K Number
K143373
Device Name
IMMULITE® 2000 Calcitonin Calibration Verification Material , IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material
Date Cleared
2015-02-26

(93 days)

Product Code
Regulation Number
862.1660
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdparty
Intended Use
The IMMULITE® 2000 Calcitonin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Calcitonin assay on the IMMULITE 2000 systems. The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE PAP assay on the IMMULITE 2000 systems.
Device Description
The IMMULITE® 2000 Calcitonin Calibration Verification Material (CVM) contains one set of four vials each 3mL after reconstitution. CVM1 contains bovine protein buffer matrix with preservatives and CVM2, CVM3, and CVM4 contain calcitonin in bovine protein buffer matrix with preservative. The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material (CVM) contains one set of four vials, 2mL each after reconstitution. CVM1 contains a bovine protein/buffer with 0.27% sodium azide and preservative. CVM2, CVM3, and CVM4 contain human prostatic acid phosphatase in a bovine protein/buffer matrix with 0.27% sodium azide and preservative.
More Information

Not Found

No
The device is a calibration verification material for in vitro diagnostic assays, not a software or analytical tool that would typically incorporate AI/ML. The description focuses on the composition and stability of the material.

No.
This device is for in vitro diagnostic use, specifically for the verification of calibration of assays, meaning it's used to check the accuracy of other diagnostic tests, not to treat patients directly.

No

This device is described as "Calibration Material" and "Calibration Verification Material" used for the "verification of calibration of the IMMULITE Calcitonin assay" and "IMMULITE PAP assay". It is used to ensure other diagnostic assays are working correctly, rather than directly diagnosing patients.

No

The device description clearly states that the device is a material (vials containing solutions) used for calibration verification, not software.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Explicit Statement in Intended Use: The "Intended Use / Indications for Use" section clearly states: "The IMMULITE® 2000 Calcitonin Calibration Material (CVM) is for in vitro diagnostic use..." and "The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Material (CVM) is for in vitro diagnostic use...". This is the most direct indicator.
  • Function: The device is a "Calibration Verification Material (CVM)". Calibration verification materials are used to confirm the accuracy of a diagnostic assay (in this case, the IMMULITE Calcitonin and PAP assays) which is performed in vitro (outside the body) on patient samples. This function is inherent to the definition of an IVD.
  • Context: The device is used with the "IMMULITE 2000 systems," which are laboratory instruments designed for performing diagnostic tests on biological samples.

Therefore, based on the provided text, the device is an In Vitro Diagnostic.

N/A

Intended Use / Indications for Use

The IMMULITE® 2000 Calcitonin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Calcitonin assay on the IMMULITE 2000 systems.
The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE PAP assay on the IMMULITE 2000 systems.

Product codes

JJX

Device Description

The IMMULITE® 2000 Calcitonin Calibration Verification Material (CVM) contains one set of four vials each 3mL after reconstitution. CVM1 contains bovine protein buffer matrix with preservatives and CVM2, CVM3, and CVM4 contain calcitonin in bovine protein buffer matrix with preservative.
The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material (CVM) contains one set of four vials, 2mL each after reconstitution. CVM1 contains a bovine protein/buffer with 0.27% sodium azide and preservative. CVM2, CVM3, and CVM4 contain human prostatic acid phosphatase in a bovine protein/buffer matrix with 0.27% sodium azide and 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

Prescription Use

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)

Calcitonin CVM Stability Study:
The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Calcitonin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 5 years when stored at -20°C prior to opening.
Open Component stability studies presents results that support 8 hours of stability at ambient or room temperature (15-25℃) after reconstitution.
The CVM study protocols are run as part of the calibrator stability testing. The stability calibrators/CVMs are run in duplicate (as a minimum) at the time points shown in Table 2, and the dose value is determined from the reference calibrator curve.
For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Calcitonin (L2KCL) kit lot 239, CVM lot 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Calcitonin CVM Value Assignment:
The IMMULITE Calcitonin CVMs are 4 level materials which are a subset of 7 level Calcitonin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Calcitonin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. Two levels of commercially available controls and 25 spiked normal patient samples were used to validate calibrator/CVM value assignments.
Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 3 different reagent kit lots and 8 IMMULITE 2000 systems. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD).

