(256 days)
The IDS Cortisol assay is an in vitro diagnostic device intended for the quantitative determination of cortisol in human serum and plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data to assist clinicians in the diagnosis and treatment of disorders of the adrenal gland.
The IDS Cortisol assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:
- MPE1:Magnetic particles coated rat anti-mouse monoclonal antibody in a phosphate buffer with Proclin as preservative.
- CONJ: Cortisol coupled with an acridinium ester derivative in = phosphate buffer with Proclin as a preservative.
- mAb: Mouse anti-cortisol monoclonal antibody in phosphate buffer with Proclin as a preservative .;
- BUF: HEPES buffer containing Proclin as preservative .
This document describes the analytical performance of the IDS Cortisol assay, an in vitro diagnostic device, and demonstrates its substantial equivalence to a predicate device (Roche Elecsys Cortisol II). The acceptance criteria and the study proving the device meets these criteria are detailed below.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this in vitro diagnostic device are primarily based on demonstrating analytical performance that is comparable to, or meets specified standards relative to, established laboratory methods and a predicate device.
| Performance Characteristic | Acceptance Criteria (from context/implied standard) | Reported Device Performance (IDS Cortisol) |
|---|---|---|
| Precision | Repeatability (Within-run): Lower CV% | Within-Run / Repeatability (n=80 per sample, 1 lot, 1 system): - 0.94 µg/dL: 7.8% CV - 1.84 µg/dL: 4.6% CV - 5.75 µg/dL: 2.4% CV - 13.06 µg/dL: 2.4% CV - 19.94 µg/dL: 1.8% CV - 44.63 µg/dL: 1.9% CV |
| Intermediate Precision (Within-System/Total): Lower CV% | Within-System (n=80 per sample, 1 lot, 1 system): - 0.94 µg/dL: 16.2% CV - 1.84 µg/dL: 10.9% CV - 5.75 µg/dL: 5.2% CV - 13.06 µg/dL: 3.9% CV - 19.94 µg/dL: 5.1% CV - 44.63 µg/dL: 4.2% CV Total (Combind 3 lots, 3 systems, n=240 per sample): - 0.88 µg/dL: 15.3% CV - 1.78 µg/dL: 10.1% CV - 5.75 µg/dL: 4.5% CV - 13.09 µg/dL: 3.3% CV - 20.22 µg/dL: 4.8% CV - 44.48 µg/dL: 5.0% CV | |
| Linearity/Reportable Range | Data should demonstrate linearity across the claimed measuring range. | Measuring Range: 0.59 to 45.00 µg/dL. Regression: Observed = 1.01 * Expected + 0.01 µg/dL; R²: 1.00 (Accepted based on R² close to 1 and slope ~1, intercept ~0) |
| Detection Limits (LoB, LoD, LoQ) | Specific quantifiable low limits. | LoB: 0.10 µg/dL LoD: 0.24 µg/dL LoQ: 0.59 µg/dL |
| Analytical Specificity (Interference) | Non-significant bias (<10%) for tested interfering substances at specified concentrations. | Interference (<10% bias): - Acetaminophen: 200 µg/mL - Bilirubin (Conj/Unconj): 40 mg/dL - Biotin: 6 µg/mL - Carbamazepine: 30 µg/mL - Haemoglobin: 500 mg/dL - HAMA: 1000 ng/mL - Ibuprofen: 500 µg/mL - Phenytoin: 50 µg/mL - RhF: 2000 IU/mL - Total protein: 12 g/dL - Triglycerides: 3000 mg/dL (All tested compounds found not to interfere significantly.) |
| Method Comparison (vs. Predicate Device) | Correlation coefficient (r) close to 1, slope close to 1, intercept close to 0, indicating strong agreement. | vs. Roche Elecsys Cortisol II (K152227): - N: 194 samples - Slope: 1.06 (95% CI: 1.04 to 1.07) - Intercept: -0.10 µg/dL (95% CI: -0.39 to 0.04) - Correlation Coefficient (r): 0.99 (Demonstrates strong agreement with predicate) |
| Matrix Comparison | Slopes close to 1 and intercepts close to 0, with high correlation coefficients, for various sample types vs. control. | vs. Red Top Serum: - SST (n=45): Slope 1.02, Int. -0.08, r 1.00 - K2 EDTA (n=45): Slope 1.03, Int. -0.11, r 1.00 - K3 EDTA (n=45): Slope 1.02, Int. -0.10, r 1.00 - Lithium Heparin (n=45): Slope 1.00, Int. 0.15, r 1.00 - Sodium Heparin (n=45): Slope 1.01, Int. 0.00, r 1.00 (All demonstrate strong agreement across sample types) |
| Stability | Demonstrates shelf-life stability. | Shelf life: 12 months (based on accelerated stability studies). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Testing:
- Per sample/concentration level (for one representative lot on one system): N=80 replicates.
