(238 days)
IDS ACTH II assay is an automated in vitro diagnostic device intended for the quantitative, determination of ACTH in human K2 and K3 EDTA plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the assessment of pituitary and adrenal gland function and the differential diagnosis of hyper- and hypo-cortisolism.
The IDS ACTH II assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:
- MP: Magnetic particles coated with mouse monoclonal anti-ACTH antibody and buffer containing phosphate with blocking proteins and ProClin 300 as preservative.
- R1: Mouse monoclonal anti-ACTH antibody labelled with an acridinium ester derivative, in buffer containing phosphate with BSA and ProClin 300 as preservative.
- R2: Buffer containing phosphate with blocking proteins and ProClin 300 as preservative.
The provided text describes the performance characteristics of the IDS ACTH II assay, which is an automated in vitro diagnostic device for the quantitative determination of ACTH in human K2 and K3 EDTA plasma. The study aims to demonstrate that the device meets the acceptance criteria for various analytical performance parameters.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" as a separate column for each test. Instead, it describes the methodology used to determine each performance characteristic and then presents the results. Based on the context and the nature of these studies, the reported values often serve as the demonstrated "performance" which, by the conclusion of the 510(k) summary, are deemed sufficient to support substantial equivalence. For analytical characteristics like Linearity, Interference, and Cross-Reactivity, the document does specify thresholds for acceptable performance.
| Performance Characteristic | Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Analytical Limits | ||
| Limit of Blank (LoB) | (Determined according to CLSI EP17-A) | 0 pg/mL |
| Limit of Detection (LoD) | (Determined according to CLSI EP17-A) | 1 pg/mL |
| Limit of Quantitation (LoQ) | Lowest concentration with within-laboratory precision CV ≤ 20% | 3 pg/mL |
| Precision | (Evaluated according to CLSI EP05-A3) | Repeatability (Within Run/Within Laboratory): CVs for various concentrations range from 0.9% to 14.5% (Within Run) and 1.7% to 26.8% (Within Laboratory). Reproducibility (Between sites/systems): CVs for various concentrations range from 1.2% to 14.4% (Repeatability) and 4.4% to 24.8% (Reproducibility). Reproducibility (Between lots): CVs for various concentrations range from 0.6% to 20.8% (Between-Run), 1.1% to 35.2% (Between-Day), and 3.2% to 50.5% (Reproducibility). |
| Linearity | Allowable Deviation of Linearity (ADL) of ≤±16.3% or ≤±4 pg/mL for concentrations below 20 pg/mL. | The IDS ACTH II is linear across the analytical measuring interval of 4 to 1000 pg/mL, within the allowable deviation of linearity. |
| Analytical Specificity (Interference) | No significant interference: ≤±10% bias (Cholesterol ≤±15%) | No significant interference (<+10% bias, excluding Cholesterol) up to specified thresholds for Bilirubin, Biotin, Haemoglobin, HAMA, Rheumatoid Factor, Total Protein, Triglyceride, Acetaminophen, Acetylsalicylic acid, Ampicillin, Ibuprofen, Dexamethasone, Metyrapone. No significant interference (≤±10% bias) observed for Total Cholesterol up to 400 mg/dL. Lowest Hemoglobin level not significantly interfering is 62.5 mg/dL. Lowest Rheumatoid Factor not significantly interfering is 324 IU/mL. |
| Analytical Specificity (Cross-Reactivity) | (Determined by % cross-reactivity formula) | Very low to negative % Cross-Reactivity for tested compounds (POMC, b-endorphin, aMSH 1-13, bMSH, ACTH 1-17, ACTH 1-24, ACTH 18-39 (CLIP), ACTH 22-39, ACTH 1-10, ACTH 11-24) across various tested concentrations (mostly below 5%, often <1%). |
| Method Comparison | Close agreement with a commercially available quantitative automated assay (predicate device). | Predicate comparison (170 samples): Slope = 1.0 (95% CI: 1.0 to 1.1), Intercept = -0.9 pg/mL (95% CI: -2.1 to 0.4), Correlation Coeff. (r) = 1.0. K2 EDTA vs K3 EDTA (55 matched samples): Slope = 1.0 (95% CI: 1.0 to 1.1), Intercept = 1.9 pg/mL (95% CI: 0.7 to 3.2), Correlation Coeff. (r) = 1.0. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Analytical Limits (LoB, LoD, LoQ):
- LoB and LoD: 60 replicates of 4 blank samples and 6 low concentration samples per reagent lot.
