August 2008

M50-A
Quality Control for Commercial Microbial
Identification Systems; Approved Guideline

This document provides guidance for quality control of commercial

systems for microbial identification from culture, including information
that pertains to manufacturers, distributors, and laboratory users. The
intent is to ensure optimal performance of a microbial identification
system in an efficient (streamlined) manner.

A guideline for US application developed through the Clinical and Laboratory Standards Institute consensus process.

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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

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.

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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.

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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.

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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standard@clsi.org

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 M50-A
Vol. 28 No. 23
ISBN 1-56238-675-1 Replaces M50-P
ISSN 0273-3099 Vol. 28 No. 2
Quality Control for Commercial Microbial Identification Systems;
Approved Guideline
Volume 28 Number 23
Nancy L. Anderson, MMSc, MT(ASCP) David H. Pincus, MS, SM(AAM)
Linda C. Bruno, MA, MT(ASCP) Jon E. Salomon, BS
Kimberle C. Chapin, MD, D(ABMM), F(CAP) Paul C. Schreckenberger, PhD, D(ABMM),
Sharon Cullen, BS, RAC F(AAM)
Judy A. Daly, PhD Cindy Somogye, MT(ASCP), MBA
Rob Eusebio, MSHA, MT(ASCP) Kathleen Todd, MT(ASCP)
Rita C. Parke, MS, MT(ASCP) SM, DLM Fredricka E. Valentine, MS, MT(ASCP) SM
Alice Weissfeld, PhD, D(ABMM), F(AAM)

Abstract
Clinical and Laboratory Standards Institute document M50-A—Quality Control for Commercial Microbial Identification
Systems; Approved Guideline includes a process for streamlined quality control (QC) of commercial microbial identification
systems (MISs) that utilize multiple substrates and/or reagents to identify aerobic or anaerobic bacteria, yeasts, moulds, or yeast-
like algae from culture. It specifies responsibilities of the manufacturer, distributor, and user. M50-A includes guidelines that
may be followed when using an MIS of proven reliability to take a modified QC approach, rather than meeting requirements
included in the Clinical Laboratory Improvement Amendments of 1988 regulations. The streamlined QC approach was developed
following an evaluation of data provided by the American Society for Microbiology for a survey conducted to determine the QC
failure rates of commercial MISs. The data showed a failure rate of less than 0.1% for all commercial MISs surveyed. This
document is based on United States (US) regulations and will also serve as a useful resource for a wider audience. It is
anticipated that M50-A will be used extensively in the United States and internationally to reduce resources spent on excessive
QC testing.

Clinical and Laboratory Standards Institute (CLSI). Quality Control for Commercial Microbial Identification Systems; Approved
Guideline. CLSI document M50-A (ISBN 1-56238-675-1). Clinical and Laboratory Standards Institute, 950 West Valley Road,
Suite 2500, Wayne, Pennsylvania 19087 USA, 2008.

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 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.

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Copyright ©2008 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.

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

CLSI. Quality Control for Commercial Microbial Identification Systems; Approved Guideline. CLSI
document M50-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.

Proposed Guideline
January 2008

Approved Guideline
August 2008

ISBN 1-56238-675-1
ISSN 0273-3099

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 Volume 28 M50-A

Committee Membership

Area Committee on Microbiology

Mary Jane Ferraro, PhD, MPH John D. Turnidge, MD Michael A. Pfaller, MD
Chairholder Women’s and Children’s Hospital University of Iowa College of Medicine
Massachusetts General Hospital North Adelaide, Australia Iowa City, Iowa
Boston, Massachusetts
Michael L. Wilson, MD Robert P. Rennie, PhD
John H. Rex, MD, FACP Denver Health Medical Center University of Alberta Hospital
Vice-Chairholder Denver, Colorado Edmonton, Alberta, Canada
AstraZeneca
Cheshire, United Kingdom Advisors Thomas R. Shryock, PhD
Elanco Animal Health
Barbara Ann Body, PhD, Nancy L. Anderson, MMSc, Greenfield, Indiana
D(ABMM) MT(ASCP)
Laboratory Corporation of America Centers for Disease Control and Jana M. Swenson, MMSc
Burlington, North Carolina Prevention Centers for Disease Control and
Atlanta, Georgia Prevention
Betty (Betz) A. Forbes, PhD, Atlanta, Georgia
D(ABMM) Ellen Jo Baron, PhD
Medical College of Virginia Stanford Hospital and Clinics Melvin P. Weinstein, MD
Campus Palo Alto, California Robert Wood Johnson University
Richmond, Virginia Hospital
Donald R. Callihan, PhD New Brunswick, New Jersey
Freddie Mae Poole BD Diagnostic Systems
FDA Center for Devices and Sparks, Maryland Matthew A. Wikler, MD, MBA, FIDSA
Radiological Health Pacific Beach BioSciences, Inc.
Rockville, Maryland Lynne S. Garcia, MS San Diego, California
LSG & Associates
Daniel F. Sahm, PhD Santa Monica, California Gail L. Woods, MD
Eurofins Medinet Central Arkansas Veterans Healthcare
Herndon, Virginia Richard L. Hodinka, PhD System
Children’s Hospital of Philadelphia Little Rock, Arkansas
Fred C. Tenover, PhD, ABMM Philadelphia, Pennsylvania
Centers for Disease Control and
Prevention James H. Jorgensen, PhD
Atlanta, Georgia University of Texas Health Science
Center
San Antonio, Texas

Subcommittee on Quality Control for Commercial Microbial ID Systems

Nancy L. Anderson, MMSc, Yvette S. McCarter, PhD, DABMM Alice Weissfeld, PhD, D(ABMM),
MT(ASCP) University of Florida College of F(AAM)
Chairholder Medicine Microbiology Specialists, Inc.
Centers for Disease Control and Jacksonville, Florida Houston, Texas
Prevention
Atlanta, Georgia David H. Pincus, MS, SM(AAM) Advisors
bioMérieux, Inc.
Linda C. Bruno, MA, MT(ASCP) Hazelwood, Missouri Paul Campognone, MS,
University of Illinois Medical MT(ASCP)SM
Center Jon E. Salomon, BS BD Diagnostic Systems
Chicago, Illinois BD Diagnostic Systems Sparks, Maryland
Sparks, Maryland
Kimberle C. Chapin, MD, Judy A. Daly, PhD
D(ABMM), F(CAP) Kathleen Todd, MT(ASCP) University of Utah-Primary
Rhode Island Hospital Centers for Medicare & Medicaid Children’s Medical Center
Providence, Rhode Island Services Salt Lake City, Utah
Baltimore, Maryland
Rob Eusebio, MSHA, MT(ASCP) David Gibbs, PhD
Siemens Healthcare Diagnostics Giles Scientific Inc.
West Sacramento, California Santa Barbara, California

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Advisors (Continued) Michael Mitchell, MD Norrine Thompson,

U Mass Memorial Medical Center BSMT(ASCP)SM
Jay M. Goodman, MS, M(ASCP) Worcester, Massachusetts Albany Medical Center
St. Mary’s Hospital Albany, New York
West Palm Beach, Florida Rita C. Parke, MS, MT(ASCP) SM,
DLM Staff
Francisca L. Lehr, MS, MT(ASCP) Laboratory Corporation of America
Centers for Medicare & Medicaid Burlington, North Carolina Clinical and Laboratory Standards
Services Institute
Seattle, Washington Megan E. Sawchuk, MT(ASCP) Wayne, Pennsylvania
The Joint Commission
Brandi Limbago, PhD Oakbrook Terrace, Illinois
Lois M. Schmidt, DA
Centers for Disease Control and
Vice President, Standards
Prevention Paul C. Schreckenberger, PhD,
Development and Marketing
Atlanta, Georgia D(ABMM), F(AAM)
Loyola University Medical Center
Linda M. Mann, PhD, D(ABMM) Maywood, Illinois Tracy A. Dooley, BS, MLT(ASCP)
Siemens Healthcare Diagnostics Staff Liaison
West Sacramento, California Cindy Somogye, MT(ASCP), MBA
bioMérieux, Inc. Melissa A. Lewis
Hazelwood, Missouri Editor

Acknowledgment

CLSI acknowledges the American Society for Microbiology and its professional committees, with special
recognition of the following individuals for their contributions that lead to the development of this
guideline:

Joseph Campos, PhD – Chair, Committee on Laboratory Practices, Public and Scientific Affairs Board
Suzanne Leous, MPA – Manager, Public Affairs
David Sewell, PhD – Committee on Professional Affairs, Public and Scientific Affairs Board
Alice Weissfeld, PhD – Chair, Committee on Professional Affairs, Public and Scientific Affairs Board

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 Volume 28 M50-A

Contents

Abstract ....................................................................................................................................................i

Committee Membership........................................................................................................................ iii

Foreword .............................................................................................................................................. vii

1 Scope .......................................................................................................................................... 1

2 Introduction ................................................................................................................................ 1

3 Standard Precautions.................................................................................................................. 2

4 Terminology............................................................................................................................... 2
4.1 Definitions .................................................................................................................... 2
4.2 Abbreviations/Acronyms .............................................................................................. 5
5 General Responsibilities of the Manufacturer, Distributor, and User ........................................ 6
5.1 Manufacturer .................................................................................................................6
5.2 The Distributor .............................................................................................................. 7
5.3 The User........................................................................................................................ 8
6 Process for Quality Control of Microbial Identification Systems .............................................. 9
6.1 Manufacturer’s Responsibilities ................................................................................... 9
6.2 User’s Responsibilities to Qualify for Streamlined Quality Control .......................... 10
7 Quality Control Procedures for Microbial Identification Systems .......................................... 12
7.1 Quality Control Organisms ......................................................................................... 12
7.2 Quality Control Testing Process ................................................................................. 13
7.3 Quality Control Testing Frequency ............................................................................ 13
7.4 Interpretation of Quality Control Test Results............................................................ 13
7.5 Corrective Action ........................................................................................................ 13
References ............................................................................................................................................. 15

Appendix A. Manufacturer’s Requirements for Streamlined Quality Control Section of Package

Insert or Product Information for a Microbial Identification System ...................................................... 16

Appendix B. User’s Requirements to Qualify for Streamlined Quality Control of a Microbial

Identification System ............................................................................................................................ 17

Appendix C. Documentation of Streamlined Quality Control Results – Minimum Record

Requirements ........................................................................................................................................ 18

Appendix D. Troubleshooting Guide for Microbial Identification System Quality Control

Failures ................................................................................................................................................. 19

Summary of Comments and Subcommittee Responses ........................................................................ 22

The Quality Management System Approach ........................................................................................ 26

Related CLSI Reference Materials ....................................................................................................... 27

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Foreword

This document is based on United States (US) regulations and will also serve as a useful resource for a
wider audience. It is anticipated that M50-A will be used extensively in the United States and
internationally to reduce resources spent on excessive quality control (QC) testing.

Historically, in the United States, the accepted practice for QC of conventional biochemical reagents or
miniaturized systems used for microbial identification from culture involved checking positive and
negative reactivity with each batch, lot number, and shipment of reagents or systems. This practice was
codified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ‘88) for any
commercial microbial identification system (MIS) using two or more substrates, two or more reagents, or
a combination of both.1 The CLIA regulations require each laboratory to test every substrate and/or
reagent that is part of an MIS for positive and negative reactivity, using biologic QC organisms, with each
batch, lot number, and shipment. Over time, as MISs have evolved and become more complex, they have
incorporated increasing numbers of reagents and substrates; this has resulted in the need for an increased
number of QC organisms to check positive and negative reactivity for all components. In addition, some
MISs now utilize identification algorithms that do not allow for total compliance with this CLIA QC
requirement, but have proven reliability in organism identification. Thus, in some cases, meeting this QC
requirement is now impossible; whereas in other cases, it imposes financial and workflow burdens on
microbiology laboratories, and may be unnecessary for MISs of proven reliability produced by
manufacturers that meet quality standards and applicable regulations for control and distribution.

After considering this issue, in 2005, the American Society for Microbiology (ASM), at the suggestion of
the Clinical Laboratory Improvement Advisory Committee (CLIAC), conducted a microbiology
laboratory survey to determine the QC failure rates of commercial MISs in a random selection of
laboratories that perform bacterial and fungal identification from culture. Two hundred ninety-two
laboratories provided valid responses to the survey for 9886 lots of MISs. The laboratories varied in the
type of facility, source of primary accreditation, and number of cultures performed per year. The number
of different MISs used in the responding laboratories to identify gram-positive and gram-negative aerobic
bacteria, Neisseria/Haemophilus, anaerobic bacteria, and yeasts ranged from 1 to 13, with the majority of
laboratories using five or more systems. Of the 9886 lots of MISs tested, 912 lots failed QC. For these
failures, 905 were caused by the QC organism(s) used; and in seven cases, the failure was due to the MIS
itself, specifically certain reagents and/or substrates that appeared to be labile and did not react as
expected. In these cases, the faulty MIS lots were replaced by the manufacturer. Based on these seven
instances, the failure rate due to the MIS was less than 0.1% for all MISs tested.2

ASM presented these QC survey data to CLIAC, and recommended that the Clinical and Laboratory
Standards Institute (CLSI) use its consensus process to analyze the data and develop guidelines to address
appropriate QC for MISs.3 Subsequently, CLSI recommended convening a subcommittee representing
laboratorians, manufacturers, and government (specifically, the Centers for Disease Control and
Prevention [CDC], Centers for Medicare & Medicaid Services [CMS], and US Food and Drug
Administration [FDA]) to determine whether and under what circumstances streamlined QC for MIS
would be acceptable. This consensus document describes the acceptable criteria for allowing streamlined
QC, as compared to the requirements specified by the CLIA regulations for MISs produced by
manufacturers that meet specific quality standards and regulations. It is intended to provide practical
guidelines for laboratories to ensure the quality of their microbial identification results when using
commercial MISs. It is anticipated that these guidelines will receive widespread use in the United States
and internationally, and could reduce unnecessary costs and other resources spent on excessive QC testing.

