The IDS-iSYS CTX-1 (CrossLaps ®) Calibration Verifiers is a device intended for the verification of the IDS-iSYS CTX-I (CrossLaps ®) Assay when performed on the IDS-iSYS Multi-Discipline Automated Analyzer

Device Description

The IDS-iSYS CTX-I (CrossLaps®) Calibration Verifiers consists of one set of four vials, 2.5 mL each in liquid form, containing horse serum with <0.1% (w/w) sodium azide as a preservative, with four concentration levels of human CTX-I:
Cal. Ver. 0: Undetectable
Cal. Ver. 1: 0.12 - 0.16 ng/mL
Cal. Ver. 2: 2.4 - 3.2 ng/mL
Cal. Ver. 3: 5.6 - 6.6 ng/mL

AI/ML Overview

The document is a 510(k) Summary for the IDS-iSYS CTX-I (CrossLaps®) Calibration Verifiers, a device intended for the verification of calibration of the IDS-iSYS CTX-I (CrossLaps®) Assay when performed on the IDS-iSYS Multi-Discipline Automated Analyzer.

Here's an analysis of the provided information to answer your request:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" for the device's performance in a table format. Instead, it defines the "Target Range" for each Calibration Verifier level, derived from the mean ± 2 standard deviations during value assignment. This target range implicitly serves as the acceptance criteria for individual measurements when verifying calibration.

CVM	Target Mean (ng/mL)	Standard Deviation (SD)	Target Range (ng/mL) (Acceptance Criteria)	Reported Device Performance (Target Mean)
Cal. Ver. 0	0 (Undetectable)	NA	NA	0 (Undetectable)
Cal. Ver. 1	0.14	0.009	0.12 - 0.16	0.14
Cal. Ver. 2	2.8	0.168	2.4 - 3.2	2.8
Cal. Ver. 3	6.1	0.366	5.6 - 6.6	6.1

Note: The "Reported Device Performance" here is the target mean derived during the value assignment process, which aligns with the center of the acceptance range. The study ensures that the device can consistently achieve these target means and fall within the defined ranges.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document describes the "value assignment" process, which functions as the primary method for establishing the performance characteristics and implicitly, the "test set" for the verifiers.

Sample Size: "Each lot-specific value assignment was tested in five runs on at least three different IDS-iSYS analyzers in triplicate, for a total of 45 replicates." This refers to 45 individual measurements for each calibrator verifier (Cal. Ver. 0, 1, 2, 3).
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given that Immunodiagnostic Systems Ltd is based in the United Kingdom, it's likely the studies were conducted there. The value assignment process described suggests a prospective study design for establishing lot-specific values.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is not applicable to this type of device. The device is a "Quality control material (assayed and unassayed)" for an in vitro diagnostic assay. Its "ground truth" (target values) is established through rigorous analytical testing and standardization against in-house reference standards, not by human expert interpretation of signals or images.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. As explained in point 3, the ground truth is established through analytical methods, not through expert adjudication.

5. 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 not a study involving human readers or AI assistance. The device is a calibration verifier for an automated immunoassay.

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

This refers to the performance of the IDS-iSYS CTX-I assay on the IDS-iSYS Multi-Discipline Automated Analyzer when calibrated and verified using these verifiers. The "value assignment" study described is a standalone performance assessment of the verifiers themselves, demonstrating their ability to consistently produce expected concentration values within a statistically defined range. The objective of the verifiers is to ensure the assay's standalone performance is accurate.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the calibrator verifiers is their assigned concentration values, which are established through:

Standardization against in-house reference standards (CTX-I in horse serum).
Derivation from the mean of multiple replicates across multiple runs and instruments. The target ranges (e.g., 0.12 - 0.16 ng/mL for Cal. Ver. 1) are determined statistically (mean ± 2SD).

8. The sample size for the training set

This concept is not directly applicable to a calibration verifier in the same way it would be for an AI algorithm. The "training" here refers to the process of standardizing the manufacturing of the verifiers and establishing their lot-specific values. The "value assignment" study (45 replicates per verifier level) serves to establish these "ground truth" values and ranges.

9. How the ground truth for the training set was established

For each lot, the "ground truth" (target mean values and ranges) was established through:

Extensive testing: "Each lot-specific value assignment was tested in five runs on at least three different IDS-iSYS analyzers in triplicate," generating a substantial dataset for statistical analysis.
Statistical analysis: The "assigned target value of each calibrator verifier was defined as the mean of all the runs for each calibrator verifier. The guideline target range is defined as the mean of all runs ± 2SD."
Standardization: The IDS-iSYS CTX-I assay (for which these verifiers are used) is itself "standardized against in-house reference standards (CTX-I in horse serum)." This implies a chain of traceability to primary or secondary reference materials.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo consists of a stylized graphic of three human profiles facing right, stacked on top of each other. The profiles are connected by a flowing line that forms the shape of a bird in flight. The graphic is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

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

March 30, 2015

IMMUNODIAGNOSTIC SYSTEMS LTD. ROMA YOUNG, REGULATORY AFFAIRS OFFICER 10 DIDCOT WAY, BOLDEN BUSINESS PARK BOLDON, TYNE & WEAR, NE35 9PD UNITED KINGDOM

Re: K143324

Trade/Device Name: IDS-iSYS CTX-I (CrossLaps®) Calibration Verifiers Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJX Dated: January 29, 2015 Received: February 6, 2015

Dear Roma Young:

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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set 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.