- Combined (3 lots on 3 systems): N=240 replicates per sample/concentration level.
- Provenance: Not explicitly stated, but clinical laboratory studies typically use samples from diverse patient populations to cover the measurement range. The study mentions "human serum samples" and "low level samples."
- Linearity Testing:
- A high human serum sample and a low human serum sample were used, along with 12 evenly spaced dilutions.
- Provenance: "high patient sample with a low patient sample."
- Detection Limit Testing (LoB, LoD, LoQ):
- 60 blank replicates and 13 low-level samples.
- Provenance: Not explicitly stated, but based on typical laboratory practices.
- Analytical Specificity (Interference):
- Human serum samples with low and high cortisol concentrations.
- For Rheumatoid Factor, a serum sample with low Cortisol and high Rheumatoid Factor was diluted 1:2 and 1:4. Each was assayed in duplicate.
- For cross-reactivity, serum samples spiked with cross-reactants and unspiked controls were assayed in 26 replicates each.
- Method Comparison (vs. Predicate Device):
- N: 194 samples.
- Provenance: Samples were "selected to represent a wide range of Cortisol concentrations" (0.64 to 44.66 ug/dL), implying patient samples. Country of origin not specified, but usually derived from laboratory settings.
- Matrix Comparison:
- N: 45 samples (36 native, 9 spiked or diluted) per matrix type.
- Provenance: "human samples" to cover the range of 0.89 to 42.38 ug/dL.
- Expected Values/Reference Range:
- N: 307 apparently healthy donors.
- Provenance: "serum samples collected from 307 apparently healthy donors" from 21 to 65 years of age. Details imply a prospective collection for this specific study, but geographical location not explicitly stated beyond "local population" for general reference ranges.
All studies mentioned state they followed CLSI (Clinical and Laboratory Standards Institute) guidelines, which implies these were prospective analytical performance studies conducted under controlled laboratory conditions.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
For an in vitro diagnostic (IVD) device like the IDS Cortisol assay, "ground truth" for the test set is established through reference methods or highly accurate comparative assays, not typically by human expert consensus or adjudicated readings. The nature of this device is a quantitative immunoassay meant to measure a biomarker.
-
Ground Truth Establishment for Analytical Performance:
- Traceability: The IDS Cortisol assay is traceable to the LC-MS/MS Candidate Reference Measurement Procedure (cRMP) Total Serum Cortisol. This is a highly accurate chemical analytical method, considered a "higher-order" reference method. The ground truth in this context is the quantitative value determined by this cRMP, often involving specialized laboratories and expert analytical chemists.
- Method Comparison: The test device's performance is compared against the Roche Elecsys Cortisol II (K152227), a previously cleared and marketed predicate device. The values obtained from the predicate device serve as the comparative "truth" for demonstrating substantial equivalence.
- Precision, Linearity, Detection Limits, Analytical Specificity, Matrix Comparison: These performance characteristics are evaluated against pre-defined statistical criteria (e.g., CV thresholds, R² values, bias limits) using controlled samples, calibrators, and reference materials. The "truth" is the known concentration or behavior of these materials, verified through standard laboratory practices and reference methods.
