← Product Code [CEW](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CEW) · K063605

# ST AIA-PACK INTACT PTH ASSAY (K063605)

_Tosoh Bioscience, Inc. · CEW · Jun 21, 2007 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CEW/K063605

## Device Facts

- **Applicant:** Tosoh Bioscience, Inc.
- **Product Code:** [CEW](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CEW.md)
- **Decision Date:** Jun 21, 2007
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1545
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## Indications for Use

The Tosoh Bioscience, Inc. ST AIA-PACK Intact PTH is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of Intact Parathyroid Hormone (Intact PTH) in human serum and EDTA plasma on specific TOSOH AIA System analyzers. The Tosoh AIA-PACK Intact PTH CONTROL SET is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK Intact PTH Assay. The Tosoh AIA-PACK Intact PTH CALIBRATOR SET is intended for IN VITRO DIAGNOSTIC USE ONLY for the calibration of the ST AIA-PACK Intact PTH.

## Device Story

ST AIA-PACK Intact PTH is a two-site immunoenzymometric assay (IEMA) for quantitative measurement of intact parathyroid hormone (PTH) in human serum and EDTA plasma. Device operates on TOSOH AIA System analyzers. Input: patient serum or EDTA plasma sample. Process: sample binds to polyclonal antibody immobilized on magnetic beads and enzyme-labeled polyclonal antibody; magnetic beads washed to remove unbound components; incubated with fluorogenic substrate 4-methylumbelliferyl phosphate (4MUP). Output: fluorescence signal directly proportional to intact PTH concentration; concentration calculated via standard curve. Used in clinical laboratory settings by trained personnel. Results assist clinicians in differential diagnosis of hypercalcemia and hypocalcemia related to calcium metabolism disorders.

## Clinical Evidence

Bench testing only. Performance characteristics include limit of detection (approx 1.0 pg/ml), assay range (1-2200 pg/ml), and total precision (CV% 3.6-4.9%). Correlation study (n=153) showed R=0.997. Recovery studies (98.1-109.0%) and interference testing (hemoglobin, bilirubin) demonstrate assay robustness. No clinical prospective/retrospective studies provided.

## Technological Characteristics

Two-site immunoenzymometric assay (IEMA). Components: magnetic beads, polyclonal antibodies, fluorogenic substrate (4MUP). Analyzers: TOSOH AIA System. Analytical sensitivity: ~1.0 pg/ml. Assay range: 1-2200 pg/ml. Specimen: serum and EDTA plasma.

## Regulatory 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.

## Predicate Devices

- Roche Elecsys Parathyroid Hormone Test System (k992680)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k063605

B. Purpose for Submission:
New Device

C. Measurand:
Parathyroid Hormone

D. Type of Test:
Quantitative, Immunoenzymatic assay

E. Applicant:
Tosoh Bioscience Inc.

F. Proprietary and Established Names:
ST AIA-PACK Intact PTH Assay
ST AIA-PACK Intact PTH Calibrator Set
ST AIA-PACK Intact PTH Control Set

G. Regulatory Information:

|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  Parathyroid Hormone (CEW) | Class II | 21 CFR 862.1545
Parathyroid hormone test system | 75 Clinical Chemistry(CH)  |
|  Product Code | Classification | Regulation Section | Panel  |
|  Calibrator (JIT) | Class II | 21 CFR 862.1150
Secondary calibrator | 75 Clinical Chemistry(CH)  |
|  Product Code | Classification | Regulation Section | Panel  |
|  Control (JJX) | Class I reserved | 21 CFR§ 862.1660
Quality control material (assayed and unassayed) | 75 Clinical Chemistry(CH)  |

H. Intended Use:

1. Intended use(s):
Refer to Indications for use below.

2. Indication(s) for use:
ST AIA-PACK Intact PTH is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of the levels of parathyroid hormone in human serum and EDTA plasma on specific TOSOH AIA System analyzers. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and

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hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.

The ST AIA-PACK Intact PTH CALIBRATOR SET is intended for IN VITRO DIAGNOSTIC USE ONLY for the calibration of the ST AIA-PACK Intact PTH Assay.

