(266 days)
Not Found
No
The device description and performance studies focus on standard immunoassay principles and calibration methods, with no mention of AI or ML.
No
The device is an in vitro diagnostic immunoassay used for quantitative determination of parathyroid hormone for diagnostic purposes (differential diagnosis of hypercalcemia and hypocalcemia), not for treatment.
Yes
The "Intended Use / Indications for Use" section states: "Immunoassay for the in vitro quantitation of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia." Differential diagnosis is a diagnostic process.
No
The device description clearly outlines the use of physical reagents (microparticles, antibodies) and is intended for use on a specific hardware analyzer (cobas e immunoassay analyzers), indicating it is a hardware-based immunoassay system, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states "Immunoassay for the in vitro quantitation of intact parathyroid hormone in human serum and plasma". The phrase "in vitro" is a key indicator of an IVD.
- Device Description: The "Device Description" also reiterates that the immunoassays are intended for the "in vitro quantitative determination of intact parathyroid hormone in human serum and plasma".
- Function: The device performs a test on biological samples (serum and plasma) outside of the body to provide diagnostic information (quantitation of parathyroid hormone for differential diagnosis of hypercalcemia and hypocalcemia). This is the core function of an IVD.
N/A
Intended Use / Indications for Use
Elecsys PTH and Elecsys PTH STAT: Immunoassay for the in vitro quantitation of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. This assay can be used intraoperatively. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers
Product codes (comma separated list FDA assigned to the subject device)
CEW
Device Description
Both the Elecsys PTH and Elecsys PTH STAT immunoassays make use of a sandwich test principle using a biotinylated monoclonal PTH-specific antibody labeled with a ruthenium complex. Both the Elecsys PTH and Elecsys PTH STAT immunoassays are intended for the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. These assays can be used intraoperatively. They are intended for use on the cobas e immunoassay analyzers.
Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.
The reagent working solutions include: Rack Pack (kit placed on the analyzer)
- M Streptavidin coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidin . coated microparticles 0.72 mg/mL; preservative.
- . R1 Anti PTH Ab~biotin (gray cap), 1 bottle, 7 mL: Biotinylated monoclonal anti PTH antibody (mouse) 2.3 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
- . R2 Anti PTH Ab~Ru(bpy) (black cap), 1 bottle, 7 mL: Monoclonal anti PTH antibody (mouse) labeled with ruthenium complex 2.0 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision:
- Repeatability and Intermediate Precision: Precision measurements were conducted for the updated Elecsys PTH and Elecsys PTH STAT assays to evaluate repeatability (within-run precision) and intermediate precision (within-laboratory precision) according to CLSI EP05-A3. All samples met the predefined acceptance criteria.
- Elecsys PTH Precision:
Sample Mean pg/mL SD pg/mL (Repeatability) CV % (Repeatability) SD pg/mL (Intermediate Precision) CV % (Intermediate Precision) HSb) 1 9.29 0.195 2.1 0.404 4.4 HS 2 13.8 0.210 1.5 0.420 3.0 HS 3 54.6 0.444 0.8 0.798 1.5 HS 4 2467 17.7 0.7 32.6 1.3 HS 5 4514 41.2 0.9 49.1 1.1 PCc) Varia 0 24.5 0.291 1.2 0.540 2.2 PC Varia 1 58.0 0.545 0.9 1.20 2.1 PC Varia 2 175 1.59 0.9 2.56 1.5 - Elecsys PTH STAT Precision:
Sample Mean pg/mL SD pg/mL (Repeatability) CV % (Repeatability) SD pg/mL (Intermediate Precision) CV % (Intermediate Precision) HSb) 1 9.27 0.224 2.4 0.409 4.4 HS 2 14.0 0.236 1.7 0.386 2.8 HS 3 54.0 0.565 1.0 0.887 1.6 HS 4 2399 14.0 0.6 36.8 1.5 HS 5 4390 34.9 0.8 49.0 1.1 PCc) Varia 0 22.3 0.292 1.3 0.515 2.3 PC Varia 1 49.9 0.534 1.1 1.07 2.1 PC Varia 2 151 1.10 0.7 2.58 1.7
- Elecsys PTH Precision:
- Reproducibility: Lot-to-lot reproducibility was performed for both the Elecsys PTH and Elecsys PTH STAT assay using three reagent lots according to CLSI EP05-A3. All predefined acceptance criteria were met.
