SMART Hemoglobin A1c (Glycated hemoglobin A1c; A1c; HbA1c) Assay Reagent Kit is intended for use with the SMART analyzer for the quantitative determination of stable HbA1c in human capillary and venous whole blood samples. Measurement of hemoglobin A1c is a valuable indicator for long-term diabetic control. For in vitro diagnostic use only.

SMART HbA1c Assay Controls are intended for use as quality controls for the SMART HbA1c Assay reagents. For in vitro diagnostic use only.

SMART analyzer is a compact cuvette based spectrophotometer machine for point-of-care use, designed to analyze readings from single use SMART reagent cuvette. The SMART Analyzer System, consisting of the SMART Analyzer, SMART HbA1c reagent kit and SMART HbA1c Assay Controls, is for in vitro diagnostic use only.

Device Description

SMART HbAlc Assay Kit contains reagents intended for use with the SMART HbA1c analyzer for the quantitative determination of stable HbA1c in human whole blood samples. Measurement of hemoglobin A1c is a valuable indicator for long-term diabetic control. SMART HbA1c assay reagents are similar to the predicate Direct Enzymatic HbA1c assay reagents (K070734). The similarities and differences in composition and format are noted in Table 1 below. The SMART HbA1c test is an enzymatic assay in which lysed whole blood samples are subjected to extensive protease digestion with Bacillus sp protease. This process releases amino acids including glycated valines from the hemoglobin beta chains. Glycated valines then serve as substrates for specific recombinant fructosyl valine oxidase (FVO) enzyme, produced in E. coli. The recombinant FVO specifically cleaves N-terminal valines and produces hydrogen peroxide. This, in turn, is measured using a horseradish peroxidase (POD) catalyzed reaction and a suitable chromagen. The HbA1c concentration is expressed directly as %HbA1c by use of a lot specific calibration curve that is stored in an RFID card provided with each SMART test kit. The manufacturer of the SMART HbA1c Assay kit is Diazyme Laboratories.

SMART HbA1c Assay Control Kit is intended for use as quality controls for the SMART HbAlc Assay Reagents and is packaged separately. The OC materials were pre market cleared with predicate device (K070734, K050178) and each lot of SMART HbA1c control kits will be tested with the SMART system during value assignment. The quality controls assist laboratory users in verification steps ensuring that the assay reagents are functioning correctly. QC materials are run exactly as samples. Users are instructed to verify the calibration curve with the controls and run controls each time a new lot of reagents are received. If QC materials fall outside laboratory acceptable range, users are instructed to re-test and call manufacturer customer service if problem persists. The manufacturer of the SMART HbA1c Assay Control kit is Diazyme Laboratories.

SMART HbA1c analyzer is a compact cuvette based spectrophotometer (10 inches x 5.5 inches x 5.5 inches) machine for point-of-care testing designed to analyze readings from single use reagent cuvettes. The instrument only uses the Diazyme Reagent System (DRS) cuvettes and caps and performs assay with a preprogrammed Radio Frequency ID (RFID) card. The DRS cuvette is supplied prefilled with R1a and the DRS cap is supplied prefilled with R2. The DRS cuvette and caps are kept separate until use. Users are instructed (see proposed labeling) to prepare hemolysate samples in micro tubes prefilled with Lysis buffer and prepare R1ab mix by transferring R1b from supplied bottle to cuvette. Users are then instructed to transfer hemolysate to cuvette, snap in place DRS cap and insert into analyzer. The instrument warms the cuvette to 37C and after a predefined period adds the second reagent found in the DRS cap. The reagents and samples are mixed magnetically and absorbance readings are taken at 700mm. The lot specific RFID card contains reagent addition time, mixing time, reading time and calibration curve.

