G5 I HBA1C TEST, G5 II HBA1C TEST

K041635 · Provalis Diagnostics , Ltd. · LCP · Aug 16, 2004 · Hematology

Device Facts

• Record ID: K041635
• Device Name: G5 I HBA1C TEST, G5 II HBA1C TEST
• Applicant: Provalis Diagnostics , Ltd.
• Product Code: LCP · Hematology
• Decision Date: Aug 16, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

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 Story

G5 I and G5 II HbA1c Test Systems are in vitro diagnostic devices for quantitative determination of glycated haemoglobin (GHb) in human whole blood. Input: capillary blood (finger prick) or EDTA whole blood. Principle: affinity chromatography. Operation: user adds sample to test cartridge, inserts into G5 instrument; instrument performs automated analysis and displays result on LCD. G5 I used in physician offices; G5 II used in home settings via prescription. Output: quantitative HbA1c percentage. Clinical utility: monitoring long-term glycemic control in diabetics. Benefits: provides rapid, factory-calibrated results without end-user calibration, facilitating management of diabetes.

Clinical Evidence

Clinical trial (n=74) demonstrated correlation of 0.96 (finger prick) and 0.97 (EDTA blood) vs. predicate. POL studies (n=3 sites) showed correlation >0.95, accuracy within ±10%, and CV <4.6%. Home use study confirmed untrained subjects achieved acceptable correlation to trained operators. Non-clinical studies confirmed linearity (6-14% HbA1c), stability (12 months), and lack of interference from lipids, bilirubin, common drugs, or haemoglobinopathies (HbS, HbC, HbF). Reproducibility studies showed CV <5%.

Technological Characteristics

Boronate affinity chromatography; single-wavelength photometer; manual sample loading; cartridge-based assay. Traceable to DCCT/NGSP. Electrical safety per IEC 61010/BS EN 60601. Software-controlled instrument. Shelf-life 16 months at 2-8°C.

Indications for Use

Indicated for monitoring time-averaged blood glucose levels in known diabetics to assess overall glycaemic control. G5 I is for professional use in physician offices; G5 II is for prescription home use. Suitable for adults and children with diabetes.

Regulatory Classification

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.

Predicate Devices

• Glycosal HbA1c Test
• Glycosal II HbA1c Test

Reference Devices

• Glycohemoglobin controls (Aalto scientific Ltd) (K952720)

Submission Summary (Full Text)

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| Introduction | According to the requirements of 21 CFR 807.92, the following<br>information provides sufficient detail to understand the basis<br>for a determination of substantial equivalence. | | |
|-------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| 1) Submitter<br>name, address,<br>contact | Owner/ Operator<br>Provalis Diagnostics Limited<br>Newtech Square<br>Deeside Industrial Park<br>Deeside<br>Flintshire CH5 2NT<br>UK | | |
| Contact Person: | Mrs Jan Barrack, Regulatory Affairs Manager | | |
| Telephone: | [phone] | | |
| Facsimile: | [phone] | | |
| Email: | [e-mail] | | |
| USA contact person Tom Tsakeris | | | |
| Company | Devices and Diagnostics Consulting Group, Inc | | |
| Address: | 16809 Briardale Road,<br>Rockville,<br>MD 20855<br>USA | | |
| Telephone: | 301 330 2076 | | |
| Facsimile: | 301 330 2568 | | |
| Email: | [e-mail] | | |
| 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 of<br>Glycated Haemoglobin in Human Whole<br>Blood. |
| | Classification: | ASSAY, GLYCOSYLATED<br>HAEMOGLOBIN |
| 3) Predicate<br>Device | The G5 I HbA₁c test is substantially equivalent to<br>other products in commercial distribution for similar use,<br>including the Glycosal HbA₁c Test. | |
| 4) Device<br>Description | Instrument read, single use in vitro test for the quantitative<br>determination of glycated haemoglobin (GHb) in diabetics. | |
| 5) Intended use | The G5 I HbA₁c assay is an affinity chromatography method<br>and is intended for the in-vitro quantitative determination of<br>HbA₁c in capillary blood taken from a finger prick or whole<br>blood in EDTA. | |
| | The test is indicated for use by diabetics for monitoring the time<br>averaged blood glucose levels of known diabetics as an<br>indicator of overall glycaemic control. | |
| | The G5 I HbA₁c assay is intended for use in a<br>physicians/doctors office. The assay is not intended for use as a<br>home use or for self-testing. | |

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| Introduction | According to the requirements of 21 CFR 807.92, the following<br>information provides sufficient detail to understand the basis<br>for a determination of substantial equivalence. | | |
|-------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| 2) Submitter<br>name, address,<br>contact | Owner/ Operator<br>Provalis Diagnostics Limited<br>Newtech Square<br>Deeside Industrial Park<br>Deeside<br>Flintshire CH5 2NT<br>UK | | |
| Contact Person: | Mrs Jan Barrack, Regulatory Affairs Manager | | |
| Telephone: | [phone] | | |
| Facsimile: | [phone] | | |
| Email: | [e-mail] | | |
| USA contact person Tom Tsakeris | | | |
| Company | Devices and Diagnostics Consulting Group, Inc | | |
| Address: | 16809 Briardale Road,<br>Rockville,<br>MD 20855<br>USA | | |
| Telephone: | 301 330 2076 | | |
| Facsimile: | 301 330 2568 | | |
| Email: | [e-mail] | | |
| Date Prepared | 5th June 2004 | | |

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| 2) Device name | Proprietary name: G5 II HbA1c Test<br>Common name: Prescription Home Use Test for the detection of Glycated Haemoglobin in Human Whole Blood.<br>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 <i>in vitro</i> 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 <i>in-vitro</i> quantitative determination of HbA1c in capillary blood taken from a finger prick<br><br>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.<br><br>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 Device<br>G5 I and G5 II HbA1c test | Primary Predicate<br>Device for G5 I<br>Glycosal™ HbA1c test | Primary Predicate<br>Device for G5 II<br>Glycosal™ II HbA1c test |
|---------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Quantitative measurement<br>of the percent of Glycated<br>Hemoglobin. | Quantitative<br>measurement of the<br>percent of Glycated<br>Hemoglobin. | Quantitative measurement<br>of the percent of Glycated<br>Hemoglobin. |
| Indications for<br>Use | Used in the management<br>and treatment of Diabetes,<br>for monitoring long term<br>glycemic control. | Used in the management<br>and treatment of<br>Diabetes, for monitoring<br>long term glycemic<br>control. | Used in the management<br>and treatment of Diabetes,<br>for monitoring long term<br>glycemic control. |
| Risk to Patient | Not a critical analyte -<br>reflects glucose<br>monitoring over time | Not a critical analyte -<br>reflects glucose<br>monitoring over time | Not a critical analyte -<br>reflects glucose<br>monitoring over time |
| Detects | Glycated Hemoglobin<br>(GHb) | Glycated Hemoglobin<br>(GHb) | Glycated Hemoglobin<br>(GHb) |
| Methodology | Rapid Affinity<br>Chromatography test | Rapid Affinity<br>Chromatography test | Rapid Affinity<br>Chromatography test |
| Does the Device<br>perform a<br>Diagnostic<br>Interpretation? | No | No | No |
| Quantitative<br>Test? | Yes | Yes | Yes |
| Calibration | Not required by end-user;<br>each instrument is factory<br>calibrated | Not required by end-<br>user; each instrument is<br>factory calibrated | Not required by end-user;<br>each instrument is factory<br>calibrated |
| Total Test time<br>Procedural Steps | 7 minutes<br>1. Add sample<br>2. Place device in<br>instrument<br>3. Record result | 4 minutes<br>1. Add sample<br>2. Incubate sample for<br>60 seconds.<br>3. Pour sample<br>4. Wash<br>5. Elute fraction<br>6. Record result | 4 minutes<br>1. Add sample<br>2. Incubate sample for 60<br>seconds<br>3. Pour sample<br>4. Wash<br>5. Elute fraction<br>6. Record result |
| Visual Display<br>Testing<br>Environment | LCD readout<br>Physicians office/Doctors<br>Office (G5 I)<br>Prescription Home Use<br>(G5 II) | LCD readout<br>Physicians<br>Office/Doctors Office | LCD readout<br>Prescription Home Use<br>Patient 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.

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#### 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

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#### G5 HbAre Quality Control Kit

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

7) 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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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 [phone]. 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 [phone] or [phone] 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

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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

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