ROCHE ELECSYS- ACTH,ACTH CALSET,ACTH CALCHECK,PRECICONTROL ACTH

K060585 · Roche Diagnostics Corp. · CKG · May 3, 2006 · Clinical Chemistry

Device Facts

• Record ID: K060585
• Device Name: ROCHE ELECSYS- ACTH,ACTH CALSET,ACTH CALCHECK,PRECICONTROL ACTH
• Applicant: Roche Diagnostics Corp.
• Product Code: CKG · Clinical Chemistry
• Decision Date: May 3, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1025
• Device Class: Class 2

Indications for Use

Elecsys ACTH Reagent: Immunoassay for the in vitro quantitative determination of adrenocorticotropic hormone (ACTH) in human EDTA plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E 170 (Elecsys module) immunoassay analyzers. Elecsys ACTH CalSet is used for calibrating the quantitative Elecsys ACTH assay on the Elecsys immunoassay analyzers. Elecsys ACTH CalCheck: For use in the verification of the calibration established by the Elecsys ACTH reagent on Elecsys 1010/2010 and MODULAR E170 immunoassay analyzers. Elesys PreciControl ACTH is used for quality control of the Elecsys ACTH immunoassay on the Elecsys immunoassay analyzers.

Device Story

Elecsys ACTH Assay is a two-step sandwich immunoassay using streptavidin-coated microparticles and electrochemiluminescence (ECLIA) detection. Input is human EDTA plasma; device transforms input via sandwich formation and ECLIA signal generation; output is quantitative ACTH concentration (pg/mL). Used in clinical laboratories on Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 analyzers; operated by laboratory technicians. Results assist clinicians in diagnosing and managing adrenal disorders. System includes dedicated calibrators (CalSet), calibration verification material (CalCheck), and quality controls (PreciControl).

Clinical Evidence

Bench testing only. Performance validated via precision studies (within-run CV 0.6-2.9%, total CV 1.7-5.4%), analytical sensitivity (1.0 pg/mL), and linearity (1-2,000 pg/mL). Method comparison against a commercially available ACTH test yielded y = 0.90x + 8.17 (r=0.992, n=180). Specificity testing confirmed no cross-reactivity with ACTH fragments or related hormones at physiological levels. No high-dose hook effect observed up to 1,000,000 pg/mL.

Technological Characteristics

Two-step sandwich immunoassay; electrochemiluminescence detection; streptavidin-coated microparticles. Analyzers: Elecsys 1010/2010 and MODULAR ANALYTICS E170. Calibrators/Controls: Lyophilized equine serum matrix. Standardization: Gravimetric with synthetic ACTH. Connectivity: Integrated with Roche immunoassay analyzer systems.

Indications for Use

Indicated for the quantitative determination of ACTH in human EDTA plasma to aid in the differential diagnosis and treatment of adrenal gland disorders, including Cushing's syndrome, adrenocortical insufficiency, and ectopic ACTH syndrome.

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

• Immulite ACTH assay (k960066)
• Elecsys Prolactin II Cal Check (k053059)
• Elecsys PreciControl Troponin T (k031990)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k060585

B. Purpose for Submission:
New Device

C. Measurand:
Adrenocorticotropic hormone (ATCH)

D. Type of Test:
Quantitative electrochemiluminescence immunoassay

E. Applicant:
ROCHE DIAGNOSTICS CORP.

F. Proprietary and Established Names:
Roche Elecsys-ACTH, ACTH CalSet, ACTH CalCheck, PreciControl ACTH

G. Regulatory Information:
1. Regulation section:
21 CFR §-862.1025-Adrenocorticotropic hormone (ACTH) test system.
21 CFR §-862.1150-Calibrator.
21 CFR §-862.1660-Quality control material (assayed and unassayed).
2. Classification:
Class II
3. Product code:
CKG - Radioimmunoassay, ACTH
JIT- Calibrator, secondary
JJX- Single (specified) analyte controls (assayed and unassayed)
4. Panel:
Chemistry (75)

H. Intended Use:
1. Intended use(s):
See Indications for use
2. Indication(s) for use:
Elecsys ACTH Assay:
Immunoassay for the in vitro quantitative determination of adrenocorticotropic
hormone (ACTH) in human EDTA plasma. The electrochemiluminescence
immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010/2010 and
MODULAR ANALYTICS E 170 (Elecsys module) immunoassay analyzers.
ACTH measurements are used in the differential diagnosis and treatment of
certain disorders of the adrenal glands such as Cushings syndrome, adrenocortical
insufficiency, and the ectopic ACTH syndrome.

Elecsys ACTH CalSet is used for calibrating the quantitative Elecsys ACTH
assay on the Elecsys immunoassay analyzers.

