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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k170147
B. Purpose for Submission:
New device
C. Measurand:
Glycated Albumin
D. Type of Test:
Quantitative colorimetric assay
E. Applicant:
Asahi Kasei Pharma Corporation
F. Proprietary and Established Names:
Lucica Glycated Albumin-L
G. Regulatory Information:
1. Regulation section:
21 CFR 864.7470
2. Classification:
Class II
3. Product code:
LCP - Assay, Glycosylated Hemoglobin
4. Panel:
Hematology (81)
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H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:
The Lucica Glycated Albumin-L is intended to be used for the quantitative measurement
of glycated albumin in human serum on compatible clinical chemistry analyzers. The
measurement of glycated albumin is useful for the intermediate term (preceding 2-3
weeks) monitoring of glycemic control in patients with diabetes. For in vitro diagnostic
use only.
3. Special conditions for use statement(s):
For prescription use only.
4. Special instrument requirements:
Performance in the studies submitted in the 510(k) are based on the Roche/Hitachi
Modular P Chemistry System.
I. Device Description:
The Lucica Glycated Albumin-L contains two glycated albumin reagents and two
albumin reagents. The kit employs liquid reagents that do not require preparation. The
glycated albumin reagent consists of GA R-1 (Pretreatment solution), GA R-2
(Enzymatic solution), ALB R-1 (pretreatment solution), and ALB R-2 (Coloring
solution).
J. Substantial Equivalence Information:
1. Predicate device name(s):
Randox Laboratories Fructosamine
2. Predicate 510(k) number(s):
k023763
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3. Comparison with predicate:
Similarities
Item
Candidate Device
Lucica Glycated Albumin
Predicate Device
Randox Fructosamine
k023763
Intended Use
The Lucica Glycated
Albumin-L is intended to be
used for the quantitative
measurement of glycated
albumin in human serum.
The measurement of
glycated albumin is useful
for the intermediate term
(preceding 2-3 weeks)
monitoring of glycemic
control in patients with
diabetes.
Same
Methodology
Enzymatic assay
Same
Sample Type
Serum
Serum or plasma
Differences
Item
Candidate Device
Lucica Glycated Albumin
Predicate Device
Randox Fructosamine
k023763
Analyte
Glycated albumin
Fructosamine
Analytical Range
173 - 979 mmol/mol
Up to 1734 µmol/L
Form
Liquid
Lyophilized
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures, 3rd
Edition
CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures; A
Statistical Approach, 2nd Edition
CLSI EP07-A2: Interference Testing in Clinical Chemistry, 2nd Edition
CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient
Samples, 3rd Edition
CLSI EP15-A3: User Verification of Precision and Estimation of Bias, 3rd Edition
CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement
Procedures, 2nd Edition
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CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents, 1st Edition
L. Test Principle:
The Lucica Glycated Albumin-L provides quantitative measurement of glycated albumin
based on an enzymatic method and quantitative albumin measurement by a colorimetric
assay. The glycated albumin value (mmol/mol) is automatically calculated by the test
system using the glycated albumin concentration (µmol/L) and the albumin concentration
(µmol/L).
Measurement of glycated albumin:
The serum sample reacts with a ketoamine oxidase to eliminate endogenous glycated
amino acids. The generated hydrogen peroxide is converted to H
2
O by reaction with
peroxidase and hydrogen donor (N, N-Bis (4-sulfobutyl)-3-methylaniline disodium salt).
The treated solution reacts with an albumin-specific protease, which converts glycated
albumin to glycated amino acids. The glycated amino acids react with a ketoamine
oxidase to form glucosone, amino acids, and hydrogen peroxide. The generated hydrogen
peroxide reacts with peroxidase in the presence of N, N-Bis (4-sulfobutyl)-3-
methylaniline disodium salt and 4-aminoantipyrine (4-AA) forming a blue-purple
pigment. Measurement of the absorbance of this blue-purple pigment quantifies the
glycated amino acids produced by glycated albumin.
Measurement of albumin:
The serum sample reacts with the pretreatment solution to convert reduced albumin to
oxidized albumin. The treated solution reacts with bromocresol purple, forming a blue
conjugate of albumin and bromocresol purple. The absorbance of this blue conjugate is
measured to quantify albumin concentration.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
An internal precision study and a multisite precision study at three centers were
performed. Precision studies used three levels of glycated albumin (GA) controls, a
human serum albumin (HSA) pool with a low glycated albumin value, and five native
serum pools. For the internal precision studies, samples were tested with 2 runs per
day, 2 replicates per run over 20 days. Results from different lots were similar.
The precision summary table of glycated albumin values (mmol/mol) for the internal
precision study is shown below.
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Sample
Description
Mean
(mmol/mol)
N
Repeatability
Within-
Laboratory
%CV
SD
%CV
SD
Control L
280.1
80
0.7%
2.0
1.1%
3.0
Control H
649.8
80
0.6%
4.0
0.8%
5.2
High GA
Control
999.5
80
0.6%
5.8
0.8%
7.8
Serum Pool
185.2
80
1.7%
3.1
2.2%
4.0
Serum Pool
228.0
80
0.8%
1.7
1.1%
2.6
Serum Pool
359.9
80
0.7%
2.6
0.9%
3.2
Serum Pool
877.7
80
0.8%
7.0
0.9%
7.8
Serum Pool
229.6
80
2.6%
6.0
3.3%
7.6
HSA Pool
120.4
80
0.8%
1.0
2.1%
2.5
Multi-site Precision Studies:
Multisite precision studies were performed at three laboratories. All three laboratories
used the same samples, which included three native serum sample pools. Samples
were assayed in replicates of five once daily for five days.
The multi-site precision summary table of glycated albumin values (mmol/mol) is
shown below.
Sample
Name
N
Mean
(mmol/mol)
Repeatability
Within-
Laboratory
Reproducibility
%CV
SD
%CV
SD
%CV
SD
Overall
Serum pool 1
75
187.7
0.8
1.6
1.0
1.9
1.6
3.0
Serum pool 2
75
363.1
0.7
2.7
0.9
3.2
0.9
3.2
Serum pool 3
75
888.2
0.7
6.4
0.8
7.4
0.9
8.2
b. Linearity/assay reportable range:
Linearity studies were conducted to assess linearity of the glycated albumin value in
mmol/mol. High and low glycated albumin native serum pools were mixed in
different proportions to generate eleven target glycated albumin target values.
Samples were tested in triplicate. The results for glycated albumin value (mmol/mol)
linearity are shown in the table below:
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Level
Target
(mmol/mol)
Mean (mmol/mol)
Recovery
1
173
173.3
100.2%
2
290
291.0
100.3%
3
395
396.0
100.3%
4
491
491.3
100.1%
5
579
574.7
99.3%
6
659
664.7
100.9%
7
733
728.3
99.4%
8
802
798.3
99.5%
9
865
862.7
99.7%
10
924
913.7
98.9%
11
978
978.7
100.1%
The linear regression equation obtained was:
y = 0.993 x + 2.880, R
2
= 0.9998
The claimed linear range of GA value 173 - 979 mmol/mol.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:
The Lucica Glycated Albumin calibrators and controls are traceable to Glycated
Albumin Certified reference material JCCRM611, which is the reference
measurement procedure and reference material for glycated albumin determination of
the Japan Society of Clinical Chemistry.
Stability:
Protocols and acceptance criteria were reviewed for reagent shelf-life and found to be
acceptable. The shelf-life for the Lucica Glycated Albumin reagents is 12 months
when stored between 2 and 8 °C.
Sample stability:
Sample stability studies were performed and demonstrate that serum samples are
stable for eight days at 2 - 8 °C, 24 months at -80°C, and six freeze/thaw cycles.
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d. Detection limit:
Limit of Blank:
The Limit of Blank (LoB) determination was made using five blank samples that
were measured in replicates of four for five days. Two reagent lots were used. The
LoB was calculated as the mean of 95th and 96th ranked values. The claimed LoB for
GA concentration is 6.9 µmol/L and 3.8 µmol/L for albumin concentration
Limit of Detection:
Eight low-level samples were measured in duplicate for five days using two reagent
lots. The LoD was calculated using the parametric procedure specified by CLSI
EP17-A2. The claimed LoD for GA concentration is 7.9 µmol/L and 7.0 µmol/L for
albumin concentration.
Limit of Quantitation:
Eight low-level serum samples were analyzed in duplicate, twice daily over 14 testing
days with two reagent lots. A precision profile curve as used to specify the GA or
albumin concentration representing 10% CV as the limit of quantitation (LoQ). The
claimed LoQ for GA concentration is 9.7 µmol/L and the claimed LoQ for albumin
concentration is 21.8 µmol/L.
e. Analytical specificity:
Interference studies were performed using a normal serum pool and a diabetic serum
pool. Six different concentration levels were prepared for each potential interferent by
mixing high and low level interferent serum pools in varying proportions. Samples
were analyzed in triplicate for glycated albumin concentration, albumin
concentration, and glycated albumin value in a single run. The effect of albumin and
total protein was evaluated by preparing specimens with high or low levels of
albumin and total protein, and spiking glycated albumin at high and low levels. The
level at which there is not significant interference (bias < ±10%) for each analyte with
glycated albumin (mmol/mol) is listed in the table below.
Interferent
Concentration at Which No
Significant Interference Observed
Albumin
7.8 g/dL
Bilirubin unconjugated
20.0 mg/dL
Bilirubin conjugated
20.0 mg/dL
Hemoglobin
288 mg/dL
Glucose
1000 mg/dL
Ascorbic Acid
100 mg/dL
Triglycerides
1516 mg/dL
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Interferent
Concentration at Which No
Significant Interference Observed
Uric Acid
1.40 mmol/L
Glibenclamide
0.66 µmol/L
Metformin Hydrochloride
310 µmol/L
Acetaminophen
1324 µmol/L
Acetylsalicylic Acid
3.62 mmol/L
Ibuprofen
2425 µmol/L
Hydroxyzine Dihydrochloride
2.67 µmol/L
Pravastatin Sodium
324.52 µmol/L
Penicillin G
29450 U/mL
Total protein
12.3 g/dL
f. Assay cut-off:
Not applicable.
2. Comparison studies:
a. Method comparison with predicate device:
Not applicable.
b. Matrix comparison:
Not applicable.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Peer-reviewed literature was provided to support the use of glycated albumin as a
marker of glycemic control based on outcomes for microvascular complications,
macrovascular complications, and prognosis in hemodialysis patients. Associations
between glycated albumin and retinopathy and nephropathy have been identified in
the Atherosclerosis Risk in Communities (ARIC) and Diabetes Control and
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Complications Trial (DCCT) (1, 2). Elevated glycated albumin was associated with
coronary heart disease and ischemic stroke in the ARIC cohort (3). In order to bridge
the assay used in these clinical studies to the candidate device, a study was performed
using n = 1831 samples that were measured by the candidate device and the research
use only glycated albumin assay with a Roche Modular P Chemistry Analyzer. The
performance of the Lucica Glycated Albumin-L assay showed good concordance (r =
0.997) with the research use only glycated albumin assay used in the literature.
1) Selvin E et al., Lancet Diabetes Endocrinol. 2014; 2(4): 279-88
2) Nathan DM, McGee P, Steffes MW, et al. Diabetes. 2014; 63(1): 282-290
3) Selvin E, Rawlings AM, Lutsey PL, et al. Circulation. 2015; 269-277
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
Healthy subjects (n = 262) with no history of diabetes were screened for diabetes using
the oral glucose tolerance test and hemoglobin A1c. The reference range was based on
the 2.5 to 97.5 percentiles for the glycated albumin of non-diabetic subjects. The glycated
albumin reference range of non-diabetic subjects is 183 - 259 mmol/mol.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a
substantial equivalence decision.