Key Words

Commercial microbial identification system (MIS), key indicator strain, quality control (QC), reagent,
streamlined QC, substrate
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Quality Control for Commercial Microbial Identification Systems;

Approved Guideline

1 Scope
This document provides quality control (QC) information for commercially available microbial
identification systems (MISs), which are test systems that utilize multiple substrates and/or reagents to
identify aerobic or anaerobic bacteria, yeasts, moulds, or yeast-like algae (eg, Prototheca species) grown
from culture. It does not address primary isolation media, chromogenic agars, direct antigen tests, stains,
or molecular methodologies used for microbial identification; nor does it address QC of antimicrobial
susceptibility tests. The document specifies the QC responsibilities of the manufacturer, distributor, and
user, and identifies conditions under which an MIS with proven reliability can qualify for streamlined QC
testing. The modified approach may be applied after the user verifies acceptable MIS performance as
specified in this guideline. Implementation of streamlined QC testing by users assumes that the MIS
performance is monitored by overall quality assurance (QA) programs on the part of the manufacturer,
distributor, and user.

This document is based on United States (US) regulations and will also serve as a useful resource for a
wider audience. It is anticipated that M50-A will be used extensively in the United States and
internationally to reduce resources spent on excessive QC testing.

2 Introduction
Prior to 1998, the US Food and Drug Administration (FDA) considered MISs used clinically as Class I
nonexempt medical devices that required premarket notification (510[k]) submission and review. Under
the FDA Modernization Act of 1997, this type of medical device was reclassified to Class I exempt status
and no longer requires 510(k) clearance.4 Today, MISs that are marketed for clinical use in the United
States should be registered and the devices listed with the FDA. In meeting the FDA Quality System
Regulation (QSR) for Current Good Manufacturing Practice requirements, the same criteria as prior to
reclassification must be met by manufacturers to support the intended use, and to establish performance
characteristics for a device just as though a 510(k) submission was required.5 The data package must be
assembled and retained through the life of the product at the manufacturer’s site, and must be available
for inspection by the FDA. If an MIS or other clinical product is marketed globally, other regulatory
agencies may require submission of a data package and/or registration of the product prior to marketing
(eg, In Vitro Diagnostic Directive 98/79/European Commission in the European Union, Ministry of
Health in Japan).

In the United States and its territories, any testing of human specimens for diagnosis, prevention, or
treatment of disease or assessment of health is subject to the Clinical Laboratory Improvement
Amendments of 1988 (CLIA ‘88) regulations.6 Also subject to CLIA are facilities outside the United
States or its territories that perform testing as described above when such tests are referred by, and the
results are returned to, a facility or authorized person in the United States or its territories. As per the
CLIA regulations effective 1 September 1992, prior to performing patient testing using a commercial
MIS, each laboratory needs to verify that it can obtain performance specifications comparable to those of
the manufacturer.7 For a commercial MIS in use before this date, no verification studies are required.
Regardless of the implementation date in a laboratory, for QC of a commercial MIS, the CLIA regulations
require a laboratory to check every reagent and/or substrate of each batch, lot number, and shipment when
prepared or opened for positive and negative reactivity (42 CFR [Code of Federal Regulations] 493.1256
[e][1]).1 The CLIA interpretive guidelines (42 CFR 493.1261[a]) also state that the laboratory must use
control organisms to verify positive and negative reactivity.8 This ongoing QC testing is a means of

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validating that the MIS continues to perform acceptably throughout its use, as was demonstrated by the
laboratory in the initial verification study.

To meet the CLIA regulations for an MIS, in many cases, laboratories need to perform extensive QC
testing, even though the perceived value of this testing is low considering the frequency of product
failures. The variable reactivity of some QC organisms can also lead to retesting that is considered of
questionable value. The 2005 American Society for Microbiology (ASM) survey conducted to determine
QC failure rates and the value of such extensive testing and retesting showed that real product failure was
extremely rare (7/9886 or <0.1%), in comparison to failure associated with QC organism variability that
was resolved after retesting (905/9886 or 9.2%).3 However, on review of the QC data with a variety of
individual test systems, predictable patterns of failure due to a specific substrate were noted for some
systems. As one example, xylose was found to be reactive when it should have been nonreactive with one
particular MIS. Thus, while testing every substrate for a positive and negative reaction may not be
necessary to identify the test system failure, evaluating the reaction of specific substrates for a given MIS
may be appropriate in a scheme for streamlined QC. In this example, because pentose sugars such as
xylose may be heat-labile, the streamlined QC recommended by the manufacturer should include
checking the stability of this carbohydrate. Data from the ASM survey suggest that before a streamlined
QC scheme is adopted by a laboratory, the manufacturer needs to recommend a scheme that includes
checking appropriate organisms (ie, key indicator strains) to assess the performance of the MIS and detect
degradation of labile reagents and/or substrates. Not all manufacturers may choose to provide this
information for their MISs. If not, the laboratories using those systems must meet the comprehensive
CLIA QC requirements.

3 Standard Precautions
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 infectious agents and thus are
more comprehensive than universal precautions, which are intended to apply only to transmission of
blood-borne pathogens. Standard and universal precaution guidelines are available from the US Centers
for Disease Control and Prevention.9 For specific precautions for preventing the laboratory transmission
of all infectious agents from laboratory instruments and materials and for recommendations for the
management of exposure to all infectious disease, refer to CLSI document M29.10

4 Terminology

4.1 Definitions

accuracy – the ability of an MIS to correctly identify the organism being tested.

automated MIS – MIS in which all, or most, steps (eg, inoculation, incubation, result interpretation) are
performed by an instrument.

batch – all tubes, plates, or containers of an MIS that have the same lot number and are received in a
single shipment.

Certificate of Analysis (COA) – document provided by the manufacturer stating that the released
product meets all Quality System Regulation (QSR) requirements and quality control specifications;
NOTE: COAs apply to individual lots of the product (ie, lot-specific).

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Certificate of Compliance (COC) – document provided by the manufacturer stating that the product
meets all Quality System Regulation (QSR) requirements and quality control specifications; NOTE:
COCs apply to all lots of the product (ie, product-specific).

comprehensive CLIA QC – the process of testing every substrate and/or reagent that is part of an MIS
for positive and negative reactivity, using biologic QC organisms, with each batch, lot number, and
shipment of MIS.

cryopreservative – a liquid, usually tryptic soy broth with glycerol or skim milk, used to preserve an
organism during fast freezing.

distributor – person or legal entity that furthers the marketing and/or selling of a device from the original
place of manufacture to the ultimate user without modifying the device, its packaging, or its labeling
(ISO/DIS 18113).11

information supplied by the manufacturer – 1) all printed, written, graphic, or other information
annexed to, or accompanying an in vitro diagnostic reagent (ISO 19001)12; 2) refers to information related
to identification, description, safety, and use of an in vitro diagnostic medical device; includes, for
example, labels, instructions for use, and promotional materials, but excludes shipping documents, safety
data sheets, and catalogues (ISO/TR 18112).13

inoculum – microorganisms dispensed or mixed in a culture medium or MIS prior to testing.

instructions for use (product insert) – information supplied by the manufacturer with an in vitro
diagnostic medical device concerning the safe and proper use of the reagent or the safe and correct
operation, maintenance, QC guidelines (streamlined and regular), and basic troubleshooting of the
instrument (modified from ISO 15197)14; NOTE: Modification from these instructions constitutes a
modified MIS.

key indicator strains – specific organisms recommended by the manufacturer of an MIS that are
necessary to test as part of the streamlined QC process; NOTE: The organisms should be those the
manufacturer has determined will best assess the performance of the MIS and detect degradation of labile
reagents and/or substrates.

labeling – all printed, written, graphic, or other information affixed to, or accompanying an in vitro
diagnostic medical device including labels on any of its packaging, user’s manuals, and package inserts
(ISO 15197)14; NOTE: All labels and other written, printed, or graphic matter upon any article or any of
its containers or wrappers, or accompanying such article (US Food, Drug, and Cosmetic Act, Section
201 [m]).

manual MIS – MIS requiring the user to inoculate, incubate, and interpret results using nonautomated
methods or devices.

manufacturer – a person or entity with responsibility for the design, manufacture, packaging, or labeling
of a medical device, assembling a system, or adapting a medical device before it is placed on the market
or put into service, regardless of whether these operations are carried out by that manufacturer or on that
manufacturer’s behalf by a third party (ISO/FDIS 14971)15; NOTE: Provisions of national or regional
regulations may apply to the definition of manufacturer.

microbial identification system (MIS) – a test system that utilizes multiple substrates and/or reagents to
identify aerobic or anaerobic bacteria, yeasts, moulds, or yeast-like algae grown from culture.

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modified MIS – a test system in which the user has modified the manufacturer’s instructions including
but not limited to use of required reagents/accessories, adherence to test instructions and conditions, and
intended use.

product failure – failure of a test system to meet the manufacturer’s specifications (including expected
QC results) when shipped, stored, and performed according to the manufacturer’s instructions.

QC failure – result that differs from the expected QC result.

quality assurance (QA) – all the planned and systematic activities implemented within the quality
system and demonstrated as needed, to provide adequate confidence that an entity will fulfill
requirements for quality (ISO 8402)16; NOTE: QA includes monitoring, evaluating, taking corrective
actions, if necessary, and monitoring the corrective actions for preanalytical, analytical, and postanalytical
activities; these activities include, but are not limited to, record keeping, calibration and maintenance of
equipment, quality control, proficiency testing, training, and competency assessment.

quality control (QC) – the operational techniques and activities that are used to fulfill requirements for
quality (ISO 9000)17; NOTE: In clinical laboratory testing, quality control includes the procedures
intended to monitor the performance of a test system to ensure reliable results.

Quality System Regulation (QSR) – revision of Good Manufacturing Practice regulation 21 CFR 820
(US Food, Drug and Cosmetic Act)5 that added design controls, production controls, process validation,
and quality assurance documentation as requirements to the manufacture of medical devices and in vitro
diagnostic products.

reagent – a substance or supplementary solution added to an MIS that produces a biochemical reaction
with a microorganism and allows a product or byproduct of that microorganism to be detected and/or
measured.

reproducibility – ability of a product, within lots and across multiple lots, to produce the same results,
while used under different conditions (eg, different sites, different operators, different instruments).

risk mitigation – a process designed to prevent or detect MIS malfunction.

robustness study – study/analysis/evaluation, performed during product development, to ascertain

performance of a product at the limits being claimed; refers to product parameters (eg, inoculum
concentration, temperature, age of culture).

semiautomated MIS – MIS in which at least one step (eg, inoculation, incubation, result interpretation)
is performed by an instrument.

shipping conditions – environmental parameters, established by manufacturer, describing how a product

is to be shipped.

shipping study – study/analysis/evaluation, performed during product development, assuring that a

product can be shipped without deterioration that negatively impacts product performance under different
adverse temperature conditions.

stability study – study/analysis/evaluation, performed during product development, to establish the

expiration date of a product and to ensure the product will perform, as expected, when used or stored as
recommended by the manufacturer.

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storage conditions – environmental parameters established by the manufacturer, describing how a

product is to be stored; NOTE: These parameters must be followed to ensure product claims are met.

streamlined QC – the reduction of QC for a commercial MIS as compared to the requirements in the
CLIA regulations; NOTE: To allow for streamlined QC, the manufacturer of the MIS will specify the key
indicator strains and reagents/substrates to be tested, as applicable. The manufacturer will also provide the
expected QC results for the indicator strains for each MIS, based on historical data and ongoing QA
programs at the site of manufacture. The laboratory user may add but may not decrease the number of
specific QC organisms and/or reagents/substrates to be tested and reviewed, as recommended by the
manufacturer for each lot number and shipment. Implementation of streamlined QC by the user can only
occur after the user has verified the performance of the test system in use.

substrate – a biochemically active ingredient used for identification that is incorporated in an MIS and is
acted upon and converted to a chemically different product.

validation – confirmation, through the provision of objective evidence, that requirements for a specific
intended use or application have been fulfilled (ISO 9000)17; NOTE 1: WHO defines validation as “the
action (or process) of proving that a procedure, process, system, equipment, or method used works as
expected and achieves the intended result” (WHO-BS/95.1793)18; NOTE 2: The components of
validation are quality control, proficiency testing, validation of employee competency, instrument
calibration, and correlation with clinical findings (CLSI/NCCLS document MM06).19

verification – confirmation, through the provision of the objective evidence, that specified requirements
have been fulfilled (ISO 9000)17; NOTE: Example: Verification of commercial laboratory information
systems, instruments, and methods; under the Clinical Laboratory Improvement Amendments of 1988, for
an unmodified, commercial MIS introduced after 1 September 1992, each laboratory must verify that it
can obtain performance characteristics (accuracy, precision, reportable range of test results) comparable
to those established by the manufacturer.

4.2 Abbreviations/Acronyms

ASM American Society for Microbiology

ATCC American Type Culture Collection
CDC Centers for Disease Control and Prevention
CFR Code of Federal Regulations
CLIA Clinical Laboratory Improvement Amendments
CLIAC Clinical Laboratory Improvement Advisory Committee
CMS Centers for Medicare & Medicaid Services
COA Certificate of Analysis
COC Certificate of Compliance
EPA Environmental Protection Agency
FDA Food and Drug Administration
ISO International Organization for Standardization
MIS microbial identification system
OSHA Occupational Safety and Health Administration
QA quality assurance
QC quality control
QSR Quality System Regulation
US United States
WHO World Health Organization

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5 General Responsibilities of the Manufacturer, Distributor, and User

The overall goal of a QA program for MISs is to ensure accurate and reliable testing results, by verifying
that all test system components are performing as specified by the manufacturer and at a quality level that
meets regulatory requirements and clinical needs of the user. The manufacturer, distributor, and user each
play a key role in meeting this goal, and may choose not to participate in streamlined QC. This section
outlines the responsibilities of each partner and defines the nature of the partnership between
manufacturers, distributors, and users of MISs.

