The G5 I HbA₁c assay is an affinity chromatography method and is intended for the in-vitro quantitative determination of HbA₁c in capillary blood taken from a finger prick or whole blood in EDTA. The test is indicated for use by diabetics for monitoring the time averaged blood glucose levels of known diabetics as an indicator of overall glycaemic control. The G5 I HbA₁c assay is intended for use in a physicians/doctors office. The assay is not intended for use as a home use or for self-testing.

The G5 II HbA1c assay is an affinity chromatography method and is intended for the in-vitro quantitative determination of HbA1c in capillary blood taken from a finger prick. The test is indicated for use by diabetics for monitoring the time averaged blood glucose levels of known diabetics as an indicator of overall glycaemic control. The G5 II HbA1c assay is intended for use as a prescription home use test.

Device Description

Instrument read, single use in vitro test for the quantitative determination of glycated haemoglobin (GHb) in diabetics.

AI/ML Overview

Here's an analysis of the G5 I HbA1c and G5 II HbA1c Test Systems based on the provided document, addressing the requested criteria:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied / Stated in document)	Reported Device Performance
Clinical Equivalence	Correlation coefficient to predicate device (Glycosal assay)	- Fresh finger prick: 0.96 - Stored EDTA blood: 0.97
POL Study - Accuracy	Accuracy within ± 10%	Achieved within ± 10% (for G5 I)
POL Study - Precision	CV less than 4.6%	Achieved less than 4.6% (for G5 I)
POL Study - Correlation	Correlation coefficients of >0.95	Achieved >0.95 (for G5 I)
Linearity	Linear over the assay range	Linear between 6% and 14% HbA1c
Reproducibility (Overall CV)	Overall CV precision of less than 5%	Achieved less than 5%
Reproducibility (Inter-batch CV)	Assay %CVs of less than 5% (intra and inter-batch)	Achieved less than 5%
Haemoglobin Range	Performs acceptably within a specified range	Acceptable within 11-18 g/dl
Haematocrit Range	Performs acceptably within a specified range	Acceptable within 35% to 55%
Cartridge Stability	Stable for a specified duration	Stable for at least 12 months at 2-8°C
Equilibration Time	Minimum time required to equilibrate to room temperature	2 hours from 2-8°C
Sample Insertion Time	Acceptable time after sample addition prior to insertion into reader	Must be inserted immediately after sample addition

2. Sample Size Used for the Test Set and Data Provenance

Clinical Trial (for G5 HbA1c - likely refers to both G5 I and G5 II):
- Sample Size: 74 patients.
- Data Provenance: Southport DGH, UK (retrospective due to using "fresh finger prick and stored EDTA blood" which implies samples were collected then analyzed/compared).
POL Studies (G5 I):
- Sample Size: At least 20 blood samples per site (across 3 sites). This means a minimum of 60 unique blood samples were used. Additionally, 5 standards were run in triplicate at each site.
- Data Provenance: Not explicitly stated, but "Physician Office Laboratory (POL) studies" suggest prospective collection in a clinical setting.
Home Use - Consumer Study (G5 II):
- Sample Size: Not explicitly stated, but involved "untrained subjects" and "trained subjects" at 3 separate sites. No specific number of subjects or samples is given.
- Data Provenance: 3 separate sites in the USA. Likely prospective, as it involved untrained subjects using the packaging.
Non-Clinical Laboratory Studies (Linearity, Haemoglobinopathies, Abnormal blood chemistries, Interfering Drugs, Labile HbA1c, Reproducibility, Inter-batch variation, Stored blood, Total Haemoglobin/Haematocrit, Cartridge Stability, Equilibration Time, Sample Insertion Time):
- Sample Size: Not explicitly stated for each individual study beyond "a study was conducted" or "a study was performed." The reproducibility studies mention "a normal and an abnormal control" and "3 %HbA1c standards."
- Data Provenance: In-house laboratory studies by Provalis Diagnostics. The references for Haemoglobinopathies and Labile HbA1c point to an external scientific publication (Ann Clin Biochem 1997; 34: 17-31 by WG John), indicating reliance on established scientific understanding rather than a direct study conducted by the company for these specific aspects.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not explicitly state the number of experts used to establish ground truth or their qualifications for any of the studies.

