(75 days)
The IMMULITE® 2000 PSA Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of PSA antigen.
The Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LPTSCVM1 contains processed chicken serum matrix with preservative. LPTSCVM2, LPTSCVM3 and LPTSCVM4 contain low, intermediate and high levels of PSA respectively, in processed chicken serum/buffer matrix with preservative.
This document describes a 510(k) premarket notification for the SIEMENS IMMULITE® 2000 PSA Calibration Verification Material (CVM). It is a quality control material used to monitor the performance of the IMMULITE Immunoassay System for the quantitative measurement of PSA antigen.
Here's an analysis of the provided text, focusing on acceptance criteria and supporting studies, while noting the absence of AI-specific information:
1. Table of Acceptance Criteria and Reported Device Performance
The primary performance criterion mentioned relates to the investigation of potential matrix effects.
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Spiking recovery: 100% ±15% | Each of the spiked samples met the acceptance criteria. |
| Overall average spiking recovery: ±10% | Siemens concluded there were no matrix effects. |
| Expected Values/Reference Range (Guidelines) | Established based on Target Mean and ± 2 Standard Deviation. |
| For Level 2: 1.28 - 1.60 ng/mL (Target Mean 1.44 ng/mL) | |
| For Level 3: 44.1 - 53.9 ng/mL (Target Mean 49.0 ng/mL) | |
| For Level (attributed as sum of 90% of Level 4 and 10% of Level 1): 137 - 167 ng/mL (Target Mean 152 ng/mL) | |
| Stability | Stable up to 60 days when stored frozen at -20℃ prior to opening. Unopened stability indicated by expiration date. |
2. Sample Size Used for the Test Set and Data Provenance
- Matrix Effects Study: Three concentrations of purified PSA antigen were spiked into human serum and an evaluation lot of chicken serum. The specific number of samples or replicates for each concentration is not explicitly stated beyond "three concentrations" and "each of the samples met the acceptance criteria."
- Expected Values/Reference Range Study: Each CVM level was tested on 27 replicates in total, comprised of nine runs, six instruments, and five different reagent kit lots.
- Data Provenance: The studies appear to be internal laboratory studies conducted by Siemens (the manufacturer) and are therefore prospective from the manufacturer's perspective, without external country of origin specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This device is a calibration verification material, not an AI diagnostic tool that requires expert human interpretation for ground truth. The "ground truth" for the performance characteristics is derived from analytical measurements and traceability to international standards.
4. Adjudication Method for the Test Set
Not applicable. As described above, expert adjudication is not relevant for establishing the performance characteristics of this type of device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
Not applicable. This submission is for an in-vitro diagnostic (IVD) calibration verification material, not an AI software or system that assists human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Not applicable. This is an IVD material, not an algorithm.
7. The Type of Ground Truth Used
- Traceability: The IMMULITE PSA Calibration Verification Materials are traceable to WHO 1st International Standard 96/670. This international standard serves as the primary ground truth for the PSA values.
- Value Assignment: The CVMs are value assigned using assigned reference calibrators, which in turn are traceable to the WHO international standard. Internal "Gold Standards" also play a role, anchored to the same WHO standard. Production lots are value assigned against the Gold Standard.
8. The Sample Size for the Training Set
- Training for Value Assignment (Internal Calibrators/Gold Standards): The document mentions "8-level Calibrators are for internal use only" and "Gold Standards are anchored to WHO international standard NIBSC 96/670." It doesn't specify a "training set" in the context of an algorithm.
- CVM Value Assignment: The CVMs were tested on 27 replicates in total comprised of nine runs, six instruments, and five different reagent kit lots. This data was used to generate target mean values and guideline ranges for the CVM levels.
- When validating CVM value assignments for production lots, 30 patient samples (10 normal male, 10 spiked human serum, and 10 PSA samples) and three levels of commercially available controls were used.
9. How the Ground Truth for the Training Set Was Established
- Ground Truth for PSA Values: The ultimate ground truth is established through traceability to the WHO 1st International Standard 96/670.
- Ground Truth for CVM Value Assignment: The CVM values are calculated based on recovered values from internal runs using assigned reference calibrators (traceable to WHO standard). Quality control is performed by calculating the recovery of patient samples and controls using the assigned values, with controls needing to fall within their target ranges. This indicates an internal verification process against established analytical targets and the WHO standard.