5.1 Manufacturer

5.1.1 Regulatory Requirements for Microbial Identification Systems

The manufacturer is required to follow quality system standards (eg, ISO 13485)20 and regulations (eg,
QSRs)5 applicable to its country or region. These include requirements for:

• design controls – documented processes covering inputs for product requirements or improvements,
validation of outputs, and postmarket surveillance;

• risk assessment – determination of device misuse or failure modes that could occur with a device, the
risk associated with that failure, and any mitigation to prevent or reduce the occurrence of the
possible failure;

• production and process controls, acceptance activities for each lot released – includes documented
processes for approval of raw materials, preventive maintenance and QC of all manufacturing
equipment, training and competency of manufacturing employees, and QC of finished goods;

• corrective and preventive action – includes trending or customer feedback, product performance,
investigations for out-of-specification performance, and all corrective actions;

• labeling, device packaging – includes full traceability for all lots shipped to customers and accurate
communication about the products, while incorporating globally required labeling standards;

• handling, storage, shipment – data in design files support all recommendations for handling, storage,
and shipment;

• installation and servicing; and

• nonconforming product and complaint investigations – includes routine procedures and record
retention for monitoring and investigating complaints and field service, as well as evaluating the need
for action to prevent occurrence of nonconformities.

5.1.2 Quality Control of Microbial Identification Systems

The manufacturer is responsible for establishing and performing adequate QC to ensure the safety and the
effectiveness of the MIS. This includes checking a positive and negative result for each reagent, substrate,
or other MIS component to ensure appropriate activity of all components when the MIS has been
manufactured properly.

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5.1.3 Quality Control Information Provided to the Users

The manufacturer is responsible for providing adequate instructions for use. This includes selection of QC
organisms appropriate for their MISs that are readily available (see Sections 6.1 and 7.1) and acceptance
criteria for QC testing.

User QC may include a comprehensive program (eg, positive and negative organisms for each
reagent/substrate) that complies with requirements specified by CLIA1 or a streamlined program that
allows for more focused QC testing using key indicator strains. To allow for streamlined user QC, the
manufacturer must provide a statement of compliance with ISO 1348520 and QSRs5 (eg, Certificate of
Analysis [COA], Certificate of Compliance [COC]), either in the instructions for use or as a separate
document available to the user. If key indicator strains are specified, the manufacturer must provide
explanation as to why these strains were selected to best assess performance of the MIS and detect
degradation of labile reagents/substrates.

The manufacturer should also provide information to users regarding the scope and effectiveness of any
design features intended to mitigate risk of potential device failures. This information includes the risk
associated with such failures, how the QC design features operate, and the studies done to verify the
effectiveness of those features. The information can be provided to the user in various ways (eg, print,
electronic, or Internet).

5.1.4 Actions Taken When User Reports Quality Control Failure

The manufacturer is responsible for maintaining complaint files. This includes establishing and
maintaining procedures for receiving, reviewing, and evaluating complaints by a formally designated unit.
The intent of such procedures is to ensure that:

• all complaints are processed in a uniform and timely manner;

• all complaints are documented upon receipt; and

• complaints are evaluated to determine whether the complaint represents an event that is required to be
reported to FDA under part 803 of Medical Device Reporting.21

The manufacturer is responsible for investigating, documenting, and monitoring complaints to determine
if the MIS still meets performance characteristics as determined by the manufacturer. This may include
identification of the potential cause of the complaint or nonconformance (eg, user error, product
deterioration, product failure) and appropriate corrective actions (eg, QC organism maintenance,
inoculation, product replacement).

5.2 The Distributor

The distributor should perform the following:

• Comply with the manufacturer’s labeled specifications for MIS storage and handling before and
during delivery to the user, including conditions to prevent physical and temperature-related damage.

• Maintain documentation that verifies compliance with such specifications and is available to users
and manufacturers if requested.

• Communicate user complaints to the manufacturer, as appropriate.

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5.3 The User

The user should perform or meet the following:

• Develop procedures to ensure adherence within the user’s institution to the manufacturer’s
recommendations for MIS storage and handling from the time the MIS is received by the institution’s
central receiving area (loading dock) until delivery to the laboratory.

• Comply with the manufacturer’s recommendations for MIS storage and handling from the time the
MIS is delivered to the laboratory storage area until it is used for routine in vitro testing.

• Ensure all individuals who perform testing with the MIS are qualified and trained to conduct testing,
and have been shown to be competent in use of that MIS.

• Retain and follow the current technical information and/or product insert containing instructions for
use provided by the manufacturer. The testing information should include instructions for:

− accurate inoculum preparation;

− proper incubation conditions; and
− correct interpretation of end points and results.

• Adhere to processes and procedures outlined in Sections 6 and 7 of this document.

• Document all MIS QC activities and corrective action as stipulated in this document.

• Comply with all applicable regulations for testing and retaining documents, including any state or
local requirements that are different and/or more stringent than federal requirements.

The user should integrate the manufacturer’s risk mitigation information with the unique characteristics of
its environment to develop effective QC protocols for in vitro diagnostic devices. Environmental
characteristics can include unique factors (eg, personnel competency, testing location, test volume,
temperature) that may impact test results.

5.3.1 Reporting Quality Control Failures to the Distributor or Manufacturer

The user should perform the following:

• Identify and correct the cause of any MIS QC failure as described in Section 7.5. Document all
corrective actions.

• Notify the manufacturer and/or distributor of the failure in a timely manner. If QC failures are not
resolved easily (eg, procedural reviews, replacement of QC organisms), the manufacturer should be
contacted early in the process of troubleshooting to provide assistance.

• Document the manufacturer and/or distributor’s response as part of the corrective action.

• If it is determined that the QC failure resulted in an MIS product failure that could cause or contribute
to serious injury or illness, report the failure to the FDA21 or appropriate regulatory authority.

MIS replacement depends on the nature of the problem and negotiation with the manufacturer.

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6 Process for Quality Control of Microbial Identification Systems

6.1 Manufacturer’s Responsibilities (see Appendix A)

The manufacturer must meet the following responsibilities in order for a laboratory user to perform
streamlined QC of MISs, as described in Section 6.2. If a manufacturer does not meet these
responsibilities, laboratories that choose to use that manufacturer’s MISs must meet the comprehensive
CLIA QC requirements.

• Register with the FDA or appropriate country, regional, or local regulatory agency(ies).

• Comply with ISO 1348520 and QSR5 requirements for MIS production, including studies to
determine:

− performance characteristics (accuracy, reproducibility);

− shipping conditions and stability; and
− storage conditions and stability.

• Provide documentation to the user of conformance with ISO 1348520 and QSR requirements.5
Examples include, but are not limited to:

− COC;
− COA; or
− certification statement included in the manufacturer’s instructions for use. A statement from the
manufacturer could be included in the QC section of the product insert or other document
containing MIS instructions for use, stating that a user of this MIS could qualify to perform
streamlined QC by following the manufacturer’s instructions and meeting the criteria specified in
this document.

• Develop an agreement with the distributor to establish and meet expectations for storage, shipping,
and handling from the time the MIS leaves the distribution warehouse until it is delivered to the user’s
facility.

• Provide adequate instructions for use of the MIS to the user, including streamlined QC, to confirm
acceptable performance after shipping/storage.

• Provide a list of recommended QC organisms to the user with expected results that will ensure
accuracy and reproducibility of the MIS, when testing is performed by the user according to the
manufacturer’s instructions. This includes the following:

− a list of the key indicator strains of QC organisms that are needed to perform streamlined QC;

− justification for streamlined QC with an explanation as to why each key indicator strain was
chosen and the expected results for that strain (eg, organism selected to evaluate performance of
the least robust substrate or to demonstrate reactivity in the greatest number of wells);

− for any MISs in which streamlined QC is not an option, a list of QC organisms that will provide
positive and negative reactivity for each reagent and/or substrate; and

− assurance that organisms recommended for user QC (comprehensive or streamlined) are

commercially available in a specific culture collection.

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6.2 User’s Responsibilities to Qualify for Streamlined Quality Control (see Appendix B)

All laboratories must have an adequate QA program to ensure accurate and reliable testing and meet
regulatory requirements for quality.22 A critical part of the QA program, QC is intended to monitor test
system performance. Laboratory users of MISs may qualify to perform streamlined QC as recommended
by the manufacturer in lieu of meeting the control requirements specified by CLIA at 42 CFR
493.1256(e)(1),1 if the manufacturer meets the responsibilities specified in Sections 5.1 and 6.1, and the
user meets criteria outlined below and in Sections 5.3 and 7 of this document. The same criteria apply to
all MISs, regardless of whether they are manual, semiautomated, or automated systems. After streamlined
QC is implemented, laboratory users must routinely monitor the streamlined QC to ensure that MIS
performance continues to meet requirements for quality.

The criteria for initiation of streamlined QC differ depending on whether verification of performance
specifications, as described by CLIA at 42 CFR 493.1253(b),7 has been conducted to show that the MIS
performs acceptably; and whether the laboratory has been performing comprehensive CLIA QC of each
reagent/substrate.1 Under CLIA, a verification study is required for all MISs implemented since 1
September 1992 prior to their use in the laboratory, and documentation is needed to show that this study
was conducted. If a laboratory has not conducted a verification study because its MIS was in use before 1
September 1992, or does not have documentation of the verification for an MIS implemented after this
date, but has been performing comprehensive CLIA QC since required in 1992 as a means of validating
its MIS performance on an ongoing basis, it may perform a historical review of its QC results to qualify
for streamlined QC. If a laboratory has not conducted a verification study and has not been performing
comprehensive CLIA QC, it does not qualify for streamlined QC until it has documentation that it has
met one of these criteria.

NOTE: A commercial MIS that is modified by the user does not qualify for streamlined QC (see the
definition of “modified MIS” in Section 4.1).

6.2.1 Initial Qualification

The user must meet the following responsibilities for each MIS to initiate performance of streamlined QC:

1. Maintain current documentation of the manufacturer’s conformance with ISO 1348520 and QSR5
requirements as described in Section 6.1. This includes certification in the form of a COC, COA, or a
certification statement in the manufacturer’s instructions for use.

2. Meet one of the following:

a. If the user has performed a verification study for the MIS to demonstrate it can obtain
performance specifications comparable to the manufacturer, as described in the CLIA regulations
at 42 CFR 493.1253(b)(1),7 streamlined QC may be implemented immediately. Documentation of
the verification study must be available.

b. If the user has not performed a verification study as described above or does not have the required
documentation, but has been performing comprehensive MIS QC as described in the CLIA
regulations at 42 CFR 493.1256(e)(1),1 the user may conduct and document a historical review of
QC performance with that MIS as follows:

i. Review QC performance for at least three consecutive lot numbers of the MIS, from three
different shipments that span at least three consecutive seasons, to assess seasonal variation
of shipping conditions.

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 Volume 28 M50-A

ii. QC testing must have been performed using positive and negative controls for each reagent
and/or substrate according to the manufacturer’s instructions.

iii. Performance shall be considered satisfactory and the user may initiate streamlined QC if at
least 95% of the reagent/substrate results are within the results specified by the manufacturer.
Performance shall be considered satisfactory and the user may initiate streamlined QC if at
least 95% of the reagent/substrate results are within the results specified by the manufacturer.
However, even if the QC results meet this 95% threshold, if the same reagent/substrate fails
repeatedly, it may be indicative of a problem. These results should be further evaluated (eg,
the user should refer to the Troubleshooting Guide in Appendix D or contact the
manufacturer for assistance).

iv. If sufficient data are not available to conduct the historical review of QC performance, or the
data do not provide expected QC results, after corrective action (as applicable), the user may
choose to assess QC performance prospectively as described above, or may verify and
document the performance specifications for the MIS as described in the CLIA regulations at
42 CFR 493.1253(b)(1).7

c. If the user has not performed a verification study and has not been performing comprehensive
MIS QC as described in the CLIA regulations,1,7 or does not have documentation of one of these
options, it must perform comprehensive CLIA QC and may not initiate streamlined QC until it
has documentation that it has met either option a or b described above.

NOTE: The user may refer to CLSI document EP1223 or professional organization guidelines24 for
assistance in conducting verification studies.

6.2.2 Continued Qualification

The user must perform the following to continue to qualify for streamlined QC on an ongoing basis:

• Maintain current documentation of the manufacturer’s conformance to QSR requirements, in the form
of the certification listed in Section 6.1.

• Maintain documentation of the results of the verification study or historical QC review, as applicable,
described in Section 6.2.1.

• Test all key indicator strains specified in the manufacturer’s instructions for streamlined QC with
each batch, lot number, and shipment of MIS.

• Perform testing according to the manufacturer’s instructions and use only manufacturer-
recommended reagents for testing.

• Monitor and document streamlined QC performance (see Appendix C).

• Investigate and resolve any QC failures, including any reagents and/or substrates that repeatedly do
not perform as expected, and verify that the key indicator strains detect any product failures that
occur. Note that product failure is not equivalent to misidentification due to inadequacy of the QC
organism tested. Refer to Section 7.5 and the troubleshooting guide in Appendix D for additional
information regarding QC failures.

• Report QC failures to the manufacturer and distributor as described in Section 5.3.1.

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7 Quality Control Procedures for Microbial Identification Systems

7.1 Quality Control Organisms

7.1.1 Selection

Each manufacturer should supply a list of QC organisms recommended for use with their MISs, including
key indicator strains for streamlined QC. The user should follow the manufacturer’s recommended
specifications for QC organism selection to ensure optimal and expected reactions. These organisms
should be easily accessible from either culture collections or commercial sources.