For the clinical trial, the "Glycosal assay" is used as the comparative method, implying it serves as the reference standard. The document doesn't detail the ground truth method for the Glycosal assay itself, but it is implied to be a legally marketed predicate device.
The POL studies involve "trained operators," but their expert qualifications or role in defining ground truth (beyond running the predicate device) are not specified.

4. Adjudication Method for the Test Set

The document does not mention any formal adjudication method (e.g., 2+1, 3+1) for establishing ground truth in the test sets. The primary method of comparison is against a predicate device (Glycosal assay), implying that the result from the predicate device serves as the reference for determining accuracy and correlation.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay for quantitative determination of HbA1c, not an AI-assisted imaging device or a diagnostic that relies on human reader interpretation of complex data that could be augmented by AI. The studies evaluate the device's performance against a predicate device and its ability to be used by trained/untrained operators.

6. If a Standalone (i.e. algorithm only, without human-in-the-loop performance) was done

This question is not directly applicable in the context of this device. The G5 HbA1c Test System is a hardware/reagent-based IVD device with an instrument reader. Its "standalone performance" is essentially what is evaluated in the reproducibility, linearity, and interference studies – how the instrument/assay performs on its own when given a sample. There isn't a separate "algorithm only" component that would be evaluated distinctly from the physical device's performance. The "human-in-the-loop" aspect relates to the operators performing the test (trained vs. untrained), which was assessed in the POL and Home Use studies.

7. The Type of Ground Truth Used

The primary type of "ground truth" used for performance evaluation is comparison against a legally marketed predicate device (Glycosal HbA1c Test / Glycosal II HbA1c Test).

For the clinical study, the G5 HbA1c assay was compared to the Glycosal assay.
For the POL studies, performance was evaluated by comparing results from the G5 I HbA1c test with results obtained by a trained operator, likely using a reference method or the predicate.
For the Home Use study, untrained subjects' results were compared to trained operators' results, implying the trained operator's result (presumably using the G5 II and/or a reference method) served as a benchmark.

8. The Sample Size for the Training Set

The document does not provide details on a specific "training set" in the context of machine learning or AI. As an IVD assay, it's developed and validated using traditional analytical and clinical performance studies, not typically "trained" in the way an AI algorithm is.

9. How the Ground Truth for the Training Set Was Established

Since there is no "training set" in the AI/ML context for this device, this question is not applicable. The development of the assay likely involved internal R&D validation using various samples with known HbA1c levels established by reference methods, but this is not described as a formal "training set" with ground truth establishment in the provided information.

Summary

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Introduction	According to the requirements of 21 CFR 807.92, the followinginformation provides sufficient detail to understand the basisfor a determination of substantial equivalence.
1) Submittername, address,contact	Owner/ OperatorProvalis Diagnostics LimitedNewtech SquareDeeside Industrial ParkDeesideFlintshire CH5 2NTUK
Contact Person:	Mrs Jan Barrack, Regulatory Affairs Manager
Telephone:	+44 1244 288888
Facsimile:	+44 1244 833441
Email:	JanBarrack@Provalis.com
USA contact person Tom Tsakeris
Company	Devices and Diagnostics Consulting Group, Inc
Address:	16809 Briardale Road,Rockville,MD 20855USA
Telephone:	301 330 2076
Facsimile:	301 330 2568
Email:	DDCGI@Comcast.net
Date Prepared	5th June 2004

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2) Device name	Proprietary name:	G5 I HbA₁c Test
	Common name:	Laboratory test for the detection ofGlycated Haemoglobin in Human WholeBlood.
	Classification:	ASSAY, GLYCOSYLATEDHAEMOGLOBIN
3) PredicateDevice	The G5 I HbA₁c test is substantially equivalent toother products in commercial distribution for similar use,including the Glycosal HbA₁c Test.
4) DeviceDescription	Instrument read, single use in vitro test for the quantitativedetermination of glycated haemoglobin (GHb) in diabetics.
5) Intended use	The G5 I HbA₁c assay is an affinity chromatography methodand is intended for the in-vitro quantitative determination ofHbA₁c in capillary blood taken from a finger prick or wholeblood in EDTA.
	The test is indicated for use by diabetics for monitoring the timeaveraged blood glucose levels of known diabetics as anindicator of overall glycaemic control.
	The G5 I HbA₁c assay is intended for use in aphysicians/doctors office. The assay is not intended for use as ahome use or for self-testing.

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Introduction	According to the requirements of 21 CFR 807.92, the followinginformation provides sufficient detail to understand the basisfor a determination of substantial equivalence.
2) Submittername, address,contact	Owner/ OperatorProvalis Diagnostics LimitedNewtech SquareDeeside Industrial ParkDeesideFlintshire CH5 2NTUK
Contact Person:	Mrs Jan Barrack, Regulatory Affairs Manager
Telephone:	+44 1244 288888
Facsimile:	+44 1244 833441
Email:	JanBarrack@Provalis.com
USA contact person Tom Tsakeris
Company	Devices and Diagnostics Consulting Group, Inc
Address:	16809 Briardale Road,Rockville,MD 20855USA
Telephone:	301 330 2076
Facsimile:	301 330 2568
Email:	DDCGI@Comcast.net
Date Prepared	5th June 2004

・

029

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2) Device name	Proprietary name: G5 II HbA1c TestCommon name: Prescription Home Use Test for the detection of Glycated Haemoglobin in Human Whole Blood.Classification: ASSAY, GLYCOSYLATED HAEMOGLOBIN
5) Predicate Device	The G5 II HbA1c test is substantially equivalent to other products in commercial distribution for similar use, including the Glycosal II HbA1c Test for prescription home use.
6) Device Description	Instrument read, single use in vitro test for the quantitative determination of glycated haemoglobin (GHb) in diabetics.
5) Intended use	The G5 II HbA1c assay is an affinity chromatography method and is intended for the in-vitro quantitative determination of HbA1c in capillary blood taken from a finger prickThe test is indicated for use by diabetics for monitoring the time averaged blood glucose levels of known diabetics as an indicator of overall glycaemic control.The G5 II HbA1c assay is intended for use as a prescription home use test.

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Technological Similarities and Differences of the G5 I HbA1c and G5 II HbA1c tests to the Predicate Devices ..............................................................................................................................................................................

Characteristic	Candidate DeviceG5 I and G5 II HbA1c test	Primary PredicateDevice for G5 IGlycosal™ HbA1c test	Primary PredicateDevice for G5 IIGlycosal™ II HbA1c test
Intended Use	Quantitative measurementof the percent of GlycatedHemoglobin.	Quantitativemeasurement of thepercent of GlycatedHemoglobin.	Quantitative measurementof the percent of GlycatedHemoglobin.
Indications forUse	Used in the managementand treatment of Diabetes,for monitoring long termglycemic control.	Used in the managementand treatment ofDiabetes, for monitoringlong term glycemiccontrol.	Used in the managementand treatment of Diabetes,for monitoring long termglycemic control.
Risk to Patient	Not a critical analyte -reflects glucosemonitoring over time	Not a critical analyte -reflects glucosemonitoring over time	Not a critical analyte -reflects glucosemonitoring over time
Detects	Glycated Hemoglobin(GHb)	Glycated Hemoglobin(GHb)	Glycated Hemoglobin(GHb)
Methodology	Rapid AffinityChromatography test	Rapid AffinityChromatography test	Rapid AffinityChromatography test
Does the Deviceperform aDiagnosticInterpretation?	No	No	No
QuantitativeTest?	Yes	Yes	Yes
Calibration	Not required by end-user;each instrument is factorycalibrated	Not required by end-user; each instrument isfactory calibrated	Not required by end-user;each instrument is factorycalibrated
Total Test timeProcedural Steps	7 minutes1. Add sample2. Place device ininstrument3. Record result	4 minutes1. Add sample2. Incubate sample for60 seconds.3. Pour sample4. Wash5. Elute fraction6. Record result	4 minutes1. Add sample2. Incubate sample for 60seconds3. Pour sample4. Wash5. Elute fraction6. Record result
Visual DisplayTestingEnvironment	LCD readoutPhysicians office/DoctorsOffice (G5 I)Prescription Home Use(G5 II)	LCD readoutPhysiciansOffice/Doctors Office	LCD readoutPrescription Home UsePatient Labelling

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6) Performance Characteristics

Clinical Studies

Clinical trial carried out at Southport DGH, UK to evaluate a rapid blood test for the measurement of Glycated protein in subjects with type I and type II diabetes mellitus

The data from 74 patients demonstrated that the G5 HbAre assay is substantially equivalent to the Glycosal assay with a correlation coefficient of 0.96 for fresh finger prick and 0.97 for stored EDTA blood.

POL Studies (G5 I)

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Evaluation of the G5 HbAie test using non-laboratory participants

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Three separate Physician Office Laboratory (POL) studies were carried out. Each consisting of 5 standards run in triplicate and at least 20 blood samples (EDTA stored blood and/or fresh finger prick) run by a trained operator and an untrained operator. Each site produced acceptable data for accuracy and precision, with correlation coefficients of >0.95. accuracy within ± 10% and CV less than 4.6%.

Home Use - Consumer Study (G5 II)

This study took place at 3 separate sites in the USA and compared untrained subjects to trained subjects. The untrained subjects using only the supplied packaging achieved acceptable correlation to the trained operators.

Non Clinical Laboratory Studies

Assessing the linearity of the G5 HbAir assay

A study was conducted to prove the G5 HbA1c is linear over the assay range. Results demonstrated that the assay is linear between 6 and 14% HbAIc.

The effect of Haemoglobinopathies on the G5 HbA1c assay

This validation is covered by reference WG John. Glycated haemoglobin analysis. Ann Clin Biochem 1997; 34: 17-31. Boronate methodology is not affected by HbS, HbC. HbF or by high levels of carbamylated haemoglobin in Uremic patients.

The Effect of Abnormal blood chemistries upon the accuracy of the GS HbA1c assay

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The effect of abnormal blood chemistries, i e. raised lipids and raised bilirubin upon the determination of %HbAir needed to be investigated. Triglycerides up to 4.0 mmol/L and Bilirubin up to 345 umol/L do not affect the test result.

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The Effect of Interfering Drugs upon Accuracy of the G5 HbA1c assay

The effect of the commonly prescribed pharmaceutical drugs (aspirin, paracetemol, caffeine and anti-histamine) upon the performance of the G5 HbA1c test needed to be assessed. None of the listed compounds affected the HbA1c test result.

Investigating the effect of labile HbA1c on the G5 HbA1c assay

This validation is covered by reference WG John. Glycated haemoglobin analysis. Ann Clin Biochem 1997: 34: 17-31. Boronate Methodology is not affected by Labile HbAic:

Investigating the analysis of variance of reproducibility of the G5 HbA1c assay

A study was performed to investigate the analysis of variance of reproducibility of the G5 HbA1c assay. Using a normal and an abnormal control, which were assayed in duplicate twice during each day over a period of 20 days, it was demonstrated that the variance was acceptable, with an overall CV precision of less than 5%.

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Investigating the assay reproducibility (Inter batch variation) of the G5 HbA1c ASSAY

A study was performed to determine the intra and inter batch variation of the G5 HbAic assay. Using 3 %HbAic standards on 3 batches of G5 devices it was demonstrated that the G5 assay was acceptable in terms of repeatability and reproducibility with assay %CV's of less than 5%.

Investigation into the use of stored blood for the G5 HbAic assay

The effect of running G5 assays with stored whole blood (EDTA) needed to be examined to assess the use of stored whole blood as an alternative to fresh finger pricks. It was demonstrated that the assay can be run acceptably with fresh finger prick, EDT A blood for up to 4 days after collection when the blood is stored at 2-8°C.

Investigating the effect of Total Haemoglobin and Haematocrit on the G5 HDAit ASSAV

The effect of the variation in total haemoglobin and haematocrit on %HbAre needed to be established. Results demonstrated that the assay performs acceptably within a haemoglobin range of 11-18g/dl and a haematocrit range of 35% to 55%.

G5 HbA1c test cartridge stability

The stability of the G5 HbA1c assay needed to be established. Results demonstrated that the assav is stable for at least 12 months at 2-8°C.

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Assessing the time required to equilibrate the G5 device to room temperature from 2-8°C

The minimum time required to equilibrate the G5 devices to room temperature before use needed to be established. The results demonstrated that the minimum time required for equilibration is 2 hours.

Assessing the acceptable time a device can be left after sample addition prior to insertion into the G5 reader

The acceptable time a device can be left after sample addition prior to insertion into the G5 reader needed to be assessed. The results demonstrated that the device needed to be inserted immediately after sample addition

G5 HbAre Quality Control Kit

Provalis use commercially available controls from Aalto scientific Ltd; Glycohemoglobin controls normal and abnormal. 510(k) K952720.

Conclusion: These performance characteristics clearly indicate substantial equivalence of the G5 I HbA1c test with the Glycosal HbA1c test and the GS II HbA1c test with the Glycosal II HbA1c test and provides a comparative accuracy to other cleared and commonly accepted methods.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of three overlapping human figures, which are meant to represent people. The graphic is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." arranged in a circular fashion.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 1 6 2004

Provalis Diagnostics Ltd. c/o Mr. Thomas M. Tsakeris Devices and Diagnostics Consulting Group, Inc. 16809 Briardale Rd. Rockville, MD 20855

K041635 Re:

Trade/Device Name: G5 II HbAic Test System G5 I HbAic Test System Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, GGM Dated: June 16, 2004 Received: June 16, 2004

Dear Mr. Tsakeris:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your became in a the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encreated 776 the enactment date of the Medical Device Amendments, or to commerce provision to may 20, 1977, in accordance with the provisions of the Federal Food, Drug, devices that have been roomstiled in ause approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, mereleve, maneve a f the Act include requirements for annual registration, listing of general controls providive, 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 n may be babject to back and 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 r loase oc advised that i Dr bristian that your device complies with other requirements of the Act that i Dr Haral statutes and regulations administered by other Federal agencies. You must or any I catal statutes and equirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice erre rart 807), tabeling the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sean M. Cooper, MS, DVM.

Jean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K041635

Device Name: G5 II HbA1c Test System

Indications For Use: Indications for Use: The G5 II HbA1c Test System is intended for testing blood taken from a fingerprick.

G5 II HbA1c Test System shows how good glucose control has been over a two to three month period.

The G5 II HbA1c Test System consists of the HbA1c test cartridge, the G5 Instrument, the G5 System Check Cartridge and the G5 HbA1c Quality Controls.

The G5 II HbA1c Test System is intended for prescription home use.

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)

Carol Benson
Division Sign-Off

Office of In Vitro Diagnost Device Evalua

Page 1 of 2

510(k) K041635

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Indications for Use

510(k) Number (if known): K041635

Device Name: G5 | HbA1c Test System

Indications For Use: Indications for Use: The G5 I HbA1c Test System is an affinity chromatography method and is intended for the in vitro quantitative determination of HbA1c in capillary blood taken from a fingerprick or whole blood in EDTA.

G5 | HbA1c Test System is indicated for monitoring the time averaged blood glucose levels of known diabetics, for professional use as an indicator of overall Glycaemic control.

The G5 I HbA1c Test System consists of the HbA1c test cartridge, the G5 Instrument, the G5 System Check Cartridge and the G5 HbA1c Quality Controls.

The G5 I HbA1c Test System is intended for use in a physicians/ doctors office.

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)

Carol Bensen
Division Sign-Off

Office of In Vitto Diagi

510(K) K041635

Page 2 of 2

Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).