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Elecsys ACTH CalCheck:

For use in the verification of the calibration established by the Elecsys ACTH reagent on Elecsys 1010/2010 and MODULAR E170 immunoassay analyzers.

Elecsys PreciControl ACTH is used for quality control of the Elecsys ACTH immunoassay on the Elecsys immunoassay analyzers.

3. Special conditions for use statement(s):

For prescription use

4. Special instrument requirements:

Roche Elecsys 1010/2010 and MODULAR ANALYTICS E 170

I. Device Description:

The Elecsys ACTH Assay consists of 3 wet reagents that include streptavidin-coated microparticles, biotinylated mouse monoclonal anti-ACTH antibody, ruthenium-labeled monoclonal mouse anti-ACTH antibody, buffer, and preservatives. Each kit includes reagents for 100 tests.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Immulite ACTH assay, Elecsys Prolactin II Cal Check, and Elecsys PreciControl Troponin T

2. Predicate 510(k) number(s):

k960066, k053059, and k031990 respectively

3. Comparison with predicate:

Substantial equivalence - similarities

| Immunoassay Comparison | | |
| --- | --- | --- |
| Feature | Elecsys ACTH | Predicate Device Immulite ACTH Assay |
| Intended Use | Immunoassay for the in vitro quantitative determination of adrenocorticotropic hormone (ACTH) in human EDTA plasma. The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E 170 (Elecsys module) immunoassay analyzers. | For in vitro diagnostic use with the Immulite 2000 analyzer – for the quantitative measurement of adrenocorticotropic hormone in EDTA, plasma, as an aid in the assessment of adrenal insufficiency and hypersecretion. |
| Indication for Use | ACTH measurements are used in the differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushings syndrome, adrenocortical insufficiency, and the ectopic ACTH syndrome. | As an aid in the assessment of adrenal insufficiency and hypersecretion. |
| Assay Protocol | Sandwich assay | Solid-phase, two site |

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| Detection Protocol | Electrochemiluminescent Immunoassay | Chemiluminescent immunometric assay |
| --- | --- | --- |
| Sample Type | Human plasma treated with K3-EDTA | Human plasma treated with EDTA |
| Calibrator | ACTH CalSet | ACTH Adjustors (LACL, LACH) |
| CalSet Comparison | | |
| --- | --- | --- |
| Characteristic | Elecsys ACTH CalSet | Predicate Device
Immulite ACTH Assay |
| Levels | Two | Same |
| Format | Lyophilized | Same |
| CalCheck Comparison | | |
| --- | --- | --- |
| Characteristic | Elecsys ACTH CalCheck | Predicate Device
Elecsys Prolactin II CalCheck |
| Levels | Three | Same |
| Format | Lyophilized | Same |
| Stability | Unopened:
Store at 2-8°C up to the printed expiration date on the bottle labels

Reconstituted:
15 – 25 °C : 4 hrs | Same |
| PreciControl Comparison | | |
| Characteristic | Elecsys ACTH PreciControl | Predicate Device
Elecsys PreciControl Troponin T |
| Levels | Two | Same |
| Format | Lyophilized | Same |
| Handling | Dissolve carefully the contents of one bottle by adding exactly 2.0 mL of distilled water and allow to stand closed for 15 minutes to reconstitute. Mix carefully, avoiding the formation of foam. | Same |

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Substantial equivalence – differences

| Immunoassay Comparison | | |
| --- | --- | --- |
| Feature | Elecsys ACTH | Predicate Device
Immulite ACTH Assay |
| Calibration Interval | E170/Elecsys 2010:
After 1 month (28 days) when using the same reagent lot.
After 7 days (when using the same reagent kit on the analyzer).
Elecsys 1010:
With every reagent kit.
After 7 days (20-25°C).
After 3 days (25-32°C). | Every four weeks. |
| Platform | Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) analyzers. | Immulite 2000 Analyzer |
| Calibration Verification | ACTH CalCheck | None stated in the package insert. |
| Controls | PreciControl ACTH | LACCM: Bi-level ACTH control module (protein based). |
| Feature | Elecsys ACTH | Predicate Device
Immulite ACTH Assay |
| Reagent Stability | Unopened:
2-8°C - Up to the stated expiration date

Opened:
2-8°C - 12 weeks
On the E170 / Elecsys 2010 – 4 weeks
On the Elecsys 1010: – 4 weeks
(stored alternately in the refrigerator and on the analyzer- ambient temperature 20-25°C; up to 20 hours opened in total.) | ACTH Reagent Wedge:
Stable at 2 – 8°C until the expiration date. |
| Measuring Range | 1 – 2,000 pg/mL | 5 – 1,250 pg/mL |

K. Standard/Guidance Document Referenced (if applicable):
CLSI - Evaluation of Precision Performance of Clinical Chemistry Devices;
Approved Guideline-Second Edition - EP05-A2

L. Test Principle:
Test principle
- Sandwich principle. Total duration of assay: 18 minutes.
- 1st incubation: 50 μL of sample, a biotinylated monoclonal ACTH-specific

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antibody, and a monoclonal ACTH-specific antibody labeled with a ruthenium complexa react to form a sandwich complex.

