Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a standard automated immunoassay system and does not mention any AI or ML components in the device description, intended use, or performance studies. The quantitation method relies on a predefined master curve and instrument-specific working curve, which is a traditional method, not AI/ML.

Therapeutic

No
The device is an in vitro diagnostic (IVD) immunoassay designed for the semi-quantitative determination of autoantibodies to aid in the diagnosis of systemic sclerosis, not for treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device "aids in the diagnosis of systemic sclerosis."

SaMD (Software as a Medical Device)

No

The device description explicitly states it is an immunoassay designed to run on the BIO-FLASH® instrument, which is described as a fully automated closed system including liquid handling hardware, luminometer, and a computer with software-user interface. The assay also utilizes a reagent cartridge format. This indicates the device is a combination of hardware, software, and reagents, not software-only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is for the "semi-quantitative determination of IgG anti-Scl-70 autoantibodies in human serum." This is a test performed on a biological sample (serum) outside of the body to provide information about a person's health status (aiding in the diagnosis of systemic sclerosis).
Device Description: The description details a laboratory assay that uses reagents and an automated instrument to analyze a patient's serum sample.
Performance Studies: The document describes analytical and clinical performance studies conducted on human serum samples to evaluate the device's accuracy and reliability in detecting the target analyte.
Comparison to Predicate Device: The comparison to a predicate device (QUANTA Lite® Scl-70 ELISA) which is also an IVD, further confirms its classification.

All of these characteristics align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

QUANTA Flash Scl-70 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-Scl-70 autoantibodies in human serum. The presence of anti-Scl-70 autoantibodies, in conjunction with clinical findings and other laboratory tests, aids in the diagnosis of systemic sclerosis.

QUANTA Flash Scl-70 Calibrators are intended for use with the QUANTA Flash Scl-70 chemiluminescent immunoassay for the determination of IgG anti-Scl-70 autoantibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.

QUANTA Flash Scl-70 Controls are intended for use with the QUANTA Flash Scl-70 chemiluminescent immunoassay for quality control in the determination of IgG anti-Scl-70 autoantibodies in human serum.

Product codes

LLL, JIT, JJX

Device Description

The QUANTA Flash Scl-70 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash Scl-70 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

Recombinant Scl-70 is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspended using resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:23.5 by the BIO-FLASH with system rinse in a disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. lsoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-Scl-70 antibodies bound to the corresponding Scl-70 on the beads.

For quantitation, the QUANTA Flash Scl-70 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash Scl-70 Calibrators. Based on the results obtained with the two Calibrators included in the Calibrator Set (sold separately), an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU)mL from the instrument signal (RLU) obtained for each sample.

The QUANTA Flash Scl-70 kit contains the following materials:
One (1) QUANTA Flash Scl-70 Reagent Cartridge
One (1) vial of Resuspension buffer
One (1) Transfer pipette
The QUANTA Flash Scl-70 Reagent Cartridge, containing the following reagents for 50 determinations:
a. Scl-70 antigen coated paramagnetic beads, lyophilized.
b. Assay Buffer 3 buffer containing protein stabilizers and preservatives.
c. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.

The QUANTA Flash Scl-70 Calibrators kit contains two vials of Calibrator 1 and two vials of Calibrator 2.

QUANTA Flash Scl-70 Calibrator 1: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human antibodies to Scl-70 in stabilizers and preservatives.
QUANTA Flash Scl-70 Calibrator 2: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human antibodies to Scl-70 in stabilizers and preservatives.

The QUANTA Flash Scl-70 Controls kit contains two vials of Negative Control and two vials of Positive Control.

QUANTA Flash Scl-70 Negative Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to Scl-70 in stabilizers and preservatives.
QUANTA Flash Scl-70 Positive Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to Scl-70 in stabilizers and preservatives.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