- LoQ: 90 replicates of 6 low concentration samples per reagent lot.
- Precision (Repeatability): 5 plasma samples, 80 replicates each (duplicate, twice a day for 20 days).
- Precision (Reproducibility – between sites/systems): 5 plasma samples, 75 replicates each (5 replicates, once a day for 5 days on 3 systems).
- Precision (Reproducibility – between lots): 5 plasma samples, 75 replicates each (5 replicates, once a day for 5 days on 1 system using 3 reagent lots).
- Linearity: The sample size isn't explicitly stated as a single number but involved testing across the analytical measuring interval of 4 to 1000 pg/mL.
- Analytical Specificity (Interference): 2 samples containing 15 and 200 pg/mL ACTH for most interfering agents; 2 samples containing 30 and 500 pg/mL ACTH for Total Cholesterol.
- Analytical Specificity (Cross-Reactivity): 2 samples containing 20 and 400 pg/mL ACTH spiked with various cross-reactants.
- Method Comparison: 170 patient samples for comparison against the predicate device.
- Matrix Comparison: 55 matched samples for K2 vs K3 EDTA comparison.
- Expected Values (Reference Interval): 140 apparently healthy adults.
Data Provenance: The document does not specify the country of origin of the data or whether the samples were retrospective or prospective, except that the submitter is based in the United Kingdom.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is an in vitro diagnostic device (an assay), not an imaging or diagnostic AI system that requires expert interpretation for ground truth. The "ground truth" for the performance characteristic studies (like LoQ, precision, linearity, interference, cross-reactivity, and method comparison) is established by the analytical measurement itself, often compared against a reference method or known spiked concentrations. For method comparison, another commercially available, quantitative automated assay serves as the comparative reference. For the reference interval study, the "ground truth" is derived from the measured ACTH concentrations in a defined population of apparently healthy adults using the IDS ACTH II assay itself, following CLSI guidelines for establishing reference intervals.
Therefore, the concept of "experts establishing ground truth" in the way it applies to imaging studies (e.g., radiologists) is not relevant here.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Adjudication methods like 2+1 or 3+1 are typically used in clinical trials or diagnostic studies where there's human interpretation involved and potential for disagreement. This document describes analytical performance studies of an IVD assay, where the results are quantitative measurements. The methods followed standard CLSI guidelines (e.g., EP17-A, EP05-A3, EP06, EP07-A3, EP-9A2, C28-A3) for laboratory testing, which do not generally involve an adjudication process in the same way clinical judgment studies would.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that involves human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is an automated in vitro diagnostic assay, meaning it operates in a standalone manner (algorithm only, without human-in-the-loop performance for result generation or interpretation, beyond standard laboratory procedures). The performance data presented are for the device's inherent analytical capabilities.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Analytical Limits, Precision, Linearity, Interference, Cross-Reactivity: Ground truth is established through controlled laboratory experiments using known concentrations (e.g., spiked samples, blank samples, reference materials) and rigorous statistical analysis as per CLSI guidelines.
- Method Comparison: The "ground truth" for method comparison is the measurement obtained from a predicate, commercially available quantitative automated assay using patient samples, against which the candidate device's measurements are compared.
- Reference Intervals: The "ground truth" for expected values is the statistical distribution of ACTH concentrations measured by the IDS ACTH II assay itself in a predefined population of apparently healthy adults (n=140).
8. The sample size for the training set
The concept of a "training set" is typically associated with machine learning or AI models. This document describes the validation of an IVD assay. The assay itself does not involve a machine learning model that requires a distinct training set. The various sample sizes mentioned in point 2 are for different performance characteristic evaluation tests.
