February 2014
MM09-A2
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Nucleic Acid Sequencing Methods in
Diagnostic Laboratory Medicine; Approved
Guideline—Second Edition
This document addresses diagnostic sequencing using both
automated capillary-based sequencers and massively parallel
sequencing instruments. Topics include specimen collection
and handling; isolation and extraction of nucleic acid; template
preparation; sequence generation, alignment, and assembly;
validation and verification; ongoing quality assurance; and reporting
results.
A guideline for global application developed through the Clinical and Laboratory Standards Institute consensus process.
Clinical and Laboratory Standards Institute
Setting the standard for quality in clinical laboratory testing around the world.
The Clinical and Laboratory Standards Institute (CLSI) is a not-for-profit membership organization that brings
together the varied perspectives and expertise of the worldwide laboratory community for the advancement of
a common cause: to foster excellence in laboratory medicine by developing and implementing clinical laboratory
standards and guidelines that help laboratories fulfill their responsibilities with efficiency, effectiveness, and
global applicability.
Consensus Process
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Consensus—the substantial agreement by materially affected, competent, and interested parties—is core to the
development of all CLSI documents. It does not always connote unanimous agreement, but does mean that the
participants in the development of a consensus document have considered and resolved all relevant objections
and accept the resulting agreement.
Commenting on Documents
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CLSI documents undergo periodic evaluation and modification to keep pace with advancements in technologies,
procedures, methods, and protocols affecting the laboratory or health care.
CLSI’s consensus process depends on experts who volunteer to serve as contributing authors and/or as
participants in the reviewing and commenting process. At the end of each comment period, the committee that
developed the document is obligated to review all comments, respond in writing to all substantive comments,
and revise the draft document as appropriate.
Appeals Process
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Comments on published CLSI documents are equally essential, and may be submitted by anyone, at any time, on
any document. All comments are addressed according to the consensus process by a committee of experts.
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If it is believed that an objection has not been adequately addressed, the process for appeals is documented in
the CLSI Standards Development Policies and Process document.
All comments and responses submitted on draft and published documents are retained on file at CLSI and are
available upon request.
Get Involved—Volunteer!
Do you use CLSI documents in your workplace? Do you see room for improvement? Would you like to get
involved in the revision process? Or maybe you see a need to develop a new document for an emerging
technology? CLSI wants to hear from you. We are always looking for volunteers. By donating your time and
talents to improve the standards that affect your own work, you will play an active role in improving public
health across the globe.
For further information on committee participation or to submit comments, contact CLSI.
Clinical and Laboratory Standards Institute
950 West Valley Road, Suite 2500
Wayne, PA 19087 USA
P: 610.688.0100
F: 610.688.0700
www.clsi.org
standard@clsi.org
ISBN 1-56238-953-X (Print)
ISBN 1-56238-954-8 (Electronic)
ISSN 1558-6502 (Print)
ISSN 2162-2914 (Electronic)
MM09-A2
Vol. 34 No. 4
Replaces MM09-A
Vol. 24 No. 40
Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine;
Approved Guideline—Second Edition
Volume 34 Number 4
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Abstract
Damon K. Getman, PhD
Tina M. Hambuch, PhD
Roger D. Klein, MD, JD, FCAP
Jamie L. Platt, PhD, CGMBS, MB(ASCP)
Lakshman Ramamurthy, PhD
Hans Scheffer, PhD
Tracy L. Stockley, PhD, FCCMG, FACMG
Patrik Vitazka, MD, PhD, FACMG
Emily S. Winn-Deen, PhD
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Thomas J. Lenk, PhD
Ira M. Lubin, PhD, FACMG
David Ross, PhD
Matthew J. Bankowski, PhD, D(ABMM)
Sarah F. Bennett, MT(ASCP)
Carey-Ann Burnham, PhD, D(ABMM)
Eric J. Duncavage, MD
Lisa M. Farwell
Tamara V. Feldblyum, MS
Manohar R. Furtado, PhD
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Sequencing methods for genotyping have moved from the research laboratory into the clinical laboratory. Sequencing is an assay
format of choice for very high-complexity genotyping, especially when hundreds or thousands of bases of genetic sequence are
analyzed. Clinical and Laboratory Standards Institute document MM09-A2—Nucleic Acid Sequencing Methods in Diagnostic
Laboratory Medicine; Approved Guideline—Second Edition addresses diagnostic sequencing using both automated capillary
electrophoresis sequencers and massively parallel sequencing instruments. Topics covered include specimen collection and
handling; isolation and extraction of nucleic acid; template preparation; sequence generation, alignment, and assembly; validation
and verification; ongoing QA; and reporting results.