The reference population for establishing and verifying the reference interval for the Scl-70 assay consisted of 254 subjects.
A separate set of samples, none of which were used in establishing the reference range, was used to validate the clinical performance of the QUANTA Flash Scl-70. A total of 498 samples were included in the Validation Set for the QUANTA Flash Scl-70.
Distribution of the cohort used in the QUANTA Flash Scl-70 validation study:
Systemic Lupus Erythematosus (N=32)
Rheumatoid Arthritis (N=31)
Idiopathic Inflammatory Myopathy (N=25)
Mixed Connective Tissue Disease (N=25)
Celiac disease (N=25)
Autoimmune thyroiditis (N=25)
Sjögren's syndrome (N=20)
Infectious disease (N=30, of which 1 positive)
Crohn's disease (N=54, of which 2 positive)
Osteoarthritis (N=28, of which 1 positive)
COPD (N=15)
Chronic Kidney Disease (N=10)
Vasculitis (N=15)
Raynaud's (N=10)
Diabetes (N=5)
Asthma (N=15)
Skin Disease (N=10, of which 1 positive)
Total controls (N=375, of which 5 positive)
Systemic Sclerosis (SSc) (N=123, of which 52 positive)
Total (N=498)

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision Study:

Study Type: Analytical performance characteristic.
Sample Size: 13 samples.
Protocol: Samples were run in duplicates, twice a day, for 20 days. Data were analyzed with the Analyse-it for Excel method evaluation software.
Key Results:
- Total %CV values were within the acceptance limit, 10%. Values ranged from 3.4% to 5.9%.

Reproducibility (Between Sites) Study:

Study Type: Analytical performance characteristic.
Sample Size: 8 samples, each with 75 replicates (25 data points per sample, per site).
Protocol: Samples were tested on three different instruments at three different sites, run in replicates of five, once a day for 5 days. Data were analyzed with Analyse-it for Excel.
Key Results:
- All %CV values were within the acceptance limit, 15%. Values ranged from 1.3% to 8.3%.

Reproducibility (Between Lots) Study:

Study Type: Analytical performance characteristic.
Sample Size: 8 samples, each with 75 data points total (25 data points per lot).
Protocol: Samples were tested with three different lots of reagents in five replicates for 5 days. Data were analyzed with Analyse-it for Excel.
Key Results:
- All %CV values were within the acceptance limit, 10%. Values ranged from 1.5% to 9.6%.

Limit of Quantitation (LoQ), Limit of Blank (LoB) and Limit of Detection (LoD) Study:

Study Type: Analytical performance characteristic.
Protocol:
- LoQ: Determined consistent with CLSI EP17-A2 guideline using the Westgard model (TE= /Bias/ + 2s) based on 120 measurements of four low level samples. Acceptance criteria: total error (TE)

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).

Summary

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

June 1, 2016

INOVA Diagnostics, Inc. Dr. Gabriella Lakos Director, Assay Development 9900 Old Grove Road San Diego, CA 92131

Re: K152635

Trade/Device Name: QUANTA Flash® Scl-70 QUANTA Flash® Scl-70 Calibrators OUANTA Flash® Scl-70 Controls Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear Antibodies Immunological Test System Regulatory Class: II Product Code: LLL, JIT, JJX Dated: April 27, 2016 Received: April 29, 2016

Dear Dr. Lakos:

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

1

as set forth in the quality systems (OS) 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 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,

Kelly Oliner -S

FOR

Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known)

Device Name

QUANTA Flash® Scl-70, QUANTA Flash® Scl-70 Calibrators, QUANTA Flash® Scl-70 Controls

Indications for Use (Describe)

QUANTA Flash Scl-70 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-Scl-70 autoantibodies in human serum. The presence of anti-Scl-70 autoantibodies, in conjunction with clinical findings and other laboratory tests, aids in the diagnosis of systemic sclerosis.

QUANTA Flash Scl-70 Calibrators are intended for use with the QUANTA Flash Scl-70 chemiluminescent immunoassay for the determination of IgG anti-Scl-70 autoantibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.

QUANTA Flash Scl-70 Controls are intended for use with the OUANTA Flash Scl-70 chemiluminescent immunoassay for quality control in the determination of IgG anti-Scl-70 autoantibodies in human serum.

