Recommendations for Premarket Notification (510(k)) Submissions for Nucleic Acid-Based Human Leukocyte Antigen (HLA) Test Kits Used for Matching of Donors and Recipients in Transfusion and Transplantation: Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Recommendations for Premarket
Notification (510(k)) Submissions for
Nucleic Acid-Based Human Leukocyte
Antigen (HLA) Test Kits Used for
Matching of Donors and Recipients in
Transfusion and Transplantation
____________________________________________________
Guidance for Industry
Additional copies of this guidance are available from the Office of Communication, Outreach
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring,
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or
from the Internet at
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm.
For questions on the content of this guidance, contact OCOD at the phone numbers or email
address listed above.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
July 2015

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Table of Contents
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 2
III. 	RECOMMENDATIONS FOR THE PREPARATION OF THE HLA TEST KIT
PREMARKET NOTIFICATION (510(k)) SUBMISSION........................................... 2
A. 	Intended Use .......................................................................................................... 2
B. 	Device Design ......................................................................................................... 3
C. 	Performance Studies ............................................................................................. 4
D. 	Software ................................................................................................................. 8
E. 	Validation of Instrumentation ............................................................................. 9
F. 	Labeling ................................................................................................................. 9
G. 	Additional Considerations ................................................................................. 10
IV. 	REFERENCES ................................................................................................................ 11

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Recommendations for Premarket Notification (510(k)) Submissions
for Nucleic Acid-Based Human Leukocyte Antigen (HLA) Test Kits
Used for Matching of Donors and Recipients in
Transfusion and Transplantation
_____________________________________________________________________________
Guidance for Industry
This guidance represents the current thinking of the Food and Drug Administration (FDA or
Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
or the public. You can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff
responsible for this as listed on the title page.
I. 	INTRODUCTION
This guidance provides recommendations to submitters (hereafter referred to as “you”) and FDA
reviewers in preparing and reviewing premarket notification submissions (hereafter referred to as
“510(k) submission” or “510(k)”) for human leukocyte antigen (HLA) in vitro diagnostic (IVD)
device test kits. This guidance applies specifically to nucleic acid-based HLA test kits used for
the matching of donors and recipients in transfusion and transplantation, whether testing is for a
single locus or for multiple loci simultaneously, for which the premarket submission to FDA will
be a 510(k).
Although this guidance applies specifically to 510(k) submissions for HLA test kits, some of the
recommendations in this guidance may also be applicable to human neutrophil antigen (HNA)
and human platelet antigen (HPA) test kits. We recommend that you consult the Office of Blood
Research and Review (OBRR) in FDA’s Center for Biologics Evaluation and Research (CBER)
for specific guidance regarding premarket submission requirements for HNA and HPA test kits.
This guidance provides detailed information on the types of studies FDA recommends for
validation of HLA test kits submitted as 510(k)s and used for the matching of donors and
recipients in transfusion and transplantation. More specifically, the document addresses the
types of studies and other information that FDA recommends be used in designing and
conducting studies for validation of nucleic acid-based HLA test kits and preparing a 510(k)
submission.
This guidance finalizes the draft guidance of the same title dated November 2013 (78 FR 69693,
November 20, 2013).