Clinical and Laboratory Standards Institute (CLSI). Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine;
Approved Guideline—Second Edition. CLSI document MM09-A2 (ISBN 1-56238-953-X [Print]; ISBN 1-56238-954-8
[Electronic]). Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087 USA,
2014.
The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for moving a document through
two or more levels of review by the health care community, is an ongoing process. Users should expect revised editions of any
given document. Because rapid changes in technology may affect the procedures, methods, and protocols in a standard or
guideline, users should replace outdated editions with the current editions of CLSI documents. Current editions are listed in
the CLSI catalog and posted on our website at www.clsi.org. If you or your organization is not a member and would like to
become one, and to request a copy of the catalog, contact us at: Telephone: 610.688.0100; Fax: 610.688.0700; E-Mail:
customerservice@clsi.org; Website: www.clsi.org.
Number 4
MM09-A2
Copyright ©2014 Clinical and Laboratory Standards Institute. Except as stated below, any reproduction of
content from a CLSI copyrighted standard, guideline, companion product, or other material requires
express written consent from CLSI. All rights reserved. Interested parties may send permission requests to
permissions@clsi.org.
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CLSI hereby grants permission to each individual member or purchaser to make a single reproduction of
this publication for use in its laboratory procedure manual at a single site. To request permission to use
this publication in any other manner, e-mail permissions@clsi.org.
Suggested Citation
Approved Guideline
December 2004
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CLSI. Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine; Approved Guideline—
Second Edition. CLSI document MM09-A2. Wayne, PA: Clinical and Laboratory Standards Institute;
2014.
Approved Guideline—Second Edition
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February 2014
ISBN 1-56238-953-X (Print)
ISBN 1-56238-954-8 (Electronic)
ISSN 1558-6502 (Print)
ISSN 2162-2914 (Electronic)
ii
Volume 34
MM09-A2
Contents
Abstract ....................................................................................................................................................i
Committee Membership........................................................................................................................ iii
Foreword .............................................................................................................................................. vii
Scope.......................................................................................................................................... 1
2
Introduction ................................................................................................................................ 1
3
Standard Precautions .................................................................................................................. 2
4
Terminology............................................................................................................................... 2
Technologies and Applications ................................................................................................ 11
5.1
5.2
6
Specimen Collection, Storage, Transport, and Preparation for Analysis ................................. 24
6.1
6.2
6.3
6.4
7
General Technology Overview ................................................................................... 11
Applications Overview ............................................................................................... 18
Specimen Collection ................................................................................................... 24
Specimen Transport and Storage ................................................................................ 25
Nucleic Acid Extraction and Purification ................................................................... 25
Sample Storage and Retention .................................................................................... 26
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5
A Note on Terminology ................................................................................................ 2
Definitions .................................................................................................................... 2
Abbreviations and Acronyms ....................................................................................... 9
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4.1
4.2
4.3
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1
Template Preparation ............................................................................................................... 26
Primer Design and Synthesis for Polymerase Chain Reaction and Sequencing ......... 27
Amplification Parameters ........................................................................................... 29
Practices to Aid in Contamination Control ................................................................. 30
Polymerase Chain Reaction Product Purification ....................................................... 31
Quantity and Quality of DNA Template ..................................................................... 33
Library Construction for Massively Parallel Sequencing ........................................... 33
Unique Sample Preparation Considerations ............................................................... 37
Massively Parallel Sample Multiplexing .................................................................... 37
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7.1
7.2
7.3
7.4
7.5
7.6
7.7
7.8
8
Sequence Generation and Potential Artifacts........................................................................... 38
8.1
8.2
8.3
8.4
9
Sequence Alignment, Assembly, and Evaluation .................................................................... 48
9.1
9.2
9.3
10
Overview ..................................................................................................................... 38
Sequencing Methods and Instrumentation .................................................................. 39
Potential Artifacts and Troubleshooting ..................................................................... 41
Base Calling and Quality Scores................................................................................. 45
Sanger Sequencing ...................................................................................................... 50