The ST AIA-PACK Intact PTH CONTROL SET is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK Intact PTH Assay.

3. Special conditions for use statement(s):

Prescription use only

4. Special instrument requirements:

For use with the specific TOSOH AIA System analyzers. Performance characteristics were established using TOSOH AIA-1800 System. The TOSOH AIA-600 or AIA-1200 Series Analyzers cannot be used to perform the ST AIA-PACK Intact PTH assay.

I. Device Description:

The ST AIA-PACK Intact PTH Assay is supplied as plastic test cups (5 trays x 20 test cups) containing twelve lyophilized magnetic beads coated with anti-PTH goat polyclonal antibody and anti-PTH goat polyclonal antibodies conjugated to bovine alkaline phosphatase with 0.1% sodium azide as a preservative.

The ST AIA-PACK Intact PTH CALIBRATOR SET contains a bovine protein matrix with assigned levels of Intact Parathyroid Hormone (0 - 2400 mg/dL). The Calibrator set has been prepared using synthesized Intact PTH.

The AIA-PACK Intact PTH CONTROL SET contains buffered bovine serum albumin with the assigned levels of Intact PTH. The Control set has been prepared using synthesized Intact PTH.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Roche Elecsys Parathyroid Hormone Test System

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

k992680

3. Comparison with predicate:

|  Assay / Feature | ST AIA-PACK Intact PTH | Roche Elecsys PTH assay (k992680)  |
| --- | --- | --- |
|  Analyte | Human Parathyroid Hormone | Human Parathyroid Hormone  |
|  Intended Use | The Tosoh Bioscience, Inc. ST AIA-PACK Intact PTH is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of Intact Parathyroid Hormone (Intact PTH) in human serum and EDTA plasma on specific TOSOH AIA System analyzers. | For the quantitative determination of intact parathyroid hormone and for differential diagnosis of hypercalcemia and hypocalcemia.  |

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|   | 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. |   |
| --- | --- | --- |
|  Specimen | Serum and Plasma | Serum and Plasma  |
|  Assay Format | The ST AIA-PACK Intact PTH assay is a two-site immunoenzymatic (“sandwich”) assay (IEMA) | Electrochemiluminescence immunoassay employing the sandwich principle (ICMA)  |
|  Result Read Time | Approximately 20 Minutes | 9 – 18 minutes  |
|  Reportable range | 1.2-2200 pg/mL | 1.2-5000 pg/mL  |
|  Analytical Sensitivity | ≈1.0 pg/ml | ≈ 1.20 pg/ml  |
|  Normal Range | 8.2 – 83.5 pg/ml | 15 – 65 pg/ml  |

K. Standard/Guidance Document Referenced (if applicable):
None referenced

L. Test Principle:
The ST AIA-PACK Intact PTH is a two-site immunoenzymatic assay which is performed entirely in the AIA-PACK. Intact PTH present in the test sample is bound with polyclonal antibody immobilized on magnetic beads and enzyme-labeled polyclonal antibody in the AIA- PACK. The magnetic beads are washed to remove unbound enzyme-labeled polyclonal antibody and are then incubated with the fluorogenic substrate 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled polyclonal antibody that binds to the beads is directly proportional to Intact PTH concentration in the test sample. A standard curve is constructed using known levels of calibrators, and unknown sample concentrations are calculated using this curve. The sponsor claims that calibration curve for the ST AIA-PACK Intact PTH is stable for up to 90 days. Calibration stability is monitored by quality control performance and is dependent on proper reagent handling and AIA System maintenance according to the manufacturer's instructions.

M. Performance Characteristics:
1. Analytical performance:
a. Precision/Reproducibility:
The sponsor determined the within run precision using three controls each of serum and plasma samples in a total of 20 runs. Within each run, one set of duplicates per control was assayed. The mean of each duplicate was used to obtain the pooled standard deviation (SD), which was then used to calculate

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the coefficient of variation (CV). Total precision was determined by the duplicate assay of three controls each of serum and plasma samples in 20 separate runs. The means of each run were used to calculate the standard deviation (SD) and coefficient of variation (CV).