-
Number of Experts & Qualifications: Not applicable in the context of human expert adjudication for image interpretation. The "experts" would be the skilled laboratory personnel and analytical chemists performing the LC-MS/MS and predicate device measurements, as well as those defining the CLSI protocols for analytical testing.
4. Adjudication Method for the Test Set
Not applicable. This is an in vitro quantitative diagnostic device, not an imaging device requiring human-in-the-loop reading and adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
Not applicable. This is an in vitro quantitative diagnostic device, not an imaging device requiring human readers or MRMC studies.
6. If a Standalone Performance (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the entire analytical performance evaluation (precision, linearity, detection limits, interference, method comparison, and matrix comparison) represents the standalone performance of the IDS Cortisol assay as an algorithm (chemical reaction + instrument measurement and calculation) without human-in-the-loop intervention for result generation. The human role is in operating the instrument and interpreting the results, but the measurement itself is automated.
7. The Type of Ground Truth Used
The primary ground truth used for this quantitative in vitro diagnostic device is:
- Reference Measurement Procedure: The IDS Cortisol assay is traceable to the LC-MS/MS Candidate Reference Measurement Procedure (cRMP) Total Serum Cortisol, which represents a highly accurate and standardized method for determining cortisol concentrations. This is a form of outcomes data in the sense of a definitive analytical outcome.
- Predicate Device Comparison: The values generated by the Roche Elecsys Cortisol II assay serve as a comparative ground truth for demonstrating substantial equivalence.
- Known Concentrations of Reference Materials/Spiked Samples: For analytical performance studies like precision, linearity, and detection limit, the ground truth is often established by using precisely prepared calibrators or samples with known, verified concentrations of the analyte.
8. The Sample Size for the Training Set
This document describes the analytical validation of a commercial diagnostic kit, not a machine learning algorithm that typically undergoes distinct "training" datasets. Therefore, there isn't a "training set" in the sense of data used to iteratively optimize an AI model.
The "development" or "design" of the assay (reagents, methodology) would have involved extensive R&D and internal testing, which could be considered analogous to a training phase in a broader sense, but no specific sample size for such a phase is provided in this regulatory submission. The data presented are for the validation of the final device.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, there isn't a distinct "training set" in the context of an AI/ML algorithm as described in this document. The "ground truth" for the development of the assay itself would have been established through a combination of:
- Biochemical principles: Understanding the cortisol molecule and its interactions with antibodies.
- Standard laboratory methods: Using established analytical techniques (like spectrophotometry, chromatography, or existing cortisol assays) to characterize reagents and ensure proper reaction kinetics.
- Reference materials: Utilizing internationally recognized reference materials and calibrators for initial assay calibration and optimization.
- Iterative development and testing: Repeated internal testing with various concentrations of cortisol in different matrices to optimize assay components (antibodies, conjugates, buffers) and instrument parameters to achieve desired performance characteristics (sensitivity, specificity, dynamic range). This iterative process involves comparing results against known concentrations or a "gold standard" method (like LC-MS/MS) during development.
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April 13, 2021
Immunodiagnostic Systems Ltd. Mick Henderson Regulatory Affairs Manager 10 Didcot Way Boldon Business Park Boldon, Tyne and Wear NE35 9PD United Kingdom
Re: K202136
Trade/Device Name: IDS Cortisol Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (Hydrocortisone And Hydroxycorticosterone) Test System Regulatory Class: Class II Product Code: CGR Dated: October 8, 2020 Received: October 13, 2020
Dear Mick Henderson:
We have reviewed vour 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrl/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Kellie B. Kelm -S
Kellie B. Kelm Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K202136
Device Name IDS Cortisol
Indications for Use (Describe)
The IDS Cortisol assay is an in vitro diagnostic device intended for the quantitative determination of cortisol in human serum and plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data to assist clinicians in the diagnosis and treatment of disorders of the adrenal gland.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| ------------------------------------------------------------------------------------ | ----------------------------------------------------------------------------------- |
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Image /page/3/Picture/0 description: The image contains the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, lowercase font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, red font. The logo is simple and modern, with a focus on the company's name and its area of expertise.