9. How the ground truth for the training set was established
As there is no "training set" in the context of an AI/ML model for this IVD assay, this question is not applicable. The assay's analytical characteristics are established through chemical and immunochemical principles and validated through the performance studies described.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. Food & Drug Administration" in blue text.
August 18, 2023
Immunodiagnostic Systems Limited Mick Henderson Regulatory Affairs Manager 10 Didcot Way, Boldon Business Park Boldon, Tyne and Wear NE35 9PD United Kingdom
Re: K223867
Trade/Device Name: IDS ACTH II Regulation Number: 21 CFR 862.1025 Regulation Name: Adrenocorticotropic Hormone (ACTH) Test System Regulatory Class: Class II Product Code: CKG Dated: July 21, 2023 Received: July 24, 2023
Dear Mick Henderson:
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. 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/cdrh/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.
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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 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.
Marianela Perez-torres -S
Marianela Perez-Torres, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K223687
Device Name IDS ACTH II
Indications for Use (Describe)
IDS ACTH II assay is an automated in vitro diagnostic device intended for the quantitative, determination of ACTH in human K2 and K3 EDTA plasma on the IDS system. Results are to be used in conjunction with other clinical and laboratory data as an aid in the assessment of pituitary and adrenal gland function and the differential diagnosis of hyperand hypo-cortisolism.
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 shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, gray font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, pink font. A registered trademark symbol is located to the upper right of the logo.
510(k) SUMMARY
| 510k Number | K223867 |
|---|---|
| Introduction | According to the requirements of 21CFR807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| Submitter | Immunodiagnostic Systems Limited10 Didcot WayBoldon Business ParkBoldonTyne and WearNE35 9PDUnited KingdomContact 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: | 16 August 2023 |
| Device Name | Proprietary names: IDS ACTH II |
| Common names: As above | |
| Classification: 21 CFR 862.1025 Adrenocorticotropic hormone (ACTH) test system.Class 2 | |
| Product Code: CKG |
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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, lowercase font, with the "i" having a red circular dot above it. Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The logo has a registered trademark symbol next to the "s".
| Predicate Device | Roche Elecsys ACTH (K060585). |
|---|---|
| Device Description | The IDS ACTH II assay consists of a reagent cartridge. The reagentcartridge contains multiple reagents:- MP: Magnetic particles coated with mouse monoclonal anti-ACTH antibody and buffer containing phosphate with blockingproteins and ProClin 300 as preservative.- R1: Mouse monoclonal anti-ACTH antibody labelled with anacridinium ester derivative, in buffer containing phosphate withBSA and ProClin 300 as preservative.- R2: Buffer containing phosphate with blocking proteins andProClin 300 as preservative. |
| Indications for Use | IDS ACTH II assay is an automated in vitro diagnostic deviceintended for the quantitative, determination of ACTH in human K2and K3 EDTA plasma on the IDS system. Results are to be used inconjunction with other clinical and laboratory data as an aid in theassessment of pituitary and adrenal gland function and thedifferential diagnosis of hyper- and hypo-cortisolism. |
| 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, sans-serif font, with the "i" having a red circular dot above it. Below the letters "ids" is the text "immunodiagnosticsystems" in a smaller, sans-serif font, with the "immuno" portion in red and the rest in gray. A registered trademark symbol is located to the upper right of the "s" in "ids".