Massively Parallel Sequencing ................................................................................... 54
Single Molecule Sequencing....................................................................................... 68
Validation and Verification...................................................................................................... 68
10.1
10.2
General Considerations ............................................................................................... 68
Technology-Specific Considerations .......................................................................... 80
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Contents (Continued)
10.3
10.4
Ongoing Quality Assurance and Quality Control .................................................................... 89
12
Definition and Purpose of Quality Assurance and Quality Control ............................ 89
Data Review................................................................................................................ 90
Sequence Software Assessment and Review .............................................................. 94
Platform Quality Assurance ........................................................................................ 94
Assay Quality Control ................................................................................................ 94
Operator Competency ................................................................................................. 95
Confirmatory Testing .................................................................................................. 95
Proficiency Testing/External Quality Assessment and Alternate Methods for the
Independent Assessment of Laboratory Performance ................................................ 96
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11.1
11.2
11.3
11.4
11.5
11.6
11.7
11.8
Interpreting and Reporting Results .......................................................................................... 97
12.1
12.2
12.3
12.4
Clinical Interpretation ................................................................................................. 97
Reports ...................................................................................................................... 102
Preservation of Records ............................................................................................ 104
Special Considerations .............................................................................................. 105
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11
Application-Specific Considerations .......................................................................... 83
Revalidation ................................................................................................................ 89
References ........................................................................................................................................... 106
Appendix. Example of Troubleshooting Guide for Sequencing Assays ............................................. 118
The Quality Management System Approach ...................................................................................... 120
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Related CLSI Reference Materials ..................................................................................................... 122
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MM09-A2
Foreword
Significant advances in clinical diagnostic sequencing prompted the development of the second edition of
this document. The original guideline focused primarily on the establishment and use of Sanger
sequencing in the clinical laboratory, which at the time was the principal means for the collection of DNA
sequence data. Since publication of the first edition, massively parallel sequencing (MPS) has become
part of the clinical laboratory repertoire. MPS is a catchall term that includes a number of technologies
that can generate a large amount of digital sequences. A feature that distinguishes MPS from Sanger
sequencing is the heavy reliance on informatics to process the raw data derived from the instrument into
interpretable DNA sequence. Laboratories have already begun to establish testing using MPS for heritable
conditions, cancer, and infectious diseases. Advances in other areas suggest that applications for analysis
of genome-wide methylation patterns, microbiomes, metagenomics, and transcriptome sequencing are
forthcoming.
Key Words
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This revised guideline provides additional details that address the implementation of MPS into the clinical
laboratory. In Section 5, users are initially oriented to the many sequencing technologies and currently
available applications; the contents of this section represent the technologies available at the time of this
publication, and users are encouraged to seek out recent reviews for the latest updates in this rapidly
evolving field. Information on the implementation of sequencing in the clinical laboratory has been
significantly expanded. Other sections have been added that discuss issues relevant to setup, running, and
QC of the instrumentation and considerations for informatics analysis. Test validation is discussed in
greater detail, and a separate section on QA and QC was also created. The final section that addresses the
reporting of results was revised primarily as a consequence of new guidance and resources that have
become available since publication of the previous edition of MM09. Sections that address Sanger
sequencing remain but have been updated as needed to reflect advances in practice. Sections addressing
specimen collection and preparation for analysis were consolidated into a much shorter section (see
Section 6) because these have become common laboratory practice and are covered in far greater detail in
other referenced CLSI documents. This revision is designed to provide guidance to experienced and
knowledgeable laboratory professionals to assist with the implementation of high-quality diagnostic
sequence analysis in the clinical laboratory.
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Capillary electrophoresis, clinical sequencing, dideoxy-terminators, electrophoresis, gel electrophoresis,
massively parallel sequencing, next generation sequencing, nucleic acid, polymerase chain reaction,
Sanger sequencing
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Volume 34
MM09-A2
Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine;
Approved Guideline—Second Edition
1
Scope
The intended users of this guideline are clinical laboratories involved in the development, validation,
verification, and implementation of sequencing-based assays.