Analytical Sensitivity:
- Limit of Blank (LoB): Determined according to CLSI EP17-A2. LoB claim: 1.2 pg/mL.
- Limit of Detection (LoD): Determined according to CLSI EP17-A2. LoD claim: 2.4 pg/mL.
- Limit of Quantitation (LoQ): Determined according to CLSI EP17-A2. LoQ claim: 6 pg/mL.
Linearity/Assay Reportable Range:
- Linearity was evaluated according to CLSI EP06-Ed2. Measuring range: 6-5000 pg/mL.
High Dose Hook Effect:
- No hook effect was seen up to 17000 pg/mL.
Human Anti-Mouse Antibodies (HAMA):
- Assessed on one cobas e 601 analyzer.
Endogenous Interferences:
- Nine endogenous substances evaluated. All predefined acceptance criteria were met. Proposed labeling claims for each endogenous substance:
- Bilirubin: ≤ 1129 µmol/L or ≤ 66 mg/dL
- Hemoglobin: ≤ 0.155 mmol/L or ≤ 250 mg/dL
- Intralipid: ≤ 1500 mg/dL
- Biotin: ≤ 4920 nmol/L or ≤ 1200 ng/mL
- Rheumatoid Factor: ≤ 1200 IU/mL
- Serum Albumin: ≤ 7.0 g/dL
- Human IgG: ≤ 1.4 g/dL
- Human IgM: ≤ 0.2 g/dL
- Human IgA: ≤ 0.48 g/dL
Analytical Specificity/Cross-Reactivity:
- No cross reactivities were found for: PTH fragment 1-34, PTH fragment 1-37 and PTH related protein (1-86).
- The assay has a 96 % cross-reactivity to the PTH fragment 7-84.
Exogenous Interferences - Drugs:
- Study conducted for 17 commonly and four specially used pharmaceutical compounds. Predefined acceptance criteria met, no interference observed.
Sample Matrix Comparison:
- Comparison of values from serum, K2-EDTA, and K3-EDTA plasma. Specifications fulfilled, supporting K2-EDTA and K3-EDTA plasma as acceptable sample types.
Method Comparison to Predicate (CLSI guideline EP09-A3):
- Elecsys PTH Method Comparison: 257 samples with concentrations between 6.16 and 4751 pg/mL.
- Passing/Bablok: y = 0.966x + 0.411, τ = 0.990
- Linear regression: y = 0.968x + 0.272, r = 1.000
- Elecsys PTH STAT Method Comparison: 216 samples with concentrations between 10.3 and 4532 pg/mL.
- Passing/Bablok: y = 0.981x -1.133, τ = 0.991
- Linear regression: y = 0.982x -1.228, r = 1.000
Stability:
- Stability studies conducted and met predefined acceptance criteria.
- Unopened at 2-8 °C: up to the stated expiration date
- After opening at 2-8 °C: 12 weeks
- On the analyzer: 28 days
Reference Range Study:
- Multi-site study with 490 apparently healthy adult samples in the United States.
- Reference range: 17.9 58.6 pg/mL (2.5th 97.5th percentiles).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Roche Diagnostics Elecsys PTH and Elecsys PTH STAT (K070709)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1545 Parathyroid hormone test system.
(a)
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.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue box. Underneath that is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 22, 2024
Amy Pierce Regulatory Affairs Project Manager 9115 Hague Rd. P.O. Box 50416 Indianapolis, Indiana 46250
Re: K231927
Trade/Device Name: Elecsys PTH, Elecsys PTH STAT Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid Hormone Test System Regulatory Class: Class II Product Code: CEW Dated: February 22, 2024 Received: February 22, 2024
Dear Amy Pierce:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,
Paula V. Caposino -S
Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K231927
Device Name Elecsys PTH and Elecsys PTH STAT
Indications for Use (Describe) Elecsys PTH and Elecsys PTH STAT:
Immunoassay for the in vitro quantitation of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. This assay can be used intraoperatively. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
Elecsys PTH and Elecsys PTH STAT 510(k) Summary for K231927
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Elecsys PTH and Elecsys PTH STAT.
