(108 days)
The LIAISON® N-tact™ PTH Assay is a chemiluminescent immunoassay to be used with the LIAISON® Analyzer for the quantitative determination of intact human parathyroid hormone in serum or EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions.
The LIAISON® N-tact™ PTH Control Set is intended for use as an assayed quality control sample to monitor the accuracy and precision of the DiaSorin LIAISON® N-tact™ PTH immunoassay.
The method for quantitative determination of PTH is a direct, two site, sandwich type chemiluminescence immunoassay (CLIA). Affinity-purified antibody to the 39-84 amino acid sequence of PTH is coated to the solid phase. The second affinity-purified antibody to the 1-34 region is conjugated to an isoluminol derivative. During the incubation, PTH binds to the solid phase, and is subsequently bound by the isolumino! conjugated antibody. After the incubation, the unbound material is removed with a wash cycle. The starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of PTH present in calibrators, controls, or samples.
Here's an analysis of the DiaSorin LIAISON® N-tact™ PTH 510(k) Premarket Notification based on the provided text, focusing on acceptance criteria and study details:
The provided document describes a diagnostic device (immunoassay) for quantitative determination of human parathyroid hormone (PTH), not a device that involves AI or human-in-the-loop performance. Therefore, several sections of your request (e.g., number of experts, adjudication method, MRMC study, human readers, standalone performance, training set details) are not applicable to this type of device and study. The "acceptance criteria" here refer to analytical performance specifications for the assay.
Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity (Analytical) | Not explicitly stated, but "high sensitivity" is a general goal. | 1.0 pg/mL (determined from 3 lots, ≤ 1.0 pg/mL for all lots) |
| Sensitivity (Functional) | %CV < 20% | 2.1 pg/mL (concentration where mean imprecision, %CV, exceeds 20%) |
| Assay Range | Broad range for clinical utility. | 2.5 - 2000.0 pg/mL |
| Total Precision (%CV) | < 10% (implied good precision for clinical use). | < 10% in range from 35 - 1289 pg/mL |
| Recovery (Mean ± SD %) | Close to 100% with low standard deviation. | 100.5% ± 7.3% |
| Linearity (Expected vs. Observed) | High correlation (r-value close to 1) and slope close to 1. | y = 0.92x + 4.6; r = 0.98 |
| PTH Fragment Cross-reactivity | Minimal cross-reactivity for other PTH fragments. | < 0.1% for 1-34, 13-34, 39-68, 39-84, 44-68, 53-84; 90.5% for 7-84 |
| Endogenous Substance Interferences | No significant interference. | No significant interference from hemoglobin; <15% from triglycerides (800 mg/dL) or bilirubin (15 mg/dL). |
| Sample Types | Compatibility with common clinical samples. | Serum or EDTA Plasma |
| Reference Ranges | Establish ranges for normal and disease states. | Normal: 7.0 - 82.0 pg/mL; Hypoparathyroidism: 0.0 - 21.0 pg/mL; Hyperparathyroidism: 48.6 - 368 pg/mL |
| Correlation with Predicate Device | High correlation and equivalent values. | r = 0.992; equivalent values by Student's t test (p = 0.172) |
| Freeze/Thaw Stability | Results equivalent to fresh samples after multiple cycles. | Results equivalent after 4 freeze/thaw cycles (p = 0.968) |
| Carryover | No carryover between samples. | No carryover observed |
Study Details
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Sample Size used for the test set and the data provenance:
- Analytical Sensitivity: Determined from 3 lots of materials. Specific sample count not provided, but it would involve multiple measurements of zero-concentration samples.
- Functional Sensitivity: Determined from serial dilution; specific sample count not provided.
- Linearity of Dilution: Demonstrated using nineteen samples and four lots of materials.
- Inter-assay Precision: Not explicitly stated how many samples were used, but performance was assessed over a concentration range of 35-1290 pg/mL, implying multiple samples at various concentrations.
