(60 days)
The ADVIA Chemistry Liquid Protein Calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the Alpha-Acid-Glycoprotein (AAG), Alpha-1-Antitrypsin (AAT), Anti-streptolysin-O_2 (ASO_2), Complement C3 (C3), Complement C4 (C4), Haptoglobin (HAPT), Immunoglobulin A_2 (IGA_2), Immunoglobulin G_2 (IGG_2), Immunoglobulin M_2 (IGM_2), Prealbumin (PREALB), Rheumatoid Factor (RF), Transferrin (TRF) methods
ADVIA Chemistry Liquid Specific Protein Calibrator is a multi-analyte, liquid buffered based product containing multiple analytes (proteins derived from human source). The kit consists of 6 vials each of 6 calibrator levels which are ready for use (no preparation is required). The constituent concentrations of these Calibrators are present at levels 2, 3, 4, 5 and 6. Level 1 is a zero level. The volume per vial is 1.0 mL. Anti-streptolysin-O (ASO), Alpha-1-Antitrypsin (AAT), Prealbumin (PREALB), Rheumatoid Factor (RF), Immunoglobulin A 2, (IGA 2), Immunoglobulin G 2 (IGG 2), Immunoglobulin M 2 (IGM 2), Complement C3 (C3), Complement C4 (C4), Haptoglobin (HAPT), Transferrin (TRF), and Alpha-Acid-Glycoprotein (AAG) are value assigned for ADVIA 1650 Chemistry systems. In addition the calibrator also contains Ferritin and CRP with no specific value assignment on ADVIA Chemistry systems at this time.
This document is a 510(k) summary for a calibrator device, not an AI/ML powered diagnostic device. Therefore, many of the requested categories for acceptance criteria and study details (such as sample size for test sets, ground truth establishment by experts, adjudication methods, MRMC studies, standalone performance, and training set information) are not applicable to this type of medical device submission.
Calibrators are used to standardize the measurements of analytical instruments. Their performance is typically assessed by demonstrating that they accurately establish a calibration curve for the specified analytes on the intended instrument, and that the calibrated system can then accurately measure controls and patient samples. The primary focus for a calibrator 510(k) is often on demonstrating substantial equivalence to a predicate device in terms of intended use, formulation, analytes quantified, and performance characteristics like stability.
However, I can extract the information relevant to the device's characteristics and the comparison made.
Device Name: ADVIA® Chemistry Liquid Specific Protein Calibrator
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a quantitative sense as one would for a diagnostic test (e.g., sensitivity/specificity thresholds). Instead, the "performance" for a calibrator is largely demonstrated by showing substantial equivalence to a legally marketed predicate device. The core "performance" demonstrated here is that the new calibrator is functionally equivalent to the predicate for calibration on the specified instruments and analytes.
| Item | New Device Performance (ADVIA® Chemistry Liquid Specific Protein Calibrator) | Predicate Device Performance (Randox Liquid Protein Calibrators - K061056 & K031608) |
|---|---|---|
| Intended Use | For in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for AAG, AAT, ASO_2, C3, C4, HAPT, IGA_2, IGG_2, IGM_2, PREALB, RF, TRF methods. | Similar intended use for calibration of various protein assays on Clinical Chemistry and Immunoassay systems, including ASO, C3, C4, CRP, Ferritin, Haptoglobin, IgA, IgG, IgM, Prealbumin, Transferrin, AAT, and RF. |
| Formulation / Analytes Present | Anti-streptolysin-O, Alpha-1-Antitrypsin, Prealbumin, Rheumatoid Factor, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Complement C3, Complement C4, Haptoglobin, Transferrin, Ferritin, Alpha-acid-glycoprotein, CRP. | Same analytes present. |
| Measured Analytes (value assigned) | Anti-streptolysin-O, Alpha-1-Antitrypsin, Prealbumin, Rheumatoid Factor, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Complement C3, Complement C4, Haptoglobin, Transferrin, Alpha-acid-glycoprotein. (Ferritin and CRP present but not value assigned on ADVIA Chemistry systems at this time). | ASO, AAT, Prealbumin, RF, IgA, IgG, IgM, Complement C3, Complement C4, HAPT, Transferrin, Alpha-acid-glycoprotein, Ferritin, CRP. |
| Instrument Compatibility | ADVIA® Chemistry Systems | Clinical Chemistry and Immunoassay systems, including numerous specific instruments listed (e.g., Abbott, Ace, Bayer Advia, Dade Dimension, Hitachi, Kone, AU series, Selectra, Synchron, ILAB, RX, Cobas). |
| Traceability for AAG | International Reference Material CRM 470 | Same. |
| Matrix | Buffered base | Same. |
| Analyte Source | Derived from human source | Same. |
| Number of Levels | Six (the lowest level is a zero-level) | Same. |
| Fill Volume | 1.0 mL each vial | Same. |
| Stability | 24 months – shelf-life | Same. |
Key takeaway for "acceptance criteria": The primary acceptance criterion for this 510(k) submission is to demonstrate substantial equivalence to the predicate device. The detailed comparison table shows that across all critical parameters (intended use, composition, analytes, matrix, and stability), the new device is either identical or sufficiently similar to the predicate to be considered substantially equivalent.
2. Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated as a test set with an 'n' number of cases. For a calibrator, "testing" typically involves technical validation on the intended instrument. This would involve running the calibrator multiple times to establish a calibration curve, and then running quality control materials and potentially patient samples calibrated by the new device to ensure accurate results. The document does not provide specifics on the number of runs, samples, or sites for these validation activities.
- Data Provenance: The document does not specify the country of origin of testing data. It is a submission by Siemens Healthcare Diagnostics Inc., located in Tarrytown, NY, USA. The study design (clinical/retrospective/prospective) is not applicable in the way it is for an AI/ML diagnostic. This is a technical performance validation of a calibrator.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable. For a calibrator, "ground truth" relates to the assigned values of the analytes. These values are established through rigorous analytical methods, often traceable to international reference materials (as noted for AAG, "International Reference Material CRM 470"). It's a scientific and metrological process, not expert consensus as in image interpretation.
4. Adjudication method for the test set:
- Not Applicable. Adjudication methods (like 2+1, 3+1) are used for resolving disagreements among human readers or experts in diagnostic studies, particularly for subjective interpretations (e.g., radiology). This is not relevant for a calibrator.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not Applicable. This is not an AI/ML diagnostic device, nor is it a device that is read or interpreted by human readers in the context of diagnostic performance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not Applicable. This is a calibrator, not an algorithm.
7. The type of ground truth used:
- Reference Material Values / Analytical Assignment: For calibrators, the "ground truth" (or target value) for each analyte level is established through highly accurate analytical methods, often by comparing to or using international reference materials (e.g., "International Reference Material CRM 470" for AAG). This is a metrological ground truth, not pathology, expert consensus, or outcomes data in the diagnostic sense.
8. The sample size for the training set:
- Not Applicable. This is a calibrator, not an AI/ML model that requires a training set.
9. How the ground truth for the training set was established:
- Not Applicable. No training set is used.
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510(k) Summary of Safety and Effectiveness for the
ADVIA® Chemistry Liquid Specific Protein Calibrators
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
A. 510(k) Number: K10 370 /
B. Date of Preparation: December 03, 2010
C. Proprietary and Established Names:
ADVIA® Chemistry Liquid Specific Protein Calibrator
D. Applicant:
Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591
Kira Gordon, Sr. Regulatory Affairs Specialist
Office: (914) 524-2996 Fax: (914) 524-2500
E. Regulatory Information:
ADVIA Chemistry Liquid Specific Protein Calibrator
-
- Regulation section: 21 CFR § 862.1150 Calibrator.
-
- Classification: Class II
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- Product Code: JIX, calibrator, multi-analyte mixture
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- Panel: Clinical Chemistry
F. Predicate Device:
Randox Liquid Protein Calibrators
ADVIA Chemistry Liquid Specific Protein Calibrator is substantially equivalent to the Randox Liquid Protein Calibrator cleared under K031608 and K061056.
G. Device Description:
ADVIA Chemistry Liquid Specific Protein Calibrator is a multi-analyte, liquid buffered based product containing multiple analytes (proteins derived from human source). The kit consists of 6 vials each of 6 calibrator levels which are ready for use (no preparation is required). The constituent concentrations of these Calibrators are
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present at levels 2, 3, 4, 5 and 6. Level 1 is a zero level. The volume per vial is 1.0 mL.
Anti-streptolysin-O (ASO), Alpha-1-Antitrypsin (AAT), Prealbumin (PREALB), Rheumatoid Factor (RF), Immunoglobulin A 2, (IGA 2), Immunoglobulin G 2 (IGG 2), Immunoglobulin M 2 (IGM 2), Complement C3 (C3), Complement C4 (C4), Haptoglobin (HAPT), Transferrin (TRF), and Alpha-Acid-Glycoprotein (AAG) are value assigned for ADVIA 1650 Chemistry systems.
In addition the calibrator also contains Ferritin and CRP with no specific value assignment on ADVIA Chemistry systems at this time.
H. Intended Use:
The ADVIA Chemistry Liquid Protein Calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the Alpha-Acid-Glycoprotein (AAG), Alpha-1-Antitrypsin (AAT), Anti-streptolysin-O 2 (ASO 2), Complement C3 (C3), Complement C4 (C4), Haptoglobin (HAPT), Immunoglobulin A 2 (IGA_2), Immunoglobulin G_2 (IGG_2), Immunoglobulin M_2 (IGM_2), Prealbumin (PREALB), Rheumatoid Factor (RF), Transferrin (TRF) methods
I. Substantial Equivalence Information:
The ADVIA Chemistry Liquid Specific Protein Calibrator and Randox Liquid Protein Calibrator were compared in the following table.
| Item | New Device | Predicate Device (K061056 and K031608) |
|---|---|---|
| Intended Use | for in vitro diagnostic use in the calibration ofADVIA® Chemistry system for the Alpha-Acid-Glycoprotein (AAG)*, Alpha-1-Antitrypsin (AAT), Anti-streptolysin-O_2(ASO_2), Complement C3 (C3), ComplementC4 (C4), Haptoglobin (HAPT), ImmunoglobulinA_2 (IGA_2), Immunoglobulin G_2 (IGG_2),Immunoglobulin M_2 (IGM_2), Prealbumin(PREALB), Rheumatoid Factor (RF),Transferrin (TRF) methods | K061056:for in vitro diagnostic use in thecalibration of ASO, Complement C3,Complement C4, CRP, Ferritin,Haptoglobin, IgA, IgG, IgM, Prealbumin, andTransferrin assays on ClinicalChemistry and Immunoassay systems |
| * - subject of this submission | K031608:for the calibration of ASO, Complement C3,Complement C4, CRP, Ferritin, IgA, IgG, IgM,Prealbumin and Transferrin assays (all neatsample assays). These calibrators also contain a-1-Antitrypsin (AAT) and Rheumatoid Factor(RF) for use in the calibration of AAT and RFassays on the Bayer Advia 1650 analyser only.for the calibration of a-1-antitrypsin, a-1-acidglycoprotein, IgA, IgG, IgM and Transferrinassays which require sample pre-dilution | |
| Formulation /analytespresent | Anti-streptolysin-O,Alpha-1-Antitrypsin,Prealbumin,Rheumatoid Factor,Immunoglobulin AImmunoglobulin G,Immunoglobulin M | same |
| Complement C3,Complement C4,Haptoglobin,Transferrin,Ferritin,Alpha-acid-glycoprotein,CRP | ||
| MeasuredAnalytes(valueassigned) | Anti-streptolysin-OAlpha-1-AntitrypsinPrealbumin,Rheumatoid Factor,Immunoglobulin A,Immunoglobulin G,Immunoglobulin M,Complement C3,Complement C4,Haptoglobin,Transferrin,Alpha-acid-glycoprotein,Ferritin - not value assigned but present in theformulation,CRP - not value assigned but present in theformulation | ASOAATPrealbuminRFIgAIgGIgMComplement C3Complement C4HAPTTransferrinAlpha-acid-glycoproteinFerritinCRP |
| Instrument | ADVIA® Chemistry Systems | Clinical Chemistry and Immunoassay systems,Abbott Spectrum, Abbott Acroset, AbbottArchitect i2000, Architect i2000sr, Aceanalyser, Bayer Advia 1650, Advia 2400, Advia1200, Dade Dimension RXL, Dimension AR,Hitachi 704, Hitachi 717,Hitachi 911, Hitachi 917, Hitachi 912, Hitachi747, Kone progress, AU800,AU600, AU400, AU2700, AU5400, SelectraVitalab, Synchron CX4, SynchronCX5, Synchron CX7, Synchron LX20,ILAB300, ILAB900, ILAB1800,ILAB600, RX Daytona, RX Imola, Cobas Mira,Cobas Mira S, Cobas Mira Plus systems |
| Traceabilityfor AAG | International Reference Material CRM 470 | same |
| Matrix | Buffered base | same |
| Analytesource | Derived from human source | same |
| Number oflevels | Six (the lowest level is a zero-level) | same |
| Fill Volume | 1.0 mL each vial | same |
| Stability | 24 months – shelf-life | same |
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J. Conclusion:
r
The multi-analyte, six level ADVIA Chemistry Liquid Specific Protein Calibrator is substantially equivalent to the Randox Liquid Protein Calibrator. They are identical in composition and both used in calibration of multiple analytes on Chemistry systems.
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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure, with its wings forming a human profile.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Siemens Healthcare Diagnostics, Inc. c/o Kira Gordon, Ph.D. Sr. Regulatory Affairs Specialist 511 Benedict Ave Tarrytown, NY 10591
FEB 1 8 2011
Re: K103701
Trade/Device Name: ADVIA® Chemistry Liquid Specific Protein Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIX Dated: December 17, 2010 Received: December 20, 2010
Dear Dr. Gordon:
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 may of subject to and the may 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 or any I edelar statutes and regulations, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical
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and the state of the state of the states of the states
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Page 2 – Kira Gordon, Ph.D.
device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please i 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/ReportalProblem/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 vours.
ia m chan
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
K103701 510(k) Number (if known):
Device Name: ADVIA® Chemistry Liquid Specific Protein Calibrators
Indications For Use:
The ADVIA Chemistry Liquid Protein Calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the Alpha-Acid-Glycoprotein (AAG), Alpha-1-Antitrypsin (AAT), Anti-streptolysin-O_2 (ASO_2), Complement C3 (C3), Complement C4 (C4), Haptoglobin (HAPT), Immunoglobulin A_2 (IGA_2), Immunoglobulin G_2 (IGG_2), Immunoglobulin M 2 (IGM 2), Prealbumin (PREALB), Rheumatoid Factor (RF), Transferrin (TRF) methods
Prescription Use (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Seena Philip
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety K103701 510(k)________________________________________________________________________________________________________________________________________________________________________
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§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.