(93 days)
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.
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.
This document describes two distinct calibration verification materials: IMMULITE® 2000 Calcitonin Calibration Verification Material and IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material. I will address each product separately as the acceptance criteria and supporting studies differ.
IMMULITE® 2000 Calcitonin Calibration Verification Material
This section describes the acceptance criteria and study for the IMMULITE® 2000 Calcitonin Calibration Verification Material (CVM).
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline Criteria % difference to assigned dose) | Acceptance Criteria (Acceptable dose range (pg/mL)) | Reported Performance (Dose values from stability study) |
|---|---|---|---|
| LCLCVM1 | N/A | ≤ 2.0 | Implicitly met if within range, no specific values reported for performance for direct comparison |
| LCLCVM2 | ±12% | 16.6 - 21.2 | Implicitly met as the study supports the claim; specific values not detailed |
| LCLCVM3 | ±10% | 284 - 348 | Implicitly met as the study supports the claim; specific values not detailed |
| LCLCVM4 | ±10% | 1874 - 2290 | Implicitly met as the study supports the claim; specific values not detailed |
Note: The document states that the stability study supports the stated claims, which implies the acceptance criteria were met, but does not provide specific performance data points for a direct, side-by-side comparison in the summary.
2. Sample size used for the test set and data provenance
- Test Set Sample Size for Stability:
- Shelf-life stability: "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."
- Time points: Day 0, 48 months, 54 months, 60 months for all 4 CVM levels.
- Therefore, at least 2 replicates x 4 levels x 4 time points = 32 measurements.
- Open Component (in-use) stability: "CVM lot 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions." No specific number of replicates or runs for this part is explicitly stated beyond "results were determined from a 2-point adjustment."
- Shelf-life stability: "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."
- Test Set Sample Size for 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."
- Data Provenance: The document does not explicitly state the country of origin. It is a submission to the FDA (USA). The study is prospective in nature as it is a stability study tracking performance over time.
3. Number of experts used to establish the ground truth for the test set and qualifications of those experts
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay, not an imaging or diagnostic AI requiring expert human interpretation for ground truth. The "ground truth" (assigned dose values) for the CVMs is established through a scientific process involving reference calibrators and measurement procedures.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
- Not applicable. This is not a study requiring human adjudication. The results are quantitative measurements against predefined criteria.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is not an AI/imaging device.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
- This is an in vitro diagnostic calibration verification material. Its performance is evaluated intrinsically through laboratory testing, essentially a "standalone" evaluation of the material's stability and value assignment, but not in the context of an AI algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- The ground truth for the CVM is its "assigned dose" values. These values are established through:
- Traceability to WHO 2nd IRP 89/620.
- Manufacture using qualified materials and measurement procedures.
- Value assignment using assigned reference calibrators, with dose values generated using curves from these reference calibrators.
- Values are calculated based on recovered values for each run on each instrument independently and 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.
8. The sample size for the training set
- Not applicable for a calibration verification material. There is no "training set" in the context of machine learning or AI for this product. The manufacturing and value assignment processes inherently involve generating data to establish the CVM's characteristics, but this isn't structured as a training set for an algorithm.
9. How the ground truth for the training set was established
- Not applicable. See #8.
IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material
This section describes the acceptance criteria and study for the IMMULITE® 2000 Prostatic Acid Phosphatase (PAP) Calibration Verification Material (CVM).
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline Criteria % difference to assigned dose) | Acceptance Criteria (Acceptable dose range (ng/mL)) | Reported Performance (Dose values from stability study) |
|---|---|---|---|
| LPACVM1 | N/A | ≤ 0.05 | Implicitly met if within range, no specific values reported for performance for direct comparison |
| LPACVM2 | ±20% | 1.04 – 1.56 | Implicitly met as the study supports the claim; specific values not detailed |
| LPACVM3 | ±15% | 4.76 - 6.44 | Implicitly met as the study supports the claim; specific values not detailed |
| LPACVM4 | ±20% | 112 – 168 | Implicitly met as the study supports the claim; specific values not detailed |
Note: The document states that the stability study supports the stated claims, which implies the acceptance criteria were met, but does not provide specific performance data points for a direct, side-by-side comparison in the summary.
