5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
Product Description
bioCSL Securacell™ Light is a basic immunohaematology
process Quality Control System used to measure the
accuracy, precision and sensitivity of laboratory tests in
clinical practice. It can be applied to a standard internal
Quality Control programme as a routine control for manual
and/or automated batch testing, or as a training tool.
bioCSL Securacell™ Light is designed to improve the safety
of and control over pre-transfusion compatibility and
antenatal testing. It is supplied as a kit with two 6mL
collection tubes containing 1.5mL of pooled human red
blood cells and 4.5mL of simulated plasma. The samples
are labelled 1 and 2.
KODE™ CA (Carbohydrate Antigen) was developed by
KODE Biotech Limited and the Biotechnology Research
Institute at Auckland University of Technology and
further developed and commercialised by bioCSL
Immunohaematology.
The application of KODE™ CA in Securacell™ Light
enables Group O human red blood cells to be converted
to an Aweakand/or Bweak cell, providing the world’s first
precise and reliable ABO blood grouping sensitivity
control. KODE™ CA technology is used to create cells
with reproducible, precisely controlled expressions of
A and B antigens to mimic the reactions of Ax and/or Bx
cell, thus eliminating variations seen in natural weak ABO
red cells. KODE™ CA technology enables the engineering
of Group Aweak and/or Group Bweak samples to give weak
reactions with a blood grouping system that is working
correctly, therefore detecting any loss in analytical
sensitivity by displaying a reduction or total loss of
appropriate reactions.
Catalogue No. Pack Size
08840201
2 x 6mL
08840205
5 x (2 x 6mL)
bioCSL Securacell™ Light is shipped
on a four week shipping cycle and
it has sufficient shelf life to allow
overlapping expiries.
Suitable Testing Platforms
p Column Agglutination Technology (CAT)
pTube
pTile
pMicroplate
Product Design
•
•
•
•
•
•
•
What is KODE™ CA?
Simulates patient samples in both format and behaviour.
Allows approximately 400 blood groups and antibody screens to be performed with each kit (depending on method and process used).
Allows parallel testing with routine patient samples to control and ensure the correct ABO and RhD Blood Group
is determined and clinically relevant unexpected
antibodies are identified and quantified.
Includes both RhD Positive and Negative Sample types to
ensure complete and reliable control of blood grouping.
Contains single or mulitple alloantibodies to control
antibody screening and identification.
Provides alloantibody specificities that detect clinically
relevant antibodies, and concentrations that give
mid-strength reactions with commonly used techniques.
Utilises novel patented KODE™ CA technology.
Benefits of bioCSL Securacell™ Light
•
•
•
•
•
•
•
Fresh – Manufactured using fresh red cells (not frozen)
Universal – Suitable for all testing platforms
Quality Assured – Proven performance, field trialled
and validated product
Stable – Confirmed stability until expiry, consistently
high level of sensitivity
Reliable – Developed and manufactured to bioCSL's
strictest quality standards (TGA and ISO accredited)
Innovative – Novel product design, utilising unique
KODE™ CA technology to create controlled
antigen expression
Superior Performance – Six primary purposes—
a complete quality control system.
This document includes:
•
•
•
•
Product specifications
Product design and performance
Recommended applications
Field trial and validation
bioCSL Immunohaematology
1 +61 3 9389 4762 | Fax: +61 3 9389 1646 | Email:[email protected] | Web: www.biocsl.com.au/IH
Tel:
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
Recommended Applications
bioCSL Securacell™ Light is a basic multipurpose QC system
designed to simulate a routine patient sample. It is used
to control, standardise and validate the following routine
immunohaematology tests:
• ABO RhD Blood Grouping Control
• Antibody Screening and Identification Control
• ABO Analytical Sensitivity Control
• Routine Process Control for Manual and
Automated Systems
• Replicate Testing Control
• Anti-D Standard
The integrity of the testing process is proven by the test
results matching those of the published results on the
accompanying 'Results Sheet'.
1. ABO RhD Blood Grouping Control
ABO blood grouping is the most important
immunohaematology testing procedure, as mistakes can
result in serious morbidity or mortalities. These errors
can occur during collection, testing and/or infusion and
includes technical errors, test failure, reagent or equipment
failure and patient misidentification. Inability to recognise
anomalous groups and subgroups may also cause grouping
errors. Despite these errors and risks, the blood group
testing procedures are often taken for granted.
The high performance of modern monoclonal reagents and
technologies almost always provide a reaction that is either
completely negative or positive. This leads to users expecting
a simple yes or no answer. This may lead to a tendency to
take less care during blood group testing and in the grading
and interpretation of reactions.
Despite these errors and risks
(in ABO blood grouping), the blood
group testing procedures are often
taken for granted.
The high potency of monoclonal reagents brings risks if the
testing process is not controlled properly. Reagents are so
potent that a very small amount of cross-contamination may
cause incorrect grouping reactions. This contamination may
occur due to errors such as incorrect dropper replacement in
vials, incorrect dispensing procedures and misuse or reuse
of pipettes.
2
Incorrect blood group reactions in Column Agglutination
Technology (CAT) systems, have been observed due to
column cross contamination as a result of aerosols (of the
monoclonal reagents), produced during the removal of the
foil seal and on pipette tips used for cell dispensing. In these
events, probably as little as a few microlitres of a monoclonal
reagent contaminating an adjacent well can cause an
incorrect grouping result.
bioCSL Securacell™ Light provides a useful routine control of
blood grouping. The Group Aweak and B Samples provide both
positive and negative reactions with anti-A and anti-B. Group
Bweak Samples are also included from time to time. Should a
complete control of all ABO blood grouping be required,
bioCSL recommends the use of Securacell™. Controls should
also be selected that have both an RhD Negative and a
relatively weak expression of RhD (such as R0r or R1r) cell.
While ABO RhD blood grouping may seem reliable and
simple, reagent failure and technical errors can occur. These
errors should be detected by checking procedures, such as
reverse (serum) groups and repeat groups. More importantly,
transcription errors can also be made. These errors are
more dangerous as they may not be picked up by checking
procedures and will not be detected by reagent controls.
For this reason it is vital that process controls are used that
mimic and are treated like patient samples. Routine use of
process controls can greatly assist detection of transcription
errors. It is also worth examining the entire testing process
to reduce the number of potential error steps.
2. Antibody Screening and Identification Control
Antibody screening controls should be chosen to challenge
the test sensitivity and specificity. Controls should generally
consist of stable, weak, clinically relevant antibodies. They
should result in weak to mid-strength reactions, so that a
loss or reduction in antibody detection scores indicates test
performance failure. Any such failure should be investigated
by examining the quality of additives and Reagent Red Blood
Cells (RRBCs), inactivation of Anti-Human Globulin (AHG)
reagent, poor temperature control, washing, timing
and centrifugation.
A negative control should also be used. Anti-D is often
used because it is the most common clinically relevant
allo-antibody encountered. This is generally not considered
to be sufficient by itself, as the RhD antigen is very robust
and may be indicative of RRBC degradation. Anti-c, anti-e
and anti-Fya are commonly used for this reason, but other
antibody specificities may also be chosen. Multiple antibodies
may be included and used for antibody investigation controls,
to control antibody identification panel quality
and specificity.
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
bioCSL Securacell™ Light provides a useful control of all
antibody screening methods and is designed to generally
provide a positive reaction in 2-3 cells of Abtectcell™ III
Screening Cells when both samples are used. Should
more advanced antibody screening be required, bioCSL
recommends Securacell™.
3. ABO Analytical Sensitivity Control
Modern, high quality Anti-A and Anti-B reagents have a
high potency. In some cases they can lose up to 95% of their
analytical sensitivity due to damage or degradation, but still
give normal strength reactions with Group A and Group B
cells. The most commonly available red cells with a weak
expression of the A antigen are Group AwB cells. Group A2B
cells simply express too much A antigen for use as a weak
A control and do not express low levels of B antigen and, as
such, are unsuitable for use as a weak B control cell. Use of
these types of control cells may give apparently satisfactory
results, even when reagents may be significantly damaged or
degraded and are actually incapable of detecting weak ABO
subgroups, such as A3 and B3 cells.
Ax cells are generally agreed to be the gold standard for
analytical sensitivity of Anti-A blood grouping reagents.
However, the antigen expression of natural Ax cells varies
by up to 500% and is difficult for most laboratories to reliably
obtain. While detection of natural Ax cells is not clinically
vital in blood recipients, it is clinically important to detect
Ax cells in blood donors, as these cells are capable of causing
haemolytic transfusion reactions.
Ax blood donors should always be typed and labelled as
Group A. It is also vital that the analytical sensitivity of any
blood grouping procedure can be measured and monitored.
In practice, this is difficult due to the unavailability of natural
Ax cells and the inherent variation in the expression of the
A antigen on Ax cells. Analytical sensitivity control of ABO
grouping may be achieved by the use of the Aweak cell
available in the bioCSL Securacell™ Light Quality Control
System. This cell is designed to react as a weak A in all
testing platforms, it is weaker than an A2 cell, this ensures
detection of loss of Anti-A reactivity far earlier than A2 cells,
guaranteeing optimum test sensitivity.
4. Routine Process Control for Manual
and Automated Systems
Immunohaematology laboratories have for many years
used reagent controls to prove reagent performance. More
recently control kits have become available, however they
are often provided in small volumes, have red blood cells
provided as 3% suspensions and are unable to be processed
like a real patient sample. They are more correctly termed
'competency assessment' or 'technical checking products'.
Some manufacturers also provide controls for automated
3
systems, but often these controls are barcoded so the
instrument's identify the sample specifically as a control
and then process the control differently to a routine sample.
This approach defeats the purpose of the control, as it is
not a blind test and does not undergo all testing steps,
and therefore cannot control the entire testing process.
The concept of a 'Process Control' is to use a control that
exactly simulates a patient sample and is processed through
the entire testing process. This approach increases the
control utility, as it can detect errors during the entire testing
process; from sample handling and dilution through to result
recording or result data transmission by electronic interfaces.
The concept of a process control applies to both manual
and automated techniques, regardless of the testing
technology used.
bioCSL Securacell™ Light is formatted and performs so
that automated systems are unaware that the control is
not a routine patient sample. It can be used as a routine
process control by testing one or both bioCSL Securacell™
Light Samples with batches of patient samples. It should
be processed in exactly the same manner as the patient
samples, including all preparation, dilution and testing steps.
Internal patient sample barcodes may be used with bioCSL
Securacell™ Light.
The concept of a 'Process Control'
is to use a control that exactly
simulates a patient sample and
is processed through the entire
testing process.
5. Replicate Testing Control
Replicate testing is a programme where staff are required to
perform immunohaematology testing (such as a blood group,
antibody screen and antibody identification) on unknown,
identical samples. Individual staff results can be examined
and compared to known results, to ensure blood groups are
correct and to monitor and correct variations in grouping
and antibody screening technique and in reaction grading.
6. Anti-D Standard
bioCSL Securacell™ Light includes a monoclonal IgG
anti-Dantibody as an Anti-D Standard. It has a defined
concentration of <0.05 IU/mL recorded on the published
‘Result Sheet’ and is designed to exceed current ANZSBT
Guideline recommendations. bioCSL Securacell™ Light can
also be used as an Antibody Precision Control.
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
Product Specifications
bioCSL Securacell™ Light is manufactured using fresh
donor units which are washed to remove plasma and any
contaminating antibodies. The red cells are pooled and
formulated to react during blood group testing as Blood
Groups A and B. The simulated plasma is formulated to
include the appropriate ABO antibodies to match the
blood group. This simulated plasma provides reaction
strengths similar to those of a patient sample.
The red blood cells are phenotyped as antigen negative for
any antibody present in the simulated plasma in the same
tube. Alloantibodies such as anti-D, anti-K, anti-Fya, anti-c
and anti-Jka are incorporated in the simulated plasma for
antibody screening and identification.
One sample of bioCSL Securacell™ Light is always Group Aweak
expressing controlled low levels of the A antigen and has
appropriate reverse (serum) group antibodies. The second
bioCSL Securacell™ Light sample is always Group B and has
appropriate reverse (serum) group antibodies. Occassionally
a weak expression of the B antigen may be provided with
Group Bweak cells used. One sample will contain an RhD
Negative cell (rr) and the other an RhD Positive cell that will
be of an R1r or R0r phenotype. One of the bioCSL Securacell™
Light samples will contain allo-antibodies with specificities
that are designed to provide weakly positive reactions (with
a score for at least one of the allo-antibodies of 3 to 5 on the
0-12 scale and +/- to 1 on the 0-4 scale) with each of the 3
cells of the Abtectcell™ III Screening Cells. The second sample
will contain no allo-antibodies and acts as a Negative Control
for screening tests.
bioCSL Securacell™ Light Performance
Each bioCSL Securacell™ Light kit includes:
• Sealed 'Results Sheet' with batch specific blood group
results, antibody identity and indicative reaction
scores derived from the 'bioCSL Reference Laboratory'.
• Blood grouping reactions and blood group
interpretation for Tile, Tube, BioVue™ and DiaMed
ID-MTS™ techniques.
• Antibody screening reactions and antibody identity for
Tube RAM, BioVue™ and DiaMed ID-MTS™ techniques.
• Anti-D standard results performed against the Bristish
Standard for Anti-D (Rho), Code No. 73/515.
• Reagents, CAT card identities, batch numbers and
expiries used are reported on the Result Sheet.