The SMART HbA1c Analyzer System thus consists of the following:

SMART HbAlc Assay Kit. Reagents are provided in prefilled tubes, cuvettes and cuvette caps. The DRS cuvette and cuvette caps can only work with the SMART HbAlc analyzer.
SMART HbA1c Assay Control Kit. Controls are provided for quality control of the SMART Hba1c assay
SMART Analyzer. SMART analyzer is a compact cuvette based spectrophotometer machine for point-of-care testing, designed to analyze readings from single use SMART reagent cuvettes.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the SMART HbA1c Assay Reagent Kit, SMART HbA1c Assay Control Kit, and SMART Analyzer:

Acceptance Criteria and Device Performance Study for SMART HbA1c Assay System

This submission details the performance verification of the SMART HbA1c Assay System, demonstrating its substantial equivalence to the predicate Diazyme Direct Enzymatic HbA1c Assay (K070734).

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria values for precision or comparison in the same way it presents the results. However, implied acceptance criteria can be inferred from the reported results and the statement that the precision was "acceptable" and correlation was "well." For the purpose of this analysis, I will assume typical acceptable ranges or infer based on the predicate device's performance.

Performance Metric	Acceptance Criteria (Inferred/Typical)	Reported Device Performance
Precision (CV%)	Within-run CV% ≤ 5% (typical for HbA1c assays)	Within Run precision CV%5.6% HbA1c: 2.4%7.4% HbA1c: 3.0%11.5% HbA1c: 1.2%Total Precision CV%5.6% HbA1c: 2.70%7.4% HbA1c: 2.50%11.5% HbA1c: 1.30%POL Sites Precision (CV%): yielded acceptable precision of CV ≤ 5% for all three levels tested (5.5%, 7.5%, 11.5% HbA1c)Between Instrument Precision: less than 5% CVLot-to-Lot Variation: less than 5% CV
Comparison (Correlation)	Correlation coefficient (r) ≥ 0.95 (typical for method comparison)	Correlation coefficient: 0.94Slope: 0.96Intercept: 0.30Range of values tested: 4.5% - 11.1% HbA1cConclusion: "correlated well with predicate method"
Interference	Less than 10% deviation (stated in text)	Interference: Less than 10% deviation observed for Ascorbic Acid (30 mg/dL), Bilirubin (15 mg/dL), Bilirubin Conjugate (5 mg/dL), Uric Acid (30 mg/dL), Triglyceride (4000 mg/dL), Glucose (5,000 mg/dL), Urea (100 mg/dL).

2. Sample Size and Data Provenance

Test Set Sample Size:
- Precision Study: 3 samples (5.6% HbA1c, 7.4% HbA1c, 11.5% HbA1c control) were tested repeatedly (40 data points per sample across the total study duration for the main precision study). For the POL study, 3 samples (5.5%, 7.5% HbAlc, and 11.5% HbAlc control) were also used. The "panel of 10 blood samples" for between-instrument and lot-to-lot studies indicates 10 unique samples for those specific evaluations.
- Comparison Study: 64 human whole blood samples.
- Interference Study: Not explicitly stated how many replicates or unique samples were used for each interferent, but the study was performed for each substance at the specified concentration.
Data Provenance: The text indicates "human whole blood specimens" and "human whole blood based HbAlc control." No specific country of origin is mentioned, but "physician office laboratories (POL)" are mentioned, implying a domestic (US, given the FDA submission) setting. The studies appear to be prospective as they were specifically designed and executed for this 510(k) submission.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth.
For the comparison study, the "predicate method" (Diazyme Direct Enzymatic HbA1c Assay, K070734) serves as the reference, which is an established and likely FDA-cleared laboratory method. For precision, the samples themselves are considered the ground truth, and the device's ability to consistently measure them is assessed.

4. Adjudication Method

No adjudication method is described as the ground truth is established either by a predicate device or by the inherent properties of the samples used (for precision). This is typical for in vitro diagnostic (IVD) assays where a direct comparison to a reference method is often performed.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was performed. This type of study is more common for imaging-based AI devices where human readers interpret images. For an IVD assay like HbA1c measurement, the "reader" is the instrument itself, and the human interaction is primarily in sample preparation and loading, not interpretation of complex data outputs. The "POL sites" study evaluated instrument performance in different user settings but was not an MRMC study comparing human reader performance.