- 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
- The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
- Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode.

# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility:

Reproducibility was determined using Elecsys reagents, pooled human plasma (HP) and controls (PC) in a modified protocol CLSI EP5-A: 6 times daily for 10 days $(n = 60)$ ; within-run precision on MODULAR ANALYTICS E170 analyzer, $n = 21$ . The following results were obtained:

| Elecsys 1010/2010 | | | Within-run precision | | | Total precision | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean pg/mL | pmol/L | SD pg/mL | pmol/L | CV % | SD pg/mL | pmol/L | CV % |
| HP 1 | 4.9 | 1.08 | 0.14 | 0.031 | 2.9 | 0.27 | 0.059 | 5.4 |
| HP 2 | 74.2 | 16.3 | 1.45 | 0.319 | 2.0 | 1.75 | 0.385 | 2.4 |
| HP 3 | 1390 | 306 | 29.8 | 6.56 | 2.1 | 36.2 | 7.97 | 2.6 |
| PC ACTH1 | 115 | 115 | 1.76 | 0.388 | 1.5 | 1.96 | 2.18 | 1.7 |
| PC ACTH2 | 970 | 214 | 15.9 | 3.50 | 1.6 | 17.6 | 3.88 | 1.8 |
| MODULAR ANALYTICS E170 | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Within-run precision | | | | | Total precision | | | | |
| Sample | Mean | | SD | | CV | Mean | | SD | | CV |
| | pg/mL | pmol/L | pg/mL | pmol/L | % | pg/mL | pmol/L | pg/mL | pmol/L | % |
| HP 1 | 4.9 | 1.08 | 0.13 | 0.03 | 2.7 | 4.96 | 1.09 | 0.266 | 0.059 | 5.4 |
| HP 2 | 64.3 | 14.2 | 0.41 | 0.09 | 0.6 | 76.1 | 16.8 | 2.67 | 0.588 | 3.5 |
| HP 3 | 1205 | 265 | 7.83 | 1.72 | 0.7 | 1444 | 318 | 53.6 | 11.8 | 3.7 |
| PC ACTH1 | 111 | 24.4 | 0.70 | 0.15 | 0.6 | 114 | 25.1 | 2.09 | 0.460 | 1.8 |
| PC ACTH2 | 968 | 213 | 11.4 | 2.51 | 1.2 | 972 | 214 | 19.1 | 4.2 | 2.0 |

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b. Linearity/assay reportable range:

The reportable range of the assay is 1.0-2000 pg/mL (0.220-440 pmol/L). This range is defined by the lower detection limit and the maximum of the master curve. Values below the detection limit are reported as < 1.0 pg/mL (< 0.220 pmol/L). Values above the measuring range are reported as > 2000 pg/mL (> 440 pmol/L).

The sponsor demonstrated linearity of the assay up to 1766.7 pg/mL.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Traceability: This method has been standardized gravimetrically with synthetic ACTH produced at Roche.

The CalSet, CalCheck and the PreciControl products are assayed and compared to reference preparations and target values and ranges are assigned. The values for ACTH are standardized against in-house reference standards (synthetic ACTH in analyte-free human plasma matrix).

Study 1: Accelerated Stability

The Elecsys ACTH calibrators were stored at 35°C for 3 weeks, the reference material at 4°C. At the end of three weeks, this on-test material was analyzed in duplicate along with a reference material. The recovery was calculated as a percent of the reference value.

Study 2: Reconstituted Stability at 20-25°C

The Elecsys ACTH calibrators were reconstituted and stored for 4 hours at 20-25°C. The respective reference material was stored at 4°C. At the end of storage time, the on-test material was analyzed in duplicate along with a reference material. The recovery was calculated as a percent of the reference value.

Study 3: Reconstituted Stability at -20°C:

The Elecsys ACTH calibrators were reconstituted and stored for 12 weeks at -20°C. The respective reference material was stored at 4°C. At the end of storage time, the on-test material was analyzed in duplicate along with a reference material. The recovery was calculated as a percent of the reference value.

The sponsor’s acceptance criterion was recovery of signal 90 – 110% of the reference value.