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)

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A Werfen Company

510(k) Summary

QUANTA Flash® Scl-70 QUANTA Flash® Scl-70 Calibrators QUANTA Flash® Scl-70 Controls

Page 1 of 19

510(k) Summary

Administrative data
Device description
Intended use(s)
Substantial equivalence
Comparison to predicate device
Value assignment and traceability of Calibrators and Controls
Analytical performance characteristics
Precision
Reproducibility
Reproducibility between sites (instruments)
Reproducibility between lots
Limit of Blank (LoB) and Limit of Detection (LoD)
Analytical Measuring Range (AMR)
Auto-rerun function and reportable results
High concentration hook effect
Linearity
Interference
Cross-reactivity
Sample stability
Reagent stability
Cut-off ( reference range) establishment and verification
Clinical performance characteristics
Clinical sensitivity, specificity
Expected values
Comparison with predicate device

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510(k) Summary QUANTA Flash® Scl-70

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Administrative data

| Submitter: | Inova Diagnostics, Inc.
9900 Old Grove Road,
San Diego, CA, 92131 | |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Purpose of submission: | New device(s) | |
| Devices in the submission: | QUANTA Flash® Scl-70
QUANTA Flash® Scl-70 Calibrators
QUANTA Flash® Scl-70 Controls | |
| Scientific contact: | Gabriella Lakos, Director of Assay Development
Inova Diagnostics, Inc.
9900 Old Grove Road, San Diego, CA, 92131
Phone: 858-586-9900/1393
Fax: 858-863-0025
email: glakos@inovadx.com | |
| Quality Systems contact: | Ronda Elliott, VP of Quality Systems and Regulatory Affairs
Inova Diagnostics, Inc.
9900 Old Grove Road, San Diego, CA, 92131
Phone: 858-586-9900
Fax: 858-863-0025/1381
email: relliott@inovadx.com | |
| Preparation date: | 08/28/2015 | |
| Device name (assay kit): | Proprietary name: QUANTA Flash® Scl-70 | |
| | Common name: | Anti-Scl-70 Chemiluminescent Immunoassay |
| | Classification name: | anti-Scl-70 antibody, antigen and control |
| Regulation Description | Antinuclear antibody immunological test system | |
| Regulation Medical Specialty | Immunology | |
| Review Panel | Immunology | |
| Product Code | LLL | |
| Regulation Number | 866.5100 | |
| Device Class | 2 | |
| Device name (Calibrators): | Proprietary name: | QUANTA Flash® Scl-70 Calibrators |
| | Common name: | Scl-70 Calibrators |
| | Classification name: | Calibrator, secondary |
| Regulation Description | Calibrator | |
| Regulation Medical Specialty | Clinical Chemistry | |
| Product Code | JIT | |
| Regulation Number | 862.1150 | |
| Device Class | 2 | |
| Device name (Controls): | Proprietary name: | QUANTA Flash® Scl-70 Controls |
| | Common name: | Scl-70 Controls |
| | Classification name: | Single (specified) analyte controls (assayed and unassayed) |
| Regulation Description | Quality control material (assayed and unassayed) | |
| Regulation Medical Specialty | Clinical Chemistry | |
| Product Code | JJX | |
| Regulation Number | 862.1660 | |
| Device Class | 1 (reserved) | |

5

6

Predicate device:

QUANTA Lite® Scl-70 ELISA, 510(k) number: K924898

Device description

The QUANTA Flash Scl-70 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash Scl-70 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

Recombinant Scl-70 is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspended using resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:23.5 by the BIO-FLASH with system rinse in a disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. lsoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-Scl-70 antibodies bound to the corresponding Scl-70 on the beads.

For quantitation, the QUANTA Flash Scl-70 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash Scl-70 Calibrators. Based on the results obtained with the two Calibrators included in the Calibrator Set (sold separately), an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU)mL from the instrument signal (RLU) obtained for each sample.

The QUANTA Flash Scl-70 kit contains the following materials:

One (1) QUANTA Flash Scl-70 Reagent Cartridge

One (1) vial of Resuspension buffer

One (1) Transfer pipette

The QUANTA Flash Scl-70 Reagent Cartridge, containing the following reagents for 50 determinations:

a. Scl-70 antigen coated paramagnetic beads, lyophilized.

7

Assay Buffer 3 buffer containing protein stabilizers and preservatives. b.
C. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.

The QUANTA Flash Scl-70 Calibrators kit contains two vials of Calibrator 1 and two vials of Calibrator 2.