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This guideline specifies recommendations for the sequencing process, including specimen collection and
handling, isolation of nucleic acid, amplification and sequencing of nucleic acids, and general
interpretation and reporting of genotyping results. It is the intent of this document to provide instruction
for verifying that the sequence obtained is accurate and suitable for subsequent interpretation; to address
general interpretation of the sequence; and to provide QA/QC considerations for each step of the process,
as appropriate. It is also intended to assist laboratories in generating appropriate and efficient validation
across sequencing methods and applications. Sanger-based DNA sequencing and general aspects of
massively parallel sequencing (MPS) are addressed in this guideline with specific examples.
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This guideline:
Does not comprehensively address platform-specific issues, because sequencing technology is rapidly
evolving

Provides general guidance for interpreting sequencing results and does not address the medical
interpretation for a given patient, which is under the purview of the health care provider

Is relevant to germline, somatic, and microbiological applications in clinical settings
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
Introduction
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Sequencing is an increasingly important tool for genotyping in molecular diagnostics. Sequencing is
routinely used in genotyping infectious disease organisms such as HIV and hepatitis C virus (HCV).
When typing tissue for transplantation, human leukocyte antigen (HLA) typing is also performed by
sequencing. There are also a variety of applications of sequencing for oncology and for diagnosing
heritable conditions. The widespread use of laboratory-developed, sequencing-based genotyping assays
and commercially available sequencing-based genotyping kits spurred the development of the original
guideline for the development, verification, validation, and implementation of sequencing-based assays.
The previous edition of this guideline focused on sequence analysis using dideoxy chain-terminating
chemistry and capillary electrophoresis (CE) instrumentation. In recent years, a number of new
technologies have been introduced commercially. One change that has occurred since the previous edition
of the guideline was published is that some instruments and assays have received regulatory approval or
clearance for Sanger or MPS clinical testing. For clinical tests that use these products, the process of test
validation and establishing QC parameters is simplified relative to a corresponding laboratory-developed
test. Additionally, there are an increasing number of clinical applications, especially for multigene panels
applied to genetic disease, for specific applications in which minor population variants can be clinically
important (eg, HIV tropism), and in oncology, where both broad coverage and low-level variant detection
can be of value. Emerging fields, such as epigenetics and the study of the microbiomes, suggest that
applications to additional complex clinical questions will only increase as sequencers are able to generate
more information at lower cost. This infusion of new technology requires a fresh look at some of the
subject matter covered for validation of CE sequencing applications, and also introduces new challenges
in the areas of platform validation and appropriate data analysis and management. This document was
©
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revised during a time of flux, with several technologies currently undergoing rapid development in both
instrumentation and software.
3
Standard Precautions
4.1
Terminology
A Note on Terminology
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Because it is often impossible to know what isolates or specimens might be infectious, all patient and
laboratory specimens are treated as infectious and handled according to “standard precautions.” Standard
precautions are guidelines that combine the major features of “universal precautions and body substance
isolation” practices. Standard precautions cover the transmission of all known infectious agents and thus
are more comprehensive than universal precautions, which are intended to apply only to transmission of
blood-borne pathogens. The Centers for Disease Control and Prevention address this topic in published
guidelines that focus on the daily operations of diagnostic medicine in human and animal medicine while
encouraging a culture of safety in the laboratory.1 For specific precautions for preventing the laboratory
transmission of all known infectious agents from laboratory instruments and materials and for
recommendations for the management of exposure to all known infectious diseases, refer to CLSI
document M29.2
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CLSI, as a global leader in standardization, is firmly committed to achieving global harmonization
wherever possible. Harmonization is a process of recognizing, understanding, and explaining differences
while taking steps to achieve worldwide uniformity. CLSI recognizes that medical conventions in the
global metrological community have evolved differently in the United States, Europe, and elsewhere; that
these differences are reflected in CLSI, International Organization for Standardization (ISO), and
European Committee for Standardization (CEN) documents; and that legally required use of terms,
regional usage, and different consensus timelines are all important considerations in the harmonization
process. In light of this, CLSI’s consensus process for development and revision of standards and
guidelines focuses on harmonization of terms to facilitate the global application of standards and
guidelines.