510(k) SUMMARY
| 510k Number | K202136 | |
|---|---|---|
| Introduction | According to the requirements of 21CFR807.92, the followinginformation provides sufficient detail to understand the basis for adetermination of substantial equivalence. | |
| Submitter | Immunodiagnostic Systems Limited10 Didcot WayBoldon Business ParkBoldonTyne and WearNE35 9PDUnited Kingdom | |
| Contact Person: Mick HendersonPhone: +44 191 5190660Fax: +44 191 5190760Email: mick.henderson@idsplc.comSecondary Contact: Lee HarrisPhone: +44 191 5190660Fax: +44 191 5190760Email : lee.harris@idsplc.com | ||
| Date prepared: 27 July 2020 | ||
| Device Name | Proprietary names: | IDS Cortisol |
| Common names: | As above | |
| Classification: | 21CFR862.1205 Cortisol (hydrocortisoneand hydroxycorticosterone) test system. | |
| Class II | ||
| Product Code: | CGR |
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Image /page/4/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, interconnected design, with a red dot above the "i". Below the letters, the words "immunodiagnostic systems" are written in a smaller font size. The color scheme is primarily gray and red.
Predicate Device The IDS Cortisol is substantially equivalent to other products in commercial distribution intended for similar use. We claim equivalency to the currently marketed Roche Elecsys Cortisol II (K152227).
The IDS Cortisol assay consists of a reagent cartridge. The reagent Device Description cartridge contains multiple reagents:
- -MPE1:Magnetic particles coated rat anti-mouse monoclonal antibody in a phosphate buffer with Proclin as preservative.
- CONJ: Cortisol coupled with an acridinium ester derivative in = phosphate buffer with Proclin as a preservative.
- mAb: Mouse anti-cortisol monoclonal antibody in phosphate buffer with Proclin as a preservative .;
- BUF: HEPES buffer containing Proclin as preservative . -
Indications for Use
The IDS Cortisol assay is an in vitro diagnostic device intended for the quantitative determination of cortisol in human serum and plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data to assist clinicians in the diagnosis and treatment of disorders of the adrenal gland.
- Conditions for use: For in vitro diagnostic use only. Rx Only
Special instrument Requirements:
IDS-iSYS Multi-Discipline Automated System (K091849)
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Image /page/5/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, connected font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The logo is simple and modern, with a focus on the company's name and area of expertise.
Comparison Tables
Similarities compared to the chosen (FDA cleared; marketed) predicate device (K152227)
| AssayPerformance | Predicate DeviceRoche Elecsys Cortisol II(K152227) | Candidate DeviceIDS Cortisol |
|---|---|---|
| Intended Use | For quantitative determinationof Cortisol | same |
| Method ofdetection (Testmethodology) | chemiluminescence | same |
Differences compared to the chosen (FDA cleared; marketed) predicate device (K152227)
| Predicate Device | Candidate Device | |
|---|---|---|
| Performance | Roche Elecsys Cortisol II | IDS Cortisol |
| (K152227) | ||
| Indications forUse | Immunoassay for the in vitroquantitative determination ofcortisol in human serum,plasma, urine and saliva. Thedetermination of cortisol isused for the recognition andtreatment of functionaldisorders of the adrenal gland.The electrochemiluminescenceimmunoassay "ECLIA" isintended for use on Elecsysand cobas e immunoassay | The IDS Cortisol assay is an invitro diagnostic device intended forthe quantitative determination ofcortisol in human serum andplasma on the IDS system. Resultsare to be used in conjunction withother clinical and laboratory datato assist clinicians in the diagnosisand treatment of disorders of theadrenal gland. |
| Sample Type | Human Serum, plasma, urineand saliva | Human Serum and plasma |
| SampleVolume | 10 µL | 30 µL |
| Range of assay | 3 - 1750 nmol/L(0.109 to 63.4 ug/dL) | 0.59 - 45 µg/dL |