Within-run Precision

|  Sample | Mean (pg/mL) | Pooled SD (pg/mL) | Coefficient of Variation (%)  |
| --- | --- | --- | --- |
|  Serum A3 | 27.7 | 0.89 | 3.2  |
|  Serum B3 | 243.6 | 8.68 | 3.6  |
|  Serum C3 | 1123.5 | 45.49 | 4.0  |
|  Plasma A3 | 27.1 | 1.07 | 3.9  |
|  Plasma B3 | 247.1 | 9.52 | 3.9  |
|  Plasma C3 | 1217.2 | 40.13 | 3.3  |

Day-to-day Precision

|  Sample | Mean (pg/mL) | Standard Deviation (pg/mL) | Coefficient of Variation (%)  |
| --- | --- | --- | --- |
|  Serum A3 | 27.7 | 1.00 | 3.6  |
|  Serum B3 | 243.6 | 8.94 | 3.7  |
|  Serum C3 | 1123.5 | 44.54 | 4.0  |
|  Plasma A3 | 27.1 | 1.32 | 4.9  |
|  Plasma B3 | 247.1 | 11.50 | 4.7  |
|  Plasma C3 | 1217.2 | 44.16 | 3.6  |

b. Linearity/assay reportable range:

Linearity studies were performed on the TOSOH AIA-1800 System. The Intact PTH Calibrators diluted to 12 equally spaced concentration levels (7.9 – 2370 pg/ml) were used for linearity analysis. Each test level was run in triplicate on the above analyzer. The sponsor established the acceptance criteria of measured values being within 90-110% of the assigned value. Based on the summarized results below and the results obtained from Limit of Detection studies (see Limit of Detection below), the sponsor has claimed the assay reportable range of 1.2 – 2200 pg/ml.

|  Concentration (pg/ml) | AVG | SD | CV | Ratio of Values Assigned/Obtained  |
| --- | --- | --- | --- | --- |
|  0 | 0.43 |  |  | 0.00  |
|  7.9 | 8.28 | 0.10 | 1.2 | 0.95  |
|  15.8 | 15.89 | 0.53 | 3.3 | 0.99  |
|  33.9 | 33.23 | 0.90 | 2.7 | 1.02  |
|  52.0 | 52.73 | 1.15 | 2.2 | 0.99  |
|  129 | 122.99 | 0.58 | 0.5 | 1.04  |
|  205 | 214.39 | 4.21 | 2.0 | 0.96  |

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|  512 | 497.08 | 13.01 | 2.6 | 1.03  |
| --- | --- | --- | --- | --- |
|  819 | 792.96 | 4.00 | 0.5 | 1.03  |
|  1207 | 1113.99 | 31.86 | 2.9 | 1.08  |
|  1595 | 1458.46 | 43.43 | 3.0 | 1.09  |
|  1983 | 1847.06 | 29.71 | 1.6 | 1.07  |
|  2370 | 2222.38 | 143.38 | 6.5 | 1.07  |

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

The sponsor’s protocols indicate that each calibrator/control lot is traceable to the manufacturer’s primary reference material. The primary reference material was prepared by diluting commercially available synthesized Intact PTH with Intact PTH Negative buffer solution. The value was originally assigned by comparing measured results with those obtained with another commercially available Intact PTH assay for patient samples.

To ensure adequate quality control, the sponsor recommends assaying two quality controls having approximate values 50 and 800 pg/mL, once each day on which Intact PTH assays are scheduled.

The sponsor claims that all unopened materials are stable until the expiration date on the label when stored at the specified temperature. ST AIA-PACK Intact PTH test cups may be stored for up to 1 day at 18-25°C. When stored unopened and refrigerated at 2-8°C, calibrators are stable until the expiration date on the label. After opening, the calibrators should be used within 24 hours. When stored unopened and refrigerated at 2-8°C, the AIA-PACK Intact PTH Control Set is stable until the expiration date on the label. Control materials should be used within 7 days of opening or reconstituting provided that the vials are kept sealed and refrigerated at 2-8°C.

d. Detection limit:

The sponsor determined the lower Limit of Detection (LOD) based on the algorithm in EP Evaluator software program version 4.0. This was defined as that concentration of Intact PTH, which corresponds to the rate of fluorescence that is two standard deviations from the mean rate of fluorescence of 5 replicate determinations of a zero calibrator.

Sensitivity = (Assigned value of non-zero calibrator) X 2 SD

(Mean rate of non-zero calibrator – mean rate of zero calibrator)

Using different lots of Intact PTH calibrator 1 with zero concentration and a non-zero calibrator (52.0 pg/ml), the sponsor determined the value to be 0.96, hence the claimed LOD is 1.0 pg/mL.

e. Analytical specificity:

The sponsor evaluated the effect of the interfering substances listed below for the recovery of PTH. Serum and plasma samples each with 3 levels of PTH (low, medium and high) were spiked with the interferents, and then compared with unspiked control. Based on the sponsor-defined interference limit of ± 10% from each sample containing no interferents, following interference limit claims were set by the sponsor.

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|  Substance | Interference  |   |   |
| --- | --- | --- | --- |
|   |  Interferent Concentration | Limit for Serum | Limit for Plasma  |
|  Hemoglobin (mg/dL) | 0-440 | 440 | 440  |
|  Lipemia (mg/dL) | 0-1666.7 | 1600 | 1600  |
|  Unconjugated bilirubin (mg/dL) | 0 – 17.4 | 17 | 17  |
|  Conjugated Bilirubin (mg/dL) | 0-17.8 | 17 | 17  |
|  Albumin (mg/dL) | 0-5000 | 5000 | 5000  |
|  Trisodium Citrate (mg/mL) | 0-20 | 20 | 20  |
|  Sodium-heparin (U/mL) | 0-100 | 100 | 100  |
|  Potassium-EDTA (mg/mL) | 0-10 | 10 | 10  |
|  Ascorbic acid (mg/dL) | 0-20 | 20 | 20  |
|  Rheumatoid factor (IU/mL) | 500 | 500 | 500  |

The following PTH fragments were tested for cross-reactivity. The cross-reactivity (%) is the percent of the PTH fragments which will be identified as Intact PTH. If these PTH fragments are present in the specimen at the same concentration as Intact PTH, the final result will be increased by these percentages.

|  PTH fragment | Cross-reactivity (%)  |
| --- | --- |
|  1-84 | 100  |
|  7-84 | 107.4  |
|  1-34 | < 0.02  |
|  13-34 | < 0.02  |
|  39-84 | < 0.02  |
|  53-84 | < 0.02  |

f. Assay cut-off:
Not Applicable

2. Comparison studies:

a. Method comparison with predicate device:
Performance of the ST AIA-PACK Intact PTH assay on AIA-1800 instrument was compared with performance of the predicate device, Roche Elecsys PTH assay using 153 patient serum samples with PTH values ranging 8 – 1537.0 pg/ml. A linear regression analysis conducted to determine the correlation between the device and the predicate resulted in the equation, $y = 1.013x - 10.457$ and correlation value of 0.997.

b. Matrix comparison:
To demonstrate comparable performance between serum and EDTA-plasma, the sponsor compared 134 paired serum and plasma samples on AIA-1800

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analyzer using ST AIA-PACK Intact PTH assay. The values for sera ranged 13.3 – 1931.7 pg/mL, and the linear regression analysis resulted in the equation, y = 0.9921x+7.8816 and R=0.9957.

The sponsor indicated in the labeling that heparinized or citrated plasma should not be used for specimen collection and handling.

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

5. Expected values/Reference range:
The sponsor established the expected reference range based on 144 samples from apparently healthy individuals. Sample values ranged 9.5 – 98 pg/ml indicated a slightly skewed pattern from Gaussian distribution. Reference range was established at 8.2 – 83.5 pg/mL based on the mean (45.9 pg/ml) ± two standard deviations (SD=18.8 pg/mL).

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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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CEW/K063605](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/CEW/K063605)

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