-QUANTA Flash Scl-70 Calibrator 1: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human antibodies to Scl-70 in stabilizers and preservatives.
QUANTA Flash Scl-70 Calibrator 2: Two (2) barcode labeled tubes containing 0.3 mL prediluted, ready to use reagent. Calibrators contain human antibodies to Scl-70 in stabilizers and preservatives.

The QUANTA Flash Scl-70 Controls kit contains two vials of Negative Control and two vials of Positive Control.

QUANTA Flash Scl-70 Negative Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to Scl-70 in stabilizers and preservatives.
। QUANTA Flash Scl-70 Positive Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to Scl-70 in stabilizers and preservatives.

Intended use(s)

QUANTA Flash Scl-70 is a chemiluminescent immunoassay for the semi-quantitative determination of lgG anti-Scl-70 autoantibodies in human serum. The presence of anti-Scl-70 autoantibodies, in conjunction with clinical findings and other laboratory tests, aids in the diagnosis of systemic sclerosis.

QUANTA Flash Scl-70 Calibrators are intended for use with the QUANTA Flash Scl-70 chemiluminescent immunoassay for the determination of IgG anti-Scl-70 autoantibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.

QUANTA Flash Scl-70 Controls are intended for use with the QUANTA Flash Scl-70 chemiluminescent immunoassay for quality control in the determination of IgG anti-Scl-70 autoantibodies in human serum.

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Substantial equivalence

The QUANTA Flash Scl-70, the QUANTA Flash Scl-70 Calibrators and the QUANTA Flash Scl-70 Controls have the same intended use and assay principle as the predicate device.

Comparison to predicate device

QUANTA Flash Scl-70 reagent kit

Similarities
Item	QUANTA Flash Scl-70	Predicate Device
Intended use	QUANTA Flash Scl-70 is a
chemiluminescent immunoassay for
the semi-quantitative determination
of IgG anti-Scl-70 autoantibodies in
human serum. The presence of anti-
Scl-70 autoantibodies, in conjunction
with clinical findings and other
laboratory tests, aids in the diagnosis
of systemic sclerosis.	QUANTA Lite Scl-70 is an enzyme-
linked immunosorbent assay (ELISA)
for the semi-quantitative detection of
Scl-70 antibodies in human serum. The
presence of Scl-70 antibodies can be
used in conjunction with clinical
findings and other laboratory tests to
aid in the diagnosis of scleroderma.
Assay methodology	Solid phase (heterogenous)
immunoassay	Solid phase (heterogenous)
immunoassay
Sample type	Serum	Serum
Shelf life	One year	One year

Differences
Item	QUANTA Flash Scl-70	Predicate Device
Detection/
Operating principle	Chemiluminescent immunoassay	Enzyme-linked immunosorbent assay
Solid phase	Paramagnetic microparticles (beads)	96-well plate
Antigen	Recombinant	Native
Conjugate	Isoluminol conjugated anti-human IgG	HRP conjugated anti-human IgG
Calibration	Lot specific Master Curve + two
Calibrators (Sold separately)	Single standard
(Included in the kit)

9

Item	QUANTA Flash Scl-70 Calibrators	Predicate Device
Intended use	QUANTA Flash Scl-70 Calibrators are
intended for use with the QUANTA
Flash Scl-70 chemiluminescent
immunoassay for the determination of
IgG anti-Scl-70 autoantibodies in
human serum. Each calibrator
establishes a point of reference for the
working curve that is used to calculate
unit values.	No separate intended use; calibrators
are part of the kit.
Analyte	Anti-Scl-70 antibodies	Anti-Scl-70 antibodies
Method	QUANTA Flash Scl-70
chemiluminescent immunoassay	QUANTA Lite Scl-70 ELISA
Unit	CU (Chemiluminescent units)
(arbitrary)	units (arbitrary)
Matrix	Human serum, stabilizers, and
preservative	Human serum, stabilizers, and
preservative
Physico-chemical
characteristics	Liquid, prediluted, ready to use	Liquid, prediluted, ready to use
Storage	2-8 °C	2-8 °C
Shelf life	One year	One year