7.1.2 Storage

For storage of refrigerated or room temperature cultures, refer to the manufacturer’s recommendations.
See below if instructions are not provided by the manufacturer.

QC Organisms Storage Type of Stock Maximum

Conditions Culture Length of
Storage
All Per Lyophilized Until expiration
manufacturer date
Rapidly growing bacteria, 2-8 °C Working QC cultures 4 weeks
yeast, and yeast-like algae
2-8 °C Stock QC cultures 12 months
< −20 °C Suspension in cryopreservative 12 months
or cryopreservative system
< −50 °C Suspension in cryopreservative Indefinite
or cryopreservative system
Anaerobes and bacteria with < −20 °C Suspension in cryopreservative 12 months
special growth requirements or cryopreservative system
< −50 °C Suspension in cryopreservative Indefinite
or cryopreservative system

7.1.3 Processing/Preparation of Stock and Working Quality Control Cultures

(1) At least once a year, prepare a stock culture of each QC organism routinely used by the laboratory
for MIS. Use lyophilized or frozen organisms.

(2) Inoculate one to two slants of an appropriate nonselective medium. Incubate under conditions
favorable for growth. Label as stock QC culture, then the name of the organism and the date of
inoculation. Tightly seal and store the slant(s) for no longer than 12 months at 2 °C to 8 °C, or as
recommended by the manufacturer. Moulds and certain fastidious bacteria, such as Neisseria
gonorrhoeae, may require 25 °C to 35 °C storage. In addition, more fastidious organisms, such as
N. gonorrhoeae or Streptococcus pneumoniae, may have limited survival on slants and may
require more frequent subculture.

(3) From the stock QC culture, prepare a second subculture (working QC culture). Store the working
QC culture at 2 °C to 8 °C for less than four weeks. Seal tightly. Prepare a fresh working QC
culture at least once per month, or as recommended by the manufacturer, from the refrigerated
stock QC culture. Avoid multiple serial subcultures of QC organisms over extended periods of
time.

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7.1.4 Disposal

In the United States, treatment and disposal of infectious waste must comply with all local ordinances,
state and federal Environmental Protection Agency (EPA) regulations, state and federal Occupational
Safety and Health Administration (OSHA) regulations, and Department of Transportation Hazmat
regulations. Regulations may be different in other countries. Refer to CLSI document M2910 for
recommendations on disposal of potentially infectious materials.

7.2 Quality Control Testing Process

The user must follow the manufacturer’s instructions for use regarding the testing process and use of QC
organisms. For optimum performance and reactivity of aerobic and facultative organisms, it is important
to use cultures that have been incubated for no more than 18 to 24 hours. For anaerobic organisms, use
cultures that have been incubated for no more than 48 hours. For storage of QC organisms, follow the
guideline outlined in Section 7.1.2.

7.3 Quality Control Testing Frequency

The frequency of QC testing, at a minimum, is defined as with every new batch, lot number, and
shipment, unless more frequent testing is recommended by the manufacturer. The number of QC
organisms tested may be streamlined if criteria specified in this document have been met and
documented.

7.4 Interpretation of Quality Control Test Results

The user should document observed reactivity or color changes for each reagent and/or substrate in an
MIS, as applicable, and document whether the observed QC result matches the manufacturer’s expected
result. MIS reagents and/or substrates perform satisfactorily if the QC organisms exhibit the
manufacturer’s expected results.

7.5 Corrective Action

7.5.1 Quality Control Failure Due to an Obvious Error

If there is an obvious reason for the QC failure, including:

• use of the wrong MIS,

• use of a damaged (eg, cracked or leaking) MIS,
• improper MIS storage or deterioration during shipping,
• use of the wrong QC organism,
• obvious contamination of the QC organism,
• nonviability of the QC organism,
• improper storage of the QC organism,
• improper test setup,
• use of the wrong reagent(s),
• use of the wrong incubation temperature or conditions during testing, or
• incorrect reading or interpretation of test reactions,

document the reason and retest the QC strain on the day the error is observed. If the repeated result is
within range, no further corrective action is required. Documentation of the investigation and the
corrective measures taken should ensure the problem was corrected before patient or clinical results are
released.
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7.5.2 Quality Control Failure Not Due to an Obvious Error

Even if there is not an obvious reason for the QC failure, the QC test should be repeated. If the test still
fails, further investigation and corrective actions are required prior to reporting patient or clinical results,
as it is likely the error is due to a system or technique issue vs a second consecutive random error. The
following common sources of error should be investigated to verify that:

• laboratory personnel adhered to all procedures;

• test system and reagents, if applicable, were transported under the proper conditions;

• in accordance with the manufacturer’s instructions, all materials were used within their expiration
dates, stored, and handled at the proper temperature and conditions;

• integrity of the MIS was maintained throughout use;

• incubator was at proper temperature and atmosphere;

• inoculum for the test was prepared from a plate incubated for the correct length of time;

• turbidity standard, if applicable, has not expired, is stored properly, meets performance
requirements, and was adequately mixed prior to use (eg, McFarland standard);

• inoculum suspensions were prepared and adjusted correctly;

• other equipment used (eg, pipettor, instrument) was functioning properly;

• all steps in the test procedure, including addition of reagents, were performed in the proper order; and

• substrate reactions were interpreted and transcribed correctly (manual methods).

Consult Appendix D that contains a troubleshooting guide for QC failures for additional criteria to check.
It may be necessary to obtain a new lot of QC organism(s) and new lots of test system and reagents, if
applicable. If the problem appears to be related to a specific manufacturer’s MIS, the manufacturer should
be contacted. Until the problem is resolved, it may be necessary to use an alternate test method.

Once the problem is corrected or sources of error are ruled out, verify acceptable performance following
repeat QC testing in triplicate. Document the error, its investigation, and corrective action taken.

If the problem is not corrected with repeat QC testing, the manufacturer should be contacted for further
investigation and follow-up. Document that the manufacturer was notified, and include the
manufacturer’s response and follow-up, for corrective action taken.

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 Volume 28 M50-A

References
1
Centers for Medicare and Medicaid Services, Department of Health and Human Services. Laboratory Requirements. 42 CFR Ch. IV,
§493.1256(e)(1). 2003.
2
David Sewell, PhD; Committee on Professional Affairs, ASM Public and Scientific Affairs Board. Update on ASM Survey of QC Failures
with Microorganism Identification Systems. 8 Feb 2006. http://wwwn.cdc.gov/cliac/pdf/Addenda/cliac0206/AddendumH.pdf. Accessed 22
August 2008.
3
Clinical Laboratory Improvement Advisory Committee. Meeting Summary, February 2006. http://wwwn.cdc.gov/cliac/pdf/CLIAC0206.pdf.
Accessed 3 June 2008.
4
US Food and Drug Administration. FDA Modernization Act of 1997 (FDAMA). http://www.fda.gov/cdrh/modact/modern.html. Accessed 3
June 2008.
5
Food and Drug Administration, Department of Health and Human Services. Food and Drugs. Medical Devices. Quality System Regulation.
21 CFR Ch. 1, §820, Subchapter H. 2006.
6
Clinical Laboratory Improvement Amendments of 1988. 42 U.S.C. 263a. PL 100-578. 1988.
7
Centers for Medicare & Medicaid Services, Department of Health and Human Services. Laboratory Requirements. Establishment of
verification of performance specifications. 42 CFR Ch. IV, §493.1253(b). 2003.
8
Centers for Medicare & Medicaid Services. Interpretive Guidelines for Laboratories. http://www.cms.hhs.gov/CLIA/downloads/apcsubk2.pdf.
Accessed 3 June 2008.
9
Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings 2007.
http://www.cdc.gov/ncidod/dhqp/gl_isolation.html. Accessed 3 June 2008.
10
CLSI. Protection of Laboratory Workers From Occupationally Acquired Infections; Approved Guideline—Third Edition. CLSI document
M29-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2005.
11
ISO. Clinical laboratory testing and in vitro diagnostic test systems – In vitro diagnostic medical devices – Information supplied by the
manufacturer (labeling). ISO/DIS 18113. Geneva: International Organization for Standardization; 2007.
12
ISO. In vitro diagnostic medical devices – Information supplied by the manufacturer with in vitro diagnostic reagents for staining in biology.
ISO 19001. Geneva: International Organization for Standardization; 2002.
13
ISO. In vitro diagnostic medical devices for professional use – Summary of regulatory requirements for information supplied by the
manufacturer. ISO/TR 18112. Geneva: International Organization for Standardization; 2006.
14
ISO. In vitro diagnostic test systems – Requirements for blood-glucose monitoring systems for self-testing in managing diabetes mellitus. ISO
15197. Geneva: International Organization for Standardization; 2003.
15
ISO. Medical devices – Application of risk management to medical devices. ISO/FDIS 14971. Geneva: International Organization for
Standardization; 2006.
16
ISO. Quality management and quality assurance – Vocabulary. ISO 8402. Geneva: International Organization for Standardization; 1994.
17
ISO. Quality management systems – Fundamentals and vocabulary. ISO 9000. Geneva: International Organization for Standardization; 2000.
18
WHO. Expert Committee on Biological Standardization. Glossary of Terms for Biological Substances Used for Texts of the Requirements.
WHO unpublished document BS/95.1793. Geneva: World Health Organization; 1995.
19
CLSI/NCCLS. Quantitative Molecular Methods for Infectious Diseases; Approved Guideline. CLSI/NCCLS document MM06-A. Wayne,
PA: NCCLS; 2003.
20
ISO. Medical devices – Quality management systems – Requirements for regulatory purposes. ISO 13485. Geneva: International
Organization for Standardization; 2003.
21
Food and Drug Administration. Medical Device Reporting (MDR). http://www.fda.gov/cdrh/mdr/. Accessed 3 June 2008.
22
Centers for Medicare & Medicaid Services, Department of Health and Human Services. Laboratory Requirements. 42 CFR Ch. IV, §493. 2003.
23
CLSI. User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline—Second Edition. CLSI document EP12-A2.
Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
24
Elder BL, Hansen SA, Kellogg JA, Marsk FJ, Zabransky RJ. Verification and Validation of Procedures in the Clinical Microbiology
Laboratory. McCurdy BW, ed. Cumitech 31: ASM Press; 1997.

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 Number 23 M50-A

Appendix A. Manufacturer’s Requirements for Streamlined Quality Control Section

of Package Insert or Product Information for a Microbial Identification System

Date when MIS was first marketed for use in the United States
Statement of compliance (eg, COA or COC) with ISO 13485 and QSR requirements and QC
specifications
Any special design features that were adopted to ensure reliability of the MIS
Justification for streamlined QC, including QC strains required (ie, key indicator strains) and
reason for their selection
Culture collection accession numbers of key indicator strains
Expected reactions for key indicator strains

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 Appendix B. User’s Requirements to Qualify for Streamlined Quality Control of a Microbial Identification System
General Develop and institute procedures to ensure proper storage and handling of the MIS.
©

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Clinical and Laboratory Standards Institute. All rights reserved.

Requirements Ensure staff is adequately trained and competent in using the MIS.
Ensure MIS technical information is readily available to all involved in testing.
Test QC and patient isolates precisely according to the manufacturer’s instructions using manufacturer-recommended reagents.
Initial Maintain current documentation of the manufacturer’s conformance with ISO 13485 and QSRs (COC, COA, or certification
Qualification statement in instructions for use).
Requirements Meet one of the following:
1. If the user has performed a verification study for the MIS to demonstrate it can obtain performance specifications
comparable to the manufacturer, as described in the CLIA regulations at 42 CFR 493.1253(b)(1), streamlined QC may be
implemented immediately. Documentation of the verification study must be available.
2. If the user has not performed a verification study as described above or does not have the required documentation, but has
been performing comprehensive MIS QC as described in the CLIA regulations at 42 CFR 493.1256(e)(1), the user may
conduct and document a historical review of QC performance with that MIS as follows:
a. Review QC performance for at least three consecutive lot numbers of the MIS, from three different shipments that
span at least three consecutive seasons, to assess seasonal variation of shipping conditions.
b. QC testing must have been performed using positive and negative controls for each reagent and/or substrate
according to the manufacturer’s instructions.
c. Performance shall be considered satisfactory and the user may initiate streamlined QC if at least 95% of the
reagent/substrate results are within the results specified by the manufacturer. Performance shall be considered
satisfactory and the user may initiate streamlined QC if at least 95% of the reagent/substrate results are within the
results specified by the manufacturer. However, even if the QC results meet this 95% threshold, if the same
reagent/substrate fails repeatedly, it may be indicative of a problem. These results should be further evaluated (eg,
the user should refer to the Troubleshooting Guide in Appendix D or contact the manufacturer for assistance).
d. If sufficient data are not available to conduct the historical review of QC performance, or the data do not provide
expected QC results, after corrective action (as applicable), the user may choose to assess QC performance
prospectively as described above, or may verify and document the performance specifications for the MIS as
described in the CLIA regulations at 42 CFR 493.1253(b)(1).
3. If the user has not performed a verification study and has not been performing comprehensive MIS QC as described in the
CLIA regulations, or does not have documentation of one of these options, it must perform comprehensive CLIA QC and
may not initiate streamlined QC until it has documentation that it met either option 1 or 2 described above.
Continued Maintain current documentation of the manufacturer’s conformance with ISO 13485 and QSRs (COC, COA, or certification
Qualification statement in instructions for use).
Requirements Maintain documentation of the results of the verification study or historical QC review, as applicable, described in Section
6.2.1.
Perform streamlined QC using all key indicator strains on each new batch, lot, and shipment of MIS.