2. Sample size used for the test set and data provenance
- Test Set Sample Size for Stability:
- Shelf-life stability: "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."
- Time points: Day 0, 96 months, 108 months, 120 months for all 4 CVM levels.
- Therefore, at least 2 replicates x 4 levels x 4 time points = 32 measurements.
- Open Component (in-use) stability: Stable for 8 hours at ambient or room temperature (15-25°C) after opening. The specific testing methodology and sample size for this claim are not detailed beyond the claim itself.
- Shelf-life stability: "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."
- Test Set Sample Size for Expected Values/Target Values/Reference Range: "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."
- Data Provenance: The document does not explicitly state the country of origin. It is a submission to the FDA (USA). The study is prospective in nature as it is a stability study tracking performance over time.
3. Number of experts used to establish the ground truth for the test set and qualifications of those experts
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay, not an imaging or diagnostic AI requiring expert human interpretation for ground truth. The "ground truth" (assigned dose values) for the CVMs is established through a scientific process involving internal standards and measurement procedures.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
- Not applicable. This is not a study requiring human adjudication. The results are quantitative measurements against predefined criteria.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is not an AI/imaging device.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
- This is an in vitro diagnostic calibration verification material. Its performance is evaluated intrinsically through laboratory testing, essentially a "standalone" evaluation of the material's stability and value assignment, but not in the context of an AI algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- The ground truth for the CVM is its "assigned dose" values. These values are established through:
- Traceability to an internal standard.
- Manufacture using qualified materials and measurement procedures.
- Value assignment using assigned reference calibrators, with dose values generated using curves from these reference calibrators.
- Values are calculated based on recovered values for each run on each instrument independently and then averaged across all systems.
- Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values, and 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.
8. The sample size for the training set
- Not applicable for a calibration verification material. There is no "training set" in the context of machine learning or AI for this product.
9. How the ground truth for the training set was established
- Not applicable. See #8.
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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
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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
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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."
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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."
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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. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045 |
|---|---|
| Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared: | Donna VelasquezRegulatory Technical Specialist(310)-645-8200 x7403 (310)-645-9999donna.velasquez@siemens.comNovember 21, 2014 |
| 2. Device NameProprietary Name:Measurand:Type of Test: | IMMULITE® 2000 Calcitonin Calibration Verification MaterialQuality Control materials for IMMULITE® 2000 Calcitonin assayCalibration Verification Material (CVM) for IMMULITE® 2000Calcitonin assay |
| Regulation Section:Classification:Products Code:Panel: | 21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX – Single (Specified) Analyte Controls (Assayed andUnassayed)Clinical Chemistry (75) |
| 3. Predicate Device NamePredicate 510(k) No: | IMMULITE® 2000 Intact PTH Calibration Verification Material(CVM)K140258 |
| 4. Device Description: | The IMMULITE® 2000 Calcitonin Calibration VerificationMaterial (CVM) contains one set of four vials each 3mL afterreconstitution. CVM1 contains bovine protein buffer matrix withpreservatives and CVM2, CVM3, and CVM4 contain calcitonin inbovine protein buffer matrix with preservative. |
| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® 2000 Calcitonin Calibration VerificationMaterial (CVM) is for in vitro diagnostic use in the verificationof calibration of the IMMULITE Calcitonin assay on theIMMULITE 2000 systems |
| Special Conditions forUse Statement(s):Special InstrumentRequirements: | For prescription use onlyIMMULITE® 2000 Systems |
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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 DeviceIMMULITE 2000 Calcitonin CVM | Predicate DeviceIMMULITE 2000 Intact PTHCVM | |
| IntendedUse | The IMMULITE® CalcitoninCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Calcitonin assay on theIMMULITE 2000 systems. | The IMMULITE® Intact PTHCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Intact PTH assay on theIMMULITE 2000 systems |
| Storage | :S-20°C | Same |
| Form | Lyophilized | Same |
| Stability | Stable unopened until theexpiration date | Same |
| Levels | 4 | Same |
| Matrix | Bovine protein buffer with preservatives | Same |
| Use | Single Use Only | Same |
| DIFFERENCES | ||
| Candidate DeviceIMMULITE 2000 Beta-2Microglobulin CVM | Predicate DeviceIMMULITE 2000 Intact PTH CVM | |
| Analyte | Calcitonin | Intact 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.