QUANTA Flash Scl-70 Calibrators

QUANTA Flash Scl-70 Controls

Item	QUANTA Flash Scl-70 Controls	Predicate Device
Intended use	QUANTA Flash Scl-70 Controls are
intended for use with the QUANTA
Flash Scl-70 chemiluminescent
immunoassay for quality control in the
determination of IgG anti-Scl-70
autoantibodies in human serum.	No separate intended use; controls are
part of the kit.
Analyte	Anti-Scl-70 antibodies	Anti-Scl-70 antibodies
Method	QUANTA Flash Scl-70
chemiluminescent immunoassay	QUANTA Lite Scl-70 ELISA
Unit	CU (Chemiluminescent units)
(arbitrary)	units (arbitrary)
Matrix	Human serum, stabilizers, and	Human serum, stabilizers, and

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Item	QUANTA Flash Scl-70 Controls	Predicate Device
	preservative	preservative
Physico-chemical
characteristics	Liquid, ready to use	Liquid, prediluted, ready to use
Levels	2 (negative and positive)	2 (negative and positive)
Storage	2-8 °C	2-8 °C
Shelf life	One year	One year

Value assignment and traceability of Calibrators and Controls

The QUANTA Flash Scl-70 Calibrators and Controls are manufactured by diluting human serum that contains high titer of antibodies with antibody stabilizer buffer, containing preservative. The human serum is obtained from commercial sources and it is tested for markers of infectious substances.

The target CU is achieved through trial dilutions on small scale. Once a dilution is selected, the Calibrators and Control are bulked, tested, and adjusted. Upon completion of the manufacturing process, the Calibrators and Controls are tested on at least two instruments, on at least two lots of reagent cartridge, in replicates of 10 to determine final value assignment.

Calibrator and Control values are directly traceable to the in-house Standards that are used to create the Master Curves for the QUANTA Flash Scl-70 assay.

Material	Assigned Value (CU)
Scl-70 Master Curve Standard 1	0.0
Scl-70 Master Curve Standard 2	12.6
Scl-70 Master Curve Standard 3	42.4
Scl-70 Master Curve Standard 4	106.4
Scl-70 Master Curve Standard 5	290.8
Scl-70 Master Curve Standard 6	786.3

List of Scl-70 Standards, Calibrators and Controls:

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| Material | Manufacturing
Target Value | Manufacturing
Target Range |
|-------------------------|-------------------------------|-------------------------------|
| Scl-70 Calibrator 1 | 13 CU | 11 - 15 CU |
| Scl-70 Calibrator 2 | 290 CU | 261 - 319 CU |
| Scl-70 Negative Control | 10 CU | 8-12 CU |
| Scl-70 Positive Control | 50 CU | 40-60 CU |

Analytical performance characteristics

Precision

The precision of the QUANTA Flash Scl-70 assay was evaluated on 13 samples containing various concentrations of Scl-70 antibodies in accordance with CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Procedures - Approved Guideline: samples were run in duplicates, twice a day, for 20 days. Data were analyzed with the Analyse-it for Excel method evaluation software, and within run, between run, between day and total imprecisions are summarized in the Table below. Total %CV values were within the acceptance limit, 10%.

| | | | Within
Run | | Between-
Run | | Between-
Day | | Total | |
|--------------|----|--------|---------------|------|-----------------|------|-----------------|------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Precision 1 | 80 | 22.9 | 0.5 | 2.1% | 0.5 | 2.0% | 0.5 | 2.3% | 0.9 | 3.7% |
| Precision 2 | 80 | 89.4 | 1.4 | 1.6% | 1.9 | 2.2% | 3.3 | 3.7% | 4.1 | 4.6% |
| Precision 3 | 80 | 22.7 | 0.5 | 2.3% | 0.5 | 2.1% | 0.6 | 2.5% | 0.9 | 3.9% |
| Precision 4 | 80 | 28.3 | 0.6 | 2.0% | 0.7 | 2.5% | 0.3 | 1.1% | 1.0 | 3.4% |
| Precision 5 | 80 | 700.3 | 13.9 | 2.0% | 11.9 | 1.7% | 30.4 | 4.3% | 35.5 | 5.1% |
| Precision 6 | 80 | 10.7 | 0.3 | 2.7% | 0.4 | 4.1% | 0.0 | 0.0% | 0.5 | 4.9% |
| Precision 7 | 80 | 10.8 | 0.6 | 5.3% | 0.2 | 1.9% | 0.2 | 1.6% | 0.6 | 5.9% |
| Precision 8 | 80 | 58.5 | 1.0 | 1.8% | 1.4 | 2.3% | 1.6 | 2.6% | 2.3 | 4.0% |
| Precision 9 | 80 | 23.62 | 0.4 | 1.6% | 0.5 | 2.3% | 0.9 | 3.7% | 1.1 | 4.6% |
| Precision 10 | 80 | 21.17 | 0.5 | 2.1% | 0.6 | 2.6% | 0.7 | 3.1% | 1.0 | 4.6% |
| Precision 11 | 80 | 23.91 | 0.4 | 1.8% | 0.5 | 2.1% | 1.0 | 4.1% | 1.2 | 5.0% |
| Precision 12 | 80 | 368.54 | 8.0 | 2.2% | 5.2 | 1.4% | 13.2 | 3.6% | 16.3 | 4.4% |
| Precision 13 | 80 | 534.33 | 10.2 | 1.9% | 12.0 | 2.2% | 19.1 | 3.6% | 24.7 | 4.6% |