| Sensitivity | LoB 1.0 nmol/L (0.036 µg/dL)LoD 1.5 nmol/L (0.054 µg/dL)LoQ 3.0 nmol/L (0.109 µg/dL)Morning hours 6-10am95th percentile 6.02-18.4 µg/dLAfternoon hours 4-8pm95th percentile 2.68-10.5 µgd/L | LoB 0.1 µg/dLLoD 0.24 µg/dLLoQ 0.59 µg/dLMorning hours 6-10am95th percentile 4.23-20.1 µg/dLAfternoon hours 4-8pm95th percentile 2.37-13.6 µg/dL |
| Precision | Repeatability n =841.4% to 7.1% in theconcentration range 0.112 to57.7 µg/dLIntermediate Precision n = 842.5% to 12.7% in theconcentration range 0.014 to0.653 µg/dL | Within Run / RepeatabilityPrecision n =801.8% to 7.8% in the concentrationrange 0.94 to 44.63 µg/dLWithin System n = 803.9% to 16.2% in the concentrationrange 0.94 to 44.63 μg/L |
| Specificity,InterferingsubstancesAndCrossReactivity | Interfering SubstancesBilirubin 25 mg/dLBiotin 30ng/mLHaemoglobin No ClaimHuman AntiMouse Antibody(HAMA) No ClaimRheumatoid Factor 600IU/mLTotal Protein No ClaimTriglycerides No ClaimAcetaminophen No Claim | Interfering SubstancesBilirubin –conjugated 40 mg/dLBilirubin –unconjugated 40 mg/dLBiotin 6 µg/dLHaemoglobin 500 mg/dLHuman AntiMouse Antibody(HAMA) 1000 ng/dLRheumatoid Factor 2000IU/mLTotal Protein 12 g/dLTriglycerides 3000mg/dLAcetaminophen 200 µg/ml |
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Image /page/6/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with a red circle above the "i". Below the letters, the words "Immunodiagnostic systems" are written in a smaller, red font.
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Image /page/7/Picture/0 description: The image shows the logo for Immuno Diagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, sans-serif font, with the 'i' having a red circular dot above it. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, sans-serif font. A registered trademark symbol is located to the upper right of the 's' in 'ids'.
Cross Reactivity 11-Deoxycorticosterone 10ug/L yields a result of 0.64% 11-Deoxycortisol 10ug/L yields a result of 4.9% 17-a-Hydroxyprogesterone 10ug/L vields a result of 0.08% Corticosterone 10ug/L vields a result of 2.48% Cortisone 10ug/L yields a result of 6.58% Dexamethasone 10ug/L yields a result of not detectable Prednisone 10ug/L yields a result of 2.23% Progesterone 10ug/L yields a result of 0.035% 21-Deoxycortisol 1 ug/L yields a result of 2.4% Prednisolone 0.1ug/L yields a result of 7.98% 6-a-Methylprednisolone
0.1µg/L yields a result of 12.0%
Cross Reactivity 11-Deoxycorticosterone 1000ug/dL yields a result of 2.2%
11-Deoxycortisol 100ug/dL yields a result of 11.5%
17-a-Hydroxyprogesterone 1000ug/dL yields a result of 2.6%
Corticosterone 100ug/dL vields a result of 19.9%
Cortisone 100ug/dL yields a result of 36.5%
Dexamethasone 1000ug/dL yields a result of 1.4%
Prednisone 100ug/dL yields a result of 43.5%
Progesterone 1000ug/dL yields a result of 0.3%
21-Deoxycortisol 100ug/dL vields a result of 37%
Prednisolone 50ug/dL yields a result of 51.3%
6-a-Methylprednisolone 10ug/dL yields a result of 0%
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Image /page/8/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with the "i" having a red circular dot above it. Below the letters, the words "Immunodiagnostic Systems" are written in a smaller, red font.
| Methodcomparison | Against Elecsys Cortisol(K070788):n = 536 | Against Elecsys Cortisol II(K152227):n = 194 |
|---|---|---|
| Elecsys Cortisol II =$0.76 x (Elecsys Cortisol) -1.85$µg/L | IDS Cortisol =$1.06 x (Roche Elecsys Cortisol II) - 0.10$ µg/dL | |
| Correlation coefficient (r) =0.968 | Correlation coefficient (r) = 0.99 | |
| Linearity | 3.0 to 1750 nmol/L | 0.59 – 45 µg/dLObserved =$1.01 x (Expected) +0.01$ µg/dLRegression coefficient R2: 1.00 |
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Image /page/9/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, gray font, with a red dot above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. A circled "R" trademark symbol is located in the upper right corner of the logo.
