The IDS-iSYS 1,25 Dihydroxy Vitamin D assay is intended for the determination of 1,25 dihydroxyvitamin D levels in serum and plasma on the IDS-iSYS Multi-Discipline Automated System. Results of the 1.25 Dihydroxy Vitamin D are used in the assessment of vitamin D sufficiency.

The IDS-iSYS 1,25 Dihydroxy Vitamin D Control Set is used for quality control of the IDS-iSYS 1,25 Dihydroxy Vitamin D assay on the IDS-iSYS Multi-Discipline Automated System

The IDS-iSYS 1,25 Dihydroxy Vitamin D Calibration Verifier is a device intended for medical purposes for use in the quantitative verification of calibration of the IDS-iSYS 1,25 Dihydroxy Vitamin D assay when performed on the IDS-iSYS Multi-Discipline Automated Analyzer.

Device Description

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AI/ML Overview

Acceptance Criteria and Study for IDS iSYS 1,25 Dihydroxy Vitamin D Assay

Based on the provided document (K123253), the device in question is the IDS iSYS 1,25 Dihydroxy Vitamin D assay. This type of device is a diagnostic assay, and as such, its performance is typically evaluated based on analytical characteristics like precision, accuracy, linearity, and interference. The document itself is a 510(k) clearance letter, which indicates substantial equivalence to a predicate device. It doesn't contain the full study reports with detailed acceptance criteria and performance data.

However, based on typical FDA requirements for in vitro diagnostic assays and the context of a 510(k) submission for a Vitamin D test system, we can infer and describe the likely acceptance criteria and the nature of studies performed. This will be a reconstruction of what would typically be included in the full submission, as the provided document is merely the FDA's clearance letter.

1. Table of Acceptance Criteria and the Reported Device Performance

Since the detailed study results are not in the provided document, the "Reported Device Performance" here refers to the outcomes that would have led to a substantial equivalence determination for an assay. The acceptance criteria are typical for a diagnostic immunoassay.

Performance Characteristic	Acceptance Criteria (Typical for Immunoassays)	Reported Device Performance (Inferred from 510(k) Clearance)
Precision (Repeatability)	%CV ≤ 10% within-run, %CV ≤ 15% total	Met acceptance criteria for various concentrations.
Accuracy (Bias/Comparison to Predicate)	Correlation coefficient (r) ≥ 0.95 and/or acceptable bias vs. predicate device.	Demonstrated substantial equivalence to the predicate device, indicating acceptable correlation and bias.
Linearity	Measured values within +/- X% of expected values across the assay range.	Demonstrated linearity across the claimed measuring range.
Analytical Measurement Range (AMR)	Established range where linearity and accuracy are maintained.	Established and verified, typically covering clinically relevant levels.
Limit of Detection (LoD)	LoD ≤ X ng/mL (specific to analyte and clinical need)	Established LoD, indicating the lowest detectable concentration.
Limit of Quantitation (LoQ)	LoQ ≤ Y ng/mL (specific to analyte, with acceptable precision)	Established LoQ, indicating the lowest quantifiable concentration with acceptable precision.
Interference	No significant interference (e.g., <10% bias) from common endogenous substances (hemoglobin, bilirubin, lipids, heterophilic antibodies) or common medications.	No significant interference found from tested substances at specified concentrations.
Specificity	Minimal or no cross-reactivity with structurally similar compounds.	Demonstrated minimal cross-reactivity with related vitamin D metabolites.

2. Sample Size Used for the Test Set and Data Provenance

For an in vitro diagnostic assay, the "test set" would typically refer to the samples used in analytical validation studies (precision, accuracy, linearity, interference) and potentially clinical concordance studies if required.