M50-A
Develop and maintain comprehensive records of QC results (see Appendix C).
17

Develop and follow procedures for investigating QC failures, taking corrective action, and documenting resolution, when
indicated.
Develop and follow procedures for reporting QC failures, as needed.
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 Appendix C. Documentation of Streamlined Quality Control Results – Minimum Record Requirements
Product name

Number 23
18

Date received
Lot number
Expiration date
Test date
Signature or initials of technologist who performed the QC test
Organism name
Organism culture collection number
Product test names/abbreviations
Expected reactions
Observed reactions
Summary of results (eg, Acceptable [Y/N])
Summary of correction action when required
Example:
Product Name________________________ Date received__________
©
Clinical and Laboratory Standards Institute. All rights reserved.

Lot #______________________________ Expiration date___________

ONPG CIT URE IND MAN ARA Tech

Expected results + − − + + + Acceptable
E. coli (Y/N)
ATCC®* 25922
9/2/06 + − − + + + Y
Date

12/1/06 + − − + + + Y
Test

2/14/07 + − − + − + N†
*
ATCC is a registered trademark of the American Type Culture Collection.
†
Corrective action (retest x 3) showed acceptable results.
ONPG CIT URE IND MAN ARA Tech
Expected results − V + − − − Acceptable
P. mirabilis (Y/N)
ATCC® 35659
9/2/06 − + + − − − Y
Date

12/1/06 − + + − − − Y
Test

M50-A
2/14/07 − + + − − − Y

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 Appendix D. Troubleshooting Guide for Microbial Identification System Quality Control Failures*

Volume 28
©

Procedural Subparameter Criteria to Check (as applicable)

Clinical and Laboratory Standards Institute. All rights reserved.

Parameter
Culture Maintenance How many subcultures were performed prior to use in testing? If coming from frozen or lyophilized stock, a minimum
of two subcultures should be performed. Refer to the manufacturer’s recommendations for specific instructions.
How long were the subcultures stored? For subculture of refrigerated or room temperature cultures, refer to the
manufacturer’s recommendations.
Isolation medium Was the correct media type used? Although many media may be allowed for normal testing, QC recommendations may
be more restrictive. Verify the manufacturer’s recommendations.
Is the culture or isolation medium contaminated?
Has the isolation medium expired?
Was the medium purchased from a commercial vendor or is it homemade? If homemade, were the instructions followed
correctly for the formulation, pH, and sterilization?
Temperature Were the storage and incubation temperatures in range?
Time Were the storage and incubation times within range?
Atmosphere Was the culture incubated and stored in the correct atmosphere (eg, aerobic, anaerobic, 3% to 5% CO2)?
Colonies Are they well isolated and pure?

Inoculum Diluent Was the sterility verified?

Was the correct diluent used (ie, water or saline)?
If saline, is the concentration correct?
If physiologic saline, be sure there is no added glucose.
Is the pH correct? For example, new, unrinsed borosilicate glass can raise pH to be out of range.
Density – manual method Was turbidity compared to an appropriate McFarland standard?
Has the McFarland standard been stored in the dark to avoid increased opacity due to light modification?
Is the McFarland standard within its expiration date?
Density – automatic method Has the instrument calibration been verified with a known standard?
Is the calibration standard within its expiration date?
Were the manufacturer’s instructions followed for adjusting the instrument to the specific tube type, as applicable?
If recommended, has the instrument linearity been adjusted for 0% and 100% transmission?
Suspension Is the suspension well mixed without clumps? For organisms that are clumpy, filamentous, or mucoid, care must be
taken to achieve a uniform suspension. This can be accomplished by crushing the inoculum against the inside surface of
the tube before entering the liquid. Gradual mixing with the liquid will allow for a uniform suspension. If clumps cannot
be avoided, allow these to settle and pipette the uniform portion of the suspension into a new tube.
Age of suspension Was the age of the suspension in range? Holding the suspension too long can decrease viability or degrade preformed
enzymes.
Time to measurement – for Suspensions should be measured directly after preparation while they are well mixed. If measurement was delayed, was

M50-A
automatic density it remixed? Delayed measurement allows settling of cells and can cause false high reading as more cells settle into the
measurement optical path.
19

Footnote

* Unless otherwise defined in Appendix D, “manufacturer” refers to the manufacturer of the MIS.
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 Appendix D. (Continued)
Procedural Subparameter Criteria to Check (as applicable)

Number 23
20

Parameter
MIS Manual method Is the MIS intact? Was it damaged in any way (eg, cracked, leaking) prior to use?
inoculation Were the correct volumes dispensed?
Were relevant tests (eg, lysine decarboxylase) overlaid (eg, with mineral oil) properly?
Automatic method Is the MIS intact? Was it damaged in any way (eg, cracked, leaking) prior to use?
Were the correct volumes dispensed? For example, if vacuum-filled, check the inoculum tube, which should be nearly
empty.

MIS Temperature Was the MIS incubated at the correct temperature?

incubation
Time Was the incubation time in range?
Atmosphere Was the MIS incubated in the correct atmosphere (eg, aerobic, anaerobic, 3% to 5% CO2)?
Time between inoculum Was the product incubated promptly after the inoculum was prepared? Does the timeframe between preparation and
preparation and beginning incubation affect the QC results? Manufacturer’s guidelines for time after inoculum preparation should be
incubation used.

MIS Self-indicating tests for Are control wells used where appropriate?
©

interpretation - color or turbidity

Clinical and Laboratory Standards Institute. All rights reserved.

manual
If a guide to interpretation of reactions is provided, has consideration been given to all potential interpretations and
reactions, including intermediate colors for color reactions?
Was the interpretation of color reactions, especially intermediate colors, affected by tinted lenses in eyeglasses?
Reagent-addition tests Was the manufacturer’s recommended reagent used in testing?
Is the reagent expired?
Was the reagent stored under the correct conditions?
Is the reagent discolored or does it contain particulate material? If so, does the manufacturer advise against its use?
Was the correct time allowed for color development?
Are control wells used where appropriate?
If a guide to interpretation of reactions is provided, has consideration been given to all potential interpretations and
reactions, including intermediate colors for color reactions?
Was the interpretation of color reactions, especially intermediate colors, affected by tinted lenses in eyeglasses?

M50-A
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 Volume 28
©
Clinical and Laboratory Standards Institute. All rights reserved.

Appendix D. (Continued)
Procedural Subparameter Criteria to Check (as applicable)
Parameter
MIS Self-indicating tests Has the instrument been maintained as recommended?
interpretation -
automatic Has the optics calibration been verified?
Reagent-addition tests Was the manufacturer’s recommended reagent used in testing?
Has the reagent expired?
Was the reagent stored under the correct conditions?
Is the reagent discolored or does it contain particulate material? If so, does the manufacturer advise against its use?
Has the instrument been maintained as recommended?
Has the optics calibration been verified?
Are all the dispensing lines and tips clear and unobstructed by precipitates?
QC Strain Culture maintenance Repeated subcultures may cause differences in phenotypic expression. Retrieve the problematic QC strain from stock
and follow the manufacturer’s instructions for culture maintenance prior to repeat testing.
General Contact the manufacturer for additional information.

M50-A
21

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 Number 23 M50-A

Clinical and Laboratory Standards Institute consensus procedures include an appeals process that
is described in detail in Section 8 of the Administrative Procedures. For further information,
contact CLSI or visit our website at www.clsi.org.

Summary of Comments and Subcommittee Responses

M50-P: Quality Control for Commercial Microbial Identification Systems; Proposed Guideline

General

1. Regarding streamlined quality control (QC) of commercial microbial identification systems (MISs), M50-P
does not go far enough into the details of what most clinical laboratories would need to do in order to begin
using streamlined QC methods as specified by their manufacturer.

• The QC approach taken in this guideline requires involvement by the manufacturer and distributor of
the MIS as well as the laboratory. Each has a role to play in the streamlined QC process. If the
laboratory has the appropriate documentation from the manufacturer for its MIS, the requirements to
initiate streamlined QC depend on whether or not the laboratory has performed a verification study, as
required by the Clinical Laboratory Improvement Amendments (CLIA) since 1992. The CLIA
requirements include verifying the accuracy, precision, and reportable range of test results, and verifying
that the manufacturer’s reference ranges (normal values) are appropriate for the laboratory’s patient
population. If the laboratory has documentation that this verification study has been successfully
completed, it may immediately begin using the streamlined QC specified by the manufacturer. If the
laboratory has not completed the verification study, or does not have the documentation, it would either
need to perform the study or complete the historical review of QC results as described in Section 6.2.1.

2. This is a well thought out document that addresses the QC of MISs. However, by my interpretation, its use will
not absolve the user of the requirement by CLIA‘88 to perform full QC. Therefore, the use of this document as
an alternative to performing full QC will still place the user at risk for being found deficient by his/her
accrediting body. While this doesn’t mean M50 should not be published, I think users should be made aware of
the conflict in what the document is recommending, and what CLIA ‘88 requires, preferably in the front matter
of the document.

• The CLIA regulatory requirements for QC of MISs are explained in M50, and these requirements will
not change as a result of this document. However, once this document has been approved, the Centers for
Medicare & Medicaid Services (CMS) intends to allow for streamlined QC as an exception to the
regulations. It will do this by notifying its surveyors of the change, and eventually incorporating the
exception into its laboratory and surveyor guidelines. This is analogous to the exceptions already
permitted under CLIA that allow weekly QC for susceptibility testing and exempt certain media from
required QC. In both of these cases, the QC protocols that are accepted in lieu of CLIA are outlined in
CLSI documents. Following any change made by CMS, CMS-approved accreditation organizations will
then need to evaluate the exception and incorporate it in their standards if they choose to do so.

In the case of streamlined QC for MISs, we remind laboratories that if they choose to follow the
guidelines in this document, it is critical that they keep the documentation of their test system verification
or their historical review of QC even longer than may be required for record retention under CLIA, since
this documentation will be needed by surveyors to justify the laboratory’s use of streamlined QC.

Foreword

3. The Foreword of this document states: “The consensus document describes the acceptable criteria for allowing
streamlined QC, as compared to the requirement specified by the CLIA regulations for MISs produced by
manufacturers that meeting specific quality standards and regulations. It is intended to provide practical
guidelines for laboratories to ensure the quality of their microbial identification results when using commercial
MISs. It is anticipated that these guidelines will receive widespread use in the United States and internationally,
and could reduce unnecessary costs and other resources spent on excessive QC testing.” Again, in the Scope of

22 ©
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 Volume 28 M50-A

the document, it states: “The document specifies the QC responsibilities of the manufacturer, distributor, and
user, and identifies conditions under which an MIS with proven reliability can qualify for streamlined QC
testing. The modified approach may be applied after the user verifies acceptable QC performance as specified in
this guideline.”

There are no described acceptable criteria allowing for streamlined QC, nor any practical guidelines included in
this document for laboratories that are users of MISs after 1992, which will be the majority of clinical
laboratories in the United States and abroad. There is not acceptable QC performance specified in this guideline
for users of MISs after 1992. Without the inclusion of these protocols, which are defined in both the Foreword
and the Scope, this document will be of little use to many clinical laboratories.

In order for this document to be valuable to a majority of laboratories using biochemical MISs implemented
after 1992, clear, concise, understandable, and attainable criteria need to be outlined and included. As many
laboratories have been following CLIA-mandated QC for their biochemical MISs for years, criteria that use
their past CLIA-QC should be allowed. This document should contain a detailed outline of what is considered
acceptable when reviewing past QC so the laboratory can switch to streamlined QC when its manufacturer is
also prepared to meet the standards of this document.

Outlining what is necessary QC review/protocols is just as important, or more so, for the users of MISs
implemented after 1992 as it is for those who are still using the same MIS system they were using before 1992.

• The guideline has been clarified to explain that the requirements do not actually differ based on the date
on which the MIS was implemented, but rather whether a verification study that meets the CLIA
requirements has been performed and documented. As explained in the response to comment 1 above, if
the laboratory has documentation that the verification study has been successfully completed (regardless
of when it was done), it may immediately begin using the streamlined QC specified by the manufacturer.
If the laboratory has not completed the verification study, or does not have the documentation, it would
either need to perform the study or complete the historical review of QC results as described in Section
6.2.1.

Section 4, Definitions (now Section 4.1)

4. Page 3, Section 4, definition of “information supplied by the manufacturer”: Can the information supplied by
the manufacturer be in electronic files?

• There is nothing in this definition that precludes the use of electronic files for conveying information.
The definition was taken from those included in ISO documents ISO 1900112 and ISO/TR 18112.13

Section 5.1.1, Regulatory Requirements for Microbial Identification Systems

5. First sentence: Add quality system regulations (QSRs) to the example in parentheses: “quality system standards
(eg, QSRs, ISO 13485).” The reason is QSRs are referred to elsewhere in the document in lieu of ISO 13485.

• This has been added as suggested.

6. After the last bullet, add “Risk assessment – determination of device misuse or failure modes that could occur
with a device, the risk associated with that failure, and any mitigation to prevent or reduce the occurrence of the
possible failure.”

• This has been added to the list as suggested. However, since it would likely occur early in the process, it
was inserted as the second bullet.

Section 5.1.3, Quality Control Information Provided to the Users

7. The second paragraph only lists QSRs, and needs to also include ISO 13485. This also applies to Section 6.1
and Appendix B.

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 Number 23 M50-A

• This information has been added as suggested in Sections 5.1.3 and 6.1, as well as Appendix B.

8. The third paragraph reads as if manufacturers don’t need to worry about this until CLSI document EP22 comes
out. This is not true. They still need to meet the requirement even without EP22 as a tool. Suggested rewording:
“...design features intended to mitigate risk of potential device failures. This information includes the risk
associated with such failures...”

• This change has been made as suggested. Since CLSI document EP22 is currently in development and
has not yet been published, the sentence regarding EP22 has been removed from the document.

9. “Note: CLSI document EP22, currently in development, is intended to serve as a tool to assist with developing
this information.”

• Since CLSI document EP22 is currently in development and has not yet been published, the sentence
regarding EP22 has been removed from the document.