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SIEMENS
- 510(k) Summary as Required by 21 CFR 807.92
:
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Abbreviated 510(k) Premarket Notification IMMULITE® 2000 PSA Calibration Verification Material
| A. 510(k) Number: | New Device |
|---|---|
| B. Purpose for Submission: | Quality Control materials for the IMMULITE® 2000 PSA assay |
| C. Measurand: | |
| D. Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000 PSA assay |
| E. Applicant: | |
| 1. Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591AUG 1 2 2013 |
| 2. Contact Person: | Garo Mimaryan, MS., RACTechnical Regulatory Affairs Specialist III |
| 3. Phone Number: | (914)-524-3270 |
| F. Proprietary andEstablished Names: | IMMULITE® 2000 PSA Calibration Verification Material |
| G. Regulatory Information: | |
| 1. Regulation Section: | 21 CFR 862.1660, Quality Control Material |
| 2. Classification: | Class I Reserved |
| 3. Products Codes: | JJX – Single (Specified) Analyte Controls (Assayed and Unassayed) |
| 4. Panel: | Clinical Chemistry (75) |
| H. Intended Use: | |
| 1. Intended Use(s): | See Indications for Use below. |
| 2. Indications for Use: | The IMMULITE® 2000 PSA Calibration Verification Material (CVM) is intended for monitoring systemperformance of the IMMULITE Immunoassay System for thequantitative measurement of PSA antigen. |
| 3. Special Conditions forUse Statement(s). | For prescription use only. |
| 4. Special InstrumentRequirements: | IMMULITE® 2000 Systems |
| I. Device Description: | The Calibration Verification Material (CVM) contains one setof four vials, 3 mL each. LPTSCVM1 contains processedchicken serum matrix with preservative. LPTSCVM2,LPTSCVM3 and LPTSCVM4 contain low, intermediate andhigh levels of PSA respectively, in processed chickenserum/buffer matrix with preservative. |
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J. Substantial Equivalence
- . Information:
- Access Hybritech p2PSA QC 1. Predicate Device Name:
-
- Predicate 510(k) No. K112603
-
- Comparison with Predicate:
- A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 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 2000 PSA CVM | Access Hybritech p2PSA QC | |
| Intended Use | The IMMULITE® 2000 PSA Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of PSA antigen. | The Access Hybritech PSA QC are tri-level controls intended for monitoring system performance of immunoenzymatic procedures for the quantitative measurement of [-2]pro PSA isoform of Prostate Specific Antigen (PSA) using the Access Immunoassay Systems. |
| Analyte | PSA | [-2]proPSA isoform of Prostate Specific Antigen (PSA) |
| Form | Liquid | Same |
| Stability | Stable until the expiration date when stored frozen. | Same |
| Storage | -20°C | -20°C |
| Matrix | Processed (pH-treated) Chicken Serum | Bovine Serum Albumin and buffering 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
-
- 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 PSA Calibration Verification Materials are traceable to WHO 1st International Standard 96/670.The CVMs are manufactured using approved reference lot manufactured with qualified materials and measurement procedures.
Stability:
The IMMULITE® 2000 Third Generation Calibration Verification Materials are stable up to 60 days when stored frozen at -20℃ prior to opening. Unopened stability is indicated by expiration date on the label when stored at -20°C.
Value Assignment:
The 8-level Calibrators are for internal use only and not available for commercial use. Calibrators are used during product release of PSA assay. Calibrators are manufactured and values ussigned using a stored curve generated with internal Gold Standards. Gold Standards are anchored to WHO international standard NIBSC 96/670. The 4-level CVM module is a subset of calibrators intended for use by customers to monitor system performance. The PSA CVMs can be run periodically as unknowns in PSA assay by the customer to monitor system performance.
The IMMULITE Calibration Verification Materials (CVMs) are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using PSA antigen stock and are traceable to WHO 1st International Standard 96/670. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs, six instruments and five 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, spiked patient samples, normal male samples and controls using the assigned values. The controls must fall within their target ranges.
Production lots of CVMs are value assigned against the Gold Standard 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, 30 patient samples consisting of 10 normal male patient samples, 10 spiked human serum samples and 10 PSA samples were used to validate CVM value assignments.
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The spiking recovery of the IMMULITE® 2000 PSA Calibration Verification Material (CVM) was determined to investigate potential matrix effects from using processed (pHtreated) 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.
-
- Comparison Studies
- a. Method Comparison with predicate device: Not Applicable
- b. Matrix Comparison: Not Applicable
-
- Clinical Studies:
- 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.
5. Expected Values/Reference Range:
Each CVM level was tested on 5 different kit lots, 6 instruments, 9 runs for a total of 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® 2000 PSA Calibration verification Material lot-specific value sheet. The expected assay range is 0.08 - 150 ng/mL. The values below can be considered as guidelines.
| Analytetarget | Level | Target Mean(ng/mL) | SD | Guideline(ng/mL)<0.085 | |
|---|---|---|---|---|---|
| levels | 1 | 0.00 | |||
| 2 | 1.44 | 0.08 | 1.28 | 1.60 | |
| 3 | 49.0 | 2.45 | 44.1 | 53.9 | |
| ব | 169 | Not Applicable | |||
| 152 (90% of 169+10% of 0.00) | 152 | 7.5 | 137 | 167 | |
| Assay | 0.08 - 150 ng/mL | ||||
| Range |
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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® 2000 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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Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized graphic of an eagle or bird-like figure with three wavy lines extending from its body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the graphic.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 12, 2013
SIEMENS HEALTHCARE DIAGNOSTICS, INC C/O MR. GARO MIMARYAN REGULATORY AFFAIRS SPECIALIST III 511 BENEDICT AVENUE TARRYTOWN, NY 10591
Re: K131536
Trade/Device Name: IMMULITE® 2000 PSA Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality Control Material (assayed and unassayed) Regulatory Class: I Product Code: JJX Dated: May 28, 2013 Received: May 29, 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, 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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Page 2-Mr. Garo Mimaryan
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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Maria.M.Chan -S
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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Indications for Use
510(k) Number (if known): K131536
Device Name: IMMULITE® 2000 PSA Calibration Verification Material
Indication for Use:
The IMMULITE® 2000 PSA Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of PSA antigen.
Prescription Use X And/Or (21 CFR Part 801 Subpart D)
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
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Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
510(k) K131536
§ 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.