- Recovery: Assessed by spiking synthetic PTH into serum samples; specific sample count not provided.
- Freeze/Thaw Stability: Not explicitly stated how many samples were used, but it involved comparing fresh samples with those subjected to 4 freeze/thaw cycles.
- Carryover: Not explicitly stated how many samples were used, but it involved testing low concentration samples directly after high concentration samples.
- Correlation with Predicate Device: Not explicitly stated how many samples were used for the comparison, but results state "the LIAISON® method correlated well with the predicate device (r = 0.992)".
- Reference Ranges: Established from "a population of normal, apparently healthy volunteers" for the normal range. "Subjects with an established diagnosis of either hypoparathyroidism or hyperparathyroidism" were used for disease-specific ranges. Specific sample sizes for these populations are not provided.
- Data Provenance: Not explicitly stated, but typical for such studies would be samples collected from a clinical laboratory setting, likely in the country of manufacturing/testing (USA, given the submission information). The studies are retrospective analyses of samples performed using the device.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable: For an immunoassay, "ground truth" is established by the analytical properties of the reference materials and the chemical/biological properties of the analytes, not by expert consensus on visual assessment or interpretation. For reference ranges, the "ground truth" for disease states is based on an "established diagnosis," likely made by clinicians following standard medical protocols, but no specific number or qualification of experts is provided as this is a standard clinical practice.
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Adjudication method for the test set:
- Not Applicable: Adjudication methods (e.g., 2+1, 3+1) are relevant for subjective assessments, particularly in medical imaging studies where multiple readers interpret cases. This is an objective, quantitative laboratory assay.
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If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not Applicable: This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool involving human readers.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes (for the analytical performance): The performance data presented (sensitivity, precision, linearity, recovery, etc.) represents the intrinsic analytical performance of the LIAISON® N-tact™ PTH Assay system (reagents + LIAISON® Analyzer) without any human interpretive overlay beyond standard laboratory procedures and result reporting. This is by nature "algorithm-only" in the context of an automated immunoassay.
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The type of ground truth used:
- Reference/Comparator Methods and Established Clinical Diagnoses:
- For analytical performance (e.g., sensitivity, linearity, recovery): Ground truth is based on known concentrations of synthetic PTH or highly characterized reference materials.
- For correlation: The predicate device (DPC Coat-A-Count® Intact PTH IRMA) served as a comparator, essentially a "ground truth" for comparative performance.
- For reference ranges: "Established diagnosis of either hypoparathyroidism or hyperparathyroidism" served as the clinical ground truth for those populations, and "normal, apparently healthy volunteers" for the normal range.
- Reference/Comparator Methods and Established Clinical Diagnoses:
-
The sample size for the training set:
- Not Applicable/Not Explicitly Stated: Immunoassays like this are not "trained" in the machine learning sense. The device's calibration curve (based on 10 points/standards) could be considered analogous, which is established using known concentrations, but it's not a "training set" in the context of AI. The stability of the Master Curve stored on the system implies it's robustly established.
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How the ground truth for the training set was established:
- Not Applicable/Known Concentrations: For the instrument's calibration (Master Curve), the ground truth is established by using "serum based standards representing concentrations from 2.5 to 2000 pg/mL." These standards contain precisely known amounts of PTH, which are manufactured and verified.
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K0334-26
DiaSorin LIAISON® N-tact™ PTH 510(k) Premarket Notification
FEB 1 2 2004
510(k) SUMMARY
SUBMITTED BY:
David M. Ikeda DiaSorin, Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 651.351.5592 Voice 651.351.5669 Fax October 22, 2003
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| NAME OF DEVICE:Trade Name: | LIAISON® N-tact™ PTH AssayLIAISON® N-tact™ PTH Control Set |
|---|---|
| Common Names/Descriptions: | Automated chemiluminescentimmunoassay for the quantitativedetermination of human parathyroidhormone (PTH) in serum or plasma. |
| Classification Name: | Parathyroid hormone test system |
PREDICATE DEVICE:
DPC Coat-A-Count® Intact PTH IRMA
INTENDED USE: The LIAISON® N-tact™ PTH Assay is a chemiluminescent immunoassay to be used with the LIAISON® Analyzer for the quantitative determination of intact human parathyroid hormone in serum or EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions.