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In order to align the usage of terminology in this document with that of ISO and CLSI document QMS013
the terms preexamination, examination, and postexamination have replaced preanalytical, analytical, and
postanalytical, respectively, when referring to the testing phases within the path of workflow in a
laboratory.
4.2
Definitions
accuracy (of measurement) – closeness of agreement between a measured quantity value and a true
quantity value of a measurand (JCGM 200:2012)4; NOTE: For nucleic acid sequence analysis, the overall
accuracy refers to the closeness of the derived assembled sequence to the true sequence.
adapter (oligonucleotide adapter) – a short sequence of deoxynucleotides used to couple segments of
oligonucleotide.
alignment – the process of lining up two or more sequences for the purpose of assessing the percent
identity shared between sequences and/or constructing a contiguous sequence from overlapping smaller
segments.
all base accuracy – calculated by determining the percentage of the bases called that agree with the
expected base call in the reference sequence.
2
©
Clinical and Laboratory Standards Institute. All rights reserved.
Number 4
MM09-A2
The Quality Management System Approach
Clinical and Laboratory Standards Institute (CLSI) subscribes to a quality management system approach in the
development of standards and guidelines, which facilitates project management; defines a document structure via a
template; and provides a process to identify needed documents. The quality management system approach applies a
core set of “quality system essentials” (QSEs), basic to any organization, to all operations in any health care
service’s path of workflow (ie, operational aspects that define how a particular product or service is provided). The
QSEs provide the framework for delivery of any type of product or service, serving as a manager’s guide. The QSEs
are as follows:
Organization
Customer Focus
Facilities and Safety
Personnel
Purchasing and Inventory
Equipment
Process Management
Documents and Records
Information Management
Nonconforming Event Management
Assessments
Continual Improvement
MM19
MM20
QMS01
MM19
MM20
QMS01
MM19
MM20
QMS01
MM19
MM19
QMS01
QMS01
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MM19
MM20
QMS01
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MM01
MM03
MM05
MM06
MM13
MM14
MM17
MM18
MM19
MM20
QMS01
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M29
MM19
MM20
QMS01
QMS02
MM19
MM20
QMS01
MM19
MM20
QMS01
Continual
Improvement
X
EP07
EP15
GP27
GP29
Assessments
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Nonconforming
Event Management
Information
Management
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Documents and
Records
Process
Management
Equipment
Purchasing and
Inventory
Personnel
Facilities and
Safety
Customer Focus
Organization
MM09-A2 addresses the QSE indicated by an “X.” For a description of the other documents listed in the grid, please
refer to the Related CLSI Reference Materials section, beginning on page 122.
GP27
GP29
GP27
MM05
MM19
MM20
QMS01
MM19
MM20
QMS01
QMS06
QMS11
QMS12
©
Clinical and Laboratory Standards Institute. All rights reserved.
Volume 34
MM09-A2
Path of Workflow
A path of workflow is the description of the necessary processes to deliver the particular product or service that the
organization or entity provides. A laboratory path of workflow consists of the sequential processes: preexamination,
examination, and postexamination and their respective sequential subprocesses. All laboratories follow these
processes to deliver the laboratory’s services, namely quality laboratory information.
MM09-A2 addresses the clinical laboratory path of workflow steps indicated by an “X.” For a description of the
other documents listed in the grid, please refer to the Related CLSI Reference Materials section on the following
page.
X
MM01
MM03
MM05
MM06
X
MM01
MM19
MM20
QMS01
MM19
MM20
QMS01
X
MM01
MM03
MM05
MM06
MM19
MM20
QMS01
MM05
MM06
MM20
QMS01
Sample
management
Results reporting
and archiving
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Interpretation
MM06
MM13
MM19
MM20
QMS01
X
MM01
MM03
MM05
MM06
Results review
and follow-up
MM06
MM13
MM19
MM20
QMS01
X
MM01
MM03
MM05
MM06
MM13
MM19
MM20
QMS01
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X
MM01
MM03
Examination
X
MM01
MM03
Postexamination
X
MM01
MM05
MM13
MM20
QMS01
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MM20
QMS01
Sample
receipt/processing
MM05
MM06
Sample transport
MM01
Examination
Sample collection
Examination
ordering
Preexamination
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MM09-A2
Related CLSI Reference Materials
Interference Testing in Clinical Chemistry; Approved Guideline—Second Edition (2005). This document
provides background information, guidance, and experimental procedures for investigating, identifying, and
characterizing the effects of interfering substances on clinical chemistry test results.
EP15-A2
User Verification of Performance for Precision and Trueness; Approved Guideline—Second Edition
(2006). This document describes the demonstration of method precision and trueness for clinical laboratory
quantitative methods utilizing a protocol designed to be completed within five working days or less.
GP27-A2
Using Proficiency Testing to Improve the Clinical Laboratory; Approved Guideline—Second Edition
(2007). This guideline provides assistance to laboratories in using proficiency testing as a quality
improvement tool.
GP29-A2
Assessment of Laboratory Tests When Proficiency Testing Is Not Available; Approved Guideline—
Second Edition (2008). This document offers methods to assess test performance when proficiency testing
(PT) is not available; these methods include examples with statistical analyses. This document is intended for
use by laboratory managers and testing personnel in traditional clinical laboratories as well as in point-of-care
and bedside testing environments.
M29-A3
Protection of Laboratory Workers From Occupationally Acquired Infections; Approved Guideline—
Third Edition (2005). Based on US regulations, this document provides guidance on the risk of transmission
of infectious agents by aerosols, droplets, blood, and body substances in a laboratory setting; specific
precautions for preventing the laboratory transmission of microbial infection from laboratory instruments and
materials; and recommendations for the management of exposure to infectious agents.
MM01-A3
Molecular Methods for Clinical Genetics and Oncology Testing; Approved Guideline—Third Edition
(2012). This document provides guidance for the use of molecular biological techniques for detection of
mutations associated with inherited medical disorders, somatic or acquired diseases with genetic associations,
and pharmacogenetic response.
MM03-A2
Molecular Diagnostic Methods for Infectious Diseases; Approved Guideline—Second Edition (2006).
This guideline addresses topics relating to clinical applications, amplified and nonamplified nucleic acid
methods, selection and qualification of nucleic acid sequences, establishment and evaluation of test
performance characteristics, inhibitors, and interfering substances, controlling false-positive reactions,
reporting and interpretation of results, quality assurance, regulatory issues, and recommendations for
manufacturers and clinical laboratories.
MM05-A2
Nucleic Acid Amplification Assays for Molecular Hematopathology; Approved Guideline—Second
Edition (2012). This guideline addresses the performance and application of assays for gene rearrangement
and translocations by both polymerase chain reaction (PCR) and reverse-transcriptase PCR techniques, and
includes information on specimen collection, sample preparation, test reporting, test validation, and quality
assurance.
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EP07-A2
MM06-A2
Quantitative Molecular Methods for Infectious Diseases; Approved Guideline—Second Edition (2010).
This document provides guidance for the development and use of quantitative molecular methods, such as
nucleic acid probes and nucleic acid amplification techniques of the target sequences specific to particular
microorganisms. It also presents recommendations for quality assurance, proficiency testing, and
interpretation of results.
MM13-A
Collection, Transport, Preparation, and Storage of Specimens for Molecular Methods; Approved
Guideline (2005). This document provides guidance related to proper and safe biological specimen collection
and nucleic acid isolation and purification. These topics include methods of collection, recommended storage
and transport conditions, and available nucleic acid purification technologies for each specimen/nucleic acid
type. A CLSI-IFCC joint project.

CLSI documents are continually reviewed and revised through the CLSI consensus process; therefore, readers should refer to
the most current editions.
122
©
Clinical and Laboratory Standards Institute. All rights reserved.
Volume 34
MM09-A2
Related CLSI Reference Materials (Continued)
Design of Molecular Proficiency Testing/External Quality Assessment; Approved Guideline—Second
Edition (2013). This document provides guidelines for a quality proficiency testing/external quality
assessment program, including reliable databases; design control in the choice of materials and measurands;
good manufacturing processes; documentation procedures; complaint handling; corrective and preventive
action plans; and responsive timing of reports. A CLSI-IFCC joint project.