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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 0100 100 100 100 100 | ||||
|---|---|---|---|---|
| CVM Level | Time-Points (Months) | |||
| LCLCVM1 | Day 0 | 48 | 54 | 60 |
| LCLCVM2 | Day 0 | 48 | 54 | 60 |
| LCLCVM3 | Day 0 | 48 | 54 | 60 |
| LCLCVM4 | Day 0 | 48 | 54 | 60 |
| 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 | AssignedDose(pg/mL) | GuidelineCriteria% differenceto assigneddose | Acceptabledose 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
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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 targetlevels | CVM Level | TargetMean(ng/mL) | StandardDeviation(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.
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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. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045 |
|---|---|
| Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared: | Donna VelasquezRegulatory Technical Specialist(310) 645-8200 x7403 (310)645-9999donna.velasquez@siemens.comNovember 21, 2014 |
| 2. Device NameProprietary Name:Measurand:Type of Test:Regulation Section:Classification:Products Code:Panel: | IMMULITE® 2000 Prostatic Acid Phosphatase (PAP)Calibration Verification Material Quality Control materials forIMMULITE® 2000 PAP assay Calibration VerificationMaterial (CVM) for IMMULITE® 2000 PAP assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX – Single (Specified) Analyte Controls (Assayed andUnassayed)Clinical Chemistry (75) |
| 3. Predicate Device NamePredicate 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 fourvials, 2mL each after reconstitution. CVM1 contains a bovineprotein/buffer with 0.27% sodium azide and preservative.CVM2, CVM3, and CVM4 contain human prostatic acidphosphatase in a bovine protein/buffer matrix with 0.27%sodium azide and preservative. |
| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® 2000 Prostatic Acid Phosphatase(PAP) Calibration Verification Material (CVM) is forin vitro diagnostic use in the verification of calibrationof the IMMULITE PAP assay on the IMMULITE 2000systems. |
| Special Conditionsfor Use Statement(s): | For prescription use only |
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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 DeviceIMMULITE 2000 PAP CVM | Predicate DeviceIMMULITE 2000 SHBG CVM | |
| IntendedUse | The IMMULITE® Prostatic AcidPhosphatase (PAP) Calibration VerificationMaterial (CVM) is for in vitro diagnosticuse in the verification of calibration of theIMMULITE PAP assay on theIMMULITE 2000 systems | The IMMULITE® SHBG CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITESHBG assay on the IMMULITE 2000systems |
| Form | Lyophilized | Same |
| Storage | 2-8°C | Same |
| Levels | 4 | Same |
| Stability | Stable unopened until the expiration date | Same |
| Use | Single Use Only | Same |
Table 1: Substantial Equivalence Comparison
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 PAP CVM | Predicate DeviceIMMULITE 2000 SHBG CVM | |
| Matrix | Bovine protein/buffer matrix with 0.27%Sodium Azide and preservatives | Buffered bovine/protein withpreservatives |
| Analyte | PAP | SHBG |
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.
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| Table 2: Stability Protocol Summary – LPACVM Lot 005 | ||||
|---|---|---|---|---|
| CVM Level | Time-Points (Months) | |||
| LCRPCVM1 | Day 0 | 96 | 108 | 120 |
| LCRPCVM2 | Day 0 | 96 | 108 | 120 |
| LCRPCVM3 | Day 0 | 96 | 108 | 120 |
| LCRPCVM4 | Day 0 | 96 | 108 | 120 |
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 | AssignedDose(ng/mL) | GuidelineCriteria% difference toassigned dose | Acceptabledose 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
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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 targetlevels | 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.
§ 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.