PAP CVM Stability Study:
The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 PAP Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 10 years when stored at 2-8°C prior to opening, and for 8 hours at ambient or room temperature (15-25°C) after opening.
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.

PAP CVM Value Assignment:
The IMMULITE PAP CVMs are 4 level materials which are a subset of 7 level PAP calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of PAP reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Six levels of commercially available controls and 27 samples (22 spiked serum samples and 5 normal female serum samples) were used to validate calibrator/CVM value assignments.
The PAP CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run on 4 IMMULITE 2000 systems and 3 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Calcitonin CVM Stability Acceptance Criteria:
The Acceptance Criteria for the Calibration Verification Material (CVM) require dose value of stability calibrators/CVM to fall between ±12% of assigned dose for CVM level 2 and ±10% for CVM levels 3 and 4 as shown in Table 3.
LCLCVM1: 0.00, Acceptable dose range :: 2.0
LCLCVM2: 18.9, ±12% difference, Acceptable dose range 16.6 - 21.2
LCLCVM3: 316, ±10% difference, Acceptable dose range 284 - 348
LCLCVM4: 2082, ±10% difference, Acceptable dose range 1874 - 2290

PAP CVM Stability Acceptance Criteria:
The Acceptance Criteria for the IMMULITE PAP Calibration Material (CVM) require dose value of stability CVMs to fall between ±20% of the assigned dose for CVM level 2 and 4 and ±15% of the assigned dose for CVM level 3 as shown in Table 3.
LPACVM1: 0.00, Acceptable dose range ::0.05
LPACVM2: 1.3, ± 20% difference, Acceptable dose range 1.04 – 1.56
LPACVM3: 5.6, ± 15% difference, Acceptable dose range 4.76 - 6.44
LPACVM4: 140, ± 20% difference, Acceptable dose range 112 – 168

Predicate Device(s)

K140258, K140541

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

§ 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.

0

Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized graphic of three human profiles facing to the right, stacked on top of each other.

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

SIEMENS HEALTHCARE DIAGNOSTICS, INC. DONNA VELASQUEZ REGULATORY TECHNICAL SPECIALIST 5210 PACIFIC CONCOURSE DRIVE LOS ANGELES CA 90045

February 26, 2015

Re: K143373

Trade/Device Name: IMMULITE® 2000 Calcitonin Calibration Verification Material IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I, Reserved Product Code: JJX Dated: December 1, 2014 Received: December 2, 2014

Dear Ms. Donna Velasquez:

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

1

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 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/ResourcesforYou/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 -A

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

Indications for Use

510(k) Number (if known) K143373

Device Name IMMULITE® 2000 Calcitonin Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® 2000 Calcitonin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Calcitonin assay on the IMMULITE 2000 systems.

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)

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 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 infonnation unless it displays a currently valid OMB number."

3

Indications for Use

510(k) Number (if known) K143373

Device Name

IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE PAP assay on the IMMULITE 2000 systems.

Type of Use (Select one or boll!, as applicable)

X 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 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."

