IDV Tecnology

PLUS:
Research
consortium
fights TB
J ANUARY/F EBRUARY 2012 VOL UME 18 NO. 1 I VDT ECHNOL OGY. COM
Outsourcing for IVD
Manufacturers
Sourcing clinical patient samples
for IVD development
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i vdt echnol ogy. com I VD TECHNOLOGY | JANUARY/FEBRUARY 2012 3
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CONTENTS
COLUMNS
TRENDS &
PERSPECTIVES
DEPARTMENTS
Regulations & Standards 17
IVD Performance Evaluation
Studies: Part 1
Understanding European requirements
for performance-evaluation studies is
crucial for marketing devices there.
Maria E. Donawa
In Person 20
Developing IVD Instruments:
Complex But Rewarding
Brad Blake of Gen-Probe talks with
us about the costly---but ultimately
worthwhile---development of IVD
instruments.
Interview by Richard Park
Final Thoughts 42
TB CDRC Fights TB with
Diagnostic Science
How the Tuberculosis Clinical
Diagnostics Research Consortium is
promoting improved diagnostic tests
to combat the global TB problem.
Jerrold Ellner
COVER STORY:
Examining the Challenges in
Developing Hematology 24
Hematology instrumenta-
tion developers must be
equipped to meet technol-
ogy challenges coupled
with IVD manufacturers
demands for speed-to-mar-
ket and cost effciency.
HENRI CHAMPSEIX AND
ERIC JOLAIN
ON THE COVER
Automated blood analyzers have become high-tech and
complex in operation, yet simple to use. Photo provided
by BIT C2 Diagnostics, a BIT company.
Knowledge and Experience
Diversity for IVD Innovation 29
By using product development
teams with experience gained
from industries beyond the
IVD world, IVD companies can
draw on trends from seemingly
unrelated felds to deliver break-
through ideas.
JARI PALANDER
Sourcing Clinical Patient Samples
for IVD Development 33
A review of current issues
encountered when sourcing
blood-based clinical patient
samples and the outlook for
IVD manufacturers.
SIMON PACKER, KELI
STOCKBRIDGE, AND PHILIP
JEWESS
IVDTechnology ONLINE
On the next page, fnd out what content is available on IVD Technologys
Web site, ivdtechnology.com .
FEATURES
January/February 2012
Vol. 18, No. 1
Examining IVD-related election
year issues 11
Industry associations discuss
mutually important issues 12
Sony buys Micronics,
extends IVD reach 14
OCDs Know Your Numbers
campaign pushes forward 16 Editors Page 8
Products & Services 39
Ad Index 41
6 I VD TECHNOLOGY | JANUARY/FEBRUARY 2012 i vdt echnol ogy. com
IVD
TECHNOLOGY
ONLINE
ABOUT IVDT CURRENT ISSUE CONTACT US INDUSTRY EVENTS
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reports called DX Directions. For
more information, please visit
ivdtechnology.com/dx-directions
ASK THE
EXPERTS
If you have a question related
to IVD development and
manufacturing that you would like
to ask our experts, please visit
ivdt.canon-experts.com
TECHNOLOGY
WEBCASTS
Watch the latest installments
in our webcast series on the
Fundamentals of IVDs at
ivdtechnology.com/webcasts
INDUSTRY BLOG:
IVDT INSIGHT
IVD Technologys blog, IVDT
Insight, discusses the latest
trends and developments in the
IVD industry. Access the blog at
ivdtechnology.com/blog

INSTRUMENTATION DEVELOPMENT
This issues featured editorial is
instrumentation development. To search
our Web archives to fnd more articles on
this topic, please visit ivdtechnology.com/
categories/instrumentation-development

ONLINE SUPPLIER SPOTLIGHTS
See the suppliers featured in this months supplier profles at
ivdtechnology.com/supplier-spotlight

LET US KNOW WHAT YOU THINK
This months online poll question:
Which types of IVD instruments is
your company primarily involved in
developing?