Sample Size for Test Set:
- Precision: Typically involves multiple replicates (e.g., 20-40 replicates per sample level) across multiple runs and days, using several pooled or spiked patient samples at different concentrations (e.g., low, mid, high).
- Accuracy/Method Comparison: Typically involves a statistically significant number of patient samples (e.g., 60-100+ uniquely different patient samples) spanning the assay's measuring range, tested on both the candidate device and the predicate device.
- Linearity: At least 5-7 different concentrations spanning the assay's range, tested in replicates.
- Interference: Samples spiked with interfering substances at varying levels (e.g., high, mid, low analyte concentrations).
Data Provenance: The document does not specify. However, for a 510(k) submission, the studies are typically conducted at the manufacturer's R&D facilities and/or qualified clinical/reference laboratories. The country of origin for the data is most likely the United Kingdom (where Immunodiagnostic Systems Ltd. is located) and potentially other regions where the product was developed or tested. Data would be prospective for the validation studies, meaning the experiments were designed and executed to gather data for the submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

For an in vitro diagnostic assay like this, "ground truth" is typically established by:

Reference Methods: For accuracy/method comparison studies, the predicate device itself serves as a "comparator" or a well-established, validated reference method (e.g., LC-MS/MS for 1,25 Dihydroxy Vitamin D).
Certified Reference Materials: For calibration and analytical measurement range verification.

Therefore, the concept of "experts establishing ground truth for the test set" is different from imaging or clinical decision support AI.

Number of 'Experts': The "experts" would be the qualified laboratory personnel who operate the reference method or predicate device and analyze the data. This could involve multiple laboratory scientists/technicians (e.g., 2-5 qualified individuals) with expertise in clinical chemistry, immunology, or mass spectrometry, possessing relevant certifications and experience (e.g., Clinical Laboratory Scientists with 5+ years of experience in IVD testing, or specialists in LC-MS/MS). They ensure the predicate/reference method is properly calibrated and run.
Qualifications of Experts: Clinical Laboratory Scientists (CLS), Medical Technologists (MT), or equivalent, with experience in immunoassay or LC-MS/MS testing, quality control, and method validation.

4. Adjudication Method for the Test Set

The concept of "adjudication" (e.g., 2+1, 3+1) is usually relevant for studies where subjective expert opinion or interpretation is being reconciled (e.g., reading medical images). For a quantitative IVD assay, adjudication in this sense is generally not applicable.

Adjudication Method: None in the traditional sense. Data reconciliation primarily involves:
- Statistical Analysis: Comparison of results from the candidate device against the predicate/reference method using statistical techniques (e.g., regression analysis, Bland-Altman plots, t-tests).
- Quality Control Procedures: Rigorous adherence to laboratory SOPs, internal and external quality control programs, and review of analytical runs by senior laboratory staff to ensure data integrity and validity.
- Discrepancy Resolution: Any significant discrepancies between duplicate runs or between the candidate and predicate methods would be investigated using predefined laboratory procedures (e.g., re-testing, sample re-collection, instrumentation checks).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study would generally not be done for this type of device.

Reason: MRMC studies are typically used for assessing the performance of diagnostic imaging devices or CADe/CADx systems where multiple human readers interpret cases, and their performance with and without AI assistance is compared. The IDS iSYS 1,25 Dihydroxy Vitamin D assay is an automated in vitro diagnostic test that provides a quantitative numerical result; it does not involve human "readers" interpreting "cases" in the same way an imaging study would.
Effect Size: Not applicable.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance assessment is inherent to the validation of an IVD assay.

Description: The entire analytical validation (precision, accuracy, linearity, LoD, LoQ, interference, specificity) assesses the "algorithm only" (which, in the case of an immunoassay, refers to the integrated system of reagents, calibrators, controls, and instrument's measurement and calculation protocols) without human intervention in the result generation process itself. The "human-in-the-loop" for such devices involves setting up the assay, loading samples, performing quality control, and clinically interpreting the final numerical result, but not directly influencing the measurement process.

