The IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of PSA antigen.

Device Description

The Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. L3PSCVM1 contains processed chicken serum matrix with preservative. L3PSCVM2, L3PSCVM3 and L3PSCVM4 contain low, intermediate and high levels of PSA respectively, in processed chicken serum matrix with preservative.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Traceability	The Calibration Verification Materials (CVMs) must be traceable.	The IMMULITE Third Generation PSA CVMs are traceable to Gold Standards prepared using purified PSA antigen stock solution whose concentration was defined by optical density. CVMs are manufactured using qualified materials and measurement procedures.
Stability (Unopened)	Stable until the expiration date when stored frozen at -20°C.	The IMMULITE®/IMMULITE 1000 Third Generation Calibration Verification Materials are stable up to 12 months when stored frozen at -20°C prior to opening. Unopened stability is indicated by expiration date on the label when stored at -20°C.
Value Assignment	CVMs are value assigned using a previous reference lot, tested on a minimum of nine runs comprised of a minimum of three systems and two different reagent kit lots. CVM values are derived by data reduction for each run on each instrument and then averaged across all systems. Production lots are value assigned against the previous reference lot using two reagent kit lots and on a minimum of three instruments.	The CVMs are value assigned using a previous reference lot of materials. Standards are prepared using purified PSA antigen stock solution. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs are tested on a minimum of nine runs comprised of a minimum of three systems and two different reagent kit lots. CVM values are derived by data reduction for each run on each instrument. CVM values are then averaged across all systems. Production lots of CVMs are value assigned against the previous reference lot using two reagent kit lots and on a minimum of three different instruments.
Matrix Effects (Spiking Recovery)	Spiking recovery of purified PSA antigen into chicken serum should demonstrate no matrix effects compared to human serum. The acceptance criteria were 100% ±15% with an overall average of ±10%.	Siemens spiked three concentrations of purified PSA antigen into human serum and an evaluation lot comprised of chicken serum. The PSA values of the evaluation lot were compared to the human serum lots. Each of the samples met the acceptance criteria (100% ±15% with an overall average of ±10%). Siemens concluded that there were no matrix effects.
Guideline Range Establishment	Each CVM level was tested for a total of 27 replicates (9 runs, 3 replicates per run). 2 different reagent kit lots and 9 different instruments were used. Guideline Range (95% confidence interval) was established based on the Target Mean and ± 2 Standard Deviation (SD).	Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 2 different reagent kit lots and 9 different instruments were used to gain the 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). Reported Values:- Level 1: Target Mean 0.000 ng/mL, Guideline Range ≤ 0.005 ng/mL- Level 2: Target Mean 0.085 ng/mL, Guideline Range 0.072 - 0.098 ng/mL- Level 3: Target Mean 4.45 ng/mL, Guideline Range 4.01 - 4.90 ng/mL- Level 4: Target Mean 18.6 ng/mL, Guideline Range 15.8 - 21.4 ng/mL

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

The provided document describes a validation study for the Calibration Verification Material (CVM) itself, not a test set for an algorithm assessing patient data. The "samples" referred to are the CVM materials and the substances used to validate them.

For demonstrating matrix effects: Three concentrations of purified PSA antigen were spiked into human serum and an evaluation lot of chicken serum. The specific number of individual samples (e.g., number of human serum samples, chicken serum samples) is not explicitly stated beyond "three concentrations."
For establishing Guideline Ranges: Each CVM level (4 levels) was tested for a total of 27 replicates. This means 4 levels * 27 replicates = 108 individual test measurements were performed to establish the guideline ranges across different runs, systems, and reagent lots.
For validating CVM value assignments: Three levels of commercially available controls, twenty-five spiked human serum samples, and five male patient samples were used.
Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics Inc. and involve laboratory testing of the CVMs. The human serum samples likely originated from a clinical setting, but the specific country of origin or whether they were retrospective/prospective is not specified. The chicken serum is a matrix component.

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

This information is not applicable to this submission. The device is a Calibration Verification Material, a quality control product, not an AI/diagnostic device that interprets patient data requiring expert ground truth for a test set. Its performance is evaluated through analytical methods like traceability, stability, and value assignment, not clinical interpretation.

4. Adjudication Method for the Test Set

This information is not applicable. There was no "test set" in the sense of a set of cases requiring adjudication by experts. Analytical measurements and statistical methods (like determining 95% confidence intervals and comparing values to acceptance criteria) were used for validation.