A. Clinical chemistry
B. Histology/Cytology
C. Immunoassays
D. Microbiology/Virology
E. Molecular diagnostics
Weigh in at ivdtechnology.com

IN CASE YOU MISSED IT
These articles recently received a high number of online visits by
your peers in the IVD industry:
1. Laboratory Quality Control Based on
Risk Management
ivdtechnology.com/article/laboratory-
quality-control-based-risk-management
2. Validation Master Planning for
Compliance and Effciency
ivdtechnology.com/article/validation-
master-planning-compliance-and-
efficiency
3. Goldman Sachs Initiates Coverage of IVD Companies
ivdtechnology.com/article/goldman-sachs-initiates-coverage-
ivd-companies
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EDITORS PAGE
A report by Kalorama Information (New York), Lab Automation
Markets, found that instrumentation and automation will increasingly become
crucial for clinical laboratories that want to achieve higher productivity and cost e -
ciency. Automation helps to streamline the workow and results in a more reproduc-
ible process with less hands-on interaction, which can signicantly reduce costs and
errors, and decreases the need for skilled labor.
Te Kalorama study discussed how one of the main motivators for harnessing instru-
mentation and automation in clinical laboratories involves minimizing non-value-added
steps, including such processes as sorting tubes, decapping, centrifugation, loading
analyzers, and prepping and sorting materials for storage. Non-value-added steps can
be addressed by automated systems, which frees up a medical technicians time. Because
labor accounts for more than 60% of the cost of producing test results, automation and
better information management systems can reduce the manual, hands-on procedures in
a lab and optimize the e ciency of labor in the laboratory.
According to the Kalorama report, when the trend toward clinical laboratory
automation rst began in the early to mid 1990s, much of the talk about instrumen-
tation and automation focused on automating all lab functions: total laboratory auto-
mation (TLA). But TLA is not an aordable or practical solution for the majority
of small to mid-sized hospitals and clinical laboratories. Te trend for most clinical
labs and many automation system manufacturers is toward modular automation,
which includes consolidated and integrated analyzers, independent work cells or
self-contained work stations, and automation for transport, handling, and pre- and
postanalytical processes.
Taking into account such trends, this issue addresses some of the latest technol-
ogy advancements in instrumentation development.
Authors Henri Champseix and Eric Jolain of BIT C2 Diagnostics, a BIT Company
located in Montpellier, France, look at the technical and business factors that must be
considered when developing hematology analyzers. Teir article, Examining the Chal-
lenges in Developing Hematology Instruments, (page 24) discusses how hematology
instrumentation developers must be equipped to meet technology challenges coupled
with IVD manufacturers demands for speed-to-market and cost e ciency.
Author Jari Palander of Invetech (Melbourne, Australia) explores how IVD
companies can draw on trends from a variety of seemingly unrelated elds to deliver
breakthrough ideas that enable them to leap ahead of their competitors and redene
markets. His article, Fueling IVD Innovations Trough Knowledge and Experience
Diversity, (page 29) gives examples of IVD companies looking to industries such as
fast-moving consumer goods, fuel innovation, and beverages for inspiration.
Richard Park
richard.park@ubm.com
Te trend for clinical labs and IVD manufacturers is moving toward modular
automation, which includes consolidated and integrated analyzers, and
independent work cells.
Reducing costs and errors
through instrumentation
Instrumentation
helps to
streamline the
lab workflow
and results
in more
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EDITORIAL ADVISORY BOARD
IVD
TECHNOLOGY
W W W . I V D T E C H N O L O G Y . C O M
10 I VD TECHNOLOGY | JANUARY/FEBRUARY 2012
Richard M. Bauer, PhD
Sta Scientist
Siemens Medical Solutions Diagnostics
Steven R. Binder
Director, Technology Development
Bio-Rad Laboratories
Avis T. Danishefsky, PhD
Scientic Reviewer
O ce of In Vitro Diagnostic Device
Evaluation and Safety, CDRH, FDA
Glen Paul Freiberg, RAC
President
RCQ Consulting
Mary Lou Gantzer, PhD
Vice President of Clinical Studies
Siemens Healthcare Diagnostics
Jeffrey N. Gibbs, JD
Director
Hyman, Phelps & McNamara
Craig M. Jackson, PhD
President and Principal Scientist
HemoSaga Diagnostics Corp.