Comparison Tables
Similarities compared to the chosen predicate device (K060585)
| AssayPerformance | Predicate DeviceROCHE ELECSYS- ACTH(K060585) | Candidate DeviceIDS ACTH II |
|---|---|---|
| Intended Use | ACTH measurements are usedin the differential diagnosis andtreatment of certain disordersof the adrenal glands such asCushings syndrome,adrenocortival insufficiency,and the ectopic ACTHsyndrome. | same |
| Method ofdetection (Testmethodology) | Chemiluminescence | same |
| Assay protocol | Sandwich assay | same |
Differences compared to the chosen predicate device (K060585)
| AssayPerformance | Predicate DeviceROCHE ELECSYS- ACTH(K060585) | Candidate DeviceIDS ACTH II |
|---|---|---|
| Indications forUse | Immunoassay for the in vitroquantitative determination ofadrenocorticotropic hormone(ACTH) in human EDTAplasma.The electrochemiluminescenceimmunoassay "ECLIA" isintended for use on the RocheElecsys 1010/2010 andMODULAR ANALYTICS E170 (Elecsys module)immunoassay analyzers. | IDS ACTH II assay is an automatedin vitro diagnostic device intendedfor the quantitative, determinationof ACTH in human K2 and K3EDTA plasma on the IDS system.Results are to be used inconjunction with other clinical andlaboratory data as an aid in theassessment of pituitary and adrenalgland function and the differentialdiagnosis of hyper- and hypo-cortisolism. |
| Sample type | Human plasma treated with K3-EDTA | Human plasma treated with K2 andK3-EDTA |
| SampleVolume | 50 µL | 150 µL |
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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, lowercase font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnostic systems' are written in a smaller, red font. The 'R' in a circle indicates that the logo is a registered trademark.
| Measuring Range | 1 – 2,000 pg/mL | 4 – 1,000 pg/mL |
|---|---|---|
| ----------------- | ----------------- | ----------------- |
Performance Characteristics
Analytical Limits at Low levels
The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were determined with guidance from CLSI EP17-A, "Protocols for Determination of Limits of Detection and Limits of Quantitation". LoB and LoD were determined with 60 replicates of 4 blank samples and 6 low concentration samples per reagent lot. LoQ was determined with 90 replicates of 6 low concentration samples per reagent lot. The LoQ was determined as the lowest concentration with a within-laboratory precision CV ≤ 20%".
| Sensitivity | Concentration (pg/mL) |
|---|---|
| Limit of Blank (LoB) | 0 |
| Limit of Detection (LoD) | 1 |
| Limit of Quantitation (LoQ) | 3 |
Precision (Repeatability/Reproducibility)
Precision was evaluated based on guidance from CLSI EP05-A3 3rd Edition, "Evaluation of Precision Performance of Quantitative Measurement Methods".
Repeatability
A total of 5 plasma samples were tested using 1 lot of reagents in duplicate, twice a day for 20 days on 1 system to assess the repeatability.
| Sample | N | Mean Conc.(pg/mL) | Repeatability(Within Run) | Within Laboratory | ||
|---|---|---|---|---|---|---|
| SD | CV% | SD | CV | |||
| 1 | 80 | 6 | 0.8 | 14.5% | 1.5 | 26.8% |
| 2 | 80 | 13 | 0.7 | 5.3% | 1.6 | 12.8% |
| 3 | 80 | 81 | 0.9 | 1.2% | 2.5 | 3.1% |
| 4 | 80 | 215 | 3.1 | 1.4% | 5.3 | 2.5% |
| 5 | 80 | 616 | 5.5 | 0.9% | 10.5 | 1.7% |
Results from one (1) representative reagents lot on one (1) system:
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Image /page/7/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, lowercase font, with a red circle above the "i". The word "immunodiagnosticsystems" is written in a smaller, red font below the "ids". A registered trademark symbol is located to the right of the "s" in "ids".
Reproducibility – between sites / systems
A total of 5 plasma sample were tested using one (1) reagents lot in 5 replicates, once a day for 5 days on 3 systems by 1 operator per system to determine the reproducibility.
| Sample | N | Mean Conc. (pg/mL) | Repeatability | Reproducibility | ||
|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | |||
| 1 | 75 | 4 | 0.6 | 14.4% | 1.0 | 24.8% |
| 2 | 75 | 17 | 0.6 | 3.6% | 1.2 | 7.2% |
| 3 | 75 | 59 | 1.5 | 2.5% | 3.5 | 6.0% |
| 4 | 75 | 213 | 2.9 | 1.4% | 9.3 | 4.4% |
| 5 | 75 | 615 | 7.5 | 1.2% | 27.8 | 4.5% |
Reproducibility - between lots
A total of 5 plasma samples were tested using three (3) reagents lot in 5 replicates, once a day for 5 days on 1 system by 1 operator per system to determine the reproducibility.