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

This information is not applicable. This is not an AI-assisted diagnostic device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This information is not applicable. This is not an algorithm or AI device.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" for this device relates to the accuracy and known concentration of the PSA antigen within the Calibration Verification Materials.

For traceability and value assignment: The ground truth is established by purified PSA antigen stock solutions whose concentrations were defined by optical density, serving as "Gold Standards." This is a highly controlled and metrologically sound reference.
For matrix effects: The ground truth is the expected recovery of known spiked amounts of purified PSA antigen.

8. The Sample Size for the Training Set

This information is not applicable. This is not a machine learning or AI device that requires a training set.

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

This information is not applicable. As mentioned above, there is no training set for this type of device.

Summary

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siemens

Abbreviated 510(k) Premarket Notification

IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material

MAR 1 4 2013

5. 510(k) Summary as Required by 21 CFR 807.92

A. 510(k) Number:	K122534
B. Purpose for Submission:	New Device
C. Measurand:	Quality Control materials for the IMMULITE®/IMMULITE1000 Third Generation PSA assay (LKUP)
D. Type of Test:	Calibration Verification Material (CVM) forIMMULITE®/IMMULITE 1000 Third Generation PSA assay
E. Applicant:
1. Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591
2. Contact Person:	Garo Mimaryan, MS, RACTechnical Regulatory Affairs Specialist III
3. Phone Number:	(914)-524-3270
F. Proprietary andEstablished Names:	IMMULITE®/IMMULITE 1000 Third Generation PSACalibration Verification Material
G. Regulatory Information:
1. Regulation Section:	21 CFR 862.1660, Quality Control Material
2. Classification:	Class I
3. Products Codes:	JJX - Single (Specified) Analyte Controls (Assayed andUnassayed)
4. Panel:	Clinical Chemistry (75)
H. Intended Use:
1. Intended Use(s):	See Indications for Use below.
2. Indications for Use:	The IMMULITE®/IMMULITE 1000 Third Generation PSACalibration Verification Material (CVM) is intended formonitoring system performance of the IMMULITEImmunoassay System for the quantitative measurement ofPSA antigen.
3. Special Conditions forUse Statement(s).	For prescription use only.
4. Special InstrumentRequirements:	IMMULITE®/IMMULITE 1000 Systems
I. Device Description:	The Calibration Verification Material (CVM) contains one setof four vials, 3 mL each. L3PSCVM1 contains processedchicken serum matrix with preservative. L3PSCVM2,L3PSCVM3 and L3PSCVM4 contain low, intermediate andhigh levels of PSA respectively, in processed chicken serummatrix with preservative.

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Abbreviated 510(k) Premarket Notification IMMULITE®IMMULITE 1000 Third Generation PSA Calibration Verification Material

J. Substantial Equivalence

Information:

Access Hybritech p2PSA QC 1. Predicate Device Name:
1. Predicate 510(k) No.
K112603
A comparison of the device features, intended use, and other 3. Comparison with information demonstrates that the IMMULITE®/ IMMULITE Predicate: 1000 PSA Calibration Verification Material (CVM) is substantially equivalent to the predicate device, Access Hybritech p2PSA QC, as summarized in the following table.

REAGENT SIMILARITIES and DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE/IMMULITE 1000 ThirdGeneration PSA CVM	Access Hybritech p2PSA QC
IntendedUse	The IMMULITE®/IMMULITE 1000Third Generation PSA CalibrationVerification Material (CVM) isintended for monitoring systemperformance of the IMMULITEImmunoassay system for thequantitative measurement of PSAantigen.	The Access Hybritech p2PSA QCare tri-level controls intended formonitoring system performance ofimmunoenzymatic procedures forthe quantitative measurement of [- 2]pro PSA isoform of ProstateSpecific Antigen (PSA) using theAccess Immunoassay Systems.
Analyte	PSA	[-2]proPSA isoform of ProstateSpecific Antigen (PSA)
Form	Liquid	Same
Stability	Stable until the expiration date whenstored frozen.	Stable until the expiration date whenstored frozen.
Storage	-20°C	-20°C or colder
Matrix	Processed (pH-treated) Chicken Serum	Bovine Serum Albumin andbuffering salts
Use	Single Use Only	Not for Single Use

K. Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators .
Guidance for Industry and FDA Staff -- Assayed and Unassayed Quality Control Material .