Daniel P. Kolk, PhD
Director Product Development
Gen-Probe Inc.
Attila T. Lorincz, PhD
Professor of Molecular Epidemiology
Wolfson Institute, University of London
Leif E. Olsen
Director of Regulatory Sciences
Hogan & Hartson
David T. Pearman
Sales Manager
Response Biomedical Corp.
Donald M. Powers, PhD
President and Principal Consultant
Powers Consulting Services
Richard T. Root
(retired)
Formerly Roche Diagnostics
Patricia B. Shrader, JD
Vice President, Regulatory, Public Policy,
and Communications
Becton, Dickinson and Co.
Katie M. Smith, PhD
Principal
Katie Smith Consulting
Vana L. Smith, PhD
Quality Assurance Manager, Global Customer
Communication Systems
Abbott Laboratories
Joanne M. Stephenson
Head of Strategic Marketing
Innovative Biosensors Inc.
Susan L. Taylor
Marketing Manager, Systems
LipoScience Inc.
Thomas M. Tsakeris
President
Devices and Diagnostics Consulting Group
Mark S. Vreeke, PhD
Partner
Rational Systems LLC
Doris-Ann Williams
Director-General
British In Vitro Diagnostics Association
Emily S. Winn-Deen, PhD
Vice President, Strategic Planning and
Business Development
Cepheid
Jack J. Zakowski, PhD
Director, Scientic Aairs and Professional
Relations
Beckman Coulter Inc.
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TRENDS & PERSPECTIVES
The editors of IVD Technology
asked industry analysts to share their
thoughts and opinions on next years
elections, the IVD-related issues that
could be raised during the election
year, and their potential impact on the
IVD industry and IVD manufacturers:
Te primary election issue for
IVD companies is the evolution of
the clearance and approval system.
My belief is that the rules and regula-
tions are ne, and OIVD manage-
ment needs to make improvements
to clarify, standardize, and speed up
the clearance and approval processes.
Compliance issues need to be dealt
with outside of the clearance/approval
system, and the IVD industry needs to
lobby on that. However, since legisla-
tors like to legislate, there is a threat of
new laws that will require changes at
FDA. In fact, there are already a series
of bills that have been introduced by
House Republicans. What the IVD
industry needs to decide is whether to
evaluate, support (or not), and com-
ment on such draft bills, or assume
that they are just campaign material.
Glen P. Freiberg, president, RCQ
Consulting (San Diego)
Tere are many important regula-
tory issues facing the IVD industry,
such as regulatory consistency, pre-
dictability, ensuring that the level
of regulation is congruent with the
level of risk, and promoting inno-
vation. Tese areas will have an
important eect on the delivery of
healthcare, costs, and the ability to
stimulate new jobs in corporations
and academic research. Unfortu-
nately, it appears that no candidate
is prepared to talk about these issues
at all, let alone discuss them in a
meaningful way.Jeffrey N. Gibbs,
JD, director, Hyman, Phelps &
McNamara (Washington, DC)
OIVD specically, and FDA in
general, appear currently to be strug-
gling between supporting the develop-
ment of novel technologies, like com-
panion diagnostics and personalized
treatments, and protecting the public
from untried and unproven technolo-
gies, like direct-to-consumer genetic
testing for as of yet non-established
diagnostic and prognostic markers.
Developing the knowledge, expertise,
and reasonable regulatory pathways to
manage these new technologies, with-
out stiing innovation or unnecessarily
delaying diagnostic test availability
(or novel therapies that they may
accompany), will be a balancing act
that the agency will face irrespective
of candidates or parties. IVD-specic
issues and policies that likely will be
in the forefront will be FDAs ever-
increasing requests for more data and
longer follow-up in establishing the
clinical truth of any diagnostic marker
and ensuring that physicians and
patients understand the true implica-
tions of any IVD test result, especially
for genetic/genomic markers and
directed drug therapies.Jonathan
S. Kahan, JD, partner, Hogan
Lovells (Washington, DC)
I will be closely following any
legislation related to FDAs reautho-
rization of the user fee act, including
any provisions that may be related to
the reform of the premarket review
programPMA or 510(k)for IVDs,
as well as legislation related to the
potential for increased FDA oversight
over diagnostic tests developed by
a clinical laboratory. So far, around
ten bills have been introduced in the
House of Representatives. Im sure
many more are to come as the user
fee statute is scheduled to sunset next
year if it is not reauthorized.
Michele Schoonmaker, PhD,
vice president, government
affairs, Cepheid (Sunnyvale, CA)
I will personally be following the
Congressional focus on changes to
the FDA regulatory approach for
diagnostics, as well as Medicare pay-
ment changes that might impact those
products. Right now, there are a lot
of good ideas being batted around on
Capital Hill and in the IVD industry.
Tey each take a somewhat dierent
approach to the same basic problem:
delays associated with introducing
important new diagnostics into the
marketplace, and the irrational dif-
ferences in the regulatory schemes
that apply to diagnostics developed
by IVD manufacturers and laborato-
ries. Some of these seek fundamental
changes in the whole regulatory para-
digm to bring us, for example, closer
to the European model, while others
are more of simple renements to the
existing FDA process. Some of these
proposals seek to harmonize the regu-
latory scheme between IVD manufac-
turers and laboratories by up-regulat-
ing laboratories, while others seek to
achieve that harmonization by mod-
erating the regulatory requirements
on IVD manufacturers.Bradley M.
Thompson, JD, attorney, Epstein
Becker Green (Washington, DC)
Examining IVD-related
election year issues
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Last October, the European
Diagnostic Manufacturers Associa-
tion (EDMA; Brussels) hosted the
European IVD Forum 2011. Te
primary purpose of the forum was to
facilitate discussions among high-level
stakeholders on the challenges faced
by healthcare systems. To this end,
the forum was attended by members
of the IVD industry, key policymakers
from European and national institu-
tions, and representatives from patient
and professional healthcare groups.
According to EDMA o cials,
the key global policy issues discussed
at the forum were the following: the
convergence of legislation at a global
level and the importance of intra-asso-
ciation cooperation in achieving solu-
tions to common global challenges;
the importance of health technology
assessment; and the crucial role of
IVDs in active and healthy aging.
As an oshoot of the forum, rep-
resentatives of six IVD associations
from around the world held a meet-
ing to discuss a number of mutu-
ally important global policy issues.
O cials from AdvaMedDx (United
States), IVD Australia, the Camara
Brasileira de Diagnostico Laboratorial
(Brazil), EDMA, the Japan Associa-
tion of Clinical Reagents Industries,
and the Japan Analytical Instruments
Manufacturers exchanged views on
the ongoing policy debates in their
respective regions and engaged in
forward-looking discussions. Te
meeting built on the longstanding
relationships among the international
partners and aimed to form the basis
for even greater cooperation in the
future in order to nd solutions to
common global challenges and ensure
the place of IVDs at the forefront of
twenty-rst-century healthcare.
We have come together to fur-
ther strengthen the ties between our
organizations and to enhance the
eectiveness of the sector by con-
tributing to policies that will advance
public health through the develop-
ment and use of innovative diagnos-
tics all around the globe, said Dr.
Jurgen Schulze, EDMAs president.
He further pointed out that this
relationship will take our coordina-
tion, collaboration, and alignment of
information and policies on mutually
important issues to a new level.
As priority issues, the delegates
identied the need to raise awareness
of the value of IVD testing, facilitate
the timely access of patients to good
diagnostic testing, and cooperate with
regulators and policymakers on issues
such as companion diagnostics, clini-
cal evidence for IVDs, and the con-
vergence of regulatory requirements
around the world.
Andy Fish, executive director at
AdvaMedDx, attended the meeting
and said that a good part of the time
the associations spent together was
taken up providