 | 98.13 | 102.93 |
| C | Rep 1 | 6.70 | 6.80 | 7.10 | 6.80 | 6.80 | 6.90 | 6.50 |
| | Rep 2 | 6.50 | 7.10 | 6.80 | 6.50 | 6.80 | 6.70 | 6.70 |
| | Rep 3 | 6.50 | 7.00 | 6.90 | 6.90 | 7.20 | 6.20 | 6.90 |
| | Mean | 6.57 | 6.97 | 6.93 | 6.73 | 6.93 | 6.60 | 6.70 |
| | % recovery | 100.00 | 106.09 | 105.58 | 102.54 | 105.58 | 100.51 | 102.03 |
| D | Rep 1 | 6.70 | 7.30 | 7.20 | 7.40 | 7.40 | 7.00 | 7.50 |
| | Rep 2 | 7.10 | 7.00 | 7.20 | 7.10 | 7.40 | 7.10 | 6.90 |
| | Rep 3 | 7.00 | 7.00 | 7.20 | 6.80 | 7.60 | 7.10 | 7.10 |
| | Mean | 6.93 | 7.10 | 7.20 | 7.10 | 7.47 | 7.07 | 7.17 |
| | % recovery | 100.00 | 102.40 | 103.85 | 102.40 | 107.69 | 101.92 | 103.37 |
| E | Rep 1 | 10.40 | 10.00 | 10.00 | 9.80 | 9.80 | 10.50 | 10.80 |
| | Rep 2 | 10.00 | 9.80 | 10.10 | 10.20 | 10.10 | 10.00 | 10.20 |
| | Rep 3 | 10.30 | 10.10 | 9.30 | 10.80 | 10.50 | 10.00 | 10.40 |
| | Mean | 10.23 | 9.97 | 9.80 | 10.27 | 10.13 | 10.17 | 10.47 |
| | % recovery | 100.00 | 97.39 | 95.77 | 100.33 | 99.02 | 99.35 | 102.28 |
| F | Rep 1 | 18.40 | 18.80 | 18.50 | 19.20 | 18.70 | 18.10 | 18.00 |
| | Rep 2 | 18.20 | 19.20 | 19.10 | 18.00 | 19.00 | 17.30 | 18.60 |
| | Rep 3 | 17.70 | 17.80 | 18.50 | 18.00 | 18.60 | 18.80 | 17.90 |
| | Mean | 18.10 | 18.60 | 18.70 | 18.40 | 18.77 | 18.07 | 18.17 |
| | % recovery | 100.00 | 102.76 | 103.31 | 101.66 | 103.68 | 99.82 | 100.37 |
| G | Rep 1 | 12.00 | 12.30 | 11.90 | 11.80 | 11.70 | 11.30 | 12.10 |
| | Rep 2 | 11.80 | 11.90 | 12.00 | 11.80 | 12.50 | 11.70 | 12.10 |
| | Rep 3 | 12.20 | 12.70 | 11.80 | 12.40 | 12.50 | 11.80 | 12.80 |
| | Mean | 12.00 | 12.30 | 11.90 | 12.00 | 12.23 | 11.60 | 12.33 |
| | % recovery | 100.00 | 102.50 | 99.17 | 100.00 | 101.94 | 96.67 | 102.78 |
| H | Rep 1 | 8.00 | 7.90 | 7.70 | 7.90 | 7.80 | 7.40 | 8.30 |
| | Rep 2 | 7.60 | 7.70 | 7.60 | 7.60 | 7.70 | 7.90 | 7.70 |
| | Rep 3 | 7.60 | 8.00 | 7.70 | 8.00 | 7.60 | 7.40 | 7.50 |
| | Mean | 7.73 | 7.87 | 7.67 | 7.83 | 7.70 | 7.57 | 7.83 |
| | % recovery | 100.00 | 101.72 | 99.14 | 101.29 | 99.57 | 97.84 | 101.29 |
| I | Rep 1 | 8.10 | 8.50 | 8.10 | 8.40 | 8.30 | 8.20 | 8.00 |
| | Rep 2 | 8.20 | 9.00 | 8.00 | 8.70 | 8.90 | 8.10 | 8.70 |
| | Rep 3 | 8.70 | 9.10 | 7.90 | 9.00 | 8.90 | 8.40 | 8.40 |
| | Mean | 8.33 | 8.87 | 8.00 | 8.70 | 8.70 | 8.23 | 8.37 |
| | % recovery | 100.00 | 106.40 | 96.00 | 104.40 | 104.40 | 98.80 | 100.40 |
| J | Rep 1 | 10.70 | 10.10 | 10.00 | 9.80 | 10.50 | 10.10 | 10.00 |
| | Rep 2 | 10.40 | 10.20 | 10.10 | 10.10 | 10.20 | 11.20 | 10.60 |
| | Rep 3 | 10.10 | 9.70 | 9.60 | 10.70 | 10.40 | 9.90 | 10.40 |
| | Mean | 10.40 | 10.00 | 9.90 | 10.20 | 10.37 | 10.40 | 10.33 |
| | % recovery | 100.00 | 96.15 | 95.19 | 98.08 | 99.68 | 100.00 | 99.36 |
| Grand mean | | 10.15 | 10.33 | 10.11 | 10.24 | 10.37 | 10.03 | 10.32 |
| Grand % recovery | | 100.00 | 101.71 | 99.61 | 100.82 | 102.17 | 98.75 | 101.64 |
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c. Instruments evaluations between ARCHITECT Cortisol i2000 and i2000SR:
The i2000 and i2000SR systems are in the ARCHITECT family of instruments differing only by inclusion on the i2000SR of a) STAT sampling hardware and software, b) composition and positioning of the RV loader and c) Auto Retesting software. To confirm acceptable ARCHITECT Cortisol assay performance on the two related systems, the following were tested on both platforms: a) precision, b) limit of detection, c) functional sensitivity, d) method comparison. These characteristics were selected as they are fitting indicators of overall performance.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
None
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
Serum cortisol levels were determined by assaying samples drawn from 150 apparently healthy individuals collected before 10am and after 5pm. Cortisol levels in urine were determined by assaying 24-hour urine samples from 128 apparently healthy individuals. The 95% reference interval was determined for each. The data is summarized in the table below.
| Specimen | N | Normal Range ug/dL | Normal Range nmol/L |
| --- | --- | --- | --- |
| Serum Before 10am | 150 | 3.7 - 19.4 | 101.2 - 535.7 |
| Serum After 5pm | 150 | 2.9 - 17.3 | 79.0 - 477.8 |
| Specimen | N | Normal Range ug/24 hours | Normal Range nmol/ 24 hours |
| --- | --- | --- | --- |
| 24 hour Urine | 128 | 4.3 - 176.0 | 11.8 - 485.6 |
N. Proposed Labeling:
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The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
**O. Conclusion:**
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.**