| Sample | N | Mean Conc. (pg/mL) | Between-Run | Between-Day | Reproducibility | |||
|---|---|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | SD | CV% | |||
| 1 | 75 | 4 | 0.8 | 20.8% | 1.4 | 35.2% | 2.0 | 50.5% |
| 2 | 75 | 17 | 0.7 | 4.1% | 0.9 | 5.5% | 1.8 | 10.9% |
| 3 | 75 | 61 | 0.8 | 1.3% | 1.5 | 2.5% | 1.9 | 3.2% |
| 4 | 75 | 217 | 1.7 | 0.8% | 4.1 | 1.9% | 7.6 | 3.5% |
| 5 | 75 | 645 | 3.8 | 0.6% | 7.3 | 1.1% | 31.8 | 4.9% |
Linearity
A Linearity study was performed based on guidance from CLSI EP06 2nd Edition, "Evaluation of the Linearity of Quantitative Measurement Procedures". The IDS ACTH II is linear across the analytical measuring interval of 4 to 1000 pg/mL, within the allowable deviation of linearity (ADL) of ≤±16.3% or ≤±4 pg/mL for concentration below 20 pg/mL
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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 a red circle serving as the dot over the 'i'. Below the 'ids' is the full name 'immunodiagnosticsystems' in a smaller, red font. The '®' symbol is located in the upper right corner of the logo.
Analytical Specificity
Interference
Interference and cross-reactivity studies were performed in accordance with the CLSI EP07-A3 Interference. The Interference study was performed in 2 samples containing 15 and 200 pg/mL concentrations of ACTH.
The Interference using paired-difference testing was calculated using the following equation:
(Average "spiked" concentration – Average "control" concentration) % Interference = x100 Average "control" concentration
- The Interference using recovery testing was calculated using the following equation:
% Recovery
=
Observed concentration
- The Interference using method comparison testing was analyzed as follow: i
- Calculate the mean of candidate device. ■
- Calculate the concentration difference of predicate device and mean candidate device in samples ≤ 20 pg/mL.
- . Calculate the relative difference (%bias) of predicate device and mean candidate device in samples above 20 pg/mL.
No significant interference (±10% bias, Cholesterol ≤±15%) was observed when the interfering agents were tested up to the following threshold concentration:
| Potentially Interfering Agent | Threshold Concentration |
|---|---|
| Bilirubin, conjugated | 40 mg/dL |
| Bilirubin, unconjugated | 40 mg/dL |
| Biotin | 3.5 µg/mL |
| Haemoglobin | 62.5 mg/dL |
| Human Anti Mouse Antibody (HAMA) | 1000 ng/mL |
| Rheumatoid Factor | 324 IU/mL |
| Total Protein | 15 g/dL |
| Triglyceride | 1500 mg/dL |
| Acetaminophen | 15.6 mg/dL |
| Acetylsalicylic acid | 3 mg/dL |
| Ampicillin | 7.5 mg/dL |
| Ibuprofen | 21.9 mg/dL |
| Dexamethasone | 1.2 mg/dL |
| Metyrapone | 1.8 mg/mL |
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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. To the left of the letters is a red circle. Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font.
- The total Cholesterol interference study was performed in 2 samples containing 30 and -500 pg/mL concentrations of ACTH. No significant interference (≤±10% bias) was observed when total Cholesterol was tested up to 400 mg/dL.
- -"The lowest Hemoglobin level that does not significantly interfere (<+10% bias) with the assay is 62.5 mg/dL. Visual hemolysis in the sample is typically already seen in samples with hemoglobin concentration of 50 mg/dL or greater [Hemolysis Palette Bookmark-P.pdf (cdc.gov)]. Visibly hemolyzed samples must not be used with IDS ACTH II assay.
- -"The lowest Rheumatoid Factor (RF) level that does not significantly interfere (≤±10% bias) with IDS ACTH II assay is 324 IU/mL."
Cross-Reactivity
The analytical specificity study was conducted by spiking the compounds in 2 samples containing 20 and 400 pg/mL concentrations of ACTH.