The LIAISON® N-tact™ PTH Control Set is intended for use as an assayed quality control sample to monitor the accuracy and precision of the DiaSorin LIAISON® N-tact™ PTH immunoassay.
98
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DEVICE DESCRIPTION: The method for quantitative determination of PTH is a direct, two site, sandwich type chemiluminescence immunoassay (CLIA). Affinity-purified antibody to the 39-84 amino acid sequence of PTH is coated to the solid phase. The second affinity-purified antibody to the 1-34 region is conjugated to an isoluminol derivative. During the incubation, PTH binds to the solid phase, and is subsequently bound by the isolumino! conjugated antibody. After the incubation, the unbound material is removed with a wash cycle. The starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of PTH present in calibrators, controls, or samples.
| Assay /Feature | DPC | Coat-A-Count® PTHAssay* | LIAISON® N-tact™ PTH Assay |
|---|---|---|---|
| Analyte | Human Parathyroid Hormone | Human Parathyroid Hormone | Human Parathyroid Hormone |
| IntendedUse | FOR IN VITRO DIAGNOSTICUSE.Coat-A-Count® Intact PTH IRMAis an immunoradiometric assaydesigned for the quantitativemeasurement of intactparathyroid hormone(parathyrin, PTH) in serum. It isintended strictly for in vitrodiagnostic use as an aid in thedifferential diagnosis ofhypercalcemia andhypocalcemia | FOR IN VITRO DIAGNOSTICUSE.The LIAISON® N-tact™ PTHAssay is a chemiluminescentimmunoassay to be used withthe LIAISON® Analyzer for thequantitative determination ofintact human parathyroidhormone in serum or EDTAplasma. Measurements ofparathyroid hormone levels areused in the differentialdiagnosis of hypercalcemia andhypocalcemia resulting fromdisorders of calciummetabolism. Assay resultsshould be used in conjunctionwith other clinical andlaboratory data to assist theclinician in making individualpatient management decisions |
TECHNOLOGICAL COMPARISON TO PREDICATE:
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| Antisera | Polyclonal specific for PTH (44- 84) | Polyclonal specific for PTH (39- 84) |
|---|---|---|
| Tracer | 125I-labelled polyclonal antibodyto PTH (1-34) | Chemiluminescent ABEIlabeled polyclonal antibody toPTH (1-34) |
| Standards | Seven lyophilized serum basedcontrols to be reconstituted inwater representingconcentrations from 0 to 3000pg/mL | Stored Master Curve based on10 points, derived from serumbased standards representingconcentrations from 2.5 to 2000pg/mL. |
| KitControls | Two concentrations oflyophilized controls | Two concentrations oflyophilized controls |
PERFORMANCE DATA: A summary of performance data is shown below.
| Parameter | Performance Results |
|---|---|
| Sensitivity (Analytical) | 1.0 pg/mL |
| Sensitivity (Functional) | 2.1 pg/mL |
| Assay Range | 2.5 - 2000.0 pg/mL |
| Total Precision (%CV) | < 10% in range from 35 - 1289 pg/mL |
| Recovery (Mean ± SD %) | 100.5% ± 7.3% |
| Linearity (Expected vs.Observed) | y = 0.92x + 4.6; r = 0.98 |
| PTH Fragment Cross-reactivity | 1 - 34 < 0.1% 13 - 34 < 0.1%39 - 68 < 0.1% 39 - 84 < 0.1%44 - 68 < 0.1% 53 - 84 < 0.1%7 - 84 90.5% |
| Endogenous SubstanceInterferences | No significant interference observed fromhemoglobin; <15% interference fromtriglycerides (800 mg/dL) or bilirubin (15mg/dL). |
| Sample Types | Serum or EDTA Plasma |
| Reference Ranges | Normal: 7.0 - 82.0 pg/mLHypoparathyroidism: 0.0 - 21.0 pg/mLHyperparathyroidism: 48.6 - 368 pg/mL |
Analytical sensitivity was determined from the assessment of three lots of materials. Analytical sensitivity was defined as the concentration corresponding to the signal obtained at two standard deviations from the mean of the signal of the zero concentration samples. Analytical sensitivity determined by this method was ≤ 1.0 pg/mL for all lots. Functional sensitivity, determined as the mean concentration at which the mean imprecision, expressed as %CV, exceeds 20%, was determined from serial dilution to be 2.1 pg/mL. Linearity of dilution was demonstrated using nineteen samples and four lots of materials. The correlation
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coefficient of the linear regression of the Expected Concentration vs. Observed Concentration was 0.98. Inter-assay precision, expressed as %CV, was < 10% over a concentration range from 35 - 1290 pg/mL. Recovery was assessed by spiking synthetic PTH at known concentrations into serum samples. Mean percent recovery (± SD) was 100.5% ± 7.3%. Samples subjected to 4 freeze/thaw cycles gave results equivalent to fresh samples (paired t test p value of 0.968). No carryover was observed in testing low concentration samples directly after high concentration samples. The LIAISON® method correlated well with the predicate device (r = 0.992), giving equivalent values when evaluated by Student's t test (p = 0.172). The reference range established from a population of normal, apparently healthy volunteers (7.0 - 82.0 pg/mL) utilizing the 2.5th to 97.50 percentiles, was very similar to the predicate device (12 - 72 pg/mL). Reference ranges were also determined for subjects with an established diagnosis of either hypoparathroidism or hyperparathyroidsim, 0.0 – 21.0 pg/mL and 48.6 - 368 pg/mL respectively.
CONCLUSIONS:
These data demonstrate the safety and effectiveness of the LIAISON® N-tact™ PTH Assay for its intended in vitro diagnostic use.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter. Inside the circle is an abstract image of an eagle.
Public Health Service
FEB 1 2 2004
Mr. David M. Ikeda Manager, Regulatory Affairs & Quality Systems Diasorin, Inc. 1951 Northwestern Aveneu P.O. Box 285 Stillwater, MN 55082-0285
Re: K033426
Trade/Device Name: Liaison® Control N-tact™ PTH Liaison® N-tact™ PTH Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid hormone test system Regulatory Class: Class II Product Code: CEW; JJX Dated: January 6, 2004 Received: January 7, 2004
Dear Mr. Ikeda:
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 rcclassified 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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
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Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) r no lotet notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, MS, DVM.
Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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K033426 DiaSorin LIAISON® N-tact™ PTH Premarket Notification
INDICATIONS FOR USE
510(k) Number (if known): K033426
Device Name:
LIAISON® Control N-tact™ PTH
Indications for Use:
The LIAISON® Control N-tact™ PTH is intended for use as assayed quality control The LIAIOON - oontrol N tax:
materials to monitor the accuracy and precision of the LIAISON® N-tact™ PTH immunoassay.
Carol Benam
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K033426
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation
Prescription Use: ✓
OR Over-the-Counter Use:
(Per 21 CFR 801.109)
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INDICATIONS FOR USE
510(k) Number (if known): 10334240
Device Name:
LIAISON® N-tact™ PTH
Indications for Use:
The LIAISON® N-tact™ PTH is a chemiluminescent immunoassay to be used with the LIAISON® Analyzer for the quantitative determination of intact human parathyroid hormone in serum or EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions.
Carol C Benson
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K033426
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation
Prescription Use:
OR Over-the-Counter Use:
(Per 21 CFR 801.109)
| LS-PTH-058 Rev. C |
|---|
| ------------------- |
§ 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.