L. Test Principle:

Not Applicable

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M. Performance Characteristics

1. Analytical Performance:
- a. Precision/Reproducibility: Not Applicable
- b. Linearity/assay Reportable Range: Not Applicable

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

Traceability: The IMMULITE Third Generation PSA Calibration Verification Materials are traceable to Gold Standards prepared using purified PSA antigen stock solution which had its concentration defined by optical density. The CVMs are manufactured using qualified materials and measurement procedures.

Stability: The IMMULITE®/IMMULITE 1000 Third Generation Calibration Verification Materials are stable up to 12 months when stored frozen at -20°C prior to opening. Unopened stability is indicated by expiration date on the label when stored at -20°C.

Value Assignment: The IMMULITE CVMs are value assigned using a previous reference lot of materials. Standards are prepared using the purified (≥98% purity) PSA antigen stock solution whose concentration was defined by optical density. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs are tested on a minimum of nine runs comprised of a minimum of three systems and two different reagent kit lots. CVM values are derived by data reduction for each run on each instrument. CVM values are then averaged across all systems.

Production lots of CVMs are value assigned against the previous reference lot using two reagent kit lots and on a minimum of three different instruments. Quality control is performed by calculating the recovery of patient sample panels and controls using the assigned calibrator and CVM values. The calibrator values are calculated based on the recovered values for each run independently. Three levels of commercially available controls, twenty-five spiked human serum samples and five male patient samples are used to validate CVM value assignments.

The spiking recovery of the IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material (CVM) was determined to investigate potential matrix effects from using processed (pH-treated) Chicken Serum. Siemens spiked three concentrations of purified PSA antigen into human serum and an evaluation lot comprised of chicken serum. The PSA values of the evaluation lot were compared to the human serum lots. The acceptance criteria were 100% ±15% with an overall average of ±10%. Each of the samples met the acceptance criteria, and Siemens concluded that there were no matrix effects.

Detection limit: Not Applicable d.
Analytical Specificity: Not Applicable e.
Assay cut-off: Not Applicable f.

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SIEMENS

IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material

Comparison Studies 2.
a. Method Comparison with predicate device: Not Applicable
b. Matrix Comparison: Not Applicable
Clinical Studies: 3.
- a. Clinical Sensitivity and Specificity: Not Applicable
- b. Other clinical supportive data (when a. and b. are not applicable): Not Applicable
Clinical Cut-off: Not Applicable 4.
1. Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 2 different reagent kit lots and 9 different instruments were used to gain the 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE®/IMMULITE 1000 PSA Calibration verification Material lot-specific value sheet. The expected assay range is 0.015 - 20 ng/mL. The values below can be considered as guidelines.

Level	Catalog andLot number	TargetMean(ng/mL)	SD	Guideline Range(ng/mL)
1	L3PSCVM1 D101	0.000		≤ 0.005
2	L3PSCVM2 D101	0.085	0.0065	0.072	0.098
3	L3PSCVM3 D101	4.45	0.2225	4.01	4.90
4	L3PSCVM4 D101	18.6	1.4	15.8	21.4

Expected Values:

Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.

N. Proposed Labeling:

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

O. Conclusion: The IMMULITE®/IMMULITE 1000 PSA Calibration verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Access Hybritech p2PSA QC.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

March 14, 2013

Siemens Healthcare Diagnostics Inc. c/o Mr. Garo Mimaryan Regulatory Affairs Specialist III 511 Benedict Avenue Tarrytown, NY 10591

Re: K122534

Trade/Device Name: IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality Control Material (assayed and unassayed) Regulatory Class: Class I Product Code: JJX Dated: March 5, 2013 Received: March 8, 2013

Dear Mr. Mimaryan:

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. Ilsting 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 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 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.

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If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 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/cdrl/industrv/support/index.html.

Sincerely yours,

Image /page/5/Picture/5 description: The image shows the name "Maria M. Chan -S" in a simple, sans-serif font. The text is horizontally oriented and appears to be a signature or label. The letters are clear and legible, with a consistent stroke weight.

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K122534

Device Name: IMMULITE®/IMMULITE 1000 Third Generation PSA Calibration Verification Material

Indication for Use:

Prescription Use X (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 Diagnostic Device Evaluation and Safety (OVD)

MariaM.Chan-S

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

K122534 510(k)

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.