Section 5.2, The Distributor

10. The first phrase uses incorrect grammar. The word “following” is an adjective that needs to modify an
appropriate noun. Please change to “perform the following activities”: This same grammatical mistake appears
also in Sections 5.3, 5.3.1, and 6.2.2.

• According to the Random House Unabridged Dictionary©, Random House, Inc. 2006, “following” can be
a noun that refers to “that which comes immediately after.” Since not all of the items in each list in these
sections are activities, rather some are requirements that need to be met, this change was not made. This
style is consistent with similar lists in other CLSI documents.

Section 5.3, The User

11. The last paragraph has the same issue as with Section 5.1.3. Suggested rewording: “develop effective QC
protocols for in vitro diagnostic devices. Environmental characteristics...” “Note: CLSI document EP23,
currently in development, is intended to serve as a tool to assist with developing this information.”

• Since CLSI document EP23 is currently in development and has not yet been published, the sentence
regarding EP23 has been removed from the document.

Section 6.1, Manufacturer’s Responsibilities; Section 6.2.1, Initial Qualification; and Appendix B. User’s
Requirements to Qualify for Streamlined Quality Control of a Microbial Identification System

12. Certificates of Analysis are not the appropriate document for certifying compliance to quality standards or
regulations. Please remove COA from these sections.

• As defined in this document (see Section 4.1), Certificates of Analysis are one source of ensuring
manufacturer compliance with QSR requirements and QC specifications. Reference to this was not
removed from Section 6.2.1 or Appendix B.

13. In Section 6.2.1, Initial Qualification (second bullet), the document explains very nicely what the user
laboratory would have to do in order to implement streamlined QC testing if it were using an MIS prior to 1992.
The third bullet does not explain to the user laboratory what would be necessary for “verification” prior to
implementing streamlined QC testing.

The majority of clinical laboratories fall under this third bullet area. So, here it is absolutely necessary for this
document to have specific protocols, etc. for allowing the implementation of streamlined QC. If these protocols
are not included, this document will not be of much value for most clinical laboratories.

I understand there might be issues regarding some systems, which do not use ± biochemical reactions in order
to select an organism’s identification; but that must not preclude the authors of this document from outlining the

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 Volume 28 M50-A

steps that need to be taken in order for the majority of laboratories using other commercial products to use this
document.

• Verification of performance specifications is required by CLIA6 for any test system implemented on or
after 1 September 1992. This includes verifying the accuracy, precision, and reportable range of test
results, and verifying that the manufacturer’s reference ranges (normal values) are appropriate for the
laboratory’s patient population. This CLIA requirement must be met before using an MIS for patient
testing, and is different from ongoing validation of test performance through QC testing. Specific
protocols for verification are not included in this guideline, as the scope of the document is focused on the
QC testing process (or validation). References are provided for guidance to users on how to conduct
verification studies. If a user has verified a test system (regardless of whether it performed the study
before or after CLIA was implemented), it may immediately initiate streamlined QC. This has been
clarified in the reorganization of Section 6.2.1. If a user has not verified its MIS, Section 6.2.1 also
specifies the approach that may be taken to initiate streamlined QC by conducting a historical review of
comprehensive CLIA QC performance. If a user has neither verified performance nor conducted the
historical QC review as described, it may not initiate streamlined QC until it has met one of these
requirements.

Section 7.2, Quality Control Testing Process

14. Page 11, Section 7.2: There might be some slow-growing bugs that need more than 14 hours (aerobic
organisms) and 48 hours (anaerobes). How about Actinomyces israeli, for instance?

• While it is true that some slow-growing or fastidious organisms may take longer to grow than the
timeframes included in this section, organisms that would be specified by manufacturers as appropriate
strains for QC would not include these types of organisms.

Section 7.3, Quality Control Testing Frequency

15. Page 11, Section 7.3: As mentioned earlier, what batch means should be clarified.

• Batch is defined on page 2 of the definitions as “all tubes, plates, or containers of an MIS that have the
same lot number and are received in a single shipment.”

Appendix D. Troubleshooting Guide for Microbial Identification System Quality Control Failures

16. Page 18, reagent-addition tests: Follow reagent temperature recommendations of the manufacturer.

• There is a question already included in this section that asks, “Was the reagent stored under the correct
conditions?” This would include the correct temperature as specified by the manufacturer.

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 Number 23 M50-A

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 approach is based on the model presented in the
most current edition of CLSI/NCCLS document HS01—A Quality Management System Model for Health Care. 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:

Documents & Records Equipment Information Management Process Improvement

Organization Purchasing & Inventory Occurrence Management Customer Service
Personnel Process Control Assessments―External & Facilities & Safety
Internal

M50-A addresses the QSEs 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.
Purchasing &

—External &

Improvement
Organization

Management

Management

Assessments
Information

Facilities &
Occurrence
Documents

Equipment
& Records

Personnel

Inventory

Customer
Internal
Control
Process

Process

Service

Safety
X
M07 GP21 EP12 MM06 M29
M02
M07
M22
M29
MM06
Adapted from CLSI/NCCLS document HS01—A Quality Management System Model for Health Care.

Path of Workflow

A path of workflow is the description of the necessary steps to deliver the particular product or service that the
organization or entity provides. For example, CLSI/NCCLS document GP26⎯Application of a Quality
Management System Model for Laboratory Services defines a clinical laboratory path of workflow, which consists
of three sequential processes: preexamination, examination, and postexamination. All clinical laboratories follow
these processes to deliver the laboratory’s services, namely quality laboratory information.

M50-A 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.

Preexamination Examination Postexamination

receipt/processing
Sample collection

Results reporting
Sample transport

Results review
and follow-up

and archiving
Interpretation
Examination

Examination

management
ordering

Sample

Sample

X X X
MM06 MM06 MM06 MM06 MM06 M02 M02 M02
M07 M07 M07
M100 M100 M100
MM06 MM06 MM06
Adapted from CLSI/NCCLS document HS01—A Quality Management System Model for Health Care.

26 ©
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 Volume 28 M50-A

Related CLSI Reference Materials∗

EP12-A2 User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline—Second Edition
(2008). This document provides a consistent approach for protocol design and data analysis when evaluating
qualitative diagnostic tests. Guidance is provided for both precision and method-comparison studies.

GP21-A2 Training and Competence Assessment; Approved Guideline—Second Edition (2004). This document
provides background information and recommended processes for the development of training and
competence assessment programs that meet quality/regulatory objectives.

M02-A9 Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Ninth
Edition (2006). This document contains the current CLSI-recommended methods for disk susceptibility
testing, criteria for quality control testing, and updated tables for interpretive zone diameters.

M07-A7 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved
Standard—Seventh Edition (2006). This document addresses reference methods for the determination of
minimal inhibitory concentrations (MICs) of aerobic bacteria by broth macrodilution, broth microdilution, and
agar dilution.

M22-A3 Quality Control for Commercially Prepared Microbiological Culture Media; Approved Standard—
Third Edition (2004). This document contains quality assurance procedures for manufacturers and users of
prepared, ready-to-use microbiological culture media.

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.

M100-S18 Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement
(2008). This document provides updated tables for the Clinical and Laboratory Standards Institute (CLSI)
antimicrobial susceptibility testing standards M02-A9 and M07-A7.

MM06-A Quantitative Molecular Methods for Infectious Diseases; Approved Guideline (2003). 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.

∗
Proposed-level documents are being advanced through the Clinical and Laboratory Standards Institute consensus process;
therefore, readers should refer to the most current editions.

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 Number 23 M50-A

NOTES

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 Volume 28 M50-A

NOTES

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 Active Membership
(as of 1 July 2008)
Sustaining Members FDA Center for Biologics Evaluation and Fio Japan Association of Clinical
Research Focus Diagnostics Reagents Industries (Tokyo, Japan)
Abbott FDA Center for Devices and Radiological Health Gen-Probe
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Chemistry Health Canada GlaxoSmithKline
AstraZeneca Pharmaceuticals Indiana State Department of Health Joanneum GR Micro LTD 5th Medical Group/SGSL (ND)
Bayer Corporation Research Forschungsgesellschaft mbH Greiner Bio-One Inc. 22 MDSS (KS)
BD Kern County Department of Health Habig Regulatory Consulting 36th Medical Group/SGSL (Guam)
Beckman Coulter, Inc. Services Helena Laboratories 55th Medical Group/SGSAL (NE)
bioMérieux, Inc. Meuhedet Central Lab HistoGenex N.V. 59th MDW/859th MDTS/MTL Wilford Hall
CLMA Ministry of Health and Social Welfare Icon Laboratories, Inc. Medical Center (TX)
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Pfizer Inc National Center of Infectious and Instrumentation Laboratory (NY) ACL Laboratories (IL)
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National Health Laboratory Service Johnson & Johnson Pharmaceutical Adams County Hospital (OH)
Professional Members (South Africa) Research and Development, L.L.C. Air Force Institute for Operational Health (TX)
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Physicians National Pathology Accreditation Krouwer Consulting (Saudi Arabia)
American Association for Clinical Advisory Council (Australia) LabNow, Inc. Alameda County Medical Center (CA)
Chemistry New York City Office of Medical Laboratory Specialists, Inc. Albany Medical Center Hospital (NY)
American Association for Laboratory Examiner LifeScan, Inc. (a Johnson & Johnson Albemarle Hospital (NC)
Accreditation New York State Department of Health Company) Alfred I. du Pont Hospital for Children
American Association for Respiratory Care NJ State Department of Health and LipoScience (DE)
American Medical Technologists Senior Services Maine Standards Company, LLC All Children’s Hospital (FL)
American Society for Clinical Ontario Ministry of Health Medical Device Consultants, Inc. Allegheny General Hospital (PA)
Laboratory Science Orange County Health Care Agency - Merck & Company, Inc. Allegiance Health (MI)
American Society for Microbiology Public Health Lab Metabolon Inc. Alpena General Hospital (MI)
American Type Culture Collection Pennsylvania Dept. of Health Micromyx, LLC Alta Bates Summit Medical Center (CA)
ASCP Saskatchewan Health-Provincial Laboratory Monogen, Inc. American University of Beirut Medical
Associazione Microbiologi Clinici Scientific Institute of Public Health Nanosphere, Inc. Center (NJ)
Italiani (AMCLI) State of Alabama Nihon Koden Corporation Anne Arundel Medical Center (MD)
Canadian Society for Medical University of Iowa, Hygienic Lab Nissui Pharmaceutical Co., Ltd. Antelope Valley Hospital District (CA)
Laboratory Science NJK & Associates, Inc. Arkansas Children’s Hospital (AR)
COLA Industry Members NorDx – Scarborough Campus Arkansas Dept of Health Public Health
College of American Pathologists NovaBiotics (Aberdeen, UK) Laboratory (AR)
College of Medical Laboratory 3M Medical Division Novartis Institutes for Biomedical Research Arkansas Methodist Medical Center (AR)
Technologists of Ontario AB Biodisk Nucryst Pharmaceuticals Asan Medical Center (Korea)
College of Physicians and Surgeons of Abbott Olympus America, Inc. Asante Health System (OR)
Saskatchewan Abbott Diabetes Care OneWorld-Lab, LLC Asiri Group of Hospitals Ltd. (Sri Lanka)
Elkin Simson Consulting Services Abbott Molecular Inc. Opti Scan Bio Medical Assoc. Asociacion Espanola Primera de Socorros
ESCMID Abbott Point of Care Inc. Optimer Pharmaceuticals, Inc. Mutuos (Uruguay)
Family Health International Access Genetics Oregon Translational Research and Aspirus Wausau Hospital (WI)
Hong Kong Accreditation Service Advanced Liquid Logic Drug Development Institute Atlantic City Medical Center (NJ)
Innovation and Technology Affymetrix, Inc. (W. Sacramento, CA) Ortho-Clinical Diagnostics, Inc. Atlantic Health Sciences Corp. (NB, Canada)
Commission Ammirati Regulatory Consulting (Rochester, NY) Auburn Regional Medical Center (WA)
International Federation of Biomedical Anapharm, Inc. Ortho-McNeil, Inc. Aultman Hospital (OH)
Laboratory Science Anna Longwell, PC Paratek Pharmaceuticals, Inc. Avera McKennan (SD)
International Federation of Clinical Arpida Ltd. PathCare Az Sint-Jan (Belgium)
Chemistry A/S Rosco PerkinElmer Genetics, Inc Azienda Ospedale Di Lecco (Italy)
Italian Society of Clinical Biochemistry and Associated Regional & University Pfizer Animal Health Baffin Regional Hospital (Canada)
Clinical Molecular Biology Pathologists Pfizer Inc Baptist Hospital for Women (TN)
JCCLS Astellas Pharma Phadia AB Baptist Hospital of Miami (FL)
The Joint Commission AstraZeneca Pharmaceuticals Powers Consulting Services Baton Rouge General (LA)
Malaria Research Training Center Aviir, Inc. PPD Baxter Regional Medical Center (AR)
National Society for Axis-Shield PoC AS QSE Consulting Bay Regional Medical Center (MI)
Histotechnology, Inc. Bayer Corporation – West Haven, CT Qualtek Clinical Laboratories BayCare Health System (FL)
Ontario Medical Association Quality Bayer HealthCare, LLC, Diagnostics Div. – Quest Diagnostics, Incorporated Baylor Health Care System (TX)
Management Program-Laboratory Elkhart, IN Quintiles Laboratories, Ltd. Bayou Pathology, APMC (LA)
Service BD Radiometer America, Inc. Baystate Medical Center (MA)
RCPA Quality Assurance Programs PTY BD Diagnostic Systems Reametrix Inc. B.B.A.G. Ve U. AS., Duzen
Limited BD Vacutainer Systems Replidyne Laboratories (Turkey)
Serbian Society of Microbiology Beckman Coulter, Inc. Roche Diagnostics GmbH Beebe Medical Center (DE)
SIMeL Beth Goldstein Consultant (PA) Roche Diagnostics, Inc. Belfast HSS Trust Royal Victoria
Sociedad Espanola de Bioquimica BG Medicine Inc Roche Diagnostics Shanghai Ltd. Hospital (Ireland)
Clinica y Patologia Molecular Bioanalyse, Ltd. Roche Molecular Systems Beloit Memorial Hospital (WI)
Sociedade Brasileira de Analises Bio-Development S.r.l. Sanofi Pasteur Ben Taub General Hospital (TX)
Clinicas Biohit Oyj. Sarstedt, Inc. The Bermuda Hospitals Board
Sociedade Brasileira de Patologia Biomedia Laboratories SDN BHD Schering Corporation (Bermuda)
Clinica bioMérieux, Inc. (MO) Sequenom, Inc. Beth Israel Medical Center (NY)
Turkish Society of Microbiology Bio-Rad Laboratories, Inc. – France Siemens Healthcare Diagnostics Bonnyville Health Center (Canada)
World Health Organization Bio-Rad Laboratories, Inc. – Irvine, CA Siemens Medical Solutions Diagnostics (CA) Boston Medical Center (MA)
Bio-Reference Laboratories Siemens Medical Solutions Diagnostics (DE) Boulder Community Hospital (CO)
Government Members Blaine Healthcare Associates, Inc. Siemens Medical Solutions Diagnostics (NY) Brantford General Hospital (Canada)
Canon U.S. Life Sciences, Inc. Specialty Ranbaxy Ltd Bridgeport Hospital (CT)
Armed Forces Institute of Pathology Cempra Pharmaceuticals, Inc. Sphere Medical Holding Limited Bronson Methodist Hospital (MI)
Association of Public Health Laboratories Center for Measurement Standards/ITRI Stirling Medical Innovations Broward General Medical Center (FL)
BC Centre for Disease Control Central States Research Centre, Inc. Streck Laboratories, Inc. Calgary Health Region (Canada)
Centers for Disease Control and Cepheid Sysmex America, Inc. (Mundelein, IL) California Pacific Medical Center (CA)
Prevention Chen & Chen, LLC (IQUUM) Sysmex Corporation (Japan) Cambridge Health Alliance (MA)
Centers for Disease Control and The Clinical Microbiology Institute Targanta Therapeutics, Inc Camden Clark Memorial Hospital (WV)
Prevention, China Comprehensive Cytometric Consulting TheraDoc Canadian Science Center for Human and
Centers for Disease Control and Copan Diagnostics Inc. Third Wave Technologies, Inc. Animal Health (Canada)
Prevention – Ethiopia Cosmetic Ingredient Review ThromboVision, Inc. Cape Breton Healthcare Complex (Canada)
Centers for Disease Control and Cubist Pharmaceuticals Transasia Bio-Medicals Limited Cape Cod Hospital (MA)
Prevention – Namibia Cumbre Inc. Trek Diagnostic Systems Cape Fear Valley Medical Center
Centers for Disease Control and Dade Behring Marburg GmbH – A Upside Endeavors, LLC Laboratory (NC)
Prevention – Nigeria Siemens Company Ventana Medical Systems Inc. Capital Health - Regional Laboratory
Centers for Disease Control and Dahl-Chase Pathology Associates PA Vital Diagnostics S.r.l. Services (Canada)
Prevention – Tanzania David G. Rhoads Associates, Inc. Watin-Biolife Diagnostics and Medicals Capital Health System Mercer Campus (NJ)
Centers for Medicare & Medicaid DiagnoCure US, GP Watson Pharmaceuticals Capital Health/QE II Health Sciences
Services Diagnostica Stago Wellstat Diagnostics, LLC Centre (Nova Scotia, Canada)
Centers for Medicare & Medicaid Docro, Inc. Wyeth Research Carilion Labs Charlotte (NC)
Services/CLIA Program Dynacare Laboratory XDX, Inc. Carl R. Darnall Army Medical Center (TX)
Chinese Committee for Clinical Dynacare NW, Inc - Seattle YD Consultant Carpermor S.A. de C.V. (Mexico)
Laboratory Standards Eiken Chemical Company, Ltd. Cavan General Hospital (Ireland)
Department of Veterans Affairs Elanco Animal Health Trade Associations Cedars-Sinai Medical Center (CA)
DFS/CLIA Certification Emisphere Technologies, Inc.
Eurofins Medinet AdvaMed