4

510(k) Summary

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: _ K143373

| 1. Submitter
Mailing Address: | Siemens Healthcare Diagnostics Inc.
5210 Pacific Concourse Drive
Los Angeles, CA 90045 |
|--------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person:
Phone Number:
Fax Number:
E-mail Address:
Date Prepared: | Donna Velasquez
Regulatory Technical Specialist
(310)-645-8200 x7403 (310)-
645-9999
donna.velasquez@siemens.com
November 21, 2014 |
| 2. Device Name
Proprietary Name:
Measurand:
Type of Test: | IMMULITE® 2000 Calcitonin Calibration Verification Material
Quality Control materials for IMMULITE® 2000 Calcitonin assay
Calibration Verification Material (CVM) for IMMULITE® 2000
Calcitonin assay |
| Regulation Section:
Classification:
Products Code:
Panel: | 21 CFR 862.1660, Quality Control Material
Class I Reserved
JJX – Single (Specified) Analyte Controls (Assayed and
Unassayed)
Clinical Chemistry (75) |
| 3. Predicate Device Name
Predicate 510(k) No: | IMMULITE® 2000 Intact PTH Calibration Verification Material
(CVM)
K140258 |
| 4. Device Description: | The IMMULITE® 2000 Calcitonin Calibration Verification
Material (CVM) contains one set of four vials each 3mL after
reconstitution. CVM1 contains bovine protein buffer matrix with
preservatives and CVM2, CVM3, and CVM4 contain calcitonin in
bovine protein buffer matrix with preservative. |
| 5. Intended Use:
Indication for Use: | See Indications for Use Statement below
The IMMULITE® 2000 Calcitonin Calibration Verification
Material (CVM) is for in vitro diagnostic use in the verification
of calibration of the IMMULITE Calcitonin assay on the
IMMULITE 2000 systems |
| Special Conditions for
Use Statement(s):
Special Instrument
Requirements: | For prescription use only
IMMULITE® 2000 Systems |

5

6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Calcitonin Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
Candidate Device
IMMULITE 2000 Calcitonin CVMPredicate Device
IMMULITE 2000 Intact PTH
CVM
Intended
UseThe IMMULITE® Calcitonin
Calibration Verification Material
(CVM) is for in vitro diagnostic use in
the verification of calibration of the
IMMULITE Calcitonin assay on the
IMMULITE 2000 systems.The IMMULITE® Intact PTH
Calibration Verification Material
(CVM) is for in vitro diagnostic use in
the verification of calibration of the
IMMULITE Intact PTH assay on the
IMMULITE 2000 systems
Storage:S-20°CSame
FormLyophilizedSame
StabilityStable unopened until the
expiration dateSame
Levels4Same
MatrixBovine protein buffer with preservativesSame
UseSingle Use OnlySame
DIFFERENCES
Candidate Device
IMMULITE 2000 Beta-2
Microglobulin CVMPredicate Device
IMMULITE 2000 Intact PTH CVM
AnalyteCalcitoninIntact PTH
Table 1:Substantial Equivalence Comparison
----------------------------------------------

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance Specifications for its intend use. The following tests were performed on the candidate device.

Stability Summary:

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Calcitonin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 5 years when stored at -20°C prior to opening.

Open Component stability studies presents results that support 8 hours of stability at ambient or room temperature (15-25℃) after reconstitution.

6

SIEMENS

Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. The stability

calibrators/CVMs are run in duplicate (as a minimum) at the time points shown in Table 2, and the dose value is determined from the reference calibrator curve.

| 1 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

100 100 100 100 100
CVM LevelTime-Points (Months)
LCLCVM1Day 0485460
LCLCVM2Day 0485460
LCLCVM3Day 0485460
LCLCVM4Day 0485460
Table 2: Stability Protocol Summary - LCLCVM Lot 005
-----------------------------------------------------------

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Calcitonin (L2KCL) kit lot 239, CVM lot 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Calibration Verification Material (CVM) require dose value of stability calibrators/CVM to fall between ±12% of assigned dose for CVM level 2 and ±10% for CVM levels 3 and 4 as shown in Table 3.

Table 3: Acceptance criteria for stability of IMMULITE 2000 Calcitonin CVM 005

| CVM Level | Assigned
Dose
(pg/mL) | Guideline
Criteria
% difference
to assigned
dose | Acceptable
dose range
(pg/mL) |
|-----------|-----------------------------|--------------------------------------------------------------|-------------------------------------|
| LCLCVM1 | 0.00 | N/A | :: 2.0 |
| LCLCVM2 | 18.9 | ±12% | 16.6 - 21.2 |
| LCLCVM3 | 316 | ±10% | 284 - 348 |
| LCLCVM4 | 2082 | ±10% | 1874 - 2290 |

Traceability:

The IMMULITE Calcitonin CVMs are traceable to WHO 2nd IRP 89/620. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE Calcitonin CVMs are 4 level materials which are a subset of 7 level Calcitonin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Calcitonin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs are manufactured using

7

SIEMENS

qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. Two levels of commercially available controls and 25 spiked normal patient samples were used to validate calibrator/CVM value assignments.