6. Standalone Performance Study

Yes, a standalone performance study was performed. The entire document describes the standalone performance of the SMART HbA1c Assay System (reagent kit, control kit, and analyzer). The precision, comparison, and interference studies directly assess the algorithm and instrument's ability to accurately and precisely measure HbA1c without human-in-the-loop interpretation post-measurement. The intent is for the device to provide the final quantitative result.

7. Type of Ground Truth Used

Comparison Study: The ground truth for the comparison study was the result obtained from the predicate device, the Diazyme Direct Enzymatic HbA1c Assay (K070734).
Precision Study: The ground truth for the precision study was the expected stable HbA1c concentration of the whole blood specimens and controls.
Interference Study: The ground truth for the interference study was the known concentration of the analytes in the presence of various interferents, with the expectation that the interferents would not significantly alter the result (less than 10% deviation).

8. Sample Size for the Training Set

The document does not specify a training set sample size. This is because the device described is an enzymatic assay and analyzer system, not a machine learning or AI model in the modern sense that typically requires a large training dataset for model development. The "calibration curve" mentioned for the RFID card is likely generated through traditional analytical chemistry methods and validated, not "trained" on a large dataset in the AI context.

9. How Ground Truth for Training Set Was Established

As there's no explicitly defined "training set" in the context of machine learning, the concept of establishing ground truth for it is not applicable here. The device operates based on known enzymatic reactions and spectrophotometric measurements, with calibration established through reference materials. The "lot specific calibration curve" mentioned is derived from the manufacturer's testing and standardization process using reference materials, rather than a data-driven training regimen.

Summary

{0}------------------------------------------------

K0-92911

510(k) Summary

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

Submitter's name:	Diazyme Laboratories
Submitter's address:	12889 Gregg CourtPoway, CA 92064USA
Name of Contact Person:	Dr. Abhijit DattaDiazyme Laboratories12889 Gregg CourtPoway, CA 92064Phone: 858-455-4762Fax: 858-455-2120
Date the Summary was Prepared: '	April 13, 2010
Name of the Device	SMART HbA1c Assay Reagent KitSMART HbA1c Assay Control KitSMART Analyzer
Trade Name:	SMART HbA1c Assay Reagent KitSMART HbA1c Assay Control KitSMART Analyzer
Common/Usual Name	Assay: Test system, Glycated hemoglobin A1cInstrument: Discrete photometric chemistry analyzerfor clinical use
Device Classification Name	Glycosylated Hemoglobin Assay
Product code:	LCP, Glycosylated HemoglobinJJX, Quality Control MaterialJJE, Analyzer, Chemistry (Photometric, Discrete) forClinical use
Submission Type	510k
Regulation Number	864.7470, Glycosylated Hemoglobin Assay862.1660, Quality Control Material862.2160, Discrete Photometric Chemistry Analyzer forClinical use

{1}------------------------------------------------

Device Class	I (Controls), II (Assay)
Predicate Device:	The SMART HbA1c Assay is substantially equivalentto the currently marketed Diazyme Direct EnzymaticHbA1c Assay (K070734).
Manufacturing Address	Diazyme Laboratories12889 Gregg CourtPoway, CA 92121USA
Establishment Registration	2032900

Description of the Device:

{2}------------------------------------------------

cuvette is supplied prefilled with R1a and the DRS cap is supplied prefilled with R2. The DRS cuvette and caps are kept separate until use. Users are instructed (see proposed labeling) to prepare hemolysate samples in micro tubes prefilled with Lysis buffer and prepare R1ab mix by transferring R1b from supplied bottle to cuvette. Users are then instructed to transfer hemolysate to cuvette, snap in place DRS cap and insert into analyzer. The instrument warms the cuvette to 37C and after a predefined period adds the second reagent found in the DRS cap. The reagents and samples are mixed magnetically and absorbance readings are taken at 700mm. The lot specific RFID card contains reagent addition time, mixing time, reading time and calibration curve.