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FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.
II. 	BACKGROUND
Most cells of the body bear human leukocyte antigens. The role of the HLA system is to allow
the human immune system to distinguish the body’s own blood, organs and tissues from foreign
substances. Clinical complications, such as graft rejection or graft-versus-host disease, may
occur if the immune system recognizes transplanted cells, tissues, organs, bone marrow, or a
transfused unit of blood or blood components as being foreign on the basis of HLA nonidentity
or if transplanted immune system cells react in response to the recipient’s HLA.
The science and technology upon which HLA test kits are based has become increasingly
complex in recent years. Testing has evolved from serology and cell-based methods with little
instrumentation to deoxyribonucleic acid (DNA) based and multiplex assays that use complex
instruments and software. HLA is one of the most polymorphic systems found in humans. This
high degree of polymorphism and the existence of rare phenotypes found in the HLA system
represent significant and unique challenges to develop and design studies that validate the
accuracy of these HLA test kits. FDA’s expectations for analytical and clinical studies
conducted in support of a 510(k) submission focus on identifying potential risks to patients if the
kits fail to perform as expected. The performance of these kits is critical for ensuring precise and
successful matching between donors and recipients of blood and blood components, cells,
tissues, bone marrow, and organs.
III. 	RECOMMENDATIONS FOR THE PREPARATION OF THE HLA TEST KIT
PREMARKET NOTIFICATION (510(k)) SUBMISSION
A. 	Intended Use
A 510(k) submission must contain, among other things, proposed labels and labeling and
advertisements sufficient to describe the device, its intended use, and the directions for its
use (21 CFR 807.87(e)). In the case of HLA test kits, the intended use should specify the
marker the device is intended to detect.
We recommend that the following statement be included in the intended use statement in
your 510(k) submission for HLA test kits:
“To be used to determine {indicate HLA locus or loci}, to aid in transfusion and
transplantation donor and recipient matching.”
Please consult CBER for specific guidance regarding HLA test kits that have a different
intended use than the one recommended in this section.

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B. 	Device Design
We recommend that you carefully characterize the design of your HLA test kits. For
example, you should describe the following elements in your 510(k) submission, where
applicable:
• 	Test platform (e.g., flow cytometry, instrumentation for multiplex test systems).
• 	Composition and layout in spatially-fixed platforms, including feature (e.g.,
probe) identity and placement, where applicable.
• 	Methods used for attaching the capture or probe material to a solid surface, if
applicable.
• 	Hybridization conditions, washing procedures, and drying conditions (e.g.,
temperature, length of time).
• 	Assay components such as buffers, enzymes, fluorescent dyes, chemiluminescent
reagents, other signaling and signal amplification reagents, instruments, software,
etc.
• 	Methodology for DNA extraction that you provide or that you recommend for
users, and other applicable preanalytical elements. If you do not provide sample
preparation reagents in your test kits, you should provide specifications (including
justification for these specifications) for assessing the quality of the assay input
sample so that users can validate their own sample preparation method and
reagents.
• 	Range of input sample concentrations that meet performance specifications.
• 	Internal controls and external controls, and calibrators that you recommend or
provide. Validation of controls and calibrators.
• 	Stability and reproducibility of the entire test procedure when used for its
intended use.
• 	For multiplex tests in which the target molecules will contact a number of
different probes, the methods used to mitigate the risk for probe cross-
hybridization.
• 	The methods used to address the potential for probe cross-contamination.
• 	The maximum number of samples that can be simultaneously processed.
We recommend that you describe in detail the test kit’s methodology for detecting alleles
and genotypes, including a detailed description of algorithms and decision trees, as
applicable. You should also briefly outline your risk analysis relating to the test kit’s
methodology for detecting alleles and genotypes.
We also recommend that you include illustrations or photographs of non-standard
equipment or methods because these can be helpful in understanding novel
methodologies, including the incorporation of features to minimize potential device
failures and user errors.

