QC Education

Laboratory Quality Control Materials

QC Workbook Series

Visit qcnet.com/resources/training-education for more information.

How to Use This Workbook
This booklet is part of an educational series offered by Bio-Rad, designed to improve your knowledge of Quality Control
(QC) materials. The workbook contains educational content as well as practice evaluation exercises.

A Certificate of Completion will be made available to you after successful completion of a short exam. Please see page 17
for details and link to the exam.

Bio-Rad proudly supports laboratory professionals and the commitment to achieving a higher standard of quality for
improved patient test results. We are dedicated to the ongoing development of educational materials to support each
laboratory's quality journey.

© 2023 Bio-Rad Laboratories, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of Bio-Rad Laboratories, Inc.
Table of Contents
Introduction

What Will You Learn?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
The Quality System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Types of QC Materials

Independent and Dependent Quality Controls. . . . . . . . . . . . . . . . . . . . . . . . 4

Liquid, Lyophilized. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Composition/Concentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Quantitative, Semi-Quantitative, and Qualitative Tests. . . . . . . . . . . . . . . . . . 7

Selection of QC Materials

Open-Vial Stability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Interlaboratory Comparison Programs and Data Management. . . . . . . . . . . 9
Shelf Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Pricing/Volume . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Matrix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Medically Relevant Decision Levels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Other Considerations When Choosing a Quality Control Product. . . . . . . . 13

Handling of QC Materials

Processing Steps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Product Inserts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Reconstitution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Levels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Storage and Handling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Frequency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Guidelines/Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Final Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Glossary: Medical Laboratory Vocabulary. . . . . . . . . . . . . . . . . . 18

1
Introduction

Introduction
Achieving quality in the medical laboratory requires the use of many tools. These include procedure manuals, maintenance
schedules, calibrations, a quality assurance program, training, continuing education, competency assessments, and
quality control materials.

Important parts of quality control in the medical laboratory are identification of proper quality control materials, and
the statistical process, used to monitor and evaluate the analytical process. The goal of quality control materials in the
laboratory is to have products that are used in the same manner as patient samples so that they can help assure that the
test systems are functioning appropriately and producing high quality patient results.

In this workbook, the background and use of different types of quality control materials are explained.

What Will You Learn? Background

■  o differentiate between open-vial stability and
T Quality control data are produced by testing quality control
shelf-life stability materials in the same manner as patient samples. QC
■ To differentiate between liquid and lyophilized materials are available in various concentrations.
quality control materials
The most common concentrations used in medical
■  o understand the criteria to consider when
T laboratory testing are a normal concentration for the analyte
selecting quality control material of interest and abnormal high and/or low concentrations.
■  o differentiate between independent and
T
dependent quality control materials Typically, laboratories test both normal and abnormal
concentrations of control materials each day. For qualitative
■  o choose and/or recommend control materials
T
molecular tests, negative and positive controls are tested
based on shelf life, open-vial stability, clinically
at a frequency consistent with compliance requirements.
relevant decision levels and an interlaboratory
For quantitative molecular tests, negative, low positive, and
comparison program
high positive controls are tested with each patient run.

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 Introduction

The Quality System

A robust quality system permeates all laboratory activities – from the point of the test order and patient reception to the
analytical bench, ending with the test result report to the caregiver. Laboratories should implement a quality control plan
which defines and monitors all aspects of testing based on the potential errors identified during the risk assessment,
including the following parameters:
■ Frequency of quality control
■ Criteria for acceptance performance (e.g., instrument calibration, reagents, and quality control)
■ Specimen quality
■ Instrument maintenance and function checks
■ Training and competency of testing personnel

There are three phases of the testing process: pre-analytical, analytical and post-analytical.
■  he pre-analytical phase covers test ordering, specimen collection, accessioning of the collected patient specimen,
T
transportation, processing of the specimen
■ The analytical phase covers performing the test on the processed sample
■ The post analytical phase covers the review and interpretation of the results, reporting the results (including report
content), and the retention and disposal of patient specimens
The laboratory can implement a variety of systems and processes to assure that quality is maintained throughout all three
phases of the testing process. One of the most important parts of the overall laboratory quality system is the Quality
Control Procedure.

The Quality Control Procedure consists of the following:

■ Quality control materials
■ Statistical process control
■ Retrospective review of data

QC results are used to evaluate whether a test system (including instruments and assay reagents) is operating within
pre-defined specifications, inferring that patient test results are reliable.

In this workbook, focus is given to the background, types, selection, and use of quality control materials.

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 3

Types of QC Materials

Types of QC Materials
Quality control material is designed to be similar to patient sample ideally made from human serum, whole blood, plasma,
urine, spinal fluid, or other body fluids. A large amount of laboratory data that is used in calculation of laboratory statistics
comes from the routine testing of quality control materials. There are also other types of quality controls, which are
surrogate controls, such as electronic signals, glass filters, or reference cassettes that are mostly used in point of care
testing devices. These typically evaluate the photometric, electronic, and computational component of the test system.
Electronic quality controls do not evaluate chemical reactions, sample, and reagent performance.

Independent and Dependent Quality Controls

Dependent controls are control materials developed and formulated to be run on specific test systems. These may be
made by the test system manufacturer (sometimes called “first party controls”) or contracted out to another company
(sometimes called “second party controls”). The use of dependent controls is defined in the package insert for the test
kit and its description of use of these "in-kit" controls must be followed by the laboratory.

Independent controls are control materials developed without direction or aid from the manufacturer of the test system.
The QC formulation of these QC materials is developed entirely by an independent company and typically can work on
multiple test systems and across any reagent lots. These controls are frequently called “third party controls.”

Independent controls may pick up errors that go undetected by dependent control materials. Dependent controls are often
designed and manufactured based on the specific test method, this means these dependent controls might be based on
the calibration materials or reagents used in the test system. This dependency might prevent the dependent control from
detecting specific errors like material degradation or reagent linked changes. As a result, independent control materials
may be suited to mimic how a patient sample interacts with the test system and provide an unbiased assessment.

Independent control manufacturers typically use human sources for the analytes in control materials. They are often
made from human materials such as serum, plasma, whole blood and urine.

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 Types of QC Materials

Guidelines

The value of using third party independent quality controls is emphasized by different guidelines. Below are three
examples of guidance related to the use of independent quality controls:

ISO 15189: “Use of third-party internal quality control material should be considered, either as an alternative to, or in
addition to, control material supplied by the reagent or instrument manufacturer.” 1

CLSI C24: “QC materials should be different from the calibrator materials to ensure that the QC results provide
an independent assessment of the measurement procedure's performance in its entirety, including the procedure
for calibration.” 2

NATA “Controls independent of those produced by the manufacturer of the test or analyzer should be used.
The laboratory must have a system of long-term monitoring of internal quality control results to assess method
performance.” 3

Note: In addition to commercially purchased QC, a quality control material could also be made by the laboratory
itself, referred to as “laboratory developed/home brewed QC”. This type of QC material could be less stable over
a longer timeframe. Potential challenges in making in-house QC are obtaining adequate patient samples to make
the QC, the time involved to produce and standardize the material, and difficulty in achieving high lot-to-lot consistency.

Self-Test
Determine if the following quality control materials are dependent or independent.

■  est system manufacturer “A” made their own

T
quality control materials to run on their test system Click for answer Dependent

■  ompany “B” is developing a quality control

C
product with its own formulation that can work Click for answer Independent
on multiple manufacturers' test system platforms

■  est system manufacturer “C” is contracting out the

T
manufacturing of quality control materials according Click for answer Dependent
to a provided formulation that will be run on its own
test system platforms

1
ISO 15189. Medical laboratories - Requirements for quality and competence. Geneva, Switzerland: International Organization for Standardization; 2022.ISO 15189:2022.
Subclause 7.3.7.2.
2
CLSI (Clinical Laboratory Standards Institute) C24-A4, Statistical Quality Control for Quantitative Measurement Procedures: Principles and Definitions;
Approved Guideline - Fourth Edition 5.2.5 Relation to Calibrators.
3
AS 4633 (ISO 15189) Field Application Document - Supplementary Requirements for accreditation in the field of Medical Testing, NATA, July 2009.

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 5

Types of QC Materials

Liquid, Lyophilized

Quality control materials could be in a liquid or lyophilized (freeze-dried) state. Lyophilized controls have good stability and
shelf life, but need to be reconstituted prior to use. Since this is a manual process, it is time-consuming and could be
error-prone if performed inconsistently. For liquid controls, no reconstitution is necessary, but are often frozen and need
consistent temperature control. The choice between liquid or lyophilized quality controls lies within the laboratory. Some
laboratories prefer liquid controls because they are convenient and merely require a thaw and no reconstitution.

Composition, Concentration

A quality control product may contain one or more analytes. For example, a general chemistry control can contain any
number of chemistry analytes including, for example, potassium, glucose, albumin, and calcium. Most laboratories prefer
to have as many analytes as possible in each control material for convenience to reduce the number of controls that need
to be tested. However, control materials should contain the analytes of greatest interest to the laboratory. When selecting
a QC material, different aspects can be taken into consideration. It is important to find the right choice for specific needs
and for balancing the different variables. As an example, it can be convenient to have 120 analytes in one QC product vial,
but when only using 20 analytes out of 120 in a laboratory, the 120-analyte approach may not be cost efficient. As another
example, a health system with multiple chemistry platforms across their laboratories may find it advantageous to buy a
chemistry QC material with many analytes that meets the needs of their health system. For certain labs, it may be more
appropriate to have a less consolidated product. The individual situation of the laboratory will determine which will be the
right choice for the specific needs.

When choosing control materials for the laboratory, the menu of analytes and the estimated concentration for each analyte
are essential and important considerations. Control materials can come in three concentrations: normal, abnormally high,
and abnormally low (or negative, low positive, and high positive controls for quantitative molecular tests). Some control
materials have normal and abnormal concentration (or negative and positive). It is important that each analyte be at a
clinically important or relevant concentration, (i.e., at the medical decision point) whenever possible.

It may be difficult to find all analytes at relevant concentrations. The purchase decision should be made on a product
that most closely meets the laboratory’s needs. Some quality control materials are delivered in ready-to-use tubes with
barcodes. These can be directly loaded on the platform and will automatically be recognized (for type and lot number) by
the instrument. Manual handling steps (program control information, labelling, pipetting and aliquoting) are significantly
reduced, which lowers the risk of errors.

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 Types of QC Materials

Quantitative, Semi-Quantitative, and Qualitative Tests

The type of quality control that will be used is also dependent on the type of test that is run in the laboratory. There are
different types of tests: quantitative, semi-quantitative and qualitative tests.

Most controls contain analytes that can be measured as a quantity, and reported numerically, such as 100 mg/dL (100
milligrams per deciliter) for a chemistry analyte. Control materials formulated in this way can be used for quantitative tests.

Semi-quantitative methods are tests that yield an approximation of the quantity and report results as a range of
measurement, such as 10-50 mIU/L (milli-International Units per liter). Some manufacturers produce control materials
specifically for these semi-quantitative methods.

Qualitative tests give a result that is more descriptive, with an indication of whether an analyte is present or not; or if a test
is positive or negative. For some qualitative assays, the data can be represented quantitatively, such as Ct values, signal/
cutoff, etc. When this is the case, QC data can be managed with the same approach as quantitative results in the data
management software.

Self-Test
Determine if the following tests are quantitative, semi-quantitative or qualitative.

■  regnancy test of human chorionic

P
gonadotrophin (HCG) in the patient's urine Click for answer Qualitative
(positive / negative)

■ +1 +2 +3 +4 indication (interval scale) of

Click for answer Semi-quantitative
hemolysis interference

■ Glucose measurement in blood (mg/dl) Click for answer Quantitative

■ Potassium in serum (mmol/l) Click for answer Quantitative

■  etected or not detected COVID-19

D
(SARS-CoV-2) antibody test saliva Click for answer Qualitative
(detected / not detected)

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Selection of QC Materials

Selection of QC Materials
Many different quality control materials are available for laboratories. Choosing the right quality control product requires
careful consideration. It may be tempting to purchase the least expensive product. Unfortunately, the cheaper alternative
may exhibit significant limitations, such as a short shelf life or open-vial stability. A reduced open-vial stability can result in
unnecessary waste if the laboratory cannot use all the material before it expires. Other materials may not be sufficiently
like patient specimens (e.g., serum or urine). This can cause problems with some test systems because these materials do
not interact with the test system in the same manner as a patient specimen.

This chapter features descriptions of factors that can be taken into consideration when selecting a quality control material,
including open-vial stability, shelf life, pricing/volume, matrix, medically relevant decision levels, interlaboratory comparison
programs and data management.

