TOTAL INTACT PTH IMMUNOCHEMILUMINOMETRIC (ICMA) ASSAY KIT

K051150 · Scantibodies Laboratory, Inc. · CEW · Jul 26, 2005 · Clinical Chemistry

Device Facts

• Record ID: K051150
• Device Name: TOTAL INTACT PTH IMMUNOCHEMILUMINOMETRIC (ICMA) ASSAY KIT
• Applicant: Scantibodies Laboratory, Inc.
• Product Code: CEW · Clinical Chemistry
• Decision Date: Jul 26, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1545
• Device Class: Class 2

Indications for Use

The Scantibodies Laboratory, Inc. Total Intact Parathyroid Hormone (PTH) test system is a device intended to measure parathyroid hormone in plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.

Device Story

The Total Intact PTH ImmunoChemiluminoMetric (ICMA) Assay is an in vitro diagnostic test system used to measure parathyroid hormone levels in human plasma samples. The device utilizes an immuno-chemiluminometric assay principle to quantify PTH concentrations. It is intended for use in clinical laboratory settings by trained laboratory personnel. The output, provided as a quantitative measurement of PTH, assists clinicians in the differential diagnosis of hypercalcemia and hypocalcemia. By identifying abnormal PTH levels, the assay aids in the clinical assessment of calcium metabolism disorders, facilitating appropriate patient management and treatment decisions.

Clinical Evidence

No clinical data provided; the submission relies on bench testing and substantial equivalence to legally marketed devices.

Technological Characteristics

Immunochemiluminometric assay (ICMA). Components: microtiter plate coated with anti-PTH (39-84) antibody, luminol-labeled anti-PTH (1-34) antibody, standards, controls, and triggering reagents. Requires microplate luminometer with dual injectors (100μL capacity). Analytical range up to 20,000 pg/mL. Standards calibrated against lyophilized primary standards. Complies with NCCLS guidelines EP6-A and C28-A.

Indications for Use

Indicated for the measurement of parathyroid hormone in plasma to assist in the differential diagnosis of hypercalcemia and hypocalcemia related to calcium metabolism disorders.

Regulatory Classification

Identification

A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.

Submission Summary (Full Text)

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

A. 510(k) Number:
k051150

B. Purpose for Submission:
New Device

C. Measurand:
Total Intact PTH

D. Type of Test:
Immunochemiluminometric assay (ICMA)

E. Applicant:
SCANTIBODIES LABORATORY, INC.

F. Proprietary and Established Names:
Total Intact PTH Immunochemiluminometric (ICMA) Assay

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1545, Radioimmunoassay Parathyroid Hormone
2. Classification:
Class II
3. Product code:
CEW
4. Panel:
75 (Chemistry)

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H. Intended Use:

1. Intended use(s):

See Indications for Use below.

2. Indication(s) for use:

The Scantibodies Laboratory, Inc. Total Intact Parathyroid Hormone (PTH) test system is a device intended to measure parathyroid hormone in plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.

3. Special conditions for use statement(s):

This kit has been designed for the quantitative determination of human total immunoreactive parathyroid hormone (Total Intact PTH) in blood samples. The Total Intact PTH level is the sum of the PTH (1-84) and N-truncated PTH fragments.

4. Special instrument requirements:

Microplate luminometer equipped with dual injectors capable of delivering 100μl each.

I. Device Description:

The Scantibodies Total Intact PTH Kit includes: PTH Standards (7 vials), PTH Controls (2 vials), PTH Antibody Coated Plate (1) 12 strips, Total Intact PTH Tracer ICMA (1 vial), Wash Concentrate (1 bottle), Trigger 1 (1 bottle), Trigger 2 (1 bottle).

J. Substantial Equivalence Information:

1. Predicate device name(s):

SCANTIBODIES LABORATORY, INC. Total Intact PTH Immunoradiometric (IRMA) Assay.

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

k004038

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3. Comparison with predicate:

Comparison table for new device compared to the predicate device

| Comparison of device to predicate | | |
| --- | --- | --- |
| Item | New Device
Total Intact PTH(ICMA)
k051150 | Predicate Device
Total Intact PTH (IRMA)
k001411 |
| Intended Use | Assay used to detect human parathyroid hormone in human blood sample without cross reaction to PTH (7-84) fragment | Assay used to detect human parathyroid hormone in human blood sample without cross reaction to PTH (7-84) fragment |
| Specimen | EDTA – Plasma | EDTA – Plasma |
| Assay Format | ICMA | IRMA |
| Result Read Time | 2 – 2.5 hours | 18 – 24 hours |
| Analytical Sensitivity | ~ 1.3 pg/mL | ~ 1.23 pg/mL |
| Normal Range | 8 – 46 pg/mL | 14 – 66 pg/mL |
| Solid Phase | Antibody Coated Plates – luminol – Ab conjugate | Antibody Coated Beads |

K. Standard/Guidance Document Referenced (if applicable):

NCCLS Guideline EP6-A.
NCCLS Guideline (C28-A)