The cross reactivity was determined using the formula below:
% cross reactivity =
(Mean conc. of spiked sample - mean conc. of un-spiked sample) x100% Final concentration of cross-reactant added
| Cross Reactant | Tested Concentration | % Cross-Reactivity |
|---|---|---|
| POMC | 500 | -2.1 % |
| 50 000 | -0.03 % | |
| 500 000 | -0.02% | |
| b-endorphin | 500 | -2.9% |
| 50 000 | -0.01% | |
| 500 000 | <0.01% | |
| aMSH 1-13 | 500 | -3.7% |
| 50 000 | -0.4% | |
| 500 000 | -0.1% | |
| bMSH | 500 | -4.6% |
| 50 000 | -0.01% | |
| 500 000 | <0.01% | |
| ACTH 1-17 | 500 | -1.8% |
| 50 000 | -0.6% | |
| 500 000 | -0.1% | |
| ACTH 1-24 | 500 | -5.8% |
| 50 000 | -0.5% | |
| 500 000 | -0.1% | |
| ACTH 18-39 (CLIP) | 500 | -6.5% |
| 50 000 | -0.3% |
Results are shown in the table below:
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| Image: ids Immunodiagnosticsystems logo | ||
|---|---|---|
| 500 000 | -0.1% | |
| 500 | 4.9% | |
| ACTH 22-39 | 50 000 | -0.4% |
| 500 000 | -0.1% | |
| 500 | -7.5% | |
| ACTH 1-10 | 50 000 | -0.1% |
| 500 000 | <0.01% | |
| 500 | -7.3% | |
| ACTH 11-24 | 50 000 | -0.1% |
| 500 000 | <0.01% |
Method Comparison
IDS ACTH II was compared against a commercially available quantitative automated assay, following CLSI EP-9A2, "Method Comparison and Bias Estimation Using Patient Samples". A total of 170 samples, selected to represent a wide range of ACTH concentrations [4 to 997 pg/mL], were tested by each method. Passing-Bablok regression analysis was performed on the comparative data:
| N | Slope | 95 % CI | Intercept(pg/mL) | 95 % CI | CorrelationCoeff. (r) |
|---|---|---|---|---|---|
| 170 | 1.0 | 1.0 to 1.1 | -0.9 | -2.1 to 0.4 | 1.0 |
Matrix comparison:
The sample matrix comparison studies were performed, based on guidance from CLSI EP35 Ed1 "Assessment of Equivalence for Suitability of Specimen Types for Medical Laboratory Measurement Procedures" were performed to assess the equivalence between K2 and K3 EDTA plasma sample matrices in the IDS ACTH II assay. A total of 55 matched samples, with concentration ranging from 6 to 1228 pg/mL, were compared against K3 EDTA. Passing-Bablok regression analysis was performed on the comparative data:
| Sample Type | N | Slope | 95% CI | Intercept (pg/mL) | 95% CI | Correlation Coeff. (r) |
|---|---|---|---|---|---|---|
| K2 EDTA | 55 | 1.0 | 1.0 to 1.1 | 1.9 | 0.7 to 3.2 | 1.0 |
Expected Values
The following ranges were determined using the IDS ACTH II and are provided for information only. The 95 % reference interval for apparently healthy adults were calculated
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by a non-parametric method following guidance from CLSI C28-A3 "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory".
| Unit | N | Mean | Median | Observed Range(2.5th to 97.5th percentile) |
|---|---|---|---|---|
| pg/mL | 140 | 22 | 19 | 6 to 51 |
The above ranges should be considered as guidelines only; it is recommended that each laboratory establish its own expected range based upon its own patient population.
ACTH concentrations vary considerably depending on physiological conditions. ACTH results must be interpreted in conjunction with the patient's clinical presentation and other information available to the physician.
Conclusion
The IDS ACTH II data, presented and provided, is complete and supports the basis for substantial equivalence to the predicate device.
§ 862.1025 Adrenocorticotropic hormone (ACTH) test system.
(a)
Identification. An adrenocorticotropic hormone (ACTH) test system is a device intended to measure adrenocorticotropic hormone in plasma and serum. ACTH measurements are used in the differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushing's syndrome, adrenocortical insufficiency, and the ectopic ACTH syndrome.(b)
Classification. Class II.