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Amy Pierce |
| Phone: (317) 440-5108 | |
| Email: amy.pierce.ap2@roche.com | |
| Date Prepared | March 11, 2024 |
| Proprietary Name | Elecsys PTH |
| Elecsys PTH STAT | |
| Common Name | Parathyroid hormone test system |
| Classification Name | Radioimmunoassay, Parathyroid Hormone |
| Product Codes, | |
| Regulation Numbers | CEW, 21 CFR 862. 1545 |
| Predicate Devices | Roche Diagnostics Elecsys PTH and Elecsys PTH STAT (K070709) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126 |
| Roche Diagnostics GmBH Penzberg, Germany: 9610529 | |
| Roche Diagnostics Indianapolis, IN United States: 1823260. |
4
1. DEVICE DESCRIPTION
Both the Elecsys PTH and Elecsys PTH STAT immunoassays make use of a sandwich test principle using a biotinylated monoclonal PTH-specific antibody labeled with a ruthenium complex. Both the Elecsys PTH and Elecsys PTH STAT immunoassays are intended for the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. These assays can be used intraoperatively. They are intended for use on the cobas e immunoassay analyzers.
Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.
The reagent working solutions include: Rack Pack (kit placed on the analyzer)
- M Streptavidin coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidin . coated microparticles 0.72 mg/mL; preservative.
- . R1 Anti PTH Ab~biotin (gray cap), 1 bottle, 7 mL: Biotinylated monoclonal anti PTH antibody (mouse) 2.3 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
- . R2 Anti PTH Ab~Ru(bpy) (black cap), 1 bottle, 7 mL: Monoclonal anti PTH antibody (mouse) labeled with ruthenium complex 2.0 mg/L; phosphate buffer 100 mmol/L, pH 7.0; preservative.
2. INDICATIONS FOR USE
The following Indications for Use is applicable to both Elecsys PTH and Elecsys PTH STAT:
Immunoassay for the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia. This assay can be used intraoperatively.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
5
TECHNOLOGICAL CHARACTERISTICS 3.
Table 1 compares Elecsys PTH (biotin update) with its predicate device, Elecsys PTH (K070709). Table 2 compares Elecsys PTH STAT (biotin update) with its predicate device, Elecsys PTH STAT (K070709).
| Feature | Candidate Device
Elecsys PTH | Predicate Device
Elecsys PTH (K070709) |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Elecsys PTH is intended for the in vitro
quantitative determination of intact
parathyroid hormone in human serum and
plasma for the differential diagnosis of
hypercalcemia and hypocalcemia. This
assay can be used intraoperatively.
The electrochemiluminescence
immunoassay "ECLIA" is intended for
use on Elecsys and cobas e immunoassay
analyzers | Elecsys PTH is intended for the in vitro
quantitative determination of intact parathyroid
hormone in human serum and plasma for the
differential diagnosis of hypercalcemia and
hypocalcemia. This assay can be used
intraoperatively.
The electrochemiluminescence immunoassay
"ECLIA" is intended for use on cobas e
immunoassay analyzers |
| Assay Method | Sandwich | Same |
| Detection Method | Electrochemiluminescence
"ECLIA" | Same |
| Applications/Test Time | 18 minute | Same |
| Sample Type/Matrix | Human serum/Plasma | Same |
| Sample Anticoagulants | K2-EDTA/K3-EDTA | Same |
| Handling of R1 and R2 | Liquid, ready to use | Same |
| Buffer composition R1 | Phosphate buffer | Same |
| Calibrator | PTH CalSet | Same |
| Calibration Method | 2-point calibration | Same |
Technical Characteristics Comparison Table between Elecsys PTH (biotin Table 1: update) and Elecsys PTH
6
| Feature | Candidate Device
Elecsys PTH | Predicate Device
Elecsys PTH (K070709) |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|
| Calibration Interval | Calibration must be performed
once per reagent lot using fresh
reagent (i.e. not more than 24
hours since the reagent kit was
registered on the analyzer).
Calibration interval may be
extended based on acceptable
verification of calibration by the
laboratory.
