ADVIA Chemistry Enzyme 1 Calibrator, ADVIA Chemistry Enzyme 2 Calibrator

K153365 · Siemens Healthcare Diagnostics, Inc. · JIX · Dec 18, 2015 · Clinical Chemistry

Device Facts

• Record ID: K153365
• Device Name: ADVIA Chemistry Enzyme 1 Calibrator, ADVIA Chemistry Enzyme 2 Calibrator
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JIX · Clinical Chemistry
• Decision Date: Dec 18, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1150
• Device Class: Class 2

Intended Use

ADVIA Chemistry Enzyme 1 Calibrator is intended for in vitro diagnostic use in the calibration of Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase P-L (LDPL), Lactate Dehvdrogenase L-P (LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems. ADVIA® Chemistry Enzyme 2 Calibrator is intended for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT); Alanine Aminotransferase, Concentrated Reagents (ALT c); Alanine Aminotransferase (P5P) (ALTP5P); Alanine Aminotransferase (P5P), Concentrated Reagents (ALTP c); Aspartate Aminotransferase (AST); Aspartate Aminotransferase, Concentrated Reagents (AST_c); Aspartate Aminotransferase (PSP)(ASTP5P); and Aspartate Aminotransferase (P5P), Concentrated Reagents (ASTP_c) assays on the ADVIA Chemistry systems.

Device Story

Liquid, multi-analyte, bovine serum albumin-based calibrators; used to calibrate enzyme assays on ADVIA Chemistry systems. Calibrators are ready-to-use; no preparation required. Value assignment involves gravimetric addition of analytes to base matrix; verification performed on ADVIA 1800 Chemistry systems using Master Lot Calibrators. Healthcare providers use these to ensure accuracy of clinical chemistry assays; results affect clinical decision-making by providing standardized reference points for patient sample testing. Benefits include reliable, traceable calibration for diagnostic enzyme measurements.

Clinical Evidence

No clinical data. Bench testing only. Stability studies (shelf-life and open-vial) conducted per CEN 13640. Value assignment verified against Master Lot Calibrators with n=20 replicates; acceptance criteria met (mean concentration within ±15% of target).

Technological Characteristics

Liquid, bovine serum albumin-based matrix. Multi-analyte. Enzyme 1: 2.5 mL/vial; Enzyme 2: 1.5 mL/vial. Storage 2-8°C. Traceability to IFCC reference materials (IFCC-452, 453, 454), molar extinction coefficients, or internal standards. No software or electronic components.

Indications for Use

Indicated for in vitro diagnostic calibration of specific enzyme assays (GGT, LDPL, LDLP, CHE, LIP, ALT, AST variants) on ADVIA Chemistry systems. No specific patient population or contraindications described.

Regulatory Classification

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.)

Special Controls

*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.

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure or a bird in flight, composed of three curved lines.

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

SIEMENS HEALTHCARE DIAGNOSTICS, INC. KIRA GORDON SR. REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591

December 18, 2015

Re: K153365

Trade/Device Name: ADVIA® Chemistry Enzyme 1 Calibrator, ADVIA® Chemistry Enzyme 2 Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIX Dated: November 19, 2015 Received: November 20, 2015

Dear Kira 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 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] 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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Katherine Serrano -S

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) k153365

Device Name ADVIA® Chemistry Enzyme 1 Calibrator

#### Indications for Use (Describe)

ADVIA Chemistry Enzyme 1 Calibrator is intended for in vitro diagnostic use in the calibration of Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase P-L (LDPL), Lactate Dehvdrogenase L-P (LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems.