Performance Characteristics (if/when applicable):
-
- Analytical performance:
- a. Precision/Reproducibility:
Precision was evaluated in accordance with a modified protocol based on CLSI EP-5A3, "Evaluation of Precision Performance of Quantitative Measurement Methods". A total of 6 samples were assayed using 3 lots of reagents in duplicate, twice a day for 20 days on 3 systems. The IDS Cortisol assay precision was established using samples with concentrations ranging from approximately 0.80 ug/dL to 46.00 ug/dL.
| Sample | N | Mean Conc.(µg/dL) | Repeatability | Within system | ||
|---|---|---|---|---|---|---|
| SD | CV | SD | CV | |||
| 1 | 80 | 0.94 | 0.07 | 7.8% | 0.15 | 16.2% |
| 2 | 80 | 1.84 | 0.08 | 4.6% | 0.20 | 10.9% |
| 3 | 80 | 5.75 | 0.14 | 2.4% | 0.30 | 5.2% |
| 4 | 80 | 13.06 | 0.31 | 2.4% | 0.52 | 3.9% |
| 5 | 80 | 19.94 | 0.36 | 1.8% | 1.02 | 5.1% |
| 6 | 80 | 44.63 | 0.85 | 1.9% | 1.89 | 4.2% |
Results from 1 representative lot on 1 system:
Results for the combined 3 lots on 3 systems:
| Sample | N | Mean Conc.(µg/dL) | Within run | Total | ||
|---|---|---|---|---|---|---|
| 1 | 240 | 0.88 | 0.06 | 7.1% | 0.14 | 15.3% |
| 2 | 240 | 1.78 | 0.08 | 4.3% | 0.18 | 10.1% |
| 3 | 240 | 5.75 | 0.13 | 2.3% | 0.26 | 4.5% |
| 4 | 240 | 13.09 | 0.25 | 1.9% | 0.43 | 3.3% |
| 5 | 240 | 20.22 | 0.35 | 1.7% | 0.96 | 4.8% |
| 6 | 240 | 44.48 | 0.74 | 1.7% | 2.22 | 5.0% |
b. Linearity/assay reportable range:
A linearity study was conducted based on guidance from the CLSI EP6-A. A high human serum sample and a low human serum sample were prepared respectively by spiking a serum sample with Cortisol high concentration solution and diluting a serum sample with Cortisol zero matrix. High and a low serum samples were analysed in addition to 12 evenly spaced dilutions which were created by mixing the high and low sample as indicated below:
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| Sample | Dilution | Dilution Factor (%) |
|---|---|---|
| 1: | Low (L) | 0 |
| 2: | 0.98L + 0.02H | 2 |
| 3: | 0.95L + 0.05H | 5 |
| 4: | 0.92L + 0.08H | 8 |
| 5: | 0.90L + 0.10H | 10 |
| 6: | 0.80L + 0.20H | 20 |
| 7: | 0.70L + 0.30H | 30 |
| 8: | 0.60L + 0.40H | 40 |
| 9: | 0.50L + 0.50H | 50 |
| 10: | 0.40L + 0.60H | 60 |
| 11: | 0.30L + 0.70H | 70 |
| 12: | 0.20L + 0.80H | 80 |
| 13: | 0.10L + 0.90H | 90 |
| 14: | High (H) | 100 |
Results:
Linearity was evaluated based on CLSI EP-6A, "Evaluation of the Linearity of Quantitative Measurement Procedures". Samples were prepared by diluting a high patient sample with a low patient sample prior to assay. The linear regression of the observed concentrations versus the expected concentrations is:
Observed = 1.01 x (Expected) + 0.01 µg/dL; Regression coefficient R2: 1.00
The IDS Cortisol assay is linear over the measuring range 0.59 to 45.00 µg/dL
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability
The IDS Cortisol assay is traceable to the LC-MS/MS Candidate Reference Measurement Procedure (cRMP) Total Serum Cortisol. Through analysis of a Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed panel of higher-order Candidate Reference Materials (CRM), the IDS Cortisol provided metrologically traceable results.