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Reproducibility

Reproducibility between sites (instruments)

Eight samples were tested on three different instruments at three different sites. Samples were run in replicates of five, once a day for 5 days, to generate 25 data points per sample, per site.

Data were analyzed with the Analyse-it for Excel method evaluation software, between sites imprecision was calculated, and the results are summarized in the Table below. All %CV values were within the acceptance limit, 15%.

QUANTA Flash Scl-70		Between Site Precision (Reproducibility)
Sample ID	Number of Replicates	Mean (CU)	SD (CU)	CV (%)
1	75	682.4	11.7	1.7
2	75	404.9	15.6	3.9
3	75	109.6	5.0	4.5
4	75	35.8	0.5	1.3
5	75	10.1	0.5	4.5
6	75	20.0	1.7	8.3
7	75	18.5	0.9	5.0
8	75	20.0	1.2	6.1

Reproducibility between lots

Lot to lot reproducibility study was performed according to CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures, by testing eight samples with three different lots of reagents in five replicates for 5 days, to generate 25 data points per lot, 75 data points total.

Data were analyzed with the Analyse-it for Excel method evaluation software, between lots imprecision was calculated, and the results are summarized in the Table below. All %CV values were within the acceptance limit, 10%.

13

| | | | Between Lot
Imprecision | |
|-----------|----|--------------|----------------------------|------|
| | | Mean
(CU) | SD (CU) | CV |
| Sample ID | N | | | |
| 1 | 75 | 14.1 | 1.0 | 6.8% |
| 2 | 75 | 61.1 | 0.9 | 1.5% |
| 3 | 75 | 202.4 | 12.9 | 6.4% |
| 4 | 75 | 513.9 | 39.4 | 7.7% |
| 5 | 75 | 564.2 | 36.2 | 6.4% |
| 6 | 75 | 20.7 | 1.4 | 6.8% |
| 7 | 75 | 19.8 | 0.8 | 4.2% |
| 8 | 75 | 19.6 | 1.9 | 9.6% |

Limit of Quantitation (LoQ), Limit of Blank (LoB) and Limit of Detection (LoD)

The Limit of Quantitation (LoQ) of the QUANTA Flash Scl-70 assay is 1.2 CU, which defines the lower limit of the AMR. The LoQ was determined consistent with CLSI EP17-A2 guideline the total error (TE) of each sample per reagent lot, using the Westgard model (TE= /Bias/ + 2s) based on 120 measurements of four low level samples. The total error (TE) for the LoQ is 786.3 CU by further diluting it by a factor specified in the assay definition file (20 fold), thereby bringing the measured value within the AMR. The final result will be calculated by the software by taking into account the additional dilution factor. As the highest value that can be measured is 786.3 CU, the highest value that can be reported is 15726 CU.

To validate the Auto-rerun function, three high positive specimens with results above the analytical measuring range were selected. The samples were run with the Auto-rerun function enabled on the BIO-FLASH. Then the specimens were manually diluted 20 fold and tested on the BIO-FLASH. The results were within the analytical measuring range after auto-rerun or manual dilution for all specimens. The % recovery values for results obtained with the auto-rerun results compared to the results obtained by manual dilution were 104%, 101% and 91% (average 102%) and are within the ± 20% acceptance limit.

High concentration hook effect

N/A

Linearity

The linearity of the AMR was evaluated by a study according to CLSI EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. Five serum samples with various Scl-70 antibody concentrations were diluted with negative serum in 10% increments (from 0% to 90% negative serum) to obtain values that cover the AMR. Diluted samples were assayed in duplicate. Percent recovery was calculated compared to expected results (based on dilution). Percent recovery for all data points ranged from 80.2% to 118.4%. Obtained values were plotted against expected values, and linear regression analysis was performed on each samples, and also on the combined results. Acceptance criteria were 80%-120% recovery, 0.9-1.1 slope and ≥0.95 R . Linear regression results are shown in the Table below.

Sample ID	Test Range (CU)	Slope (95% CI)	R²
Sample 2	72.0 - 727.5	1.00 (0.96 to 1.04)	0.99
Sample 3	7.9 - 101.3	1.03 (1.00 to 1.05)	1.00
Sample 4	1.8 - 20.2	1.01 (0.98 to 1.04)	1.00
Sample 5	1.7 - 9.7	1.01 (0.98 to 1.04)	1.00
Sample 6	81.2 - 739.6	0.96 (0.92 to 1.00)	1.00
All	1.7 - 739.6	1.01(0.99 to 1.02)	0.99

Interference

The interference study was performed according to CLSI EPO7-A2, Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition. Three specimens were tested (negative: 10.7 CU; low: 21.5 CU; positive: 49.4 CU). Interfering substances were spiked into every specimen at three different

15

510(k) Summary QUANTA Flash® Scl-70

concentrations in 10% of total specimen volume, and the resulting samples were assessed in triplicates with the Scl-70 assay. Recovery of the unit values was calculated compared to control samples spiked with the same volume of diluent (10% of total). Acceptance criteria for the interference studies were 85% - 115% recovery. The following interfering substances were tested:

| Interfering
substance | concentration #1
tested | concentration #2
tested | concentration #3
tested |
|--------------------------|----------------------------|----------------------------|----------------------------|
| Bilirubin, conjugated | 10 mg/dL | 5 mg/dL | 2.5 mg/dL |
| Hemoglobin | 200 mg/dL | 100 mg/dL | 50 mg/dL |
| Triglicerydes | 1000 mg/dL | 500 mg/dL | 250 mg/dL |
| Cholesterol | 332.5 mg/dL | 166.3 mg/mL | 83.1 mg/mL |
| Human IgG | 70 mg/mL | 35 mg/mL | 17.5 mg/mL |
| RF IgM | 500 IU/mL | 300 IU/mL | 100 IU/mL |
| Prednisone | 0.3 mg/mL | 0.15 mg/mL | 0.08 mg/mL |
| Naproxen | 25.6 mg/mL | 12.8 mg/mL | 6.4 mg/mL |

No interference was detected with bilirubin up to 10 mg/dL (recovery: 88% to 101%), hemoglobin up to 200 mg/dL (recovery: 93% to 105%), triglycerides up to 1000 mg/dL (recovery: 89% to 97%), cholesterol up to 224.3 mg/dL (recovery: 93% to 106%), human IgG up to 70 mg/mL (recovery 90-109%m or

Intended Use / Indications for Use

Product codes

Device Description

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Mentions AI, DNN, or ML

Input Imaging Modality

Anatomical Site

Indicated Patient Age Range

Intended User / Care Setting

Description of the training set, sample size, data source, and annotation protocol

Description of the test set, sample size, data source, and annotation protocol

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

§ 866.5100 Antinuclear antibody immunological test system.

Kelly Oliner -S

FOR

Indications for Use

Indications for Use (Describe)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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510(k) Summary

510(k) Summary

Table of Contents

510(k) Summary QUANTA Flash® Scl-70

Administrative data

Device description

Intended use(s)

Substantial equivalence

Comparison to predicate device

QUANTA Flash Scl-70 Controls

Value assignment and traceability of Calibrators and Controls

Analytical performance characteristics

Precision

Reproducibility

Reproducibility between lots

Limit of Quantitation (LoQ), Limit of Blank (LoB) and Limit of Detection (LoD)

High concentration hook effect

Linearity

Interference

510(k) Summary QUANTA Flash® Scl-70