MM17-A
Verification and Validation of Multiplex Nucleic Acid Assays; Approved Guideline (2008). This
guideline provides recommendations for analytic verification and validation of multiplex assays, as well as a
review of different types of biologic and synthetic reference materials.
MM18-A
Interpretive Criteria for Identification of Bacteria and Fungi by DNA Target Sequencing; Approved
Guideline (2008). Sequencing DNA targets of cultured isolates provides a quantitative metric within which to
perceive microbial diversity, and can serve as the basis to identify microorganisms. This document is an effort
to catalyze the entry of molecular microbiology into clinical usage by establishing interpretive criteria for
microorganism identification.
`
Establishing Molecular Testing in Clinical Laboratory Environments; Approved Guideline (2011). This
guideline provides comprehensive guidance for planning and implementation of molecular diagnostic testing,
including strategic planning, regulatory requirements, implementation, quality management, and special
considerations for the subspecialties of molecular genetics, infectious diseases, oncology, and
pharmacogenetics.
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MM19-A
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MM14-A2
Quality Management for Molecular Genetic Testing; Approved Guideline (2012). This document
provides guidance for implementing international quality management system standards in laboratories that
perform human molecular genetic testing for inherited or acquired conditions.
QMS01-A4
Quality Management System: A Model for Laboratory Services; Approved Guideline—Fourth Edition
(2011). This document provides a model for medical laboratories that will assist with implementation and
maintenance of an effective quality management system.
QMS02-A6
Quality Management System: Development and Management of Laboratory Documents; Approved
Guideline—Sixth Edition (2013). This document provides guidance on the processes needed for document
management, including creating, controlling, changing, and retiring a laboratory’s policy, process, procedure,
and form documents in both paper and electronic environments.
QMS06-A3
Quality Management System: Continual Improvement; Approved Guideline—Third Edition (2011).
This guideline considers continual improvement as an ongoing, systematic effort that is an essential
component of a quality management system. A continual improvement program may consist of fundamental
processes and common supporting elements described in this guideline.
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MM20-A
QMS11-A
Management of Nonconforming Laboratory Events; Approved Guideline (2007). This guideline provides
an outline and the content for developing a program to manage a health care service’s nonconforming events
that is based on the principles of quality management and patient safety.
QMS12-A
Development and Use of Quality Indicators for Process Improvement and Monitoring of Laboratory
Quality; Approved Guideline (2010). This document provides guidance on development of quality
indicators and their use in the medical laboratory.
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Clinical and Laboratory Standards Institute. All rights reserved.
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As we continue to set the global standard
for quality in laboratory testing, we’re
adding initiatives to bring even more
value to our members and customers.
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Explore the Latest
Offerings from CLSI!
Power Forward
with this Official
Interactive Guide
Individuals
Introducing CLSI’s New Individual Membership! CLSI is offering a new membership opportunity for individuals
who support or volunteer for CLSI but whose organizations are not currently members.
Student Member ($25)—Full-time students enrolled in an academic program
Benefits include:
Participation on document development committees
Discount on educational products
Associate Member ($75)—Professionals associated with the health care profession and/or clinical and laboratory services
Benefits include:
Fundamentals for implementing
a quality management system
in the clinical laboratory.
Participation on document development committees
Discount on educational products
A 15% discount on products and services
Full Member ($250)—Professionals associated with the health care profession and/or clinical and laboratory services
Benefits include:
Participation on document development committees
Voting on all documents (concurrent with delegate voting)
Participation in governance activities (vote for the Board of Directors, be nominated for the Board, and
be eligible to be selected for Board committee service)
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Effective January 1, 2013, all CLSI volunteers are required to be members at one of the above levels if their organization is not a
CLSI member. For current volunteers (those who are still actively on committees as of January 1), we have waived the requirement
of membership until the end of their current volunteer assignment, and they may continue participating without incurring any
membership fees. Please feel free to contact CLSI’s Membership department with any questions at membership@clsi.org.
Apply Today! Visit www.clsi.org/membership for an application.
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