CLB-09266; No.

of pages: 2; 4C:
Clinical Biochemistry xxx (2016) xxx–xxx

Contents lists available at ScienceDirect

Clinical Biochemistry

journal homepage: www.elsevier.com/locate/clinbiochem

Commentary

Lot change for reagents and calibrators

Andrew C. Don-Wauchope ⁎
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, L8S 4K1, Ontario, Canada
Hamilton Regional Laboratory Medicine Program, 50 Charlton Avenue East, Hamilton, L8N 4A6, Ontario, Canada

A R T IC L E IN F O practice and avoid the commutability limitations of quality control ma-

Article history:
Received 8 March 2016
Received in revised form 29 March 2016
Accepted 5 April 2016
Available online xxxx
Keywords:
Lot change
Laboratory quality
Quality control
1. Introduction
Evaluating lot change is an important part of clinical laboratory prac-
tice. The major reason is to maintain a reasonable degree of consistency
in results for our users [1]. The CLSI has provided guidance for
performing lot evaluations and this covers all the important compo-
nents of doing lot evaluations [2]. This article will describe a practical
approach to doing lot evaluations that has been developed with team
of laboratory professionals and technologists in the Hamilton Regional
Laboratory Medicine program. We find it a useful and pragmatic ap-
proach to our lot evaluations for both reagents and calibrators across
the range of assays that we offer in our six laboratories.
The CLSI document described the reasons for doing lot evaluations in
detail [2]. As a clinician who works in laboratory medicine, the most im-
portant of these are maintaining accuracy for results and complying
with local regulatory best practice. As a profession we need to do our
best to facilitate optimal patient care and one way we can do this is by
maintaining our assays to be as consistent as possible. The industry
who provide the reagents need to participate in this by providing lots
that are manufactured to meet targets expected by the users of the clin-
ical laboratory [1].
2. Method description for lot evaluation
2.1. Selecting samples for the lot evaluation
There are a number of descriptions of different sample types. We
prefer to use individual patient samples as these best reflect clinical
terials [3]. Quality control (QC) material is another sample type that
could be considered once the described limitations have been consid-
ered and tighter targets applied [4]. The patient samples are chosen ac-
cording to expected patient values. Typically we would select three low
range patient samples, three mid-range patient samples and three high
range patient samples. One additional sample that could be an extreme
value that tests either limit of detection or upper linearity is also select-
ed. These samples would provide a good range of results that should
evaluate the assay over the full analytical spectrum. In addition to the
patient samples we run each QC level in triplicate to estimate QC perfor-
mance when we change lot.
2.2. Running the samples
The QC for the selected assay is reviewed on an instrument running
the assay. If the QC is meeting performance criteria the lot evaluation
can be run. The selected patient samples and QC material are run on
the instrument performing the assay. The instrument is then taken
off-line and the new reagent lot loaded and calibrated as per specifica-
tion and, once ready, the patient samples and QC material is analyzed.
Some assays are run in duplicate according to assay methodology but
most are run in singleton.
2.3. Selecting the acceptance target
This is a crucial step in the process of deciding whether or not a lot is
acceptable for use. The CLSI makes suggestions about selecting accept-
ability targets [2]. The recommendations are based on the Stockholm
criteria [5] and could now be updated to the more recently agreed
criteria [6]. In Hamilton we debated the options available and decided
to base the criteria for accepting lots on the total error allowable (TEa)
for each analyte. Our ideal target is one third of TEa but if this is not
met then we can consider other options. These include total TEa for
bias and the slope of the regression line between 0.9 and 1.1. Some as-
says still struggle to meet these requirements and then professional
opinion is required to make a decision based on the nature of the ana-
lyte, the method being used and the clinical use of the assay.
2.4. Analyzing the data

⁎ Core Laboratory, Juravinski Hospital and Cancer Centre, 711 Concession Street,
We use Microsoft Excel spreadsheets to evaluate data as this soft-
Hamilton, L8V 1C3, Ontario, Canada. ware is readily available in our laboratory to all users (example available
E-mail address: donwauc@mcmaster.ca. as a supplement file). The individual and mean differences between

http://dx.doi.org/10.1016/j.clinbiochem.2016.04.003
0009-9120/© 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Please cite this article as: A.C. Don-Wauchope, Lot change for reagents and calibrators, Clin Biochem (2016), http://dx.doi.org/10.1016/
j.clinbiochem.2016.04.003
2 A.C. Don-Wauchope / Clinical Biochemistry xxx (2016) xxx–xxx
specimens for the old and new lots are calculated, individual and mean
percentage bias from the old to the new lot are calculated, a linear re-
gression line between the old (x) and new (y) results is derived. Each
individual patient sample is reviewed for bias and it is expected that
all 10 meet the target criteria. The linear regression equation is
reviewed to make sure it falls within 10% of equivalence. The QC results
are reviewed to see if the results fall within 2 standard deviations of the
current mean.
3. Discussion
Preparing this protocol did present some challenges as we had a
range of different practices in each of the laboratories. There was no
real authoritative guidance at the time we consolidated the laboratory
approach. Since then the CLSI guidance has been released and this
does provide guidance and confirms some of the choices we made.
The difference of opinion between professional staff members added
to the discussion. The two major areas that we had to debate were the
type and number of samples and the criteria for acceptance.
For some the use of QC material was adequate and the introduction
of patient material is an unnecessary and labor intensive step. For others
the number of samples suggested was too few and for some it was too
many. Typically we find our approach does give us good and useful in-
formation about assay performance. We can detect both consistent
and proportional bias. We are able to provide our suppliers with details
about why we are not happy with a lot change and demonstrate to our
proficiency testing scheme that our lot changes meet our criteria. I have
carefully reviewed the CLSI method for calculating the number of pa-
tient samples and followed the guideline to work out the details for a
few assays [2]. Each required a significant amount of time and the sam-
ples required would be more challenging to identify for the laboratory
technologist.
The criteria of acceptance likewise generated some difference of
opinion. Previous practice had included review of bias, slope and QC
material performance. The debate around contribution of analytical im-
precision and biological variation to reagent and calibrator continues.
Some would like to base the acceptance of the lot on analytical perfor-
mance of the assay while others prefer using biological variation as
the base for acceptance. As this is a matter of professional opinion we
compromised on the one third of TEa (based on biological variation)
which is a pragmatic approach to analytical performance to achieve a bi-
ological variation target [6]. It must be noted that many of the reagent
manufacturers use wider limits of acceptance for lot changes. If the
assay does not meet the one third of TEa criteria each professional mem-
ber of staff can use their knowledge of the assay and apply alternative
Please cite this article as: A.C. Don-Wauchope, Lot change for reagents and calibrators, Clin Biochem (2016), http://dx.doi.org/10.1016/
j.clinbiochem.2016.04.003
targets. The alternative target is then recorded on the approval form. If
assays still do not meet criteria then further troubleshooting is initiated.
4. Conclusion
There is variability in professional practice for evaluating lot chang-
es. It is however an important competent of laboratory practice and
each of us applying professional judgment should be able to back up
our decisions with data interpretation. The CLSI document is a good
source of information to help us in this regard. Our approach, while it
does not entirely follow the CLSI guide, is a practical and useful
alternative.
Acknowledgments
The Clinical Laboratory staff of the Hamilton Regional Laboratory
Medicine program including Drs. Stephen Hill, Pete Kavsak and Cynthia
Balion; and technologists from our laboratories including Lynn Ford,
Lorna Clark, and John Beattie who all contributed to the development
of a combined protocol for our core laboratories and Pat Hudecki who
produced early versions of the spreadsheet that we adapted for use. In-
stitute for Quality Management in Healthcare who encouraged me to
present on this subject for their annual symposium on two occasions.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.clinbiochem.2016.04.003.
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