Stability
The stability based on accelerated stability studies determined a shelf life of 12 months
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Image /page/11/Picture/0 description: The image shows the logo for Immuno Diagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The logo is simple and modern, with a focus on the company's name and area of expertise.
d. Detection limit:
The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were determined with guidance from CLSI EP17A2, "Protocols for Determination of Limits of Detection and Limits of Quantitation" using 60 blank replicates and 13 low level samples.
| Sensitivity | Concentration (µg/dL) |
|---|---|
| Limit of Blank (LoB) | 0.10 |
| Limit of Detection (LoD) | 0.24 |
| Limit of Quantitation (LoQ) | 0.59 |
e. Analytical specificity:
Interference and cross-reactivity studies were performed in accordance with the CLSI EP07-A3 Interference.
The potential interference of each substance in the specific detection of Cortisol, with the exception of Rheumatoid Factor (see the description of the Rheumatoid Factor interference), was tested using human serum samples with low and high cortisol concentrations. Interference substances were spiked into the serum samples and the results were measured and compared between the spiked and unspiked samples.
% Interference was calculated using the following formula:
$$% \text{Interference} = \underbrace{(\text{mean spilled concentration} - \text{mean unspilled concentration})}_{\text{mean unspilled concentration}} \ge 100$$
To determine potential interference of Rheumatoid Factor, a serum sample with low Cortisol and high Rheumatoid Factor concentration was diluted 1:2 and 1:4 in cortisol zero matrix and each dilution was assayed in duplicate. Linearity on dilution was assessed.
% Observed/Expected (%O/E) was calculated using the following formula:
% O/E= observed mean concentration x 100 expected concentration
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Image /page/12/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with a red circle above the "i". Below the letters, the words "immunodiagnostic systems" are written in a smaller, sans-serif font. The color scheme is primarily gray and red.
The following compounds were tested and found not to interfere significantly with the test, based on the predefined acceptance criteria of non-significant interference of <10% bias between the test and control samples:
| Potentially Interfering Agent | Threshold Concentration |
|---|---|
| Acetaminophen | 200 µg/mL |
| Bilirubin (Conjugated) | 40 mg/dL |
| Bilirubin (Unconjugated) | 40 mg/dL |
| Biotin | 6 µg/mL |
| Carbamazepine | 30 µg/mL |
| Haemoglobin | 500 mg/dL |
| HAMA | 1000 ng/mL |
| Ibuprofen | 500 µg/mL |
| Phenytoin | 50 µg/mL |
| RhF | 2000 IU/mL |
| Total protein | 12 g/dL |
| Triglycerides | 3000 mg/dL |
Cross-reactivity testing was performed for Cortisone, Corticosterone, Dexamethasone, Prednisone, Prednisolone, 21-deoxycortisol, 6-a-Methylprednisolone, 17-a-Hydroxyprogesterone, 6-b-Hydroxycortisol, Progesterone, 11-Deoxycortisol, 11-Deoxycorticosterone, Aldosterone.
For each serum sample spiked with a cross-reactant, a control (unspiked sample) was prepared by replacing the cross-reactant with the same volume of cross-reactant solvent. Both spiked and unspiked samples were assayed in 26 replicates each.