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C. 	Performance Studies
Performance studies should demonstrate with a high level of confidence that the test kit
performs within the established specifications. You should identify the performance
characteristics that are to be assessed and establish validation methods and acceptance
criteria.
The following subsections include specific recommendations for accuracy studies,
precision studies including reproducibility and repeatability, and clinical comparison
studies, including recommendations for the study design, samples, and a description of
concordance.
1. 	Accuracy Studies
Accuracy studies for molecular detection methods should address all
probes and/or primers included in the HLA test kit. However, due to the
large number of polymorphisms within the HLA system, we realize that it
may be impractical to individually measure the accuracy of each
polymorphism that a test kit claims to detect. Therefore, we recommend
that the accuracy study, which may be conducted in-house, challenge the
performance parameters of the test system as follows:
• 	The study should use nationally or internationally recognized well-
characterized DNA samples (described in this section) that
represent the most prevalent HLA alleles, and, if possible, also
include rare alleles.
• 	The sample size for each locus should meet the following criteria:
use a sufficient number of well-characterized DNA samples such
that you can demonstrate that the one-sided 95% lower confidence
limit of overall agreement (i.e., concordance) exceeds 0.95 for
each test kit (locus) in the submission. The samples in this study
should be tested once and cover a reasonable range of genotypes.
Sponsors are encouraged to discuss sample selection with FDA in
advance to reach an agreement on this process
• 	Results should be reported using statistically appropriate practices
as outlined in the FDA guidance document entitled, “Guidance for
Industry and FDA Staff: Statistical Guidance on Reporting Results
from Studies Evaluating Diagnostic Tests,” dated March 13, 2007
(Ref. 1). That guidance provides recommendations on the
handling of equivocal results, discrepant result resolution and how
comparison of the results to non-reference standards and methods
should be reported.
Sample Types - We recommend the use of well-characterized DNA
samples recognized in the United States ( U.S.) or abroad that have been
extensively tested using a variety of HLA testing methods, including DNA

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sequence-based typing. The term “well-characterized DNA sample” will
be used henceforth in this document to describe the abovementioned
samples.
Concordance Description - The HLA typing results from your test are
concordant with the well-characterized DNA sample if one pair of the
reported alleles is the same as the typing results of the well-characterized
DNA sample.
2. 	Precision Studies including Repeatability and Reproducibility
Precision studies should capture possible sources of variation including
within run, run-to-run, day-to-day, operator-to-operator, instrument-to-
instrument, site-to-site and lot-to-lot variation. Because within run
variability can be captured using a measure of how closely measurements
within the same run agree (e.g., percent agreement of results within the
same run), we refer to this as the repeatability estimate. The repeatability
estimate can be captured using data from an internal study or by
combining results collected at multiple sites in a reproducibility study. A
reproducibility study should be performed at multiple sites using multiple
operators with skill levels similar to those of your intended users. You
should also perform testing over several weeks and at different times of
the day to maximize detection of potential sources of variability. For
reagents recommended to be used with automated instruments, the
submission should include testing on three separate instruments, one at
each site.
You may choose to combine the repeatability study and the reproducibility
study into a single study.
We recommend the following precision study design:
• 	Three study sites, including at least two external sites, with two
operators at each site. If feasible, each operator should perform
two runs per day.
• 	Each sample is run in duplicate (for repeatability), on five
nonconsecutive days over 20 days using one lot of the test kit.
NOTE: Kit and component lot-to-lot studies, using three different
lots, may be conducted in-house using the same panel as the
external sites.
• 	The study outlined in this section should be used on each
instrument for which you are seeking clearance.
• 	If you plan to submit a bundled submission, conduct a precision
study for each test kit.
• 	Operator experience may have an impact on test system
performance; therefore, operator training is an important

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consideration when designing validation studies. Your precision
study protocol should include training requirements for the
operators. If applicable, operators should be certified prior to
participating in the study and the protocol should include
certification acceptance criteria. The training program should
reflect the training to be received by operators once the product is
marketed.
• 	In general, complete agreement should be expected. Sponsors
should perform an investigation and provide justification if there is
disagreement.
Sample Types - Perform precision studies using well-characterized DNA
samples (precision panel) that ideally should cover every genotype
reported by the device. However, due to the large number of possible
HLA alleles that may be detected by your test kit, it may not be possible to
cover every genotype in the precision panel; therefore, we recommend the
following:
• 	The precision panel should be blinded and should consist of well-
characterized DNA samples representing significant diversity of
the detectable alleles represented in the test kit. It is preferable that
the panel samples differ from those used in the accuracy study.
• 	The lowest DNA concentration suggested by the test kit’s
“Instruction for Use” should be used with all samples in the panel,
though additional testing using higher concentrations of DNA can
also be added.
Concordance Description - The precision study results are concordant
with the well-characterized DNA sample results if one pair of the reported
alleles is the same as the typing results of the well-characterized DNA
sample. In addition, any uncertainty in the typing assignment (i.e., the list
of ambiguities) should be reported and compared between operators, sites,
runs, repeats, and days.
3. 	Clinical Comparison Studies
Clinical comparison studies are performed to evaluate the proposed
device’s performance in a clinical setting, using random clinical
specimens and the assay instructions outlined in the proposed labeling.
Clinical comparison studies of investigational IVD devices are subject to
the investigational device exemption (IDE) provisions of section 520(g) of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360j(g)), and related
implementing regulations. You should consider how FDA regulations at
21 CFR Part 812 (Investigational Device Exemptions) apply to your
particular study, and also refer to 21 CFR Part 50 (Informed Consent) and