Expected Values/Target Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 3 different reagent kit lots and 8 IMMULITE 2000 systems. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The target values are provided in the IMMULITE® 2000 CVM Calibration Material lotspecific value card. The expected assay range is 2 to 2000 pg/mL. The target values in Table 4 can be considered as guidelines.

| Analyte target
levels | CVM Level | Target
Mean
(ng/mL) | Standard
Deviation
(SD) | Guideline ±2SD Range
(ng/mL) |
|--------------------------|-----------------|---------------------------|-------------------------------|---------------------------------|
| | LCLCVM1 | 0.00 | - | 0.00 :$2.0 |
| | LCLCVM2 | 18.9 | 2.95 | 13 24.8 |
| | LCLCVM3 | 316 | 16 | 284 348 |
| | LCLCVM4 | 2082 | 125 | 1832 2332 |
| Assay Range | 2 to 2000 pg/mL | | | |

Table 4: Analyte Target Range 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.

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 ●

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 Calcitonin Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Calcitonin Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

8

510(k) Summary

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: K143373

| 1. Submitter
Mailing Address: | Siemens Healthcare Diagnostics Inc.
5210 Pacific Concourse Drive
Los Angeles, CA 90045 |
|------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person:
Phone Number:
Fax Number:
E-mail Address:
Date Prepared: | Donna Velasquez
Regulatory Technical Specialist
(310) 645-8200 x7403 (310)
645-9999
donna.velasquez@siemens.com
November 21, 2014 |
| 2. Device Name
Proprietary Name:
Measurand:
Type of Test:
Regulation Section:
Classification:
Products Code:
Panel: | IMMULITE® 2000 Prostatic Acid Phosphatase (PAP)
Calibration Verification Material Quality Control materials for
IMMULITE® 2000 PAP assay Calibration Verification
Material (CVM) for IMMULITE® 2000 PAP assay
21 CFR 862.1660, Quality Control Material
Class I Reserved
JJX – Single (Specified) Analyte Controls (Assayed and
Unassayed)
Clinical Chemistry (75) |
| 3. Predicate Device Name
Predicate 510(k) No: | IMMULITE 2000 SHBG Calibration Verification Material (CVM)
K140541 |
| 4. Device Description: | The IMMULITE® 2000 Prostatic Acid Phosphatase (PAP)
Calibration Verification Material (CVM) contains one set of four
vials, 2mL each after reconstitution. CVM1 contains a bovine
protein/buffer with 0.27% sodium azide and preservative.
CVM2, CVM3, and CVM4 contain human prostatic acid
phosphatase in a bovine protein/buffer matrix with 0.27%
sodium azide and preservative. |
| 5. Intended Use:
Indication for Use: | See Indications for Use Statement below
The IMMULITE® 2000 Prostatic Acid Phosphatase
(PAP) Calibration Verification Material (CVM) is for
in vitro diagnostic use in the verification of calibration
of the IMMULITE PAP assay on the IMMULITE 2000
systems. |
| Special Conditions
for Use Statement(s): | For prescription use only |

9

Image /page/9/Picture/0 description: The image shows the word "SIEMENS" in a bold, sans-serif font. The color of the text is a bright teal. The letters are evenly spaced and the word is horizontally oriented. The background is white.

Special Instrument Requirements:

IMMULITE® 2000 Systems

  • A comparison of the device features, intended use, and other 6. Technological Characteristics information demonstrates that the IMMULITE® 2000 PAP and Substantial Equivalence Calibration Verification Material (CVM) is substantially equivalent Comparison with Predicate: to the predicate device as summarized in Table 1.
SIMILARITIES
Candidate Device
IMMULITE 2000 PAP CVMPredicate Device
IMMULITE 2000 SHBG CVM
Intended
UseThe IMMULITE® Prostatic Acid
Phosphatase (PAP) Calibration Verification
Material (CVM) is for in vitro diagnostic
use in the verification of calibration of the
IMMULITE PAP assay on the
IMMULITE 2000 systemsThe IMMULITE® SHBG Calibration
Verification Material (CVM) is for in
vitro diagnostic use in the verification
of calibration of the IMMULITE
SHBG assay on the IMMULITE 2000
systems
FormLyophilizedSame
Storage2-8°CSame
Levels4Same
StabilityStable unopened until the expiration dateSame
UseSingle Use OnlySame

Table 1: Substantial Equivalence Comparison

DIFFERENCES
Candidate Device
IMMULITE 2000 PAP CVMPredicate Device
IMMULITE 2000 SHBG CVM
MatrixBovine protein/buffer matrix with 0.27%
Sodium Azide and preservativesBuffered bovine/protein with
preservatives
AnalytePAPSHBG

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

Stability Summary:

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 PAP Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 10 years when stored at 2-8°C prior to opening, and for 8 hours at ambient or room temperature (15-25°C) after opening.

Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.

10

Table 2: Stability Protocol Summary – LPACVM Lot 005
CVM LevelTime-Points (Months)
LCRPCVM1Day 096108120
LCRPCVM2Day 096108120
LCRPCVM3Day 096108120
LCRPCVM4Day 096108120

Table 2: Stability Protocol Summary – LPACVM Lot 005

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE PAP Calibration Material (CVM) require dose value of stability CVMs to fall between ±20% of the assigned dose for CVM level 2 and 4 and ±15% of the assigned dose for CVM level 3 as shown in Table 3.

Table 3: Acceptance criteria for stability of IMMULITE 2000 PAP CVM Lot 005

| CVM level | Assigned
Dose
(ng/mL) | Guideline
Criteria
% difference to
assigned dose | Acceptable
dose range
(ng/mL) |
|-----------|-----------------------------|-----------------------------------------------------------|-------------------------------------|
| LPACVM1 | 0.00 | N/A | ::0.05 |
| LPACVM2 | 1.3 | $\u00b1$ 20% | 1.04 – 1.56 |
| LPACVM3 | 5.6 | $\u00b1$ 15% | 4.76 - 6.44 |
| LPACVM4 | 140 | $\u00b1$ 20% | 112 – 168 |

Traceability:

The IMMULITE PAP CVMs are traceable to an internal standard. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE PAP CVMs are 4 level materials which are a subset of 7 level PAP calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of PAP reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Six levels of commercially available controls and 27 samples (22 spiked serum samples and 5 normal female serum samples) were used to validate calibrator/CVM value assignments.

Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The PAP CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run on 4 IMMULITE 2000 systems and 3 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered

11

SIEMENS

values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is 0.2 to 100 mg/L. The target values in Table 4 can be considered as guidelines.

| Analyte target
levels | CVM Level | Target Mean
(ng/mL) | Standard Deviation
(SD) | Guideline ±2SD Range
(ng/mL) | |
|--------------------------|--------------------------------|------------------------|----------------------------|---------------------------------|------|
| | LPACVM1 | 0.00 | - | 0.00 to ≤0.05 | |
| | LPACVM2 | 1.05 | 0.105 | 0.84 | 1.26 |
| | LPACVM3 | 5.40 | 0.54 | 4.32 | 6.48 |
| | LPACVM4 | 142 | - | - | - |
| | 75% LCRPCVM4 +
25% LCRPCVM1 | 107 | 12.84 | 81.3 | 133 |
| Assay Range | Up to 100 ng/mL | | | | |

Table 4: Analyte Target Range Levels

NOTE: CVM4 requires dilution to ensure that the target value is within the +10% of the top of the

reportable range of the assay.

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.

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 .

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 PAP Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 PAP Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.