The cross reactivity was determined using the formula below:
% cross reactivity =
(Mean conc. of spiked sample - mean conc. of un-spiked sample) x 100%
Final concentration of cross-reactant added
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| Potentially Cross reactant | Tested Concentration | % cross reactivity |
|---|---|---|
| Aldosterone | 1000 µg/dL | 0.0 |
| Cortisone | 100 µg/dL | 36.5 |
| Corticosterone | 100 µg/dL | 19.9 |
| Dexamethasone | 1000 µg/dL | 1.4 |
| Prednisone | 100 µg/dL | 43.5 |
| Prednisolone | 50 µg/dL | 51.3 |
| 21-deoxycortisol | 100 µg/dL | 37.0 |
| 6-a-Methylprednisolone | 10 µg/dL | -0.4 |
| 17-a-Hydroxyprogesterone | 1000 µg/dL | 2.6 |
| 6-b-Hydroxycortisol | 100 µg/dL | 0.4 |
| Progesterone | 1000 µg/dL | 0.3 |
| 11-Deoxycortisol | 100 µg/dL | 11.5 |
| 11-Deoxycorticosterone | 1000 µg/dL | 2.2 |
f. Assay cut-off:
Not applicable
2. Comparison studies:
a. Method comparison against the predicate device:
The IDS Cortisol assay was compared against the Roche Elecsys Cortisol II for the quantitative determination of Cortisol, following CLSI EP-9A3, "Method Comparison and Bias Estimation Using Patient Samples". A total of 194 samples, selected to represent a wide range of Cortisol concentrations [0.64 to 44.66 ug/dL], were assayed by each method. Passing-Bablok regression analysis was performed on the comparative data:
| n | Slope | 95% CI | Intercept(µg/dL) | 95% CI | CorrelationCoefficient (r) |
|---|---|---|---|---|---|
| 194 | 1.06 | 1.04 to 1.07 | -0.10 | -0.39 to 0.04 | 0.99 |
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Image /page/14/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The logo is simple and modern, with a focus on the company's name and area of expertise.
b. Matrix comparison:
The IDS Cortisol matrix comparison study was performed to evaluate the difference across tube types (serum separator tubes (SST), lithium heparin plasma, sodium heparin plasma, K2 EDTA plasma and K3 EDTA plasma) versus the control samples (red top serum, without additive) following the CLSI EP9-A3 guideline. A total of 45 samples (36 native, 9 spiked or diluted) to cover the range of 0.89 to 42.38 ug/dL. Passing-Bablok regression analysis was performed on the comparative data:
| Sample type | N | Slope | 95% CI | Intercept(µg/dL) | 95% CI | Corr.Coeff. (r) |
|---|---|---|---|---|---|---|
| SST | 45 | 1.02 | 0.99 to 1.03 | -0.08 | -0.18 to 0.10 | 1.00 |
| K2 EDTA | 45 | 1.03 | 1.01 to 1.04 | -0.11 | -0.23 to 0.03 | 1.00 |
| K3 EDTA | 45 | 1.02 | 0.99 to 1.03 | -0.10 | -0.29 to 0.08 | 1.00 |
| Lithium Heparin | 45 | 1.00 | 0.99 to 1.02 | 0.15 | -0.01 to 0.33 | 1.00 |
| Sodium Heparin | 45 | 1.01 | 1.00 to 1.03 | 0.00 | -0.16 to 0.18 | 1.00 |
3. Expected values/Reference range:
The cortisol concentration was measured in serum samples collected from 307 apparently healthy donors using the IDS Cortisol assay. The study cohort included subjects from 21 to 65 years of age, with normal blood pressure (120/80) and normal BMI, (18.5 to 29.0). Individuals who were pregnant, breast feeding, had personal history of chronic disease, under any prescription medication or any doctor prescribed diet were excluded from the study. The 95 % reference intervals for apparently healthy adults were calculated by a non-parametric method following guidance from CLSI C28-A3 "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory".
The package insert recommends that 'Each laboratory should determine ranges for their local population.
| Morning hours | Afternoon hours | |
|---|---|---|
| 6 - 10 am | 4 - 8 pm | |
| Number of subjects | 151 | 156 |
| Mean µg/dL | 11.6 | 7.46 |
| SD (µg/dL) | 3.88 | 2.81 |
| Median µg/dL | 11.3 | 7.15 |
| Observed 2.5th to 97.5th percentile µg/dL | 4.23-20.1 | 2.37-13.6 |
Conclusion:
The IDS Cortisol assay data presented and provided are complete and supports the basis for substantial equivalence to the predicate device.
§ 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.