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 Central Kansas Medical Center (KS) Easton Hospital (PA) Institute of Medical & Veterinary Memorial Hermann Healthcare System
Central Texas Veterans Health Care Edward Hospital (IL) Science (Australia) (TX)
System (TX) Effingham Hospital (GA) Integrated Regional Laboratories Memorial Hospital at Gulfport (MS)
Centralized Laboratory Services (NY) Eliza Coffee Memorial Hospital South Florida (FL) Memorial Hospital Laboratory (CO)
Centre Hospitalier Anna-Laberge (AL) International Health Management Memorial Medical Center (IL)
(Canada) Emory University Hospital (GA) Associates, Inc. (IL) Memorial Medical Center (PA)
Centre Hospitalier Brome-Missisquoi- Evangelical Community Hospital IWK Health Centre (Canada) Memorial Regional Hospital (FL)
Perkins (Canada) (PA) Jackson County Memorial Hospital (OK) Mercy Franciscan Mt. Airy (OH)
Chaleur Regional Hospital (Canada) Evans Army Community Hospital Jackson Health System (FL) Mercy Hospital (ME)
Changhua Christian Hospital (Taiwan) (CO) Jackson Purchase Medical Center Methodist Dallas Medical Center (TX)
Charleston Area Medical Center (WV) Exeter Hospital (NH) (KY) Methodist Hospital (TX)
The Charlotte Hungerford Hospital (CT) Federal Medical Center (MN) Jacobi Medical Center (NY) Methodist Hospital Pathology (NE)
Chatham - Kent Health Alliance Fletcher Allen Health Care (VT) John C. Lincoln Hospital (AZ) MetroHealth Medical Center (OH)
(Canada) Fleury S.A. (Brazil) John T. Mather Memorial Hospital (NY) Metropolitan Hospital Center (NY)
Chesapeake General Hospital (VA) Florida Hospital (FL) Johns Hopkins Medical Institutions Metropolitan Medical Laboratory, PLC
Chester County Hospital (PA) Florida Hospital Waterman (FL) (MD) (IA)
Children’s Healthcare of Atlanta (GA) Fort St. John General Hospital Johns Hopkins University (MD) The Michener Inst. for Applied
The Children’s Hospital (CO) (Canada) Johnson City Medical Center Hospital Health Sciences (Canada)
Children’s Hospital and Medical Forum Health Northside Medical (TN) Mid Michigan Medical Center – Midland
Center (WA) Center (OH) JPS Health Network (TX) (MI)
Children’s Hospital & Research Fox Chase Cancer Center (PA) Kadlec Medical Center (WA) Middelheim General Hospital (Belgium)
Center at Oakland (CA) Frankford Hospital (PA) Kaiser Permanente (CA) Middletown Regional Hospital (OH)
Children’s Hospital Medical Center (OH) Fraser Health Authority Kaiser Permanente (MD) Mike O'Callaghan Federal Hospital (NV)
Children’s Hospital of Philadelphia (PA) Royal Columbian Hospital Site Kaiser Permanente (OH) Mississippi Baptist Medical Center (MS)
Children’s Hospitals and Clinics (MN) (Canada) Kaiser Permanente Medical Care (CA) Mississippi Public Health Lab (MS)
Children’s Medical Center (OH) Fresenius Medical Care/Spectra East Kantonsspital Aarau AG (Switzerland) Monongalia General Hospital (WV)
Children’s Medical Center (TX) (NJ) Kenora-Rainy River Reg. Lab. Montefiore Medical Center (NY)
Children’s Memorial Hospital (IL) Fundacio Joan Costa Roma Consorci Program (Canada) Montreal General Hospital (Quebec,
The Children’s Mercy Hospital (MO) Sanitari de Terrassa (Spain) King Abdulaziz University Hospital Canada)
Childrens Hosp. – Kings Daughters (VA) Gamma-Dynacare Laboratories (Saudi Arabia) Morton Plant Hospital (FL)
Childrens Hospital Los Angeles (CA) (Canada) King Fahad Medical City (Saudi Arabia) Mt. Sinai Hospital - New York (NY)
Childrens Hospital of Wisconsin (WI) Garden City Hospital (MI) King Fahad National Guard Hospital MuirLab (CA)
Chilton Memorial Hospital (NJ) Garfield Medical Center (CA) KAMC - NGHA (Saudi Arabia) Nassau County Medical Center (NY)
Christiana Care Health Services (DE) Geisinger Medical Center (Danville, King Faisal Specialist Hospital (MD) National Cancer Center (S. Korea)
Christus St. John Hospital (TX) PA) King Hussein Cancer Center (Jordan) National Healthcare Group (Singapore)
CHU Sainte-Justine (Quebec, Canada) Genesis Healthcare System (OH) Kings County Hospital Center (NY) National Institutes of Health, Clinical
City of Hope National Medical George Washington University Kingston General Hospital (Canada) Center (MD)
Center (CA) Hospital (DC) Lab Medico Santa Luzia LTDA (Brazil) National Naval Medical Center (MD)
Clarian Health – Clarian Pathology Ghent University Hospital (Belgium) Labette Health (KS) National University Hospital Department
Laboratory (IN) Good Samaritan Hospital (OH) Laboratory Alliance of Central New of Laboratory Medicine (Singapore)
Clinical Labs of Hawaii (HI) Good Shepherd Medical Center (TX) York (NY) Nationwide Children's Hospital (OH)
Clinton Memorial Hospital (OH) Grana S.A. (TX) LabPlus Auckland Healthcare Services Naval Hospital Great Lakes (IL)
CLSI Laboratories, Univ. Pittsburgh Grand Strand Reg. Medical Center Limited (New Zealand) Naval Medical Center Portsmouth (VA)
Med. Ctr. (PA) (SC) Labway Clinical Laboratory Ltd (China) NB Department of Health (Canada)
Colchester East Hants Health Authority Gundersen Lutheran Medical Center Lafayette General Medical Center (LA) The Nebraska Medical Center (NE)
(Canada) (WI) Lakeland Regional Laboratories (MI) New England Baptist Hospital (MA)
College of Physicians and Surgeons Guthrie Clinic Laboratories (PA) Lakeland Regional Medical Center (FL) New England Fertility Institute (CT)
of Alberta (Canada) Haga Teaching Hospital Lancaster General Hospital (PA) New Lexington Clinic (KY)
Columbia Regional Hospital (MO) (Netherlands) Landstuhl Regional Medical Center (APO, New York City Department of Health and
Commonwealth of Virginia (DCLS) Hagerstown Medical Laboratory (MD) AE) Mental Hygiene (NY)
(VA) Halton Healthcare Services (Canada) Langley Air Force Base (VA) New York University Medical Center
Community Hospital of the Monterey Hamad Medical Corporation (Qatar) LeBonheur Children’s Medical Center (NY)
Peninsula (CA) Hamilton Regional Laboratory Medicine (TN) Newark Beth Israel Medical Center (NJ)
Community Medical Center (NJ) Program (Canada) Legacy Laboratory Services (OR) Newton Memorial Hospital (NJ)
Community Memorial Hospital (WI) Hanover General Hospital (PA) Lethbridge Regional Hospital (Canada) North Bay Hospital (FL)
Consultants Laboratory of WI LLC Harford Memorial Hospital (MD) Lewis-Gale Medical Center (VA) North Carolina Baptist Hospital (NC)
(WI) Harris Methodist Fort Worth (TX) Licking Memorial Hospital (OH) North Coast Clinical Laboratory,Inc.
Contra Costa Regional Medical Health Network Lab (PA) LifeBridge Health Sinai Hospital (MD) (OH)
Center (CA) Health Partners Laboratories Bon LifeLabs (Canada) North District Hospital (Hong Kong,
Cook Children’s Medical Center (TX) Secours Richmond (VA) LifeLabs Medical Laboratory Services China)
Cork University Hospital (Ireland) Health Sciences Research Institute (Canada) North Mississippi Medical Center (MS)
Cornwall Community Hospital (Japan) Loma Linda University Medical (CA) North Shore Hospital Laboratory (New
(Canada) Health Waikato (New Zealand) Long Beach Memorial Medical Zealand)
Corpus Christi Medical Center (TX) Heidelberg Army Hospital (APO, AE) Center (CA) North Shore-Long Island Jewish Health
Covance CLS (IN) Helen Hayes Hospital (NY) Los Angeles County Public Health System Laboratories (NY)
The Credit Valley Hospital (Canada) Hema-Quebec (Canada) Lab. (CA) Northeast Pathologists, Inc. (MO)
Creighton University Medical Center Hennepin Faculty Association (MN) Louisiana Office of Public Health Northridge Hospital Medical Center (CA)
(NE) Henry Ford Hospital (MI) Laboratory (LA) Northside Hospital (GA)
Crozer-Chester Medical Center (PA) Henry M. Jackson Foundation (MD) Louisiana State University Medical Ctr. Northwest Texas Hospital (TX)
Darwin Library NT Territory Health Henry Medical Center, Inc. (GA) (LA) Northwestern Memorial Hospital (IL)
Services (Australia) Hi-Desert Medical Center (CA) Lourdes Hospital (KY) Norton Healthcare (KY)
David Grant Medical Center (CA) Hoag Memorial Hospital Maccabi Medical Care and Health Fund Ochsner Clinic Foundation (LA)
Daviess Community Hospital (IN) Presbyterian (CA) (Isreal) Ohio State University Hospitals (OH)
Deaconess Hospital Laboratory (IN) Holy Cross Hospital (MD) Mackay Memorial Hospital (Taiwan) Onze Lieve Vrouw Ziekenhuis (Belgium)
Deaconess Medical Center (WA) Holy Family Medical Center (WI) Madison Parish Hospital (LA) Ordre Professionel des Technologistes
Dean Medical Center (WI) Holy Name Hospital (NJ) Mafraq Hospital (UAE) Medicaux du Quebec (Quebec, Canada)
DeWitt Healthcare Network (USA Holy Spirit Hospital (PA) Magnolia Regional Health Center (MS) Orebro University Hospital (Sweden)
Meddac) (VA) Hopital Cite de La Sante de Laval Main Line Clinical Laboratories, Inc. (PA) Orlando Regional Healthcare System (FL)
DHHS NC State Lab of Public (Canada) Makerere University Walter Reed Project Ospedale Casa Sollievo Della Sofferenza
Health (NC) Hopital du Haut-Richelieu (Canada) Makerere University Medical School – IRCCS (Italy)
Diagnostic Laboratory Services, Inc. Hôpital Maisonneuve - Rosemont (Uganda) The Ottawa Hospital (Canada)
(HI) (Montreal, Canada) Maricopa Integrated Health System (AZ) Our Lady of Lourdes Medical Center (NJ)
Diagnostic Services of Manitoba Hôpital Sacré-Coeur de Montreal Marquette General Hospital (MI) Our Lady of Lourdes Reg. Medical Ctr.
(Canada) (Quebec, Canada) Marshfield Clinic (WI) (LA)
Diagnósticos da América S/A Hopital Santa Cabrini Ospedale Martha Jefferson Hospital (VA) Our Lady’s Hospital for Sick Children
(Brazil) (Canada) Martin Luther King, Jr. Harbor Hospital (Ireland)
Diaz Gill-Medicina Laboratorial Hospital Albert Einstein (Brazil) (CA) Overlake Hospital Medical Center (WA)
S.A. (Paraguay) Hospital das Clinicas-FMUSP (Brazil) Martin Memorial Health Systems (FL) Palmetto Health Baptist Laboratory (SC)
Dimensions Healthcare System Hospital Dirino Espirito Santa Mary Hitchcock Memorial Hospital (NH) Pathology and Cytology Laboratories,
Prince George's Hospital Center (Portugal) Mary Imogene Bassett Hospital (NY) Inc. (KY)