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21 CFR Part 56 (Institutional Review Boards) for other applicable
requirements.
Informed Consent
For studies of an investigational device, the definition of a (human) subject includes
an individual on whom or on whose specimen an investigational device is used (see
21 CFR 812.3(p)). Because section 520(g)(3)(D) of the Federal Food, Drug, and
Cosmetic Act and the regulations in 21 CFR Part 812 require informed consent under
21 CFR Part 50 for FDA-regulated human subject research, informed consent must be
obtained before specimens can be used, except in limited circumstances as specified
in the regulations.1 Note that the guidance document entitled, “Guidance for
Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff:
Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using
Leftover Human Specimens that are Not Individually Identifiable,” dated April 25,
2006 (Ref. 2) provides that FDA intends to exercise enforcement discretion, under
certain circumstances, with regard to the regulations governing the requirement for
informed consent when human specimens are used for FDA-regulated IVD device
investigations. As described in that guidance document, FDA does not intend to
object to the use, without informed consent, of leftover human specimens (i.e.,
remnants of specimens collected for routine clinical care or analysis that would
otherwise have been discarded) in investigations that meet the criteria for exemption
from the IDE regulation in 21 CFR 812.2(c)(3), as long as subject privacy is protected
by using only specimens that are not individually identifiable.
Note that sponsors must comply with the requirements for institutional review board
review, if applicable, as set forth in 21 CFR Part 56 unless they meet the exemption
criteria outlined in 21 CFR 56.104 or 56.105.
Study Design for Clinical Comparison Studies
We recommend the following study design:
• 	The study should include three sites, including at least two external sites of
which at least one is in the U.S. The sites should cover different geographic
regions and include a representation of major ethnic groups found in the U.S.
in order to increase the probability of covering the many HLA genotype
variants found in the U.S. population. You can refer to published literature for
the U.S. prevalence of HLA alleles. For example, the National Marrow Donor
Program (http://www.bethematch.org) provides frequency information for
HLA haplotypes found in the U.S. population.
• 	Your protocol should include training requirements for the operators involved
in the studies. If applicable, operators should be certified prior to participating
in the study and the protocol should include certification acceptance criteria.
The certification/training requirements should reflect those that will be
1 21 CFR 50.23 and 50.24.

