IDS ACTH II

K223867 · Immunodiagnostic Systems Limited · CKG · Aug 18, 2023 · Clinical Chemistry

Device Facts

• Record ID: K223867
• Device Name: IDS ACTH II
• Applicant: Immunodiagnostic Systems Limited
• Product Code: CKG · Clinical Chemistry
• Decision Date: Aug 18, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1025
• Device Class: Class 2

Intended Use

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.

Device Story

IDS ACTH II is an automated in vitro diagnostic assay for quantitative measurement of ACTH in human K2 and K3 EDTA plasma. The device uses a sandwich chemiluminescence immunoassay protocol on the IDS-iSYS Multi-Discipline Automated System. The reagent cartridge includes magnetic particles coated with mouse monoclonal anti-ACTH antibody, an acridinium ester-labeled mouse monoclonal anti-ACTH antibody, and buffer. The system processes the sample, performs the immunoassay, and provides a quantitative result in pg/mL. It is intended for use in clinical laboratories by trained personnel. Healthcare providers use the ACTH concentration results, alongside other clinical and laboratory data, to assess pituitary and adrenal gland function and diagnose hyper- or hypo-cortisolism. The device provides a standardized, automated method for ACTH testing, facilitating clinical decision-making regarding adrenal and pituitary disorders.

Clinical Evidence

Bench testing only. Performance evaluated per CLSI guidelines: LoB (0 pg/mL), LoD (1 pg/mL), LoQ (3 pg/mL). Linearity confirmed 4–1000 pg/mL. Precision (repeatability/reproducibility) evaluated across 5 samples; CVs generally <10% at higher concentrations. Interference testing showed no significant bias (≤±10%) for common substances (bilirubin, biotin, hemoglobin, HAMA, RF, etc.) up to specified thresholds. Cross-reactivity with related peptides (POMC, endorphins, MSH, ACTH fragments) was negligible. Method comparison (N=170) against a commercial automated assay showed high correlation (r=1.0, slope 1.0). Matrix comparison (N=55) confirmed equivalence between K2 and K3 EDTA plasma.

Technological Characteristics

Electrochemiluminescence immunoassay. Components: mouse monoclonal anti-ACTH antibody-coated magnetic particles, acridinium-labeled ACTH antibody conjugate, phosphate buffers, BSA, ProClin 300 preservative. Automated on IDS-iSYS Multi-Discipline Automated Analyzer. Measuring range: 4-1000 pg/mL. LoD: 1 pg/mL; LoQ: 3 pg/mL. Complies with CLSI EP05-A3, EP07, EP09c, EP17-A2, EP28-A3c, EP35, and EP37 standards.

Indications for Use

Indicated for quantitative determination of ACTH in human K2 and K3 EDTA plasma to aid in assessment of pituitary and adrenal gland function and differential diagnosis of hyper- and hypo-cortisolism. No specific age or gender restrictions provided.

Regulatory Classification

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.

Predicate Devices

• Roche Elecsys- ACTH (K060585)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

| <span>☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span>☐</span> 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 Limited<br>10 Didcot Way<br>Boldon Business Park<br>Boldon<br>Tyne and Wear<br>NE35 9PD<br>United Kingdom<br>Contact Person: Mick Henderson<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail]<br>Secondary Contact: Lee Harris<br>Phone: [phone]<br>Fax: [phone]<br>Email : [e-mail] |
| 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.<br>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 reagent<br>cartridge contains multiple reagents:<br>- MP: Magnetic particles coated with mouse monoclonal anti-<br>ACTH antibody and buffer containing phosphate with blocking<br>proteins and ProClin 300 as preservative.<br>- R1: Mouse monoclonal anti-ACTH antibody labelled with an<br>acridinium ester derivative, in buffer containing phosphate with<br>BSA and ProClin 300 as preservative.<br>- R2: Buffer containing phosphate with blocking proteins and<br>ProClin 300 as preservative. |
| Indications for Use | IDS ACTH II assay is an automated in vitro diagnostic device<br>intended for the quantitative, determination of ACTH in human K2<br>and K3 EDTA plasma on the IDS system. Results are to be used in<br>conjunction with other clinical and laboratory data as an aid in the<br>assessment of pituitary and adrenal gland function and the<br>differential diagnosis of hyper- and hypo-cortisolism. |
| Conditions for use | For in vitro diagnostic use only.<br>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)

| Assay<br>Performance | Predicate Device<br>ROCHE ELECSYS- ACTH<br>(k060585) | Candidate Device<br>IDS ACTH II |
|----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------|
| Intended Use | ACTH measurements are used<br>in the differential diagnosis and<br>treatment of certain disorders<br>of the adrenal glands such as<br>Cushings syndrome,<br>adrenocortival insufficiency,<br>and the ectopic ACTH<br>syndrome. | same |
| Method of<br>detection (Test<br>methodology) | Chemiluminescence | same |
| Assay protocol | Sandwich assay | same |

## Differences compared to the chosen predicate device (k060585)

| Assay<br>Performance | Predicate Device<br>ROCHE ELECSYS- ACTH<br>(k060585) | Candidate Device<br>IDS ACTH II |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>Use | Immunoassay for the in vitro<br>quantitative determination of<br>adrenocorticotropic hormone<br>(ACTH) in human EDTA<br>plasma.<br>The electrochemiluminescence<br>immunoassay "ECLIA" is<br>intended for use on the Roche<br>Elecsys 1010/2010 and<br>MODULAR ANALYTICS E<br>170 (Elecsys module)<br>immunoassay analyzers. | IDS ACTH II assay is an automated<br>in vitro diagnostic device intended<br>for the quantitative, determination<br>of ACTH in human K2 and K3<br>EDTA plasma on the IDS system.<br>Results are to be used in<br>conjunction with other clinical and<br>laboratory data as an aid in the<br>assessment of pituitary and adrenal<br>gland function and the differential<br>diagnosis of hyper- and hypo-<br>cortisolism. |
| Sample type | Human plasma treated with K3-<br>EDTA | Human plasma treated with K2 and<br>K3-EDTA |
| Sample<br>Volume | 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.<br>(pg/mL) | Repeatability<br>(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<br>(pg/mL) | 95 % CI | Correlation<br>Coeff. (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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Image /page/11/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 red, in a smaller, sans-serif font. The 'R' in a circle indicates that the logo is a registered trademark.

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<br>(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.