{1}------------------------------------------------

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -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

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K143324

Device Name

IDS-iSYS CTX-I (CrossLaps®) Calibration Verifiers

Type of Use (Select one or both, as applicable)

Indications for Use (Describe)

☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
------------------------------------------------------------------------------------	-----------------------------------------------------------------------------------

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

K143324

510(k) SUMMARY

According to the requirements of 21CFR807.92, the following Introduction information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter Immunodiagnostic Systems Ltd 10 Didcot Way Boldon Business Park Boldon Tyne and Wear NE35 9PD United Kingdom
Contact Person: Roma Young Phone: +44 191 5190660 Fax: +44 191 5190760 Email: roma.young@idsplc.com
Secondary Contact: Mick Fenton Phone: +44 191 5190660 Fax: +44 191 5190760 Email: michael.fenton@idsplc.com
March 23rd, 2015 Date Prepared:
Device Name: Proprietary names: IDS-iSYS CTX-I (Crosslaps®) Calibration Verifiers Common names: As above
- Classification: 21CFR862.1660 (Class I, Reserved)

Product Code: JJX

The IDS-iSYS CTX-I (CrossLaps®) Calibration Verifiers consists of Device Description: one set of four vials, 2.5 mL each in liquid form, containing horse serum with <0.1% (w/w) sodium azide as a preservative, with four concentration levels of human CTX-I:
Cal. Ver. 0: Undetectable Cal. Ver. 1: 0.12 - 0.16 ng/mL Cal. Ver. 2: 2.4 - 3.2 ng/mL Cal. Ver. 3: 5.6 - 6.6 ng/mL
Predicate Device: IDS-iSYS CTX-I (Crosslaps ®) Calibration Verifiers
Predicate 510(k): K111650

{4}------------------------------------------------

Special Conditionsfor Use:	For in vitro diagnostic use; for prescription use.
Special instrumentRequirements:	IDS-iSYS Multi-Discipline Automated Analyzer
Intended Use:	The IDS-iSYS CTX-1 (CrossLaps®) Calibration Verifiers is a deviceintended for the verification of calibration of the IDS-iSYS CTX-1(CrossLaps®) Assay when performed on the IDS-iSYS Multi-Discipline Automated Analyzer.

Comparison with predicate:

Similarities	Predicate Device	Candidate Device
Indications for Use	The IDS-iSYS CTX-ICrossLaps®) CalibrationVerifiers is a device intendedfor the verification ofcalibration of the IDS-iSYSCTX-I (CrossLaps ®) Assaywhen performed on the IDS-iSYS multi-disciplinedautomated analyzer.	Same
Analyte	CTX-I	Same
Values	Cal. Ver. 0: 0.0 ng/mLCal. Ver. 1: 0.6 ng/mLCal. Ver. 2: 3.0 ng/mLCal. Ver. 3: 5.0 ng/mL	Cal. Ver. 0: UndetectableCal. Ver. 1: 0.12 - 0.16 ng/mLCal. Ver. 2: 2.4 - 3.2 ng/mLCal. Ver. 3: 5.6 - 6.6 ng/mL
Levels	Levels 0, 1, 2, 3	Same
Analyzer System	IDS-iSYS Multi-DisciplineAutomated Analyzer	Same
Stability	2-8°C - unopened untilexpiration dateOn board stability: Single use-use then discard	2-8°C - unopened untilexpiration dateOn board stability: 3 hours,single use only.
Differences	Predicate device	Candidate device
Matrix	Liquid, phosphate bovineserum albumin	Horse serum containing CTX-Iand sodium azide as preservative(<0.1%). 1 vial each of levels 0-3(2.5 mL).

Table 1

{5}------------------------------------------------

Performance Characteristics

Traceability and Value Assignment

The IDS-iSYS CTX-I assay is standardized against in-house reference standards (CTX-I in horse serum). Four levels of calibrator verifiers were used to validate the calibration on the IDS-iSYS and validate the range of the analytical measurement. Each lot-specific value assignment was tested in five runs on at least three different IDS-iSYS analyzers in triplicate, for a total of 45 replicates. The assigned target value of each calibrator verifier was defined as the mean of all the runs for each calibrator verifier. The guideline target range is defined as the mean of all runs ± 2SD.

The following target mean values and ranges for each calibrator verifier provided in Table 2 are typical for the product and are intended as a guide only. Values may vary from lot to lot.

CVM	Target Mean(ng/mL)	Standard Deviation(SD)	Target Range(ng/mL)
Cal. Ver. 0	0 (Undetectable)	NA	NA
Cal. Ver. 1	0.14	0.009	0.12 - 0.16
Cal. Ver. 2	2.8	0.168	2.4 - 3.2
Cal. Ver. 3	6.1	0.366	5.6 - 6.6

Table 2

Stability

On board stability studies in accordance with the CLSI guideline EP25-A (Evaluation of stability of In Vitro Diagnostic Reagents) were performed with kit calibrators and controls. 250ul of each were placed in 500ul cups. Five sets of calibration verifiers were placed on board. At each of five time points (T0=0, T1=1h, T2=2h, T3=3h and T4=4.5h) one set was tested. The concentrations of samples were interpolated from a validated 2point calibration. Data produced supports a claim of three hours on board stability.

Accelerated stability studies performed in accordance with the CLSI guideline EP25-A (Evaluation of stability of In Vitro Diagnostic Reagents) using two point calibration support a shelf life stability claim of twelve months.

All acceptance criteria were met.

Real time stability studies in accordance with the CLSI guideline EP25-A (Evaluation of stability of In Vitro Diagnostic Reagents) to support the above claims are ongoing.

Proposed Labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.