Renewed calibration is
recommended as follows:
after 12 weeks when
using the same reagent lotafter 7 days (when using
the same reagent kit on
the analyzer)as required: e.g. quality
control findings outside
the defined limits | Same |
| Controls | PreciControl Varia | Same |
| Traceability/Standardization | Standardized against a
commercial PTH test (RIA). | Same |
| Reagent Stability | Reagent stability for on analyzer
is now 28 days. | unopened at 2-8 °C: up to the
stated expiration dateafter opening at 2-8 °C: 12
weekson analyzers: 8 weeks |
| Measuring Range | 1.20-5,000 pg/mL | 6-5,000 pg/mL |
| Biotin Tolerance | Up to 1200 ng/mL | Up to 50 ng/mL |
Table 2: PTH STAT vs PTH STAT
| Feature | Candidate Device
Elecsys PTH STAT | Predicate Device
Elecsys PTH STAT(K070709) |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Elecsys PTH STAT is intended for the in
vitro quantitative determination of intact
parathyroid hormone in human serum and
plasma for the differential diagnosis of
hypercalcemia and hypocalcemia. This
assay can be used intraoperatively.
The electrochemiluminescence
immunoassay "ECLIA" is intended for
use on Elecsys and cobas e immunoassay
analyzers | Elecsys PTH STAT is intended for the in vitro
quantitative determination of intact parathyroid
hormone in human serum and plasma for the
differential diagnosis of hypercalcemia and
hypocalcemia. This assay can be used
intraoperatively.
The electrochemiluminescence immunoassay
"ECLIA" is intended for use on cobas e
immunoassay analyzers |
| Feature | Candidate Device
Elecsys PTH STAT | Predicate Device
Elecsys PTH STAT(K070709) |
| Assay Method | Sandwich | Same |
| Detection Method | Electrochemiluminescence
"ECLIA" | Same |
| Applications/Test Time | 9 minute | Same |
| Sample Type/Matrix | Human serum/Plasma | Same |
| Sample Anticoagulants | K2-EDTA/K3-EDTA | Same |
| Handling of R1 and R2 | Liquid, ready to use | Same |
| Buffer composition R1 | Phosphate buffer | Same |
| Calibrator | PTH STAT CalSet | Same |
| Calibration Method | 2-point calibration | Same |
| Calibration Interval | Calibration must be performed
once per reagent lot using fresh
reagent (i.e. not more than 24
hours since the reagent kit was
registered on the analyzer).
Calibration interval may be
extended based on acceptable
verification of calibration by the
laboratory.
Renewed calibration is
recommended as follows:
• after 12 weeks when
using the same reagent lot
• after 7 days (when using
the same reagent kit on
the analyzer)
• as required: e.g. quality
control findings outside
the defined limits | Same |
| Controls | PreciControl Varia | Same |
| Traceability/Standardization | Standardized against a
commercial PTH test (RIA). | Same |
| Reagent Stability | Reagent stability for on analyzer
is now 28 days. | • unopened at 2-8 °C: up to the
stated expiration date
• after opening at 2-8 °C: 12
weeks
• on analyzers: 8 weeks |
| Measuring Range | 1.20-5,000 pg/mL | 6-5,000 pg/mL |
| Biotin Tolerance | Up to 1200 ng/mL | Up to 50 ng/mL |
7
8
NON-CLINICAL PERFORMANCE EVALUATION 4.
The following performance data are provided in support of the substantial equivalence determination. All performance specifications were met.
Precision 4.1.
Repeatability and Intermediate Precision 4.1.1.
Precision measurement were conducted for the updated Elecsys PTH and Elecsys PTH STAT assays to evaluate repeatability (within-run precision) and intermediate precision (withinlaboratory precision) according to CLSI EP05-A3. All samples met the predefined acceptance criteria.
| cobas e 601 analyzer | |||||
|---|---|---|---|---|---|
| Repeatability | Intermediate | ||||
| precision | |||||
| Sample | Mean | ||||
| pg/mL | SD | ||||
| pg/mL | CV | ||||
| % | SD | ||||
| pg/mL | CV | ||||
| % | |||||
| HSb) 1 | 9.29 | 0.195 | 2.1 | 0.404 | 4.4 |
| HS 2 | 13.8 | 0.210 | 1.5 | 0.420 | 3.0 |
| HS 3 | 54.6 | 0.444 | 0.8 | 0.798 | 1.5 |
| HS 4 | 2467 | 17.7 | 0.7 | 32.6 | 1.3 |
| HS 5 | 4514 | 41.2 | 0.9 | 49.1 | 1.1 |
| PCc) Varia 0 | 24.5 | 0.291 | 1.2 | 0.540 | 2.2 |
| PC Varia 1 | 58.0 | 0.545 | 0.9 | 1.20 | 2.1 |
| PC Varia 2 | 175 | 1.59 | 0.9 | 2.56 | 1.5 |
Elecsys PTH Precision
9
Elecsys PTH STAT Precision
| cobas e 601 analyzer | |||||
|---|---|---|---|---|---|
| Repeatability | Intermediate | ||||
| precision | |||||
| Sample | Mean | SD | CV | SD | CV |
| pg/mL | pg/mL | % | pg/mL | % | |
| HSb) 1 | 9.27 | 0.224 | 2.4 | 0.409 | 4.4 |
| HS 2 | 14.0 | 0.236 | 1.7 | 0.386 | 2.8 |
| HS 3 | 54.0 | 0.565 | 1.0 | 0.887 | 1.6 |
| HS 4 | 2399 | 14.0 | 0.6 | 36.8 | 1.5 |
| HS 5 | 4390 | 34.9 | 0.8 | 49.0 | 1.1 |
| PCc) Varia 0 | 22.3 | 0.292 | 1.3 | 0.515 | 2.3 |
| PC Varia 1 | 49.9 | 0.534 | 1.1 | 1.07 | 2.1 |
| PC Varia 2 | 151 | 1.10 | 0.7 | 2.58 | 1.7 |
4.1.2. Reproducibility
Lot-to-lot reproducibility was performed for both the Elecsys PTH and Elecsys PTH STAT assay using three reagent lots according to CLSI EP05-A3. All predefined acceptance criteria was met for the lot-to-lot reproducibility experiment.
Analytical Sensitivity 4.2.
4.2.1. Limit of Blank (LoB)
The Limit of Blank (LoB) was determined according to CLSI EP17-A2. The LoB claim in the labeling will be set to 1.2 pg/mL.
Limit of Detection (LoD) 4.2.2.
The Limit of Detection (LoD) was determined according to CLSI EP17-A2. The LoD claim in the labeling will be set to 2.4 pg/mL.
10
4.2.3. Limit of Quantitation (LoQ)
The Limit of Quantitation (LoQ) was determined according to CLSI EP17-A2. The LoO claim in the labeling will be set to 6 pg/mL.
4.3. Linearity/Assay Reportable Range
Linearity was evaluated according to CLSI EP06-Ed2 with the Elecsys PTH and Elecsys PTH STAT assays on one cobas e 601 analyzer. The dilution series contained a minimum of 9 concentrations throughout the measuring range. A measuring range of 6-5000 pg/mL will be claimed in the labeling.
High Dose Hook Effect 4.4.
The high-dose hook effect (HDHE) of the Elecsys PTH and Elecsys PTH STAT assays was assessed on one cobas e 601 analyzer using a dilution series. No hook effect was seen up to 17000 pg/mL.
4.5. Human Anti-Mouse Antibodies (HAMA)
The effect of the presence of human anti-mouse antibodies (HAMA) on the Elecsys PTH assay was assessed on one cobas e 601 analyzer.
Endogenous Interferences 4.6.
Nine endogenous substances were evaluated for potential interference with Elecsys PTH and Elecsys PTH STAT on the cobas e 601 analyzer. All predefined acceptance criteria were met, and the proposed labeling claims for each endogenous substance can be found below (applicable to both Elecsys PTH and Elecsys PTH STAT:
| Compound | Concentration tested |
|---|---|
| Bilirubin | ≤ 1129 µmol/L or ≤ 66 mg/dL |
| Hemoglobin | ≤ 0.155 mmol/L or ≤ 250 mg/dL |
| Intralipid | ≤ 1500 mg/dL |
| Biotin | ≤ 4920 nmol/L or ≤ 1200 ng/mL |
| Rheumatoid Factor | ≤ 1200 IU/mL |
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| Compound | Concentration tested |
|---|---|
| Serum Albumin | ≤ 7.0 g/dL |
| Human IgG | ≤ 1.4 g/dL |
| Human IgM | ≤ 0.2 g/dL |
| Human IgA | ≤ 0.48 g/dL |
Analytical Specificity/Cross-Reactivity 4.7.
A cross-reactivity study was conducted with Elecsys PTH and Elecsys PTH STAT on the cobas e 601 analyzer to evaluate the potential cross-reacting compounds using human serum samples. Samples were measured in the presence and absence of the potential cross-reactants and crossreactivity was calculated. No cross reactivities were found for: PTH fragment 1-34, PTH fragment 1-37 and PTH related protein (1-86). The assay has a 96 % cross-reactivity to the PTH fragment 7-84.
Exogenous Interferences - Drugs 4.8.
An exogenous interference study was conducted to evaluate 17 commonly and four specially used pharmaceutical compounds for potential interference with Elecsys PTH and Elecsys PTH STAT assays on the cobas e 601 analyzer. The predefined acceptance criteria was met for all drugs tested, and no interference was observed.
Sample Matrix Comparison 4.9.
The effect on quantitation of analyte in the presence of anticoagulants with Elecsys PTH and Elecsys PTH STAT immunoassays was determined by comparing values obtained from samples drawn into serum, K2- and K3-EDTA plasma primary tubes. The specifications were fulfilled and thus the resulting data support the package-insert claim that K2-EDTA and K3-EDTA plasma are acceptable sample types.
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4.10. Method Comparison to Predicate
A method comparison study was performed in concordance with the CLSI guideline EP09-A3 using the Elecsys PTH biotin updated assay and the current Elecsys PTH assay. A method comparison study was also performed using the Elecsys PTH STAT biotin updated assay and the current Elecsys PTH STAT assay. Samples span the measuring range. The results can be found below:
Elecsys PTH Method Comparison
The sample concentrations were between 6.16 and 4751 pg/mL for 257 samples.
| Passing/Bablok | Linear regression |
|---|---|
| $y = 0.966x + 0.411$ | $y = 0.968x + 0.272$ |
| $τ = 0.990$ | $r = 1.000$ |
Elecsys PTH STAT Method Comparison
The concentrations were between 10.3 and 4532 pg/mL for 216 samples.
| Passing/Bablok | Linear regression |
|---|---|
| $y = 0.981x -1.133$ | $y = 0.982x -1.228$ |
| $\u03c4 = 0.991$ | $r = 1.000$ |
4.11. Stability
Stability studies were conducted for Elecsys PTH and Elecsys PTH STAT and met the predefined acceptance criteria. Stability data below are applicable to both Elecsys PTH and Elecsys PTH STAT.
| Stability: | |
|---|---|
| unopened at 2-8 °C | up to the stated expiration date |
| after opening at 2-8 °C | 12 weeks |
| on the analyzer | 28 days |
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REFERENCE RANGE STUDY 5.
A multi-site study was performed to determine the reference range for the Elecsys PTH and Elecsys PTH STAT assay with 490 apparently healthy adult samples in the United States. The reference range was determined to be 17.9 58.6 pg/mL (2.5th 97.5th percentiles).
ADDITIONAL INFORMATION 6.
Elecsys PTH and Elecsys PTH STAT are intended to be used with the following calibrators and controls:
- CalSet PTH (for use with Elecsys PTH) .
- CalSet PTH STAT (for use with Elecsys PTH STAT) .
- PreciControl Varia (for use with both Elecsys PTH and Elecsys PTH STAT) .
There have been no changes to these items marketed with the new Elecsys PTH and Elecsys PTH STAT assays.
CONCLUSIONS 7.
The information provided in this 510(k) Premarket Notification supports the determination that the Elecsys PTH immunoassay (updated material number 08928380160) is substantially equivalent to the predicate device, Elecsys PTH system (current assay, material number 11972103160). The information also supports the determination that the Elecsys PTH STAT immunoassay (updated material number 08928410160) is substantially equivalent to the predicate device, Elecsys PTH STAT system (current assay, material number 04892470160).