4
bioCSL Securacell™ Light Field Trial
and Validation
A stability trial was conducted by bioCSL on three preproduction batches of bioCSL Securacell™ Quality Control
products to fully performance test the product during its
shelf life. bioCSL Securacell™ Light had excellent stability
and has been assigned a shelf life of 10 weeks from the
earliest donor pack date of bleed. This allows a 4 weekly
shipping frequency, with a significant safety margin of
expiry overlap.
A field trial to validate bioCSL Securacell™ Quality Control
products on all immunohaematology testing technologies
and automated systems was conducted in July 2002 in 18
Australian immunohaematology laboratories over a period
of 14 weeks. Testing was also replicated in three separate
bioCSL immunohaematology laboratories. The product
design and format were examined to ensure they met user
requirements and for any improvements that could be
incorporated. The reaction strengths of the blood groups
and antibodies were varied during the trial to "fine tune"
these reactions to best meet customer needs and to ensure
that bioCSL Securacell™ products perform well on all testing
platforms. These lessons have been transferred across to
improve the bioCSL Securacell™ Light product.
A total of 1,360 samples were manufactured, 8,800 blood
groups and 1,979 antibody screens were performed and
60,000 data points were generated. An interesting outcome
was that 30 clerical errors were identified during this trial.
The bioCSL Securacell™ technology was further tested
in conjunction with the RCPA in the form of the QAP
Educational Exercise in March 2004. This exercise comprised
a special bioCSL Securacell™ Light formulation with three
Aweak cells and one Bweak cell being provided to all participants.
Further validation work was performed to ensure the KODE™
CA AweakBweak cells performed satisfactorily in all technologies
and that there were no clonal specificity issues. This testing
compared reaction scores obtained for KODE™ cells using
commonly available monoclonal reagents in tube methods
(Table 1). Weak A and B donor cells were also compared with
KODE™ Aweak and Bweak cells in available CAT cards (Table 2
and 3). Results demonstrated that all commonly used clones,
reagents and CAT systems were capable of detecting KODE™
CA red blood cells and thus perform in exactly the same
manner as donor red blood cells.
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
bioCSL Securacell™ Field Trial
Representative Data
KODE™ Cells
Aweak
Bweak
bioCSL Epiclone™ Anti-A
1
0
bioCSL Epiclone™ Anti-B
0
2
bioCSL Epiclone™ Anti-A/B
1
1
Gammaclone™ Anti-A
1
0
Gammaclone™ Anti-B
0
1
Gammaclone™ Anti-A/B
2
2
ORTHO Bioclone™ Anti-A
+/-
0
ORTHO Bioclone™ Anti-B
0
1
ORTHO Bioclone™ Anti-A/B
1
1
Table 2 KODE™ specificity data for CAT using donor cells
Cell
Card/Cassette ID
Anti-A Anti-B
ID
Ax
Donor Cells
Table 1 KODE™ specificity data for test tube
B3
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
+/-
0
ID-MTS™ DiaClon ABO/D+
Reverse grouping
+/-
0
BioVue™ Anti-A/Anti-B/Anti-D
1
0
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
0
2
ID-MTS™ DiaClon ABO/D+
Reverse grouping
0
2
BioVue™ Anti-A/Anti-B/Anti-D
0
2
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
4
3
4
3
BioVue™ Anti-A/Anti-B/Anti-D
4
4
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
4
0
ID-MTS™ DiaClon ABO/D+
Reverse grouping
4
0
BioVue™ Anti-A/Anti-B/Anti-D
4
0
A1B3 ID-MTS™ DiaClon ABO/D+
Reverse grouping
A2
5
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
Table 3 KODE™ specificity data for CAT using KODE™ CA cells
Cell
Card/Cassette ID
Anti-A Anti-B
ID
KODE™ CA Cells
Aw
Bw
AwBw
ID-MTS™ DiaClon Confirmation
1
for donors ABD (VI+)
0
ID-MTS™ DiaClon ABO/D+
Reverse grouping
2
0
Diaclon™ Confirmation for
patients (VI-)
1
0
BioVue™ Anti-A/Anti-B/Anti-D/
3
Control/Reverse
0
Storage and Handling
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
0
2
Store at 2° to 8°C (Do Not Freeze)
ID-MTS™ DiaClon ABO/D+
Reverse grouping
0
1
Diaclon™ Confirmation for
patients (Vi-)
0
1
BioVue™ Anti-A/Anti-B/Anti-D/
0
Control/Reverse
4
ID-MTS™ DiaClon ABD
Confirmation for donors (VI+)
1
+/-
ID-MTS™ DiaClon ABO/D+
Reverse grouping
2
1
Diaclon Confirmation for
patients (Vi-)
+/-
+/-
BioVue™ Anti-A/Anti-B/Anti-D/
3
Control/Reverse
2
Precautions
• The material from which bioCSL Securacell™ Light is
derived is found to be non-reactive for specified markers
for HIV 1 and 2, Hepatitis B and C, HTLV and Syphilis by
currently approved methods. However, no known method
can assure that products derived from human blood will
not transmit infectious agents, therefore good laboratory
practice requires safe handling procedures.