ACTH CalCheck and PreciControl ACTH: followed the same study protocols as above. The sponsor’s acceptance criterion was recovery of concentration 85 – 115% of the reference value.

d. Detection limit:

1.0 pg/mL (0.220 pmol/L)

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The detection limit represents the lowest measurable analyte level that can be distinguished from zero (limit of the blank). It is calculated as the value lying two standard deviations above that of the lowest standard (master calibrator, standard 1 + 2 SD, within-run precision, n = 21).

e. Analytical specificity:

The Elecsys ACTH two-site immunoassay measures intact ACTH 1-39. When ACTH fragments or peptides were added to a patient's plasma sample with defined ACTH concentration, no interference was observed with ACTH 1-10, ACTH 11-24, beta-MSH, and beta-Endorphin. Other ACTH fragments (ACTH 1-17, ACTH 1-24, ACTH CLIP 18-39, ACTH 22-39, alpha-MSH 1-13) > approx. 5000 pg/mL can bind to one of the antibodies and thereby negatively interfere with the sandwich formation and lead to lower ACTH values. See table below:

| Cross-Reactant | Concentration of cross-reactant [pg/mL] | Apparent ACTH [pg/mL] | Change in ACTH concentration [pg/mL] | % Cross-reactivity |
| --- | --- | --- | --- | --- |
| None (control) | 0 | 44.1 | -- | -- |
| ACTH 1-17 | 50000 | 10.6 | -33.5 | -0.07 |
| | 5000 | 36.9 | -7.2 | -0.14 |
| | 500 | 42.6 | -1.5 | -0.31 |
| ACTH 1-24 | 50000 | 10.2 | -33.8 | -0.07 |
| | 5000 | 37.9 | -6.2 | -0.12 |
| | 500 | 42.5 | -1.6 | -0.32 |
| ACTH 18-39 | 50000 | 2.0 | -42.1 | -0.08 |
| | 5000 | 14.9 | -29.2 | -0.58 |
| | 500 | 37.0 | -7.0 | 1.41 |
| ACTH 22-39 | 50000 | 0.00 | -44.1 | -0.09 |
| | 5000 | 6.3 | -37.8 | -0.76 |
| | 500 | 29.4 | -14.7 | -2.94 |
| alpha MSH | 50000 | 12.3 | -31.8 | -0.06 |
| | 5000 | 34.3 | -9.8 | -0.20 |
| | 500 | 41.3 | -2.8 | -0.56 |

Pro-opiomelanocortin (POMC - partially purified from an adenoma cell line) showed approximately 1.6% cross-reactivity at 1560 pmol/L.

The following pharmaceutical compounds were spiked into plasma samples and tested by the Elecsys ACTH on Elecsys 2010 Immunoassay Analyzer.

Each compound was found to be non-interfering at the concentration listed below.

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| Compound | Concentration |
| --- | --- |
| Acetaminophen | 20 mg/L |
| Acetylcysteine | 30 mg/L |
| Acetylsalicylic acid | 300 mg/L |
| Ampicillin | 200 mg/L |
| Ascorbic acid | 30 mg/L |
| Ca- Dobesilate | 20 mg/L |
| Cefoxitin | 250 mg/L |
| Cyclosporine | 1 mg/L |
| Doxycycline | 10 mg/L |
| Heparin | 10 U/mL |
| Ibuprofen | 50 mg/L |
| Levodopa | 4 mg/L |
| Methyldopa | 2 mg/L |
| Metronidazole | 10 mg/L |
| Phenylbutazone | 100 mg/L |
| Rifampicin | 20 mg/L |
| Theophylline | 10 mg/L |

The assay is unaffected by icterus (bilirubin < 25 mg/dL), hemolysis (Hb < 0.4 g/dL), lipemia (Intralipid < 1500 mg/dL), or biotin (< 60 ng/mL). Rheumatoid factor above 400 IU/mL may interfere with the assay results. The sponsor’s acceptance criterion was recovery within ± 15% of initial value.

Studies evaluating high-dose hook effect demonstrated that samples containing ACTH concentrations up to 1*10⁶ pg/mL do not give falsely low results with this assay.

f. Assay cut-off:
Not Applicable

2. Comparison studies:

a. Method comparison with predicate device:
A comparison of the Elecsys ACTH assay (y) with a commercially available ACTH test (x) using clinical samples gave the following regression statistics (units = pg/mL):
Number of samples measured: 180

Passing/Bablok
y=1.08x+1.23 τ = 0.898
Linear regression
y=0.90x+8.17 r = 0.992
SD (md68) = 2.55
Sy.x = 13.8

The sample concentrations were between 5.0 and 941 pg/mL (1.1 and 207 pmol/L).

b. Matrix comparison:

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Not Applicable

3. Clinical studies:
a. Clinical Sensitivity: Not Applicable
b. Clinical specificity: Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable

4. Clinical cut-off: Not Applicable

5. Expected values/Reference range: Studies with the Elecsys ACTH assay using plasma samples from 354 apparently healthy adults gave the following results (5th-95th percentile): 7.2-63.3 pg/mL (1.6-13.9 pmol/L)

N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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