Type of Use (Select one or both, as applicable)

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 [e-mail]

"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."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

## Indications for Use

510(k) Number (if known) k153365

Device Name ADVIA® Chemistry Enzyme 2 Calibrator

#### Indications for Use (Describe)

ADVIA® Chemistry Enzyme 2 Calibrator is intended for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT); Alanine Aminotransferase, Concentrated Reagents (ALT c); Alanine Aminotransferase (P5P) (ALTP5P); Alanine Aminotransferase (P5P), Concentrated Reagents (ALTP c); Aspartate Aminotransferase (AST); Aspartate Aminotransferase, Concentrated Reagents (AST_c); Aspartate Aminotransferase (PSP)(ASTP5P); and Aspartate Aminotransferase (P5P), Concentrated Reagents (ASTP_c) assays on the ADVIA Chemistry systems.

Type of Use (Select one or both, as applicable)

2 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 [e-mail]

"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."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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## 510(k) Summary of Safety and Effectiveness for the ADVIA® Chemistry Enzyme 1 Calibrator and ADVIA® Chemistry Enzyme 2 Calibrator

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.

## 1. 510(k) Number: k153365

## 2. Applicant:

Contact: Kira Gordon, PhD Sr. Regulatory Affairs Specialist Siemens Healthcare Diagnostics Inc Address: 511 Benedict Ave, Tarrytown, NY 10591 [phone] Phone: [phone] (FAX)

- 3. Date: November 19, 2015
## 4. Proprietary and Established Names:

ADVIA® Chemistry Enzyme 1 Calibrator ADVIA® Chemistry Enzyme 2 Calibrator

## 5. Regulatory Information:

Regulation section: 21 CFR \$862.1150, calibrator, multi-analyte mixture Classification: Class II Product Code: JIX Panel: Clinical Chemistry

#### 6. Predicate Device:

Device Name: Dimension® Vista ENZ 1 CAL; Dimension® Vista ENZ 2 CAL 510(k) Number: k061923; k103612 Manufacturer: Siemens Healthcare Diagnostics Inc.

## 7. Intended Use:

See Indications for Use

## 8. Indications for Use:

ADVIA® Chemistry Enzyme 1 Calibrator is for in vitro diagnostic use in the calibration of Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase P-L (LDPL), Lactate Dehydrogenase L-P (LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems

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ADVIA® Chemistry Enzyme 2 Calibrator is for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT); Alanine Aminotransferase, Concentrated Reagents (ALT_c); Alanine Aminotransferase (ALTP5P); Alanine Aminotransferase (P5P), Concentrated Reagents (ALTP_c); Aspartate Aminotransferase (AST); Aspartate Aminotransferase, Concentrated Reagents (AST c); Aspartate Aminotransferase (PSP) (ASTP5P); and Aspartate Aminotransferase (P5P), Concentrated Reagents (ASTP c) assays on the ADVIA Chemistry systems

Special Conditions for Use Statement(s): For prescription use only

# 9. Device Description:

The ADVIA® Chemistry Enzyme 1 Calibrator and Enzyme 2 Calibrator are liquid, multianalyte, bovine serum albumin based products. Enzyme 1 Calibrator kit consists of six vials of the same calibrator which is ready for use (no preparation is required). The volume per vial is 2.5 mL. Enzyme 2 Calibrator kit consists of six vials of calibrator of the same level which is ready for use (no preparation is required). The volume per vial is 1.5 mL.

# 10. Test Principle

ADVIA® Chemistry Enzyme 1 Calibrator is intended for in vitro diagnostic use in the calibration of Chemistry Gamma-Glutamy] Transferase (GGT), Lactate Dehydrogenase (LDPL and LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA® Chemistry systems

ADVIA® Chemistry Enzyme 2 Calibrator is intended for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT, ALT_c, ALTP5P, ALTP_c) Assays and Aspartate Aminotransferase (AST, AST_c, ASTP5P, ASTP_c) Assays on the ADVA® Chemistry systems

# 11. Substantial Equivalence Information:

Predicate device name: Dimension® Vista Enzyme 1 Calibrator Predicate K number: k061923 Comparison with Predicate:

| Item | New Device: | Predicate Device: |
|------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | for in vitro diagnostic use in the<br>calibration of Gamma-Glutamyl Transferase (GGT),<br>Lactate Dehydrogenase P-L (LDPL), Lactate Dehydrogenase L-P (LDLP),<br>Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems | in vitro diagnostic product for the<br>calibration of Amylase (AMY),<br>Gamma-Glutamyl Transferase (GGT),<br>Lactate Dehydrogenase (LDH), Lipase (LIPL), and Pseudocholinesterase (PCHE) methods |
| Instrument | ADVIA Chemistry Systems | Dimension Vista Clinical Chemistry System |
| Measured<br>Analytes (value<br>assigned) | Gamma-Glutamyl Transferase,<br>Lactate Dehydrogenase,<br>Lipase,<br>Cholinesterase (Pseudocholinesterase) | Gamma-Glutamyl Transferase,<br>Lactate Dehydrogenase,<br>Lipase,<br>Pseudocholinesterase<br>Amylase |
| Form | Liquid | Same |

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| Matrix | bovine serum albumin based product | Same |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte source | gamma-glutamyl transferase (bovine<br>kidney)<br>lactate dehydrogenase (chicken heart)<br>lipase (porcine pancreas)<br>pseudocholinesterase (horse serum) | gamma-glutamyl transferase (bovine<br>kidney)<br>lactate dehydrogenase (chicken heart)<br>lipase (porcine pancreas)<br>pseudocholinesterase (horse serum)<br>amylase (human saliva) |
| Number of levels | One | Two |
| Target<br>concentrations<br>(U/L) | Gamma-glutamyl transferase - 840<br>Lactate dehydrogenase L-P - 350<br>Lactate dehydrogenase P-L - 780<br>Lipase - 100<br>Cholinesterase – 14200<br>Amylase – N/A | Gamma-glutamyl transferase – 0, 840<br>Lactate dehydrogenase – 0, 350<br>Lipase - 0, 1612<br>Cholinesterase - 0, 14700<br>Amylase – 0, 682 |
| Fill Volume | 2.5 mL | Same |
| Stability | Shelf-life – minimum 6 months at 2-8°C<br>at launch<br>Open-vial - 30 days at 2-8°C | Shelf-life – 12 months at 2-8°C<br>Open-vial – 30 days at 2-8°C |

Dimension® Vista Enzyme 2 Calibrator Predicate device name:
Predicate K number: k103612 Comparison with Predicate:

| Item | New Device: | Predicate Device: |
|------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | for in vitro diagnostic use in the<br>calibration of Alanine Aminotransferase<br>(ALT); Alanine Aminotransferase,<br>Concentrated Reagents (ALT_c); Alanine<br>Aminotransferase (ALTP5P); Alanine<br>Aminotransferase (P5P), Concentrated<br>Reagents (ALTP_c); Aspartate<br>Aminotransferase (AST); Aspartate<br>Aminotransferase, Concentrated<br>Reagents (AST_c); Aspartate<br>Aminotransferase (P5P) (ASTP5P); and<br>Aspartate Aminotransferase (P5P),<br>Concentrated Reagents (ASTP_c) assays<br>on the ADVIA Chemistry systems | Is an in vitro diagnostic product for<br>the calibration of alanine<br>aminotransferase (ALT and ALTI)<br>and aspartate aminotransferase (AST)<br>methods |
| Instrument | ADVIA Chemistry Systems | Dimension Vista Clinical Chemistry<br>System |
| Measured<br>Analytes (value<br>assigned) | Alanine aminotransferase and aspartate<br>aminotransferase | Same |
| Form | Liquid | Same |
| Matrix | bovine serum albumin based product | Same |
| Analyte source | alanine aminotransferase (porcine heart)<br>aspartate aminotransferase (porcine<br>heart) | Same |

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| Number of levels | One | Two |
|-----------------------------------|---------------------------------------------------------------------------------|-----------------------------------------------------------------|
| Target<br>concentrations<br>(U/L) | AST, AST_c, ASTP5P, ASTP_c – 500<br>ALT, ALT_c, ALTP5P, ALTP_c – 500 | AST – 0, 1050<br>ALT – 0, 1050 |
| Fill Volume | 1.5 mL | Same |
| Stability | Shelf-life – min 6 months at 2-8°C at<br>launch<br>Open-vial - 30 days at 2-8°C | Shelf-life – 12 months at 2-8°C<br>Open-vial - 30 days at 2-8°C |

# 12. Standard/Guidance Document Reference

The following recognized standard and guidance documents were used:

- CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic ● Calibrators

# 13. Performance Characteristics

The following studies are not applicable for the purpose of this submission:

- Precision/Reproducibility ●
- Linearity/Assay Reportable Range .
- Detection limit ●
- Method and Matrix Comparison Studies
- Analytical Specificity
- Assay cut-off
- Expected Values/Reference Interval ●

## Stability:

Real-time stability studies for shelf-life and open-vial claims have been conducted and acceptance criteria were met.

ADVIA Chemistry Enzyme 1 Calibrator is to be stored at 2-8°C until the expiration date printed on each carton. ADVIA Chemistry Enzyme 2 Calibrator is to be stored at 2-8℃ until the expiration date printed on each carton. Real-time stability studies for shelf-life are ongoing. The final shelf life claims will be based on the completed real-time study results. For opened products, once the cap is removed, assigned values are stable for 30 days when recapped immediately after use and stored at 2-8℃.

# Traceability and Value Assignment

To manufacture calibrator, a stock solution is prepared by gravimetrically adding quantities of analytes to bovine serum albumin base to the target concentrations. The stock solution concentration is determined by comparing the recovery of the stock solution versus the Master Lot assigned bottle values. Calculated quantities of the stock solution are added to the bovine serum albumin base to the target concentrations to produce the commercial calibrator lot. The concentration of each analyte is verified to be within acceptable range by using an instrument calibrated with Master Lot Calibrators.

Production lot calibrator value assignments are completed using two ADVIA 1800 Chemistry systems, two reagents lots, and three vials of calibrator. Each instrument is

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calibrated using the Masterpool. The calibrators are run as unknowns with n=20 replicates. Acceptance criteria is the mean concentration should be within ±15% of the target value. Traceability: The assigned values of the Enzyme 1 Calibrator and Enzyme 2 Calibrator are traceable as listed in the following table:

| Product | Analyte | Traceability |
|------------|-------------------------------------|------------------------------------------------------|
| Enzyme 1 | CHE | molar extinction coefficient of the reaction product |
| Calibrator | LDLP | IFCC Reference material (IFCC-453) |
| | LDPL | extinction coefficient of the NADH |
| | LIP | Internal Standard |
| | GGT | IFCC Reference material (IFCC-452) |
| Enzyme 2 | ALT (ALT, ALT_c,<br>ALTP5P, ALTP_c) | IFCC Reference material (IFCC-454) |
| Calibrator | AST (AST, AST_c,<br>ASTP5P, ASTP_c) | IFCC Reference method |

# 14. Conclusions

The ADVIA Chemistry Enzyme 1 Calibrator is substantially equivalent to the Siemens Dimension Vista ENZ 1 Calibrator cleared under k061923. Based on the testing and the comparisons with the predicate device, the ADVIA Chemistry Enzyme 1 Calibrator is substantially equivalent to the Dimension Vista ENZ 1 Calibrator.

The ADVIA Chemistry Enzyme 2 Calibrator is substantially equivalent to the Siemens Healthcare Diagnostics Dimension Vista ENZ 2 Calibrator cleared under k103612. Based on the testing and the comparisons with the predicate device, the ADVIA Chemistry Enzyme 2 Calibrator is substantially equivalent to the Dimension Vista ENZ 2 Calibrator.