• bioCSL Securacell™ Light contains Neomycin Sulphate and
Chloramphenicol as antibacterial agents and Thiomersal
as a preservative. Users should take appropriate
precautions when handling and discarding this product.
• bioCSL Securacell™ Light is manufactured from pooled
red blood cells and should not be used for controlling
phenotyping techniques.
• For in vitro diagnostic use only.
6
Incorrect reactions may occur due to:
1. Failure to comply with the recommended procedures.
2. Variations in time and temperature of incubation,
centrifuge speeds and reaction reading methods.
3. Contamination of test samples, reagents or
supplementary materials.
4. Use of aged or expired samples or reagents.
5. Incorrect red blood cell suspension strengths.
Refrigerate at 2° to 8°C when not in use
Take appropriate precautions to maintain sterility
Do not use if:
• Subjected to prolonged periods of high temperature
• Signs of gross haemolysis are present in red cell suspensions or the simulated plasma component
is turbid
• Expiration date has passed.
bioCSL Securacell™ Light is designed to be treated exactly
like a patient sample. Before use, it should be left for a
period of time to allow the red blood cells to separate or it
may be centrifuged prior to use, using a method suitable
for patient sample separation.
bioCSL Securacell™ Light is designed as a whole blood
control product. Red blood cells and plasma should not be
separated and stored individually. Red cell suspensions for
grouping should be made immediately prior to testing and
not be stored for later analysis. If bioCSL Securacell™ Light
is stored upright and handled gently, repeat centrifugation
will not be required.
5
Securacell™ Light Quality Control System
PRODUCT INFORMATION: 5
References
1. Scientific Subcommittee of the Australian and New
Zealand Society of Blood Transfusion Inc. Guidelines for
Pretransfusion Laboratory Practice. 5th Ed. 2007.
2. Scientific Subcommittee of the Australian and New
Zealand Society of Blood Transfusion Inc. Guidelines for
Blood Grouping & Antibody Screening in the Antenatal
& Perinatal Setting. 3rd Ed. 2007.
3. Green R, et al. Basic Blood Grouping Techniques and
Procedures. 2nd Ed. Victorian Immunohaematology
Discussion Group 1992.
4. Harmening DM. Modern Blood Banking and Transfusion
Practices. 5th Ed. FA Davis Company. Philadelphia 2005.
5. Roback, J.D, et al. American Association of Blood Banks
Technical Manual. 16th Ed. Bethesda, Maryland 2008.
6. Serious Hazards of Blood Transfusion (SHOT).
Annual Reports 2003-07.
7. National Pathology Accreditation Advisory Council
(NPAAC). Standards for Pathology Laboratory Participation
in External Proficiency Testing Programs 2004.
8. National Association of Testing Authorities (NATA).
ISO/IEC 17025 Application Document. 2000; Version 1.
9. Lapierre Y, Rigal D, Adam J. The gel test: A new way to
detect red cell antigen-antibody reactions. Transfusion
1990; 30: 109-13.
10.Reis KJ, Chachowski R, Cupido A, Davies D, Jakaway
J, Setcavage. Column agglutination technology: The
antiglobulin test. Transfusion 1993; 33: 639.
11.Malyaka H, Welland D. The gel test. Laboratory Medicine
1994; 25: 81.
12.Butch SH, Judd WJ. Requirements for the computer
crossmatch (letter). Transfusion 1994; 34: 187.
13.Butch SH, Judd WJ, Steiner EA. Electronic verification of
donor-recipient compatibility: The computer crossmatch.
Transfusion 1994; 34: 105-9.
14.Heist H. Pretransfusion blood group serology: limited
value of the antiglobulin phase of the crossmatch when
a careful screening test for unexpected antibodies is
performed. Transfusion 1979; 19: 761-3.
15.Mollison PL, Engelfriet CP, Contreras M. Blood Transfusion
in Clinical Medicine. 10th Ed. Blackwell Science 1997.
October 2013
No expressed, implied or contingent liability is assumed for
product use or patent infringements. Products detailed are
for purposes described within the product leaflet only. All
information contained is copyright bioCSL Limited.
bioCSL Immunohaematology
7 +61 3 9389 4762 | Fax: +61 3 9389 1646 | Email:[email protected] | Web: www.biocsl.com.au/IH
Tel: