Improvement Advisory Committee
The Secretary of Health and Human Services is authorized under Section 353 of
the Public Health Service Act, as amended, to establish standards to assure
consistent, accurate, and reliable test results by all clinical laboratories in
the United States. The Secretary is authorized under Section 222 to establish
The Clinical Laboratory Improvement Advisory Committee (CLIAC) was chartered in
February 1992 to provide scientific and technical advice and guidance to the
Secretary and the Assistant Secretary for Health regarding the need for, and
the nature of, revisions to the standards under which clinical laboratories are
regulated; the impact on medical and laboratory practice of proposed revisions
to the standards; and the modification of the standards to accommodate
The Committee consists of 20 members, including the Chair. Members are selected
by the Secretary from authorities knowledgeable in the fields of microbiology,
immunology, chemistry, hematology, pathology, and representatives of medical
technology, public health, clinical practice, and consumers. In addition, CLIAC
includes three ex officio members, or designees: the Director, Centers for
Disease Control and Prevention; the Commissioner, Food and Drug Administration;
the Administrator, Centers for Medicare & Medicaid Services (formerly,
Health Care Financing Administration); and such additional officers of the U.S.
Government that the Secretary deems are necessary for the Committee to
effectively carry out its functions. CLIAC also includes a non-voting liaison
representative who is a member of AdvaMed (formerly, Health Industry
Manufacturers Association) and such other non-voting liaison representatives
that the Secretary deems are necessary for the Committee to effectively carry
out its functions.
Due to the diversity of its membership, CLIAC is at times divided in the
guidance and advice it offers to the Secretary. Even when all CLIAC members
agree on a specific recommendation, the Secretary may not follow their advice
due to other overriding concerns. Thus, while some of the actions recommended
by CLIAC may eventually result in changes to the regulations, the reader should
not infer that all of the Committees recommendations will be automatically
accepted and acted upon by the Secretary.
Dr. Toby Merlin, CLIAC Chair, called the meeting to order and welcomed the
Committee members. Dr. Edward Baker, Director, Public Health Practice
Program Office (PHPPO), Centers for Disease Control and Prevention (CDC),
recounted the events of September 11, 2001, the subsequent incidents involving
anthrax, and the consequential effects on the nation, CDC, and the CLIAC
meeting scheduled for September 12-13, 2001, which was cancelled. He
related CDCs role in providing support to the states during the challenging
days and months following these events and pointed out the National Laboratory
System (NLS) is moving from a concept to a reality, with help from many
people. He appealed to CLIAC to give its strong support for the NLS at
CDC. Dr. Robert Martin, Director, Division of Laboratory Systems (DLS),
PHPPO, CDC, added his welcome to the Committee and explained he was in India at
the time of the September 11 events assisting with the development of an
integrated-laboratory system for disease surveillance. CLIAC members then
made self-introductions and disclosure statements of their financial interests
relevant to topics to be discussed during the meeting.
Division of Clinical Laboratory
Dr. Steven Gutman, Director, Division of Clinical Laboratory Devices (DCLD),
Office of Device Evaluation (ODE), Center for Devices and Radiological Health
(CDRH), FDA, updated CLIAC on FDA activities relevant to CLIA. He reviewed the
status of FDA and DCLD personnel changes, summarized the workload levels for
the 510(k) and the premarket approval (PMA) review processes, and discussed
FDAs initiative relative to down-classifications of analyzers and tests. In
addition, he provided information demonstrating that FDA has categorized more
than 1,800 submissions received for test categorization and continues to work
with other agencies on genetic initiatives, bioterrorism preparedness, and a
task force to combat antimicrobial resistance. Dr. Gutman also addressed FDAs
re-engineering plans to reduce burden, which include identifying ways to
streamline the submission process and increasing flexibility by offering an
expanded menu of submission choices. New options for test device review were
presented, followed by a summary of FDAs strategic plan to ensure the health of
the public throughout the total product life cycle.
One Committee member inquired about FDAs new options for test device review. Dr.
Gutman replied these processes are evolving and FDA is asking professional
groups for help, particularly with guidelines for the abbreviated 510(k)
review. This review relies on the manufacturers ability to use established
standards, such as those contained in NCCLSs EP-05A document (Evaluation of
Precision Performance of Clinical Chemistry Devices; Approved Guideline);
however, these standards need to be further defined. At present, these
standards focus on laboratory practice rather than manufacturer practice.
Dr. Elliott Cowan, Division of Emerging and Transfusion Transmitted Diseases,
Center for Biologics and Research, FDA, reported on the June 14, 2001, Blood
Products Advisory Committee (BPAC) meeting. At this meeting, BPAC was asked to
consider whether FDA, in light of the known benefits and risks of rapid HIV
testing, should waive simple and accurate HIV testing from CLIA under its draft
waiver guidance. Fifteen members of the Committee voted against waiver of rapid
HIV tests and two members abstained. BPAC further recommended that some
oversight is needed for rapid HIV tests and pre- and post-analytic concerns
such as counseling and confirmatory testing should be considered. The Committee
unanimously voted in favor of pursuing other approaches under CLIA (e.g.,
limited public health testing) to promote wider access to rapid HIV testing.
Since the June meeting, FDA has withdrawn its draft waiver guidance and is
using the criteria listed in the September 1995 proposed rule for its waiver
reviews. In closing, Dr. Cowan requested additional input from CLIAC on the
criteria and process for waiver determinations.
One CLIAC member, also present at the BPAC meeting, concurred with Dr. Cowans
summary and added there were impassioned pleas by some of the meetings
attendees to waive rapid HIV tests. However, many of these pleas were based on
misconceptions of testing accessibility. In addition, CMS data presented at the
meeting illustrated some of the problems occurring in laboratories performing
waived testing, particularly related to failure to follow manufacturers
instructions. With this in mind, BPAC felt it would be impossible to control
the quality of testing in non-traditional testing sites without some type of
oversight, which would not occur if the testing was waived.
Another CLIAC member noted a false positive or false negative HIV result would
not only be devastating to an individual, it would also be a public health
risk. Other members agreed and pointed out these same issues could apply to
CLIAC members agreed that promoting the use of CLIAs limited public health
testing exception is preferable to waiving these tests. This exception permits
not-for-profit federal, state, or local government laboratories that engage in
limited (that is, a combination of 15 moderately complex or waived tests) to
file a single application for a CLIA certificate.
Dr. Donna-Bea Tillman, Division of Cardiovascular and Respiratory Devices, ODE,
CDRH, FDA, summarized FDAs review process for respiratory and cardiovascular
monitoring devices, which include pulmonary function tests, cardiovascular
monitors, pulse oximeters, and indwelling arterial sensors. These monitoring
devices measure a variety of physiological parameters and are not addressed in
the CLIA regulations. Dr. Tillman explained that, as part of the 510(k) review
program, a manufacturer must provide performance testing studies to demonstrate
a device is substantially equivalent to a predicate device. In an effort to
assure consistency among devices, FDA encourages manufacturers to meet
voluntary standards, such as International Organization for Standardization
(ISO) and International Electrotechnical Commission (IEC) standards. In
addition, the Quality System Regulation (QSR), also known as current good
manufacturing practice (cGMP), requires design controls and design control
validation to ensure the quality of the finished device.
Update Directors of Laboratories Performing High Complexity Testing
One member asked if respiratory and cardiovascular monitoring devices provide
reference intervals or normal ranges. Another member asked whether the accuracy
of these devices is comparable to traditional laboratory tests. One member
expressed concern that some indwelling sensors are providing electrolyte values
used for diagnostic purposes. Dr. Tillman replied that while the manufacturers
studies must include testing the device over the range of values you would
expect to see, these devices do not indicate whether results are normal or
abnormal--they only report a number. In general, these devices are not as
accurate as traditional laboratory tests and this is reflected in the device
labeling. They are intended to show trends, not to give absolute values.
In response to a members concerns about the accuracy of a devices results when,
for example, some indwelling arterial sensors are left in place for a week or
more and clotting may occur, Dr. Tillman stated the manufacturer must provide
data to support the claims it makes in the devices labeling. If the
manufacturer wants to make a change, such as in the time period a device may be
used, it must submit validation data to support its new claim. Once approved,
the labeling may then be revised to reflect the extended performance period.
She added, FDA can address labeling, but cannot address the clinician who uses
the device off-label.
When asked how FDA handles problems with respiratory and cardiovascular
devices, Dr. Tillman responded that FDA monitors post-market usage of these
products through Medwatch. Also, companies are required to have a system in
place for monitoring complaints and reporting problems to FDA.
Dr. Merlin acknowledged the practical limitations of extending CLIA authority
to this realm of testing. He noted that CLIA may not be the appropriate
oversight program; instead, he suggested that professional organizations be
encouraged to adopt and promote appropriate standards.
Ms. Valerie Coppola, Division of Outcomes and Improvement, Center for Medicaid
and State Operations, CMS, announced that a Notice of Proposed Rule Making
(NPRM) addressing revisions to and expansion of the qualification requirements
by which an individual with a doctoral degree may qualify as a director of a
laboratory performing high complexity testing was published in the Federal
Register on December 28, 2001. She noted the public comment period ended
January 28, 2002, and that CMS and CDC are working on development of a final
rule for publication by the end of the year.
The Committees discussion focused on the NRPMs proposed requirement at
493.1443(b)(3)(iii), which would allow an individual with an earned doctoral
degree in a chemical, physical, biological, or clinical laboratory science and
at least six years of laboratory training or experience or both, including two
years directing or supervising high complexity testing, to serve as a director
of a laboratory performing high complexity testing.
Many members felt this proposed qualification route is a step backward and the
specified experience inconsistent with the responsibilities for directors of
high complexity testing listed in the CLIA regulations at 493.1445. Several
members were concerned this pathway would result in a decrease in the standard
Many members also viewed this qualification pathway as requiring less
documented laboratory experience and expertise than is required for
certification by an HHS-approved board (another qualification pathway). Several
members emphasized that board certification requires documentation of
education, training, and experience and an examination that assesses knowledge
and competencies. In addition, to maintain board certification, recertification
is required, which involves documentation of continuing education. Whereas, the
proposed requirement at 493.1443(b)(3)(iii) did not include a mechanism for
validation of basic knowledge and skills, especially in clinical laboratory
practice and management, and offered no incentive for individuals to update
their knowledge base.
Some members believed the proposed option would be in conflict with the more
stringent director requirements (i.e., specialty-specific experience and
training) proposed in the Notice of Intent; Genetic Testing under the Clinical
Laboratory Improvement Amendments (65 FR 25928) published in the Federal
Register on May 4, 2000, which may be included in the NPRM for genetics testing
(in development). The Committee was reminded that any conflicts between
proposed rules would be resolved as comments are considered and the rule-making
finalized. Furthermore, CLIAs technical supervisor requirements for the various
laboratory specialty areas address specialty-specific education and training.
CLIAC members questioned why this option was included in the NPRM. Ms. Rhonda
Whalen, DLS, PHPPO, CDC, explained its inclusion was in response to comments
received following the publication of the earlier date extension regulations
suggesting an alternative be developed to qualify individuals with a doctoral
degree on the basis of laboratory training or experience instead of requiring
board certification. In addition, this proposed alternative seeks to address
two significant healthcare issues--workforce supply and its role in maintaining
access to and delivery of services.
CLIAC members were asked to consider the potential impact on the healthcare
system if this option was removed in the final rule and whether enough
individuals would qualify as directors of laboratories performing high
complexity testing. Several members believed there would be sufficient numbers
of high complexity laboratory directors without providing this qualification
pathway. Others stated that personnel shortages and access to care should not
be used as a basis for lowering standards.
Some members noted that in the past decade, HHS-approved boards have developed
a variety of non-traditional routes to attain certification, thus providing
additional avenues for certification to more candidates. One member suggested
CLIA laboratory and director demographics from the CMS database could be
helpful in establishing the current workforce matrix and determining the
potential impact of requiring board certification. There was general agreement
that available data be carefully reviewed and considered in regard to workforce
supply and laboratory quality.
In closing the discussion, Dr. Merlin summarized the Committees belief that the
high complexity laboratory director requirements should be consistent with the
respective responsibilities outlined in the CLIA regulations. In addition,
CLIAC officially recommended the proposed qualification requirement at 493.1443
(b) (3) (iii) of the December 28, 2001, NPRM be deleted or at least modified to
require a more formal mechanism for documenting laboratory expertise, including
validation of skills in the broad area of high complexity laboratory testing
and evidence of continuing education, as currently demonstrated through board
Delegation of Authority for CLIA
Ms. Coppola reviewed the delegation of authority for the CLIA program,
explaining that legal authority for CLIA was given to CMS by the Secretary of
Health and Human Services (HHS) pursuant to the CLIA statute. CMS, in turn,
established written agreements with CDC and FDA specifying the functions and
responsibilities of each agency, as well as the disbursement of CLIA funding to
each agency commensurate with the assigned functions and responsibilities. She
described how the three agencies work together to draft and publish CLIA
regulations, with implementation of a regulation delegated to a specific
agency. As an example of the tri-agency cooperative effort, Ms. Coppola noted
that although the final waiver rule is being developed by all three agencies,
FDA will be responsible for its implementation.
Several members inquired about the status of the genetics NPRM and the quality
control(QC)/quality assurance(QA) final rule. Dr. Joe Boone, DLS, PHPPO, CDC,
informed the Committee the proposed genetics regulation is being drafted and
the impact analysis still needs to be done. The goal is to publish the genetics
proposed rule by the end of the year. Ms. Coppola stated the QC/QA rule is in
the final stages of development. After agency clearance by CDC and CMS, it will
be forwarded to HHS for department clearance.
One member inquired about the status of a recommendation from a Cytology
workgroup meeting suggesting the FDA PMA process use an interagency group, with
the FDA as the lead, to determine individual workload labeling as part of the
approval of cytology devices. Dr. Gutman indicated the suggested interaction
would be helpful as FDA does not have experience in evaluating manual workload
associated with instrumentation.
Dr. Janet Nicholson, Associate Director for Laboratory Science, National Center
for Infectious Diseases (NCID), CDC, provided an overview of the agencys
laboratory bioterrorism response activities, which began October 13, 2001, with
the second identified case of anthrax. She described the operational oversight,
staffing, and organizational design of the Emergency Operations Center (EOC)
that was established to coordinate preparedness and response activities. This
included providing a glimpse into how volunteer lists were compiled throughout
CDC by skill levels; how protocols for monitoring and managing laboratory
testing were developed; and how internal and external communication lines were
established. Dr. Nicholson also described how NCID laboratories rapidly
expanded their space and capacity to handle the numerous challenges encountered
in processing and testing the large, and sometimes unpredictable, influx of
diverse specimens. She complimented the many volunteers who worked long hours
to provide the multitude of skills and 24 hour/7 day a week coverage the EOC
and laboratories required. In closing, Dr. Nicholson shared the lessons learned
and summarized what needs to be done to prepare for future events, emphasizing
the imminent need to plan using real scenarios from the anthrax event.
CLIAC members recognized and applauded CDCs rapid response and heroic efforts
in meeting the challenges of this unprecedented public health emergency.
Several members asked how CDC plans to address the types of specimen tracking
challenges encountered during the anthrax investigations. Dr. Nicholson
indicated a field module, a hand-held device, has been developed for outbreak
situations. This module provides menus for logging samples/specimens and
selecting couriers, and includes a mechanism to alert laboratories to the
expected time of sample/specimen arrival. She said a barcode labeling system
still needs to be developed for field use.
One member asked how laboratorians outside CDC could volunteer in the event of
future incidents or outbreaks. Dr. Nicholson indicated a mechanism, including a
personnel database, needs to be developed. The database should include both
private-sector and government employees and provide information such as
laboratory skills, availability, and the necessary work clearances.
Another member stated that many Level A laboratories felt disenfranchised and
would have been willing to help. Dr. Nicholson emphasized there is a system in
place for outbreak response that works. Protocol indicates specimens and
questions should first go to the local public health facility, then to the
state public health laboratory. CDC then works with the state public health
laboratory. Many of the challenges encountered during the anthrax
investigations arose when this system was by-passed and specimens sent directly
When asked about the questions CDC received from the public, Dr. Nicholson
responded the agency was overwhelmed with questions. All information released
to the public had to be cleared first and it was sometimes difficult to provide
timely and complete responses.
CLIAC members acknowledged the need to remain focused on the importance of
building and maintaining a strong public health infrastructure that can respond
rapidly to outbreaks and catastrophic events.
Dr. John Ridderhof, DLS, PHPPO, CDC, began his presentation by describing the
current network of laboratories performing tests of public health significance
(such as agents of bioterrorism, tuberculosis, HIV, blood lead) as a loose
association of public health, hospital, and independent laboratories throughout
the country where collaboration and communication is often inconsistent. He
referenced several independent government reports identifying the lack of
proactive federal leadership as contributing to the weaknesses identified in
the nation's public health surveillance system. In response, CDC's Office of
Laboratory Systems Development, within DLS, PHPPO, has developed strategic
initiatives utilizing professional organizations, federal partners, and
federally-funded state projects to assess laboratory capabilities, address gaps
in training, establish uniform standards of laboratory practice, and improve
collaboration of laboratories at the local level. Dr.Ridderhof closed by urging
CLIAC support for DLS strategic initiatives to develop a National Laboratory
System to assure consistent laboratory capacity for public health response
across the nation.
Committee Discussion (See discussion following next presentation)
Dr. Lawrence Sturman, CLIAC member and Director, Wadsworth Center, New York
State Department of Health, presented an overview of the Wadsworth Centers
experience with environmental anthrax threats. Dr. Sturman began by reporting
that from 1943 to1960, most of the states human anthrax cases involved workers
in the carpet and leather industries, with the last reported case in 1961. He
then shared with CLIAC some of the problems faced and the lessons learned as a
result of the bioterrorism events of 2001.
Dr. Sturman first outlined the organizational structure of the Wadsworth Center
and reviewed the design of its biosafety level-3 laboratory. He then provided
data on the number of environmental samples received, described the varied
packaging and unique sample types, and cited sample accessioning and tracking
as major problems needing to be addressed. Dr. Sturman noted, of the more than
900 samples submitted for testing since October 2001, some were of valid
concern with 24 testing positive for anthrax. However, the vast majority of the
samples received, which included paper currency and clothing, were the result
of hoaxes and/or public hysteria. He also recounted the Centers problems with
and lack of preparedness for handling and testing a multiple/mixed agent
hazard, a possible weapon of mass destruction in the future.
Dr. Sturman stressed integrated state and national response capabilities and
capacities must be developed before they are actually needed. He concluded by
sharing New York States recommendations for BT laboratory preparedness, which
address laboratory design and functions; a triage system and protocols for
specimen/sample handling, tracking, and testing; and a result reporting system.
Committee Discussion ( combined for both Dr. Ridderhofs and Dr. Sturmans
Members agreed the anthrax threat was a "wake up call," clearly
illuminating the need to improve the current public health laboratory
infrastructure and develop lines of communication between regional and local
laboratories. Members also concurred efforts in this regard must be sustained
and long-term; it is imperative that federal support and funding not dissipate
over time. With this in mind, the Committee requested a letter to the Secretary
of HHS be developed expressing the Committees support of NLS efforts (Addendum
The Committee discussed the necessity of collaboration among public, private,
and government agency laboratories on technical knowledge and experience in
test methodologies and development. This is essential to ensuring universal
test availability, validation, and standardized utilization, as well as
appropriate post-test counseling and follow-up. However, one member pointed out
the advantage of having laboratories using different testing methodologies
rather than all laboratories using the same method; it increases the likelihood
of detecting an organism.
Several members emphasized the importance of communication among local, state
and federal public health agencies and private laboratories. They also stressed
the necessity for data interchange standards. One member cited the National
Cancer Institute-funded Pathology Informatics Demonstration Project as an
example, and asked if there is a similar laboratory data interchange standard
that has achieved a broad consensus. Dr. Ridderhof responded by describing the
National Electronic Disease Surveillance System (NEDSS) as a model
communication system. This system is being developed by CDC to assure accurate,
complete, and timely reporting of data for outbreak detection by implementing
national data standards for surveillance and reporting by state and local
health departments to CDC. Eventually, it will become an Internet-based
communications infrastructure integrating public health information and
healthcare data systems.
A suggestion was made to have NEDSS as an agenda item for the next CLIAC
Dr. Merlin re-introduced the recommendations made by CLIAC in a June 8, 2001,
letter to FDA in response to its draft waiver guidance. Since FDA has withdrawn
its draft guidance, he asked the Committee if it would like to readdress these
recommendations in a letter to the Secretary of HHS as general recommendations
to be used in rule-making relative to the waiver review criteria and processes.
Committee discussion centered around the CLIA statute, as modified by the FDA
Modernization Act of 1997 (FDAMA), which automatically waives all tests
approved by the FDA for home use. In particular, members continue to be
concerned about the lack of uniformity in the two routes for waiver approval,
that is, FDAs criteria for home use approval and the CLIA review criteria for
waiver approval. FDAs home use approval criteria do not include a threshold for
accuracy, which is a criterion under CLIA (accuracy is used to demonstrate low
risk of an erroneous result), and home use approval does not consider the
expanded use of these products in the clinical setting when they are waived.
The Committee agreed its letter of June 8, 2001, should be readdressed to the
Secretary and references to the draft waiver guidance eliminated. They
emphasized the letter should include a recommendation that a statutory change
be pursued, as needed, to ensure that all waived products are simple and have
an insignificant risk of an erroneous result when used in clinical settings.
Dr. Barbara Goldsmith reported on the deliberations of the August 8, 2001,
Unregulated Tests Workgroup meeting. During this meeting, the workgroup
discussed possible criteria for determining whether CLIA should apply to breath
tests and other currently unregulated tests. This included considering whether
there are any unique testing contexts for which CLIA regulation is not
appropriate. Workgroup members also discussed the value of CLIA oversight as
well as the impact of regulations. They questioned if professional
organizations voluntary guidelines and standards are adequate to ensure quality
testing, especially in nontraditional testing sites. They also questioned
whether it would be appropriate to create a new CLIA category for this type of
testing with unique requirements for personnel qualifications, quality control,
etc. Alternatives to CLIA regulation, such as encouraging professional
organizations and manufacturers to develop standards and guidelines for testing
as well as strengthening existing voluntary guidelines and standards, were also
There was much discussion as to whether this testing falls under CLIA
regulation. One member suggested separating physiological tests from laboratory
tests and considering only in-vitro tests using specimens that are tested in
the laboratory (i.e., removed from the body for testing) as laboratory
procedures. Dr. Goldsmith acknowledged the difficulty involved in separating
these physiological procedures from laboratory tests.
Dr. Gutman was asked how the FDA makes decisions as to whether devices are
in-vitro or in-vivo and how FDA determines which Center has review
responsibility. Dr. Gutman replied the process at FDA has evolved and there is
not a specific algorithm.
One member stated some tests, even if physiological, should fall under some
type of oversight. This member continued, suggesting if CLIAC were to recommend
that voluntary standards be followed, it may be helpful to the Joint Commission
on the Accreditation of Healthcare Organizations (JCAHO) and could influence
compliance with practice guidelines and voluntary standards.
The Committees industry representative commented hospital quality/accreditation
systems could address some of these concerns and a letter to CMS, the agency
responsible for hospital certification, may be the best approach.
Several members expressed caution in advancing into areas not stipulated
by CLIA. They felt professional organizations representing pulmonary,
cardiovascular, and radiological services/medicine would have more authority
and credibility and are in a better position to develop standards of practice.
Dr. Merlin stated that while much of the concerns about unregulated testing is
really a quality issue, all aspects of medical care cannot be addressed by
CLIA. He suggested the Quality Institute, tentatively planned for Spring 2003,
may be a good forum for this discussion.
In discussing breath testing, one member commented that breath is a specimen
source and there is technological development occurring in this area. For
example, devices are being developed that may be able to use breath to evaluate
renal or urinary tract infection. This member felt that at minimum, results
from these devices should correlate with laboratory tests.
Dr. Merlin proposed that a breath specimen, when taken from a patient, then
transported to the laboratory for testing, should be subject to CLIA. A member
noted the breath could be collected from the patient, with testing performed at
the bedside, while another member cautioned this could quickly move into
Dr. Martin reminded the Committee that technology is rapidly evolving and some
can provide measurements without removing substances from the body. He cited
laser technology for non-invasive glucose and bilirubin determinations as an
example. He asked whether CLIA should also address this testing, even though a
specimen is not removed from the human body and taken to the laboratory. Ms.
Whalen advised that for this testing to be regulated under CLIA it would have
to go through rule-making, and Ms. Coppola added, this may need a legal
decision, since the CLIA statute pertains to a specimen derived from the human
Members agreed these issues will remain on the horizon with the development of
more non-invasive testing that is performed outside of the traditional
After much discussion, a motion was made and seconded to include breath, when
derived from the human body and tested in a laboratory as defined by CLIA (...a
facility for the biological, microbiological, serological, chemical,
immuno-hematological, hematological, biophysical, cytological, pathological, or
other examination of materials derived from the human body for the purpose of
providing information for the diagnosis, prevention, or treatment of any
disease or impairment of, or the assessment of the health of human beings.), as
a specimen source under CLIA.
Mr. Phillip Bongiorno, representing the College of American Pathologists (CAP),
addressed the Health Insurance Portability and Accountability Act (HIPAA) and
its potential impact on CAP's accreditation activities performed as a deemed
organization under CLIA. He stated HIPAA defines accreditation organizations
and entities such as CAP as "business associates" rather than as
" health oversight agencies." According to CAP, an accrediting
organization would be required to execute a written "business
associate" agreement with each laboratory it accredits. Mr. Bongiorno
claimed establishing written agreements with each laboratory is burdensome and
costly to both CAP and the laboratory and does not add any assurances relative
to the privacy of patient information. In that HHS is currently drafting
modifications to the final HIPAA privacy rule, CAP asked that CLIAC express
support by letter to HHS recommending CAP, in its role as a deemed
organization, be recognized in the final rule as a "health oversight
agency" and thus, not subject to the "business associate"
One member reminded the Committee that CAP activities are not limited solely to
its deemed status activities relative to the accreditation of laboratories
under CLIA and questioned whether there might be unintended consequences from
designation of the CAP as a health oversight agency.
Most members expressed concern about the apparent undue burden of HIPAA on
deemed laboratory accreditation organizations acting on behalf of CMS. CLIAC
proposed a letter to the Secretary expressing its concerns, but asked for CDC
and CMS legal counsel review prior to proceeding.
Members acknowledged having limited knowledge on HIPAA and suggested a future
CLIAC agenda item address HIPAA and its impact on CLIA.
Dr. Joe Boone, DLS, PHPPO, presented plans for a fifth critical issues
conference, the Quality Institute, to be held in Atlanta mid-late April 2003.
Previous conferences were held in 1984, 1986, 1989, and 1995. The purpose of
this conference will be to develop a framework for a national report on the
health laboratory system. The report will define the nations laboratory system
and a set of quality indicators for the system. Dr. Boone noted while there are
many good efforts toward quality in existence, they are not connected. This
institute would provide the opportunity for connection. Some of the project
areas for the institute are: making the laboratory a partner in patient safety;
developing quality indicators for laboratory personnel shortages; and
developing an integrated approach to laboratory testing of public health
importance. The conference will include plenary sessions, workgroups, and
poster sessions. It is hoped an ongoing Quality Institute will be created to
foster continuous data collection and analysis with dissemination of this
information via the Internet for use by legislators, patient advocacy groups,
One member suggested the Quality Institute look at developing data on workforce
shortages and whether there is correlation with the frequency of laboratory
errors, which result in poor patient outcomes. Others questioned how to collect
risk-management data organizations gather but are reluctant to release. One
issue to consider is whether errors occur because of unqualified personnel or
overworked staff, or are the errors due to poor management. Another member
added the relationship between the clinician and the laboratorian should be
considered. In some cases, the knowledge of the laboratorian about testing
services exceeds that of the laboratory user.
Dr. Boone replied the difficulty in gathering laboratory/medical error
information may be a social and legal problem. Our society tends to assign
blame and punish rather than identify and address the problem. We need to get
past a punitive viewpoint and change to one of problem identification and
The Committees industry representative stated the Medical Device Reporting
regulations require manufacturers to report deaths, hazards, and events to the
government. Manufacturers are held accountable and are not provided
confidentiality when reporting errors. Improvements in industry have occurred
when manufacturers evaluate errors and use the information to make better
products. She added, this reporting requirement needs to be extended to
hospitals and other healthcare settings for quality improvement purposes.
Dr. Merlin stated JCAHO attempted to require participating institutions to
report incidents, but the institutions persuaded JCAHO to reconsider this
requirement because of concerns over liability. Without a major change with
respect to protection, voluntary reporting does not seem to be workable.
One commenter suggested we need to find a way to gain Congressional support for
making the changes necessary to allow institutions and organizations to share
data without fear of liability.
The Committee strongly supported the concept of a Quality Institute and
expressed the need for a systematic approach for looking at quality and
translating it into a sustainable process. They noted good data are needed to
formulate good policies and agreed this forum could serve as a stepping stone
to gather such data. A balance between access and quality must be achieved.
Dr. Patricia Charache, CLIAC member and Program Director, Quality Assurance and
Outcomes Assessment, Johns Hopkins Medical Institutions, summarized the focus
and activities of the SACGT from 1999 through 2001. She related the progress of
the five SACGT workgroups on data collection, education, rare disease testing,
access, and informed consent and institutional review boards (IRBs). She also
updated CLIAC on the development and pilot testing of an FDA pre-market review
template for new genetic tests. Dr. Charache highlighted activities of the
SACGT workgroups, as listed below.
The goal of this workgroup is to increase knowledge relative to the clinical
utility of genetic tests through improved data collection and analysis. SACGT
is concerned about several issues related to data collection: the definition of
a test; mechanisms to obtain both clinical and laboratory data; privacy and
costs of data collection efforts; and approaches of secondary data synthesis.
Thus far, a cooperative agreement between CDC and the Foundation for Blood
Research has evaluated three common genetic tests and has developed a framework
for analyzing the validity and utility of genetic tests.
This workgroup held a roundtable meeting in November 2001 to consider the needs
and appropriate approaches to providing genetics education to healthcare
professionals, patients, and other users of genetic testing services. SACGT is
planning a two-day workshop in May 2002, entitled Genetic Testing and Public
Policy: Preparing Health Professionals, to explore the integration of genetics
into routine patient care and to address the needs for ensuring appropriate use
of genetic tests.
This workgroup has developed a brochure to serve as a model for explaining
genetic testing and informed consent to the general public. The workgroup is
also preparing a white paper on principles, content, and level of informed
consent for different types of genetic tests. However, SACGT acknowledged it is
outside its purview to define the specific type of consent needed for each
test. The workgroup is concerned with defining the role of professional
organizations, FDA, and laboratories in assuring appropriate informed consent
for genetic tests.
Rare Disease Testing Workgroup
The goal of this workgroup is to develop knowledge of and access to quality
testing for rare diseases. Dr. Charache briefly outlined the presentations by
representatives of academic research laboratories, commercial genetic testing
laboratories, FDA, and the National Institutes of Health at the November 2001
SACGT meeting. She pointed out some approaches proposed to SACGT were illegal,
such as allowing research laboratories (not CLIA-certified) to perform patient
testing and report negative results, if confirmatory testing is provided by a
This workgroup focused on issues centering around access to genetic testing such
as the patients need for information; reimbursement issues; and the impact of
patents on access to and quality of testing. Some of the reimbursement issues
addressed were the views of payers, test costs (including the large number of
non-reimbursed laboratory costs), and counseling needs and costs.
Several members expressed concerns about the complexity of collecting and
analyzing genetic testing data; the need to address quality assurance issues
for patient testing offered by laboratories that primarily conduct research;
and appropriate approaches to assuring informed consent for genetic tests.
One member commented that establishing the validity and utility of genetic
tests is more complicated than addressed by the Data Workgroup, since the
relationship of genes and diseases are complex and true single-gene disorders
may not exist.
Another member expressed concern about the over-simplification of the terms
used in the data collection projects presented to SACGT, as the clinical
significance of a genetic alteration is sometimes unclear and
genotype-phenotype correlation is often complex. This member commented on the
inability of those terms to capture the richness and complexity of genetic
tests. Dr. Charache responded these comments were appreciated and would be
conveyed to SACGT.
Several members recommended developing approaches allowing research
laboratories to offer rare disease testing while complying with federal and
state laws. One member commented that such approaches are needed, particularly
since researchers may be requested to release test results to research
subjects. Another member suggested academic institutions should be involved in
the development of appropriate approaches.
Regarding informed consent for genetic tests, one member noted informed consent
is required for every laboratory test and is dictated by state-based case law,
rather than statutes. Another member suggested genetics professional
organizations should be involved in defining appropriate informed consent and
the role of health professionals and laboratories in obtaining this consent. In
addition, concern was expressed that requiring informed consent through the FDA
test review process might not be the best approach.
Dr. Boone suggested CLIAC consider potential non-regulatory approaches to
ensuring informed consent for genetic testing, as it might not be possible to
solve medical practice issues through regulation. He also noted several patient
advocacy groups, concerned with the appropriateness of documenting patient
consent by check-boxes, have requested that patient signatures be required for
all genetic tests. Dr. Charache responded that a white paper under development
by the Consent/ IRB Workgroup would allow flexibility by recommending a
gradient of informed consent requirements for different types of tests. She
further suggested that a CPT code might be needed to reimburse laboratories for
the work entailed in contacting clinicians to ensure patient consent has been
Ms. Kay Setzer, CLIAC Advanced Medical Technology Association liaison, provided
an overview of in-vitro diagnostic (IVD) statutory and regulatory requirements.
She focused on the Quality System Regulation, which governs manufacturers, and
emphasized that the companys senior management is accountable for the
establishment and maintenance of an effective Quality System that addresses
planning, commitment, actions, and follow-up. She also reviewed the FDAs PMA
and 510(k) review processes. The key points in her presentation were IVDs are
subject to regulation under numerous statutes; the manufacturer is required to
maintain a Quality System that is audited by the FDA for all devices; and
higher risk devices require submission of more supportive information to
demonstrate safety and effectiveness.
One member questioned how one manufacturer evaluates another manufacturer when
considering the company for purchase. Ms. Setzer replied a very careful quality
system review and evaluation is performed to evaluate the company prior to
purchase. Another member acknowledged the increased quality of products on the
market today, complimenting the IVD industry and FDAs efforts and commitment in
Dr. Gutman was asked what qualifies a product as exempt from PMA or 510(k)
review. Dr. Gutman replied exemption is based on low risk. As background, most
Class I and many Class II devices considered to be low risk are exempt from the
premarket notification requirements under FDAMA. In addition, some Class III
devices (subject to PMA review) have been down-classified to Class II with a
510(k) review because the risk is considered to be lower than a PMA review
warrants. However, the law still requires PMA review of a new device with no
predicate device for comparison, even if it is simple.
One member expressed concern with the inclusion of QC materials and several
immunological products on FDAs exemption list. Ms. Setzer replied that even
though these products are exempt from submission, they still require design
controls and all products are required to meet cGMP. In addition, these data
must be available for inspection by FDA.
One member asked how a device is down-classified. Dr. Gutman responded this
generally begins with a request from the manufacturer, with data to support the
request, but can also be initiated by FDA during the review process.
Ms. Karen Hickey, Vice President, Regulatory and Clinical Affairs, Binax, Inc.,
recounted the companys experiences with the CLIA waiver process during the
transition of waiver responsibility from CDC to FDA. Binax submitted waiver
applications for two products in 1998 and 1999, and the respective waiver
determinations are still pending. She requested the Committee, as it provides
advice and guidance relative to the waiver regulation under development, to
consider the impact on manufacturers and the benefit to public health.
Dr. Merlin adjourned the meeting. The next CLIAC meeting is scheduled for
September 11-12, 2002.
I certify that this summary report of the January 30-31, 2002, meeting of the
Clinical Laboratory Improvement Advisory Committee is an accurate and correct
representation of the meeting.