SMILE
Johns Hopkins University
Baltimore, MD USA
Author:
Validation Committee
Review History
Document Number:
Equ35-A-06
Effective (or Post) Date:
19 Dec 2008
Date of last review:
11 August 201
Reviewed by:
Heidi Hanes
SMILE Comments: This document is provided as an example only. It must be revised to accurately reflect your lab’s
specific processes and/or specific protocol requirements. Users are directed to countercheck facts when considering
their use in other applications. If you have any questions contact your SMILE representative.
SMILE Linearity Requirements-Chemistry
SMILE AMR and Requirements-Chemistry
Subject
Guidelines for establishing AMR and CRR on a chemistry
analyzer.
Document Number
240
Effective Date
19 Dec 2008
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1 of 1
Supercedes
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116100990
Page 1 of 5
13 February 2016
19 Dec 2008
Erin Gover
SMILE
Johns Hopkins University
Baltimore, MD USA
SMILE Chemistry AMR and CRR Verification Guidelines
The ANALYTICAL MEASUREMENT RANGE (AMR) is the range of analyte values that a
method can directly measure on the specimen without any dilution, concentration, or other
pretreatment not part of the usual assay process. AMR validation is the process of
confirming that the assay system will correctly recover the concentration or activity of the
analyte over the AMR. The manufacturer defines the AMR. It is the laboratory’s
responsibility to verify it.
The CLINICAL REPORTABLE RANGE (CRR) is the range of analyte values that a method
can report as a quantitative result, allowing for specimen dilution, concentration or other
pretreatment used to extend the direct AMR. The laboratory should establish a CRR that
covers a range inclusive of Grade 4 Adverse Events on the DAIDS Toxicity Table without
exceeding the manufacturer’s recommendations for dilution.
I. Analytical Measurement Range (AMR)
A. Sample Criteria
1. Quality control, calibrators or commercial linearity standards should
be used.
2. It may be necessary to dilute the lowest sample to verify the low end
of Analytical Measurement Range (AMR).
3. The high end of the AMR will only be as high as the highest sample.
B. Testing
1. At a minimum, run each sample in duplicate and average the
results.
2. Data should be evaluated immediately to identify and correct any
problems.
C. Evaluation of data:
1. AMR
a. The reportable range must be within the manufacturer’s AMR.
b. Refer to Appendix 1 for Total Allowable Error (TEa) limits.
c. Upper Limit Verification - The manufacturer’s upper limit can
be accepted if the known sample is within the percent TEa of
your AMR upper limit.
i.
Your measured value must also be within TEa of the
known sample.
ii.
Upper Limit Example:
Bilirubin (mg/dL)
TEa %
20%
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Page 2 of 5
TEa - Minimum
Detectable Difference
0.4
13 February 2016
AMR
0 - 25
SMILE
Johns Hopkins University
Baltimore, MD USA
iii.
Measured values needed:
Bilirubin Standard (mg/dL)
Acceptable
Known
Range
Value
AMR ± TEa
25 ± 20% =
Upper
20-30
24.0
AMR
mg/dL
iv.
v.
Laboratory Measured Results
Allowable
Measured
AMR
Measured Error
Value
Verified?
(Known Std ± TEa)
24.0 ± 20% =
19.2 - 28.8 mg/dL
29.5
mg/dL
If TEa is 20%, an upper AMR of 25 can be verified with
a known sample of 20 - 30 if the measured sample is
within TEa of the known sample. In the example
above, the measured value must be between 19.2 28.8.
If a sample within TEa cannot be obtained, the highest
known sample measured and within TEa should be
used as the highest reportable undiluted value.
i. For Example:
Bilirubin Standard (mg/dL)
Acceptable
Known
Range
Value
AMR ± TEa
25 ± 20% =
Upper
20-30
10.0
AMR
mg/dL
Laboratory Measured Results
Allowable
Upper AMR
Measured
Measured Error
(25 mg/dL)
Value
(Known Std ± TEa)
Verified?
10.0 ± 20% =
8 - 12 mg/dL
10.5
mg/dL
ii. New upper AMR = 10.5 mg/dL
d. Lower Limit Verification - The manufacturer’s lower limit can
be accepted if the known sample is within the minimum
detectable difference or percent TEa of the lower limit
(whichever is greater).
i.
Your measured value must also be within TEa of the
known sample.
ii.
Lower Limit Example:
Bilirubin (mg/dL)
TEa %
20%
116100990
No
Page 3 of 5
TEa - Minimum
Detectable Difference
0.4
13 February 2016
AMR
0 - 25
No
SMILE
Johns Hopkins University
Baltimore, MD USA
iii.
Measured values needed:
Bilirubin Standard (mg/dL)
Acceptable
Known
Range
Value
AMR ± TEa
Lower
0 - 0.4
0.3
AMR
mg/dL
iv.
v.
vi.
Laboratory Measured Results
Allowable
Measured
AMR
Measured Error
Value
Verified?
(Known Std ± TEa)
0.3 ± 0.4 =
0.5 mg/dL
Yes
0.0 - 0.7 mg/dL
If TEa is 0.4, a lower AMR of 0.0 can be verified with a
known sample of 0.0 to 0.4 if the measured sample is
within the minimum detectable difference or TEa,
whichever is greater. In the example above the
measured value must be between 0.0-0.7).
For analytes that round to the nearest whole number, a
proximity limit of 1 is acceptable to verify the lower
range of 0.
Serial dilution should be used to obtain a sample within
the desired range. However, if a sample within TEa
cannot be obtained, the lowest known sample
measured and within the acceptable TEa will be used
as the lowest reportable range.
i. For Example:
Bilirubin Standard (mg/dL)
Acceptabl
e Range
Known
AMR ±
Value
TEa
Lower
AMR
0 ± 0.4 =
0-0.4
mg/dL
0.7
Laboratory Measured Results
Allowable Measured Error
(Known Std ± TEa or Min.
Dectable Diff.)
Measured
Value
AMR
(0 mg/dL)
Verified?
TEa: 0.5 ± 20% = 0.4 - 0.6
Or
Min. Detectable Diff:
0.5 ± 0.4 = 0.1 - 0.9 mg/dL
0.7 mg/dL
No
ii. New lower AMR = 0.7 mg/dL
2. CRR
a. The Clinical Reportable Range (CRR) must extend the AMR in
order to include grade 4 events of the Division of AIDS Toxicity
Table.
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Page 4 of 5
13 February 2016
SMILE
Johns Hopkins University
Baltimore, MD USA
b. The lab should establish what dilutions are necessary to cover
this range, bearing in mind that a minimum amount of dilution
is ideal since accuracy decreases with increasing dilution.
c. The laboratory should decide the maximum value of dilution
that will be allowed without exceeding the manufacturer’s
recommendations for dilution.
d. Any samples that do not give a numerical value beyond this
allowed dilution should be reported as greater than the upper
end of the CRR.
II. References
A. GCLP Workshop and Workbook18-20 May 2008, Verification of Performance
Specifications, pages 1-33.
B. Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity
of Quantitative Measurement Approved Guideline-Second Edition, CLSI
document EP6-A (ISBN 1-56238-498-8) Clinical and Laboratory Standards
Institutes, 940 West Valley Road, Suite 100, Wayne, Pennsylvania 190981898 USA, 2005.
C. EP Evaluator Release 8, David G. Rhoads Associates Inc.,
www.dgrhoads.com.
D. James O. Westgard, Online Validation Training, Westgard QC, Inc.
www.westgard.com, Sections 9-Determining Reportable Range.
116100990
Page 5 of 5
13 February 2016