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implemented once the device is marketed in order to best assess the device
performance under actual use conditions.
• 	Sample size – sufficient number of samples should be tested that would allow
one to establish that the one-sided 95% lower confidence limit for the overall
agreement with the comparison device exceeds 0.95 for each HLA locus in
the submission.
• 	In your study, you should compare two distinct lots of your product either to a
device legally marketed in the U.S. or to results obtained by bi-directional
sequencing. Bi-directional sequencing entails sequencing both strands of
amplified genomic DNA. Include all test kits that will be described/listed in
your submission in the study. The statistical analysis plan should be defined
prior to the start of the study and should be consistent with FDA’s guidance
document entitled, “Guidance for Industry and FDA Staff: Statistical
Guidance on Reporting Results from Studies Evaluating Diagnostic Tests,”
dated March 13, 2007 (Ref. 1).
• 	The protocol should include evaluation of sample preparation reagents
provided with the test kit. If you do not include sample preparation reagents
in the test kit, each site should use and validate its own specimen processing
procedures and demonstrate that the resulting sample meets the HLA kit
manufacturer-supplied specifications.
• 	Discordant results should be investigated and the results of your investigation
should be reported in the submission. However, calculations should be
performed on the original results, not the resolved results. Please refer to
FDA’s guidance document entitled, “Guidance for Industry and FDA Staff:
Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic
Tests,” dated March 13, 2007 (Ref. 1).
Sample Types - Use blinded random samples.
Concordance Description - HLA typing results are concordant with the results from
the comparison device if at least one pair of alleles at a specific locus is the same
between the two devices, either by allele group or by full allele name. We
recommend that you provide an explanation if the list of ambiguities for the predicate
device includes a common and well documented (CWD) allele(s) that is not also
reported by your device.
NOTE: The term “allele group” refers to those groups of alleles with identical
sequences in the exons that encode for the domains of the antigen recognition site
(ARS). These HLAs likely present similar or identical peptide binding and
immunologic characteristics.
D. 	Software
If your HLA test kit includes software, you should perform validation as recommended in
the FDA guidance document entitled, “General Principles of Software Validation; Final

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Guidance for Industry and FDA Staff,” dated January 11, 2002 (Ref. 3) in preparing your
510(k) submission.
You should determine the “level of concern” of your software and submit the
documentation recommended for that level of concern as discussed in the FDA guidance
document entitled, “Guidance for Industry and FDA Staff: Guidance for the Content of
Premarket Submissions for Software Contained in Medical Devices,” dated May 11,
2005 (Ref. 4). If applicable, you should describe how your software addresses concerns
such as background correction, normalization, etc.
If your test kit uses off-the-shelf software, you should follow the recommendations
contained in the FDA guidance document entitled, “Guidance for Industry, FDA
Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices” dated
September 9, 1999 (Ref. 5).
Algorithms contained in the design of the device are critical to determining the correct
genotype and phenotype; therefore, these algorithms should be described in the 510(k)
submission.
E. 	Validation of Instrumentation
If you provide, or recommend, specific instrumentation for your test kit, whether
manufactured by you or by another company, you should include specific information
about the instrument(s) in your submission.
If you provide the instrument to the end-user as part of your test kit, your demonstration
of substantial equivalence will need to address the inclusion of this instrument in your
device. You should address this by submitting instrument validation data in the 510(k).
The instrument may be included in the 510(k) for the HLA test kit or the instrument may
be submitted as a stand-alone device under a separate 510(k) submission. In the latter
case, the HLA test kit and the instrument are reviewed at the same time.
F. 	Labeling
Under 21 CFR 807.87(e), the 510(k) submission must include proposed labels, labeling,
and advertisements sufficient to describe the device, its intended use, and the directions
for its use. Where applicable, photographs or engineering drawings should be supplied.
IVDs, including the HLA test kits covered in this guidance, are subject to labeling
requirements under 21 CFR Part 809 (In Vitro Diagnostic Products for Human Use).
You must label the product in accordance with these provisions. Furthermore, in addition
to the information required in 21 CFR 809.10(b)(2), you should include in the labeling
the following statement:
“Should not be used as the sole basis for making a clinical decision.”

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G. 	Additional Considerations
Bundling - You may bundle the test kits for different HLA loci in a single 510(k)
submission. However, as is true for any 510(k), you must provide the information
required by 21 CFR 807.87. This includes appropriate supporting information for each of
the devices or indications for use, as well as data from performance studies under
21 CFR 807.92(b), when applicable. See “Guidance for Industry and FDA Staff:
Bundling Multiple Devices or Multiple Indications in a Single Submission,” dated June
22, 2007 (Ref. 6).
Changes to the Device - Section 807.81(a)(3) requires a new 510(k) for any change or
modification that “could significantly affect” either the safety or the effectiveness of a
device. See the FDA guidance document entitled, “Deciding When to Submit a 510(k)
for a Change to an Existing Device (K97-1),” dated January 10, 1997 (Ref. 7).
Please note, for the addition of a new test kit locus, submit a traditional 510(k). For
example, if your HLA kit was cleared to provide resolution of Class II DRB locus, you
need to submit a new 510(k) if you are modifying your kit to include the resolution of
Class II DQB locus. We recommend validation testing in accordance with the
recommendations described in this guidance. For further information on traditional
510(k)s, see the FDA guidance document entitled “Guidance for Industry and FDA Staff:
Format for Traditional and Abbreviated 510(k)s,” dated August 12, 2005, and corrected
on November 17, 2005 (Ref. 8).

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IV. 	REFERENCES
1. 	Guidance for Industry and FDA Staff: Statistical Guidance on Reporting
Results from Studies Evaluating Diagnostic Tests, March 13, 2007.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm071148.htm
2. 	Guidance for Sponsors, Institutional Review Boards, Clinical Investigators
and FDA Staff: Guidance on Informed Consent for In Vitro Diagnostic
Device Studies Using Leftover Human Specimens that Are Not
Individually Identifiable, April 25, 2006.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm078384.htm
3. 	General Principles of Software Validation; Final Guidance for Industry
and FDA Staff, January 11, 2002.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm085281.htm
4. 	Guidance for Industry and FDA Staff: Guidance for the Content of
Premarket Submissions for Software Contained in Medical Devices, May
11, 2005.
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGui
dance/GuidanceDocuments/UCM089593.pdf
5. 	Guidance for Industry, FDA Reviewers and Compliance on Off-the-Shelf
Software Use in Medical Devices, September 9, 1999.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm073778.htm
6. 	Guidance for Industry and FDA Staff: Bundling Multiple Devices or
Multiple Indications in a Single Submission, June 22, 2007.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm089731.htm
7. 	Deciding When to Submit a 510(k) for a Change to an Existing Device
(K97-1), January 10, 1997.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm080235.htm
8. 	Guidance for Industry and FDA Staff: Format for Traditional and
Abbreviated 510(k)s, August 12, 2005, corrected on November 17, 2005.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm084365.htm
9. 	The International Immunogenetics (IMGT) Information System,
http://www.imgt.org
10. 	Guidance for Industry and FDA Staff: Pharmacogenetic Tests and Genetic Tests for
Heritable Markers, June 19, 2007.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm077862.htm

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11. 	Guidance for Industry and FDA Staff: In Vitro Diagnostic (IVD) Device
Studies – Frequently Asked Questions, June 25, 2010.
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGui
dance/GuidanceDocuments/UCM071230.pdf
12. 	Guidance for Industry and FDA Staff: Use of Symbols on Labels and in
Labeling of In Vitro Diagnostic Devices Intended for Professional Use,
November 30, 2004.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guid
anceDocuments/ucm085404.htm
13. 	D.W. Tholen, A. Kallner, J.W. Krouwer, and K. Meier. Evaluation of
Precision Performance of Quantitative Measurement Methods; Approved
Guideline - Second Edition, Clinical Laboratory Standards Institute, EP05-
A2, August 20, 2004. http://www.clsi.org/
14. 	R.J. McEnroe, M.F. Burritt, D.M. Powers, D.W. Rheinheimer, and B.H.
Wallace. Interference Testing in Clinical Chemistry; Approved Guideline
- Second Edition, Clinical Laboratory Standards Institute, EP07-A2,
November 23, 2005. http://www.clsi.org/
15. 	C.J. Brown and C.V. Navarrete. Clinical Relevance of the HLA System in
Blood Transfusion. Vox Sanguinis (2011); 101(2): 93-105.
16. 	J. Klein and A. Sato. The HLA System (Part I). The New England
Journal of Medicine (2000); 343:702-709.
17. 	J. Klein and A. Sato. The HLA System (Part II). The New England
Journal of Medicine (2000); 343:782-786.
18. 	U. Shankarkumar. The Human Leukocyte Antigen System. International
Journal of Human Genetics (2004); 4(2):91-103.