Open-Vial Stability

When purchasing a quality control product, it is important to know the approximate volume of the control to be used each
day to determine the open-vial stability requirements. Open-vial stability refers to the amount of time, after being opened,
that the QC remains stable, and analytes do not degrade. For example, consider a general chemistry control material that
can be purchased in 10 mL vials. Laboratories that use 10 mL or more per day would be less concerned with open-vial
stability for this product. But for those laboratories that use a lower volume of control (1 mL/day for example), open-vial
stability becomes an important issue.

Quality control open-vial stability should match or exceed the laboratory’s normal usage rate to avoid waste. For example,
a laboratory that purchases a quality control product that offers only a five-day open-vial stability, when the lab’s usage
rate would require 10 days to fully use the product, will waste 50% of the product. Consequently, if a laboratory paid
$0.18/mL for the product, the actual cost based on usage becomes twice that or $0.36/mL. A more cost-efficient option
would be to purchase a quality control product that offers a 10-day open-vial stability for all analytes, even though it may
be a higher price. In this example, quality control material with the same analytes and a 10-day open vial stability, at the
higher price of $0.28/mL is a better value.

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 Selection of QC Materials

Interlaboratory Comparison Programs and Data Management

Participation in an interlaboratory quality control comparison program is highly recommended. In such programs,
laboratories anonymously submit QC results for different assay/platform combinations. This allows participating
laboratories to compare their QC results with peer labs using the same test systems. One of the easiest methods to
assess trueness and imprecision is to compare the within-laboratory method means and standard deviations with other
laboratories (peer group) using the same instrument and method. Confirmation that the QC manufacturer provides
an interlaboratory comparison program and the number of laboratories that use the program are important factors to
consider when selecting and purchasing QC materials. Without such programs, the laboratory becomes a statistical
island and has no means to regularly verify the reliability of its work in reference to other laboratories.

Easy access to QC data management software can help achieve greater efficiency, allowing laboratories to identify trends
and make corrections before results are compromised. More specifically, this will help with data review and run validation
and provide access to advanced charts and reports for data analysis. Access to a QC software package is an additional
factor to consider when making the decision about which type of QC material to choose.

Selection criteria based on laboratory type

Reference Lab Small Lab

As a reference lab with 4 high throughput

analyzers, we prefer quality control materials that We are a small lab, with one analyzer.
are consolidated, with a significant amount of analytes. The open-vial stability is an important factor when
Open-vial stability is not so important to us, as we have choosing a quality control material. As we are using
high volume use. The shelf life is important to us – a limited amount of QC each day, we try to optimize
with a long shelf life we limit the usage of the complete vial over multiple days.
crossover costs. For our menu of tests, we try to minimize
the amount of separate QC material vials
by choosing consolidated products.

An easy-to-use data management

QC software, that gives specific access
to all team members (each with their own log-in),
The data management software helps
is important to us. As an accredited lab it is important
us to identify trends and make corrections
for us to follow and track all steps of our QC process.
if appropriate. It is important to us to compare
We also create greater efficiency. Interlaboratory
to the interlaboratory group to evaluate
comparison program also helps us to compare
our performance.
to our peers around the globe. We prefer QC materials
where no reconstitution is necessary and ideally
in barcoded tubes, as the instrument has
QC onboard storage.

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Selection of QC Materials

Shelf Life

Another important factor to take into consideration when buying quality control materials is shelf life. Shelf life in this
context refers to the expiration date of the unopened product. A long shelf life provides the ability to measure performance
over a long time, including reagent and calibrator lot changes. A longer shelf-life results in fewer QC lot change studies
that need to be performed. Fewer crossover studies also, ultimately result in a lower cost.

Pricing/Volume

For quality control products, the pricing can be based on various factors. Specific pricing models can be dependent on
the volume within the individual vials, or the specific number of vials included in a box. Higher vial fill volumes can be less
expensive but can run the risk of less optimal usage and waste. It is recommended to have an idea of the cost of the
quality control product per mL and use this information when comparing QC materials.

Matrix

The primary purpose of a control material is to evaluate a testing procedure’s ability to perform as expected and to confirm
that the patient test results are suitable for use in providing medical care. When choosing a quality control material, it is
important to choose a product that matches the matrix of the patient sample as closely as possible. The matrix is the
substance that contains the measuring analytes. If a chemistry analyzer tests glucose on both serum and urine samples,
QC material for each of these matrices should be used.

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 Selection of QC Materials

Self-Test
Open-vial stability and price/volume

Evaluate the different quality control products that are available,

and choose the optimal product for the individual laboratories.

Quality Control Product A Quality Control Product B Quality Control Product C

A
1 2 3 4 5 6 7 8
B C

1 2size:
Vial 3 4105mL 6 Vial size: 20 mL 1 2 size:
Vial 3 4 10
5 mL
6 7 8
Open-vial stability: 5 days Open-vial stability: 10 days Open-vial stability: 10 days
Price: Price: Price:

1 2 3 4 5 1 2 3 4 5 6 7 8 1 2 3 4 5 6

1 2 3 4 5 6 1 2 3 4 5

1 2 3 4 5
Which quality control product to choose?

Laboratory X Laboratory Y Laboratory Z

Usage: 1 mL/day Usage: 2 mL/day Usage: 3 mL/day

C B BB

Product C Product B Product B

Click for answer Click for answer Click for answer

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 11

Selection of QC Materials

Medically Relevant Decision Levels

It is important that the analyte concentration of quality control materials be at clinically relevant levels.

As an example, assume a laboratory’s objective is to purchase a trilevel (three level) quality control that allows the lab to
“control” (evaluate) the method curve for low thyroid stimulating hormone (TSH) (<3.0 µIU/mL), normal TSH (between 3.0 µIU/
mL and 10 µIU/mL) and abnormal high TSH (>10 µIU/mL). The lab’s instrument has a reportable range up to 50 µIU/mL.

A quality control vendor offers an immunoassay control with three levels:

■ Low Level (1.03 - 1.23 µIU/mL)
■ Normal Level (7.5 - 9.6 µIU/mL)
■ High Abnormal Level (27.9 - 34.5 µIU/mL)
This product meets the laboratory’s diagnostic criteria. It contains three distinct levels at the decision limits used by the
laboratory.

A second vendor also offers a trilevel product, but for a reduced price:
■ Low Level (3.0 - 5.0 µIU/mL)
■ Normal Level (8.0 - 10.0 µIU/mL)
■ High Abnormal Level (45 - 55 µIU/mL)
In this case, the less expensive product does not cover low TSH because the level is higher than the laboratory decision
limit. Furthermore, it does not provide adequate control on the high end of the curve because the level for the high control
may exceed the reportable range.. The price is lower, but the product provides less value.

Note: It is often difficult to find a perfect quality control product for every instrument, kit or method available. When
deciding on a quality control vendor, assess the entire test menu of the instrument or department. As an example,
assume the immunoassay instrument used in a laboratory has a test menu that includes about 50 different hormones
and therapeutic drugs. One quality control product which may be more expensive provides trilevel diagnostic utility for
45 analytes. A less expensive product may provide true trilevel utility for only 30 of the 50 analytes of the test menu.
It may be not cost-effective to buy the less expensive quality control that has fewer analytes, as other materials will
need to be purchased or made in-house to cover the missing analytes.

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 Selection of QC Materials

Other Considerations When Choosing a Quality Control Product

While the pricing and appropriateness of analyte concentrations are important, the quality control product purchase
decision should also take into consideration the value of other value-added services such as QC technical and
educational support provided by the manufacturer. Another important evaluation to consider is checking whether the
manufacturer has ISO (or other) certifications to indicate consistency in the observance of quality standards.

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 13

Handling of QC Materials

Handling of QC Materials
In this chapter, key points and suggestions on the usage and handling of control materials are described. Country
regulations and/or local guidance documents, product inserts and instructions for use can provide more specific
background and guidance.

Processing Steps

Control materials are tested along with patient samples and should undergo all pre-treatments (if any) just like a patient
sample. For example, if a patient sample goes through an extraction process, the control material should also go
through the same process as well, if possible. (Note: It may not be possible in every case to find a control material that
can undergo a specific pre-treatment process, but it is important for the laboratory to make that determination and use
materials that can mimic the patient sample processing as much as possible).

Product Inserts

Product inserts for control materials provide a variety of important information. Printed paper inserts may be shipped with
the product, but most manufacturers today have moved product inserts to an online, digital format. Product inserts are
used to publish claims associated with each lot number of the control material. Claims typically include:

■ The stability for specific analytes after reconstitution or thaw

■ The expiration date (shelf life)
■ The open-vial stability of the product
■ Instructions for reconstitution or thawing
■ For quantitative products, an estimate of the mean for each analyte along with a range of acceptable means if it is an
assayed control

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 Handling of QC Materials

The published means and ranges are derived by replicate analyses and are specific for each control lot. The published
insert ranges are +/-2s or +/-3s range, unless specified by the manufacturer. Typically, they are derived from a variety of
sources (such as clinical laboratories or instrument manufacturers) to determine the values (along with the manufacturer’s
value assignment, if any) and therefore represent interlaboratory, not intralaboratory, performance.

It is recommended that each laboratory establish its own acceptable ranges and use those provided only as guides.
Laboratory-established ranges may vary from those listed in the package insert during the life of a QC product. Variations
over time and between laboratories may be caused by differences in laboratory technique, instrumentation, reagent lots
and calibrator lots or by the manufacturer’s test modifications.

Reconstitution

Always follow the manufacturer instructions for reconstitution of the control material. If reconstitution requires the use of a
calibrated volumetric pipette to deliver a specific amount of diluent, using a non-calibrated pipette is unacceptable. Use
care and caution when mixing a control to dissolve the lyophilized pellet into a solution. Specific reconstitution procedures
are contained in the Instructions for Use (IFU) of each specific quality control product.

Levels

The medical decision point should determine whether to test the abnormal high or low control. If the decision point is
at a low level, the abnormal low control should be tested. If the decision point is at an elevated level, the abnormal high
control should be tested. Normal control is always tested because most patient results fall within the normal range.
For quantitative molecular tests, negative, low positive, and high positive controls are tested with each patient run.

Many guidelines recommend running two levels of control for each day of patient testing. It's common to run a normal
and abnormal level (or positive/negative for qualitative tests). Some laboratories may for some tests routinely test an
abnormal low control and an abnormal high control, assuming that if the low and high controls are in control then the
normal range will be in control as well. This assumption may work for some linear methods, but it is not recommended
for all analytes. Two levels may not be sufficient for non-linear methods. Non-linear methods often require three controls
to cover the full measurement range. Most immunoassay and toxicology tests have these curves, and they might need a
three-level control.

Control material corresponding to abnormal values should be tested based on the patient test results produced. If a lab
routinely tests an abnormal high control but does not test a low control and the batch of patient samples being tested has
one or more low results, then a low abnormal control should be tested as well.

It is recommended that laboratories use a minimum of two levels of QC.

4.4 +3s

4.3 +2s
Range (mmol/L)

4.2 +1s

4.1 Mean

4.0 -1s

3.9 -2s

1 2
3.8 -3s
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Run Number

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Handling of QC Materials

Storage and Handling

The quality control product IFU will also contain information regarding appropriate storage and handling procedures.
Before a laboratory decides to aliquot and freeze quality control material, the product insert should be reviewed to ensure
the manufacturer states that this is acceptable. Some refrigerated and even frozen materials may not remain stable when
frozen or thawed and re-frozen. To eliminate temperature fluctuation during long storage, avoid using a frost-free freezer.

If the control product is to be kept refrigerated after thawing or reconstitution, do not allow the material to remain at room
temperature by sitting too long on the workbench and never use a control product past its expiration date.

Frequency

While the frequency of testing quality controls is an important decision to make, it rarely is part of the criteria for selection
of QC materials, except as it relates to volume needed. Regional guidelines and/or government regulations may provide
guidance on QC use and frequency. As with any regulations or guidelines, the requirements are regularly reviewed and
often updated. Laboratories should periodically review the applicable documents to ensure they remain in compliance
and are following current guidance.

Training

The use and handling of QC materials is an important activity that has a direct impact on the analytical performance of
the laboratory. Therefore, all the steps involved – from preparation, use, analysis, review, follow up and storage of quality
control materials – should be followed very meticulously. All the individual steps should be noted in operating procedures.

Continuing education is an important part of maintaining laboratory quality. A good QC provider can be a source of
education and training on QC theory and good lab practices.

16 Laboratory Quality Control Materials © 2023 Bio-Rad Laboratories, Inc.

 Guidelines/Regulations

Guidelines/Standards
There are country/regional specific guidelines as well as international standards and guidelines that are not discussed in this
workbook. These guidelines are typically published by standards development organizations, local bodies, and professional
societies and organizations. Depending on a lab’s local situation, it is important to take these additional guidelines into
consideration.

Final Examination
When you are ready, click on the link below to take the final exam. A certificate of completion will be awarded to
anyone who scores 70% or higher. To receive P.A.C.E. credits, please fill out the survey.

Link to Final Examination

Bio-Rad Laboratories is approved as a provider of continuing education in the clinical laboratory sciences by the P.A.C.E. Program through
the American Society of Clinical Laboratory Science. This basic to intermediate self instructional course is approved for 2 contact hours.
This course is also approved for California clinical licensees under the P.A.C.E. California Accrediting Agency License No. 0001.

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 17

Glossary

Medical Laboratory Vocabulary

Because official scientific definitions are often sourced to international standards, they can often be complicated and
potentially confusing for an introductory workbook. The following collection of glossary terms are defined here in
layperson’s terms.

A H
Aliquot Hemolysis
A specific amount of material that has been removed Interference factor that occurs when the red blood cells
(usually by a pipette) from a larger quantity of that material. rupture and release their contents into surrounding fluid.
As a result, hemolysis causes a reddish hue in the plasma,
Analyte
serum and may cause false results in some tests.
Commonly used term to identify the component of a
patient specimen that is being detected in a medical I
laboratory test. Interlaboratory
Between multiple laboratories.
C
Calibration
Interlaboratory Comparison Programs
Process where the response that is obtained is compared
Program methodology is used to assess reliability and
with or adjusted to the known response of a specimen.
imprecision through comparison with other laboratories
Concentration (peer group) using the same instrument and method.

The amount or quantity of a substance contained

ISO
within a matrix.
International Organization for Standardization.
CLSI
ISO 15189
Clinical Laboratory Standards Institute.
International standard of practice for medical laboratories:
Control Materials requirements for quality and competence.

See Quality Control Materials.

L
Levels of Control
Crossover Studies
The process utilized when a new lot of quality control Another way to refer to control materials of different
material is put into use. The material is tested alongside concentrations.
the quality control materials currently in use. One example
would be when the values for a new lot number used in Lyophilize(d)
statistical process control are verified by being compared A process used to freeze-dry quality control materials.
with the current lot. Lyophilized materials require reconstitution before they
can be used.
Ct Value
Cycle threshold value is the number of cycles required for
the fluorescent signal to exceed background levels in a
real time polymerase chain reaction (PCR).

18 Laboratory Quality Control Materials © 2023 Bio-Rad Laboratories, Inc.

 Glossary

M R
Matrix Reagent
A substance that contains other constituents. For example, A substance is added to a system, causing a chemical
a human matrix such as serum or plasma contains reaction, often used to indicate the presence of another
elements such as calcium and potassium as well as analyte.
proteins such as thyroglobulin.
S
N Statistical Process Control (SPC)
NATA A process that uses basic statistics such as mean and
National Association of Testing Authorities (Australia). standard deviation to construct a framework for monitoring
the quality of laboratory testing.
P
Peer group Serum
A group that shares common characteristics. For statistical Clear part of the blood (when blood cells and clotting
process control, a peer group consists of laboratories that proteins have been removed).
use the same instrument, reagent, method and units of
measure for a particular test. T
Test System
Photometry Includes the instrument, reagents, calibrators, sampling
Measurement of light absorbed, used to determine mechanism, measurement modules etc.
the amount of an analyte in a test solution.
TSH
Plasma Thyroid Stimulating Hormone.
Clear (if separated) yellowish circulatory fluid of the
blood (contains anticoagulant) that carries water, salts V
and enzymes. Vial
Small container, often made of glass, used for holding liquid.
Q
QC Data Management Software W
Software tools that help to review data, identify trends Whole Blood
and provide charts and reports for data analysis. Whole blood contains white blood cells, red blood cells, and
platelets suspended in blood plasma.
Quality Control (QC)
A process that uses materials of known value, reaction or
performance along with preset parameters (often statistical
in nature) to monitor the reliability of medical laboratory
testing.

Quality Control Materials

Liquid or freeze-dried (lyophilized) materials that are
tested alongside patient samples to verify that the system
analytical performance meets expectations and that results
for patient samples are suitable for intended use.

© 2023 Bio-Rad Laboratories, Inc. Laboratory Quality Control Materials 19

BIO-RAD is a trademark of Bio-Rad Laboratories, Inc. P.A.C.E. is a registered trademark of the American Society of Clinical Laboratory Science.

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