L. Test Principle:

The Scantibodies Total Intact PTH Coated Bead Kit is an immunochemiluminometric assay (ICMA) utilizing polyclonal PTH antibodies directed against PTH 1-34 and PTH 39-84. The anti PTH1-34 (N-Terminal fragment) antibody is labeled with luminol. The antibody directed against 39-84 (C-terminal PTH fragments) is bound to the wells of the micro titer plate. The Total Intact PTH in the patient sample is bound both to the wells of the micro titer plate strips ant to the luminol-PTH antibody. After incubation, free and bound luminol-antibody fractions are separated by discarding the supernatant. Wash steps reduce the non-specific binding (NSB). The concentration of Total Intact PTH is directly proportional to the photons emitted from the wells upon addition of triggering reagents. The concentration of Total Intact PTH is unknown patient samples and controls are determined by interpolation using a calibration curve.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

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The inter-assay precision was evaluated by performing 20 separate Total Intact PTH assays on three samples in duplicate over a two week period. The inter-assay precision is presented in the table below.

| Precision (inter-assay) | | | |
| --- | --- | --- | --- |
| Sample | Mean Value (pg/mL) | SD (pg/mL) | %CV |
| 1 | 51.6 | 2.72 | 5.26 |
| 2 | 169.3 | 12.70 | 7.50 |
| 3 | 462.8 | 23.37 | 5.05 |

The intra-assay precision was also evaluated by performing 20 replicates of the Total PTH assays on three samples. The intra-assay precision is presented in the table below.

| Precision (intra-assay) | | | | |
| --- | --- | --- | --- | --- |
| Kit Batch | Sample | Mean Value (pg/mL) | SD (pg/mL) | % CV |
| 1 | 1 | 55.71 | 2.19 | 3.9 |
| | 2 | 186.20 | 7.59 | 4.1 |
| | 3 | 459.22 | 12.64 | 2.8 |
| 2 | 1 | 47.72 | 2.33 | 4.9 |
| | 2 | 164.62 | 6.52 | 4.0 |
| | 3 | 440.96 | 15.50 | 3.5 |
| 3 | 1 | 48.59 | 2.26 | 4.7 |
| | 2 | 169.18 | 4.71 | 2.8 |
| | 3 | 453.18 | 9.78 | 2.2 |

b. Linearity/assay reportable range:

The high dose hook response of the Scantibodies Laboratory, Inc. Total Intact PTH ICMA Diagnostic Kit was determined as 20,000 pg/mL PTH. Samples greater than the highest standard (approximately 2300 pg/mL) and up to 20,000 pg/mL will produce RLU values greater than that of the highest standard.

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

The traceability of controls and standards is not available through NIST or WHO for PTH, the sponsor indicated that they rely on the "primary standards". Values are assigned by testing new lots a minimum of 5 times using multiple analysts over multiple days. The average of the values obtained when tested against lyophilized "primary standards" was used for the value assignment of the standards.

New lots of controls were value assigned by assaying the controls a minimum of 5 times using multiple analysts over multiple days. A value

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of +/- 20% of the average of the data obtained was calculated and applied to both control I (low control) and control II (high control).

The Scantibodies PTH Calibrators were prepared analytically on a mass basis. These standards are further evaluated against lyophilized “primary standards” which are stored at -70° C to maintain potency.

d. Detection limit:

The detection limit of the assay is defined as the lowest measurable value distinguishable from calibrator A. This sensitivity was determined by assaying calibrator A 20 times in the same assay. The minimum detectable dose was approximately 1.3 mg/mL at 2 standard deviations above the first PTH calibrator.

e. Analytical specificity:

The Scantibodies Total Intact PTH assay did not show any cross-reaction to the following PTH fragments at 100,000 pg/mL:

| PTH 1-34 | Undetected |
| --- | --- |
| PTH 39-84 | Undetected |
| PTH 39-68 | Undetected |
| PTH 53-84 | Undetected |
| PTH 44-68 | Undetected |

Interferences:

The sponsor indicated that specimens containing up to 250 mg/dL triglyceride, 15 mg/dL hemoglobin and 30 mg/dL bilirubin do not exhibit any significant effect on the assay. However it is strongly recommended that grossly hemolyzed or lipemic samples should not be used in this assay.

f. Assay cut-off:

Not Applicable for this type of device.

2. Comparison studies:

a. Method comparison with predicate device:

The comparison study was conducted by preparing 3 different lots of Total Intact PTH ICMA Kits which included multiple lots of components to introduce adequate variations in manufacturing. Samples of EDTA plasma were drawn from 120 normal donors and 120 dialysis donors with elevated levels of PTH.

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All samples were tested on both the Total Intact PTH ICMA Kit and the predicate Total Intact PTH IRMA Kit with no data exclusions.

Data was compiled into 3 categories: Normal, Patient, All Samples (all samples represent a compilation of the Normal and Patient samples).

Correlation data was evaluated from the 3 categories. For Normal samples the linear correlation with the predicate device is $y = 0.88x + 1.11$ with $R = 0.932$. For donors on dialysis the linear correlation with the predicate device is $y = 0.95x + 7.35$ with $R = 0.954$. The overall correlation with the predicate is $y = 0.96 + 1.90$ with $R = 0.970$.

b. Matrix comparison:

Not applicable - this device is intended for use with plasma samples only.

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):

4. Clinical cut-off:

Not applicable for this type of device

5. Expected values/Reference range:

The normal value range was determined following the NCCLS guidelines (C28-A) using 120 samples from apparently healthy individuals. It is recommended that each laboratory establish its own range of normal values. The values given are only indicative and may vary from other published data.

| Patient Classification | Total PTH Range (pg/mL) |
| --- | --- |
| Normal | 8-46 |
| Hyperparathyroidism | >46 |

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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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