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April 5, 2017
Introduction 3
Procedural and Maintenance Changes 23
Technical Support FAQ 24-32
Tables
▪ Table 1: Kit Configuration Changes 4-7
▪ Table 2: Individual Kit Component Availability 8-9
▪ Table 3: Kit Buffer Usage 22
▪ Table 4: Additional Differences 33-36
Figures
Figure 1: Non-diabetic Patient 10
Figure 2: Diabetic Patient Report 11
Figure 3: Elevated HbF Patient Report 12
Figure 4: HbAE Patient Report 13
Figure 5: HbAD Patient 14
Figure 6: HbAS Patient 15
Figure 7: HbAC Patient 16
Figure 8: Elevated Labile A1c (LA1c) 17
Figure 9: Elevated Carbamylated Hemoglobin (CHb) 18
Figure 10: β-thalassemia trait sample 19
Figure 11: HbA2' (prime) sample 20
Figure 12: Summary Report 21
Figure 13: Parameter Selection Error Message 25
Figure 14: Results of Hemoglobin Interference Study 26
Figure 15: Results of Precision Study (%NGSP) 28
Figure 16: ADA HbA1c Range Recommendations 30
Figure 17: Drug Interferences 32
Introduction
The VARIANT™ II TURBO HbA1c Kit – 2.0, PIN 12000447 project was executed to obtain
FDA clearance for a new Indication for Use as an aid in diagnosis of diabetes and as an aid in
identifying patients who may be at risk for developing diabetes. There are no formulation
changes to the VARIANT™ II TURBO HbA1c Kit – 2.0, PINs 12000447 from PINs 270-2455
and 270-2455EX. The product labeling for PIN 12000447 has new performance data in the
Instruction Manual which is different and more extensive than PINS 270-2455 and 270-2455EX
to meet the strict requirements by the FDA to support the new Indication for Use. The new part
number segregates the existing kit PINs 270-2455 and 270-2455EX in inventory until all
countries worldwide have converted customers to PIN 12000447.
This guide is intended to help the Technical Support groups navigate and quickly identify
possible problems and resolutions when troubleshooting with the customer.
Product Features
Performance Characteristics
• HbA1c is reportable in the presence of HbF concentrations up to 25%.
• Carbamylated hemoglobin (CHb), labile A1c (LA1c) and acetylated hemoglobin do not
interfere with the assay at physiologically occurring concentrations.
• HbA1c is reportable in the presence of heterozygous hemoglobins E, D, S and C.
Expected Workflow
• The cartridge lifetime is 2500 injections.
• The cartridge on-board stability is 90 days.
• Double prime once after every new cartridge installation.
• Calibrate once after installation and priming of every new cartridge.
• The prefilter lifetime is 500 injections.
• The prefilter improves the overall performance of the cartridge.
• Different lots of Buffer A and Buffer B can be interchanged within a cartridge resin lot.
Buffer and cartridge labels are coded using an alphabetical letter to indicate
compatibility.
*NOTE: Cartridge pressure range may change from resin lot to resin lot. Refer to the Cartridge
Resin Release Notes or Customer Notification: Release of VARIANT™ II TURBO HbA1c Kit -
2.0, REF 12000447 (12005280revA) for further details.
PIN 12005138
CD Contains VARIANT™ II TURBO HbA1c
Kit - 2.0 test parameters.
PIN 12000997
HbS trait, HbC trait, HbD trait HbA1c is reportable in the presence of
and HbE trait the heterozygous forms of these traits
*NOTE: Refer to page 27 of the Tech Support FAQ section for additional information.
**NOTE: Refer to Figure 17 on page 32 of the Tech Support FAQ section for
additional information.
Figure 1: Non-diabetic patient report from VARIANT™ II TURBO HbA1c Kit - 2.0;
Note the arrows showing IFCC and NGSP result options with CDM 5.1 and above.
Figure 6: HbAS and Multiple Unknown Peaks on VARIANT™ II TURBO HbA1c Kit - 2.0
Figure 8: Elevated Labile A1c (LA1c) on VARIANT™ II TURBO HbA1c Kit - 2.0
V2_Turbo_A1c_2.0
Figure 12: Summary Report with VARIANT™ II TURBO HbA1c Kit - 2.0
The following is the buffer configuration for the VARIANT™ II TURBO HbA1c Kit – 2.0,
2500 Tests (PIN 12000447):
*NOTE: Wash/Diluent is available as a separate pack (270-2730) of four (4) bottles, 2500
ml each. At least one box of four (4) bottles is required for each kit.
The following grid estimates how many additional Buffer A and Buffer B and Wash buffer
bottles a customer will require per kit based on their workflow. See example on next page.
In order to run 2500 tests, a customer running fifty (50) samples per day over three (3) runs that
same day would need to order:
Database maintenance when switching to the VARIANT™ II TURBO HbA1c Kit – 2.0
When switching from another method to the VARIANT™ II TURBO HbA1c Kit – 2.0, PIN
12000447, the current database must be backed up and cleared and CDM must be restarted prior
to installing the new Update Kit CD. This is necessary for laboratories using the QC Data feature
of the Clinical Data Management (CDM) system to generate Levey-Jennings charts or export
result to Unity
Calibration Frequency
Calibration only needs to be performed once after the installation and priming of a new
analytical cartridge. This will cover an injection limit of 2500 or 90 days (cartridge on-board
stability) whichever comes first.
Pressure Differences
The acceptable cartridge operating pressure range is 40-150 kg/cm2. The pressure range may
vary slightly in resin lots. Refer to the Cartridge Resin Release Notes or Customer Notification:
Release of VARIANT™ II TURBO HbA1c Kit - 2.0, REF 12000447 (12005280revA) for details.
Over the lifetime of a cartridge and prefilter, there can be an increase of pressure. Small
particulates from rotor seals, pump seals or other sources can contribute to increased pressure
during the lifetime. This is typical performance.
LIS Output
Switching from PIN 270-2455 (VARIANT™ II TURBO HbA1c Kit – 2.0) or PIN 270-2455EX
(VARIANT™ II TURBO HbA1c Kit – 2.0 – Export Only) to PIN 12000447 (VARIANT™ II
TURBO HbA1c Kit – 2.0) requires no changes to LIS. Switching from other kits to PIN
12000447 requires no changes to LIS, if only reporting HbA1c.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
Customers will ask questions regarding some, if not all, of the changes made. This next section
is intended to help explain some anticipated questions the customer may ask.
Can this kit be installed on the VARIANT™ II TURBO Link Hemoglobin Testing System?
Yes. The VARIANT™ II TURBO Link Hemoglobin Testing System Operation Manual or
Quick Guide should be referenced for additional information. The VARIANT™ II TURBO
Link Hemoglobin Testing System is only available in the US and Canada.*
Why does the Update Kit CD (PIN 12000997) contain two parameter sets?
One parameter set is for the use of this assay on the VARIANT™ II TURBO Hemoglobin
Testing System (PIN: 270-2600 or PIN: 270-2601). The other parameter set is specific for the
use of this assay on the VARIANT™ II TURBO Link Hemoglobin Testing System (PIN: 270-
2700 or PIN: 270-2701). The VARIANT™ II TURBO Link Hemoglobin Testing System is
only available in the US and Canada.* Unique report headers will distinguish one system from
the other when this assay is in use.
*NOTE: This Technical Support Guide is for the VARIANT™ II TURBO HbA1c Kit - 2.0 (PIN:
12000447) run on the VARIANT™ II TURBO Hemoglobin Testing System.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
The IFU states HbA1c should not be reported if the following conditions are exhibited:
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
Is HbA1c reportable if the P3 and P4 peaks are added together and is greater than 10?
Each peak should be evaluated separately. If each individual peak is less than
the concentrations defined above, then the HbA1c can be reported. For example, if P3 is ≤5% and
P4 is ≤10% for hemoglobin variant samples (HbS-, HbC-, HbD-, HbE-trait), the HbA1c can be
reported. Do not add the peaks together!
Figure 14: Results of Hemoglobin Interference Study from the VARIANT™ II TURBO
HbA1c Kit - 2.0 Instructions for Use (12005531revB)
NOTE: Relative % Bias (StDEV) results are mean values obtained across the entire study
for each represented Hb variant trait.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
What happens when a peak is identified in the Variant window?
HbA1c is reportable in the presence of HbS-, HbC-, HbD- and HbE. The graphs in Figures 4, 5,
6, and 7 can be used as guides. If a graph presentation differs from those examples, then it is
recommended that the customer follow their site procedures.
Will the HbA2 be automatically excluded from the final HbA1c calculation when HbE trait
is present? If not, how will this impact the final HbA1c value?
Yes, HbA2 will be excluded. The calibration of normal samples, control samples and the
calibrators is determined by excluding normal amounts of HbA2. When HbE trait samples are
run, the applied calibration already factors the removal of a normal amount of HbA2.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
Figure 15: Results of Precision Study (%NGSP) from the VARIANT™ II TURBO
HbA1c Kit - 2.0 Instructions for Use (12005531revB)
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
How should customers perform their precision study when installing an HbA1c diagnostic
kit?
The precision study performed by Bio-Rad and submitted to the FDA is an extensive study and is not
feasible for customers to perform. Customers should follow their site procedures for determining
acceptable precision. Customers can use a target CV of ≤3% for %NGSP results and opt for the example
defined in the CLSI precision protocol CLSI EP15-A2 “User Verification for Performance of Precision;
Approved Guideline – Second Edition,” Vol 25, No. 17”*. The example protocol involves analyzing 2
patient sample concentrations and controls in 1 run per day with 3 replicate samples each for 5 days using
one kit lot. Then the following %CV’s can be calculated: Within-run precision (or repeatability), and
within-laboratory precision.
The IFU %CV target of ≤3% was used to determine within-laboratory precision. The precision results
posted on the NGSP website from CAP surveys reflect the between-laboratory reproducibility. NGSP
uses a target of ≤3.5%, which is an arbitrary limit. (http://www.ngsp.org/CAPdata.asp)
*CLSI EP15-A2, “User Verification for Performance of Precision; Approved Guideline – Second
Edition,” Vol 25, No. 17, pgs. 4, 5 and 45. Bio-Rad cannot provide this CLSI document to customers due
to copyright laws, so if interested, contact CLSI directly at Clinical and Laboratory Standards Institute,
940 West Valley Road, Suite 1400, Wayne, Pennsylvania, 19087-1898, USA.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
Can this assay be used to monitor people with diabetes?
Yes. This HbA1c method can be used to monitor long-term glycemic control in all individuals
with diabetes.
Can this assay be used as an aid in identifying patients who may be at risk for developing
diabetes?
Yes.
Explain the criteria for identifying patients at risk for developing diabetes and as an aid in
diagnosing diabetes.
HbA1c testing has been recommended for the diagnosis of Type 2 diabetes by the International
Expert Committee (IEC)*, the American Diabetes Association (ADA)**, and the World Health
Organization (WHO).*** All three bodies recommend a diagnostic threshold of ≥6.5% or
≥48 mmol/mol. The following HbA1c ranges in Figure 16 recommended by the American
Diabetes Association (ADA) may be used as an aid in the diagnosis of diabetes mellitus and
those at risk for developing diabetes (also known as “pre-Diabetic”). For diagnosis purposes,
results should be interpreted in conjunction with the patient’s medical history and clinical
findings. See Figure 16.
*International Expert Committee. Report on the Role of the A1c Assay in the Diagnosis of
Diabetes. Diabetes Care 2009, 32 (7). 1327-1334.
**American Diabetes Association, Diagnosis and Classification of Diabetes Mellitus. Diabetes
Care 2010, 33 (Suppl. 1), S62-S69.
***World Health Organization. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of
Diabetes Mellitus. http://www.who.int/diabetes/publications/diagnosis diabetes2011/en/
(accessed July 2014).
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
• The HbA1c test should not be used to replace glucose testing in pediatric patients, pregnant
women, or patients with Type 1 diabetes.
• In cases of rapidly evolving Type 1 diabetes, the increase of HbA1c values might be delayed
compared to the acute increase in glucose concentrations. In these conditions, diabetes mellitus
must be diagnosed based on plasma glucose concentration and/or the typical clinical symptoms.
• The HbA1c test should not be used to diagnose diabetes during pregnancy or to diagnose
gestational diabetes.
• The HbA1c test should not be used to diagnose diabetes in patients with the following
conditions:
□ Any condition that alters the life span of the red blood cells, including recent blood loss,
transfusion, significant iron deficiency, hemolytic anemia (including hereditary
spherocytosis) or other hemolytic diseases, hemoglobinopathies and thalassemias, as the
altered red blood cell turnover interferes with the relationship between mean blood glucose
and HbA1c values.
Tech Support FAQ: Frequently Asked Questions for Tech Support Issues
Was a drug interference study performed?
Yes. A new drug interference study was performed based on the CLSI EP07-A2 guideline,
“Interference Testing in Clinical Chemistry” to determine the effect of common drugs on HbA1c
measurement. Specimens with hemoglobin concentrations of approximately 6.5%
(48 mmol/mol) and ≥8.0% (≥64 mmol/mol) were spiked with the interferent drug. The study
concludes that the tested common drugs at therapeutic concentrations do not interfere with this
assay. See Figure 17.
QC Requirement Run once each day Include with every run Include with every run
* NOTE: Refer to the VARIANT™ II TURBO Operation Manual (L70241503 or later) for the
full procedure. .