7. The Type of Ground Truth Used

Type of Ground Truth: The ground truth for this diagnostic assay would be established through a combination of:
- Reference Methods: A more accurate or established laboratory method, often a Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method, or a well-characterized and FDA-cleared predicate immunoassay.
- Certified Reference Materials: Commercial reference materials with assigned target values for 1,25 Dihydroxy Vitamin D.
- Method Comparison: Comparison against the legally marketed predicate device (as indicated by the 510(k) process focusing on "substantial equivalence"). The predicate device's performance, having been previously cleared/approved, serves as a benchmark for "true" values within the context of the comparison study.

8. The Sample Size for the Training Set

For a traditional in vitro diagnostic immunoassay like the IDS iSYS 1,25 Dihydroxy Vitamin D assay, there isn't a "training set" in the sense of machine learning. The device does not "learn" from data; it operates based on a pre-defined chemical reaction and measurement principle.

Training Set Concept (Reinterpreted for IVDs): If one were to loosely interpret "training set" for an IVD, it would refer to:
- Reagent Development and Optimization: The studies and samples used during the development phase to formulate reagents, optimize reaction conditions, and establish initial calibrator ranges. This is an iterative process.
- Calibration: The specific set of calibrator materials (standards) used to establish the standard curve that converts raw signal (e.g., luminescence, absorbance) into a quantitative concentration. This would involve a small, defined set of calibrator points (e.g., 5-7 levels) run in multiple replicates.
Sample Size: This would be highly variable and proprietary during the R&D phase. For the final calibration curve, it's a fixed, small number of calibrator points.

9. How the Ground Truth for the Training Set Was Established

Again, applying the "training set" and "ground truth" concepts to an IVD:

Reagent Development/Optimization: The "ground truth" for optimizing the assay during development would be established through:
- Spiking studies: Adding known amounts of purified 1,25 Dihydroxy Vitamin D to serum/plasma.
- Comparative analyses: Testing early formulations against established research methods or highly purified reference materials.
- Internal standards: Using internal reference standards during the development process.
Calibration: The ground truth for establishing the calibrator values (the "training data" for the standard curve) would be established by:
- Gravimetric preparation: Precisely weighing and dissolving purified, traceable 1,25 Dihydroxy Vitamin D to create primary calibrator stocks.
- Comparison to reference methods: Analysing the prepared calibrator materials using a highly accurate reference method (e.g., LC-MS/MS) to assign their exact concentration.
- Traceability: Ensuring the calibrator values are traceable to higher-order reference materials or methods, often internationally accepted standards.

Summary

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 18, 2013

Immunodiagnostic Systems Ltd. C/O Mick Fenton 10 DIDCOT WAY, BOLDON BUSINESS PARK, BOLDON, TYNE AND WEAR UNITED KINGDOM NE35 9PD

Re: K123253

Trade/Device Name: IDS iSYS 1,25 Dihydroxy Vitamin D IDS iSYS 1.25 Dihydroxy Vitamin D Control Set IDS iSYS 1,25 Dihydroxy Vitamin D Calibration Verifier Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: 11 Product Code: MRG, JJX

Dated: June 06, 2013 Received: June 11, 2013

Dear Mr. Fenton:

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 (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. 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.

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2-Mr. Fenton

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use Form

510(k) Number (if known): K123253

Device Name:

IDS iSYS 1,25 Dihydroxy Vitamin D IDS iSYS 1.25 Dihydroxy Vitamin D Control Set IDS iSYS 1,25 Dihydroxy Vitamin D Calibration Verifiers

Indications for Use:

The IDS-iSYS 1,25 Dihydroxy Vitamin D Control Set is used for quality control of the IDS-iSYS 1,25 Dihydroxy Vitamin D assay on the IDS-iSYS Multi-Discipline Automated System

Prescription Use × (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung W. Johan -S

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K123253 510(k)

Regulation Number and Section

§ 862.1825 Vitamin D test system.

(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.