(MD) The Hospital for Sick Children (Canada) Massachusetts General Hospital (MA) Pathology Associates Medical
Dr. Erfan & Bagedo General Hospital Hôtel Dieu Grace Hospital Library Mayo Clinic (MN) Laboratories (WA)
(Saudi Arabia) (Windsor, ON, Canada) Mayo Clinic Scottsdale (AZ) Pathology Associates of Boone (NC)
DRAKE Center (OH) Hunter Area Pathology Service (Australia) Meadows Regional Medical Center (GA) Penn State Hershey Medical Center (PA)
Driscoll Children’s Hospital (TX) Imelda Hospital (Belgium) Mease Countryside Hospital (FL) Pennsylvania Hospital (PA)
DUHS Clinical Laboratories Franklin Indian River Memorial Hospital (FL) Medecin Microbiologiste (Canada) The Permanente Medical Group (CA)
Site (NC) Inova Fairfax Hospital (VA) Medical Center Hospital (TX) Peterborough Regional Health Centre
Dundy County Hospital (NE) Institut fur Stand. und Dok. im Med. Medical Center of Louisiana at NO- (Canada)
Durham VA Medical Center (NC) Lab. (Germany) Charity (LA) Piedmont Hospital (GA)
DVA Laboratory Services (FL) Institut National de Santé Publique du Medical Center of McKinney (TX) Pitt County Memorial Hospital (NC)
Dwight D. Eisenhower Medical Quebec Centre de Doc. – INSPQ (Canada) Medical Centre Ljubljana (Slovenia) Prairie Lakes Hospital (SD)
Center (KS) Institute Health Laboratories (PR) Medical College of Virginia Presbyterian Hospital of Dallas (TX)
E. A. Conway Medical Center (LA) Institute of Clinical Pathology and Hospital (VA)
East Central Health (Canada) Medical Research (Australia) Medical Specialists (IN)
East Georgia Regional Medical Institute of Laboratory Medicine Medical Univ. of South Carolina (SC)
Center (GA) Landspitali Univ. Hospital (Iceland) MediCorp - Mary Washington Hospital
Eastern Health Pathology (Australia) (VA)
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 Presbyterian/St. Luke’s Medical St. John’s Mercy Medical Center Suncoast Medical Clinic (FL) The University of Texas Medical
Center (CO) (MO) Sunnybrook Health Science Center Branch (TX)
Prince County Hospital (Canada) St. John’s Regional Health Center (ON, Canada) University of the Ryukyus (Japan)
Princess Margaret Hospital (Hong (MO) Sunrise Hospital and Medical Center University of Virginia Medical
Kong, China) St. Joseph Health Center (MO) (NV) Center (VA)
Providence Alaska Medical Center St. Joseph Mercy – Oakland (MI) Sydney South West Pathology Service University of Washington (WA)
(AK) St. Joseph Mercy Hospital (MI) Liverpool Hospital (Australia) UPMC Bedford Memorial (PA)
Providence Health Care (Canada) St. Joseph’s Hospital (FL) T.J. Samson Community Hospital (KY) U.S.A. Meddac (Pathology Division)
Providence Medford Medical Center St. Joseph’s Medical Center (CA) Taipei Veterans General Hospital (Taiwan) (MO)
(OR) St. Joseph’s Regional Medical Taiwan Society of Laboratory UW Hospital (WI)
Provincial Health Services Authority Center (NJ) Medicine (Taiwan) UZ-KUL Medical Center (Belgium)
(Vancouver, BC, Canada) St. Jude Children’s Research Hospital Tallaght Hospital (Ireland) VA (Asheville) Medical Center (NC)
Provincial Laboratory for Public (TN) Tartu University Clinics (Estonia) VA (Chillicothe) Medical Center (OH)
Health (Edmonton, AB, Canada) St. Louis University Hospital (MO) Texas Children's Hospital (TX) VA (Cincinnati) Medical Center (OH)
Queen Elizabeth Hospital (Canada) St. Luke’s Hospital (FL) Texas Department of State Health Services (TX) VA (Dallas) Medical Center (TX)
Queen Elizabeth Hospital (China) St. Luke’s Hospital (IA) Thomason Hospital (TX) VA (Dayton) Medical Center (OH)
Queensland Health Pathology St. Luke’s Hospital (PA) Timmins and District Hospital VA (Decatur) Medical Center (GA)
Services (Australia) St. Martha’s Regional Hospital (Canada) VA (Hines) Medical Center (IL)
Quest Diagnostics, Inc (Canada) The Toledo Hospital (OH) VA (Indianapolis) Medical Center (IN)
Quest Diagnostics JV (IN, OH, PA) St. Mary Medical Center (CA) Touro Infirmary (LA) VA (Long Beach) Medical Center (CA)
Quest Diagnostics Laboratories St. Mary's Hospital (WI) Tri-Cities Laboratory (WA) VA (Miami) Medical Center (FL)
(WA) St. Michael’s Hospital Diagnostic Trident Medical Center (SC) VA New Jersey Health Care System
Quincy Hospital (MA) Laboratories & Pathology (Canada) Trinity Medical Center (AL) (NJ)
Rady Children’s Hospital San Diego St. Tammany Parish Hospital (LA) Tripler Army Medical Center (HI) VA Outpatient Clinic (OH)
(CA) Sampson Regional Medical Center Tufts New England Medical Center VA (San Diego) Medical Center (CA)
Redington-Fairview General (NC) Hospital (MA) VA (Seattle) Medical Center (WA)
Hospital (ME) Samsung Medical Center (Korea) Tulane Medical Center Hospital & Clinic VA (Sheridan) Medical Center (WY)
Regional Health Authority Four San Francisco General Hospital- (LA) Valley Health (VA)
(RHA4) (Canada) University of California San Francisco Turku University Central Hospital (Finland) Vancouver Hospital and Health
Regions Hospital (MN) (CA) UC Davis Health System (CA) Sciences Center (BC, Canada)
Reid Hospital & Health Care Sanford USP Medical Center (SD) UCI Medical Center (CA) Vancouver Island Health Authority (SI)
Services (IN) SARL Laboratoire Carron (France) UCLA Medical Center (Canada)
Renown Regional Medical Center Saudi Aramco Medical (Saudi Clinical Laboratories (CA) Vanderbilt University Medical Center (TN)
(NV) Arabia) UCSD Medical Center (CA) Via Christi Regional Medical Center (KS)
Research Medical Center (MO) Schneck Medical Center (IN) UCSF Medical Center China Basin Virga Jessezieukenhuis (Belgium)
Riverside Regional Medical Center Scott & White Memorial Hospital (CA) Virtua - West Jersey Hospital (NJ)
(VA) (TX) UMass Memorial Medical Center (MA) WakeMed (NC)
Riyadh Armed Forces Hospital, Scott Air Force Base (IL) UMC of Southern Nevada (NV) Walter Reed Army Medical Center (DC)
Sulaymainia (Saudi Arabia) Seoul National University Hospital UNC Hospitals (NC) Warren Hospital (NJ)
Rockford Memorial Hospital Assn. (Korea) Union Clinical Laboratory (Taiwan) Washington Hospital Center (DC)
(IL) Seton Medical Center (CA) United Christian Hospital (Hong Kong) Waterbury Hospital (CT)
Roxborough Memorial Hospital Shamokin Area Community Hospital United Clinical Laboratories (IA) Waterford Regional Hospital (Ireland)
(PA) (PA) Unity HealthCare (IA) Wayne Memorial Hospital (NC)
Royal Victoria Hospital (Canada) Sheik Kalifa Medical City (UAE) Universita Campus Bio-Medico (Italy) Weirton Medical Center (WV)
Rush North Shore Medical Center Shore Memorial Hospital (NJ) Universitair Ziekenhuis Antwerpen Wellstar Douglas Hospital Laboratory (GA)
(IL) Shriners Hospitals for Children (SC) (Belgium) Wellstar Paulding Hospital (GA)
SAAD Specialist Hospital (Saudi Singapore General Hospital University College Hospital (Ireland) Wellstar Windy Hill Hospital Laboratory
Arabia) (Singapore) University Hospital Center Sherbrooke (CHUS) (GA)
Sacred Heart Hospital (FL) SJRMC Plymouth Laboratory (IN) (Canada) West China Second University Hospital,
Sacred Heart Hospital (WI) Sky Lakes Medical Center (OR) University Medical Center at Princeton Sichuan University (P.R. China)
Sahlgrenska Universitetssjukhuset South Bend Medical Foundation (IN) (NJ) West Valley Medical Center Laboratory
(Sweden) South Miami Hospital (FL) University of Alabama Hospital Lab (AL) (ID)
Saint Francis Hospital & Medical Southern Health Care Network University of Arkansas for Medical Sci. (AR) Western Baptist Hospital (KY)
Center (CT) (Australia) University of Chicago Hospitals (IL) Western Healthcare Corporation (Canada)
Saint Mary's Regional Medical Southern Maine Medical Center (ME) University of Colorado Health Sciences Wheaton Franciscan & Midwest Clinical
Center (NV) Speare Memorial Hospital (NH) Center (CO) Laboratories (WI)
Saints Memorial Medical Center Spectrum Health - Blodgett Campus University of Colorado Hospital (CO) Wheeling Hospital (WV)
(MA) (MI) University of Iowa Hospitals and Clinics William Beaumont Army Medical Center
St. Anthony Hospital (OK) Stanford Hospital and Clinics (CA) (IA) (TX)
St. Anthony’s Hospital (FL) State of Connecticut Department of University of Kentucky Med. Ctr. (KY) William Beaumont Hospital (MI)
St. Barnabas Medical Center (NJ) Public Health (CT) University of Maryland Medical System William Osler Health Centre (Canada)
St. Christopher’s Hospital for State of Hawaii Department of Health (MD) Winchester Hospital (MA)
Children (PA) (HI) University of Miami (FL) Winn Army Community Hospital (GA)
St. Elizabeth Community Hospital State of Washington-Public Health Labs University of MN Medical Center - Wisconsin State Laboratory of Hygiene
(CA) (WA) Fairview (MN) (WI)
St. Eustache Hospital (Canada) Stillwater Medical Center (OK) University of MS Medical Center (MS) Wishard Health Sciences (IN)
St. Francis Hospital (SC) Stony Brook University Hospital University of So. Alabama Children’s and Womack Army Medical Center (NC)
St. John’s Hospital (IL) (NY) Women’s Hospital (AL) Woodlawn Hospital (IN)
St. John’s Hospital & Health Ctr. Sudbury Regional Hospital (Canada) University of Texas Health Center (TX) York Hospital (PA)
(CA)

OFFICERS BOARD OF DIRECTORS

Gerald A. Hoeltge, MD, Maria Carballo

President Health Canada Timothy J. O’Leary, MD, PhD
Cleveland Clinic Department of Veterans Affairs
Russel K. Enns, PhD
Janet K.A. Nicholson, PhD, Cepheid Robert Rej, PhD
President-Elect New York State Department of Health
Centers for Disease Control and Prevention Prof. Naotaka Hamasaki, MD, PhD
Nagasaki International University Donald St.Pierre
Mary Lou Gantzer, PhD, FDA Center for Devices and Radiological Health
Secretary Valerie Ng, PhD, MD
Siemens Medical Solutions Diagnostics Alameda County Medical Center/ Michael Thein, PhD
Highland General Hospital Roche Diagnostics GmbH
W. Gregory Miller, PhD,
Treasurer Luann Ochs, MS James A. Thomas
Virginia Commonwealth University BD Diagnostics – TriPath ASTM International

Robert L. Habig, PhD,

Immediate Past President
Habig Regulatory Consulting

Glen Fine, MS, MBA,

Executive Vice President

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