The SMART analyzers are manufactured for Diazyme Laboratories by Eurolyser Diagnostica, GMBH (Eurolyser Diagnostica GmbH, Bayernstraße 11a, 5020 Salzburg, AUSTRIA; www.eurolyser.com; Fon: +43 662 432100; Fax: +43 662 432100 50). Eurolyser Diagnostica, GMBH establishment registration number is 3006490192. Eurolyser Diagnostica developed and commercialized the SMART analyzers in Europe with their contract manufacturing partner AKATech, GMBH (AKAtech Produktions- und Handels GmbH, Untermühlberg 1, 4890 Frankenmarkt, AUSTRIA;

http://www.akatech.at/en/index.php?option=com_content&task=view&id=31&I.: +43 (7684) 88 04-0; Fax: +43 (7684) 88 04-9). AKATech is ISO13485 and ISO 9001 quality system certified.

The SMART HbA1c Analyzer System thus consists of the following:

1. SMART HbAlc Assay Kit. Reagents are provided in prefilled tubes, cuvettes and cuvette caps. The DRS cuvette and cuvette caps can only work with the SMART HbAlc analyzer.
1. SMART HbA1c Assay Control Kit. Controls are provided for quality control of the SMART Hba1c assay
1. SMART Analyzer. SMART analyzer is a compact cuvette based spectrophotometer machine for point-of-care testing, designed to analyze readings from single use SMART reagent cuvettes.

Indications for Use:

SMART Hemoglobin A1c (Glycated hemoglobin A1c; A1c; HbA1c) reagents are intended for use with the SMART analyzer for the quantitative determination of stable HbA1c in human capillary and venous whole blood samples. Measurement of hemoglobin A 1c is a valuable indicator for long-term diabetic control. For in vitro diagnostic use only.

SMART HbA1c Assay Controls are intended for use as quality controls for the SMART HbA1c Assay reagents. For in vitro diagnostic use only.

{3}------------------------------------------------

Diazyme Direct Enzymatic HbA1c Assay Kit(predicate K070734)	SMART HbA1c Assay Kit
Kit can be used on automated chemistry analyzersusing validated parameters	Kit can ONLY be used with SMART HbA1c analyzers
Lysis buffer1 bottle	Lysis buffer20 micro centrifuge tubes (prefilled)
100mM CHES 1% Triton X-100 0.45% SDS 0.5mM Redox agents	100mM CHES 1% Triton X 100 0.45% SDS 0.5mM Redox agents <0.1% antifoam
Reagent 1 a1 bottle	Reagent 1a20 DRS cuvettes (prefilled)
5mM MES buffer 4KU/mL Proteases 0.5% Triton X-100 >10µM Redox agents	5mM MES buffer 4KU/mL Proteases 0.5% Triton X-100 >10µM Redox agents
Reagent 1 b	Reagent 1 b
1mM MES <3mM Redox agent	1mM MES <7mM Redox agent <0.1% Brilliant Blue 0.1% Triton X-100
Reagent 21 bottle	Reagent 220 DRS caps (prefilled)
15 mM Tris pH 8.0 >10 U/mL FVO enzyme 90U/mL POD 0.8mM Chromagen	15 mM Tris pH 8.0 >10 U/mL FVO enzyme 90U/mL POD 0.8mM Chromagen
Calibrator set	Calibrator
1 x 0.5mL Calibrator 1	1 x preprogrammed lot specific RFID card in each kit
1 x 0.5mL Calibrator 2
Control Set	Control Set
1 x 0.5mL Control 1	1 x 0.5mL Control 1
1 x 0.5mL Control 2	1 x 0.5mL Control 2

Table 1 Summary of Assay Kit Components

・

{4}------------------------------------------------

Performance Testing Summaries:

Precision Study Summary

The precision of the SMART HbA1c Assay was evaluated according to Clinical and Laboratory Standards Institute (CLSI) EP5-A guideline with the following modifications: In the study, two unaltered whole blood specimens containing 5.6% and 7.4% HbA1c, one whole blood based HbAlc control containing 11.5% HbA1c were tested with 2 runs per day with duplicates over 10 working days. Reagent Lot 1 was used over the first 5 days and Reagent Lot 2 was used over the remaining 5 days. Both lots of reagents were used on three different SMART HbA1c analyzers. The precision evaluation data are listed below:

The mean value (Mean), standard deviation, within run imprecision and total imprecision CV% are calculated and summarized in the following tables:

	5.6% HbA1c	7.4% HbA1c	11.5% HbA1c
Total data points	40	40	40
Mean (%)	5.4	7.4	11.4
SD (%)	0.13	0.22	0.13
CV%	2.4%	3.0%	1.2%

Within Run precision CV%

Total Precision CV%

	5.6% HbA1c	7.4% HbA1c	11.5% HbA1c
Total data points	40	40	40
Mean (%)	5.4	7.4	11.4
SD (%)	0.15	0.19	0.15
CV%	2.70%	2.50%	1.30%

The precision of the SMART HbA1c assay was also evaluated in three physician office laboratories (POL) by trained medical technicians to test systemic and random error on three different Diazyme HbA1C SMART analyzers. Two unaltered human whole blood HbA1c specimens containing about 5.5%, 7.5% of HbAlc and one whole blood based control containing 11.5% HbAlc were used. For the three levels of samples tested at the three POL sites, the Diazyme Enzymatic HbA1c SMART assay yielded acceptable precision of CV ≤ 5%.

Between instrument precision and lot-to-lot variation studies were also performed on SMART Hbalc analyzers using a panel of 10 blood samples of blood controls. In both studies, less than 5% of CV was obtained indicating good lot-to-lot consistency and between instrument precision.

{5}------------------------------------------------

Comparison Study Summary

Human whole blood samples were tested with the SMART HbA1c Assay and results obtained were compared to the predicate method. A total of 64 samples ranging from 4-12% HbA1c were tested in both assays. The above described accuracy study showed that the SMART HbA1c assay results correlated well with predicate method with a correlation coefficient of 0.96 with a slope of 0.94 and 0.30 intercept.

	Whole blood application
n	64
Slope	0.96
Intercept	0.30
Correlation coeffi	0.94
Range of values	4.5% - 11.1% HbA1c

Interference Study Summary

The following substances normally present in the blood produced less than 10% deviation when tested at levels equal to the concentrations listed below:

Interference	Concentration
Ascorbic Acid	30 mg/dL
Bilirubin	15 mg/dL
Bilirubin Conjugate	5 mg/dL
Uric Acid	30 mg/dL
Triglyceride	4000 mg/dL
Glucose	5,000 mg/dL
Urea	100 mg/dL

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle or other bird-like figure.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Diazyme Laboratories c/o Dr. Abhijit Datta, Director, Technical Operations 12889 Gregg Court Poway, CA 92064

APR 2 6 2010

Re: K092911

Trade Name: SMART HbA1c Assay Reagent Kit, SMART HbA1c Assay Control Kit, SMART Analyzer Regulation Number: 21 CFR §864.7470 Regulation Name: Glycosylated Hemoglobin Assay Regulatory Class: Class II Product Codes: JJX, JJE Dated: March 18, 2010 Received: March 22, 2010

Dear Dr. Datta:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{7}------------------------------------------------

Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{8}------------------------------------------------

Indications for Use

510(k) Number (If Known): K092911

Device Name: SMART HbA1c Assay Reagent Kit, SMART HbA1c Assay Control Kit, SMART Analyzer

Indications for Use:

SMART HbA1c Assay Controls are intended for use as quality controls for the SMART HbA1c Assay reagents. For in vitro diagnostic use only.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K092911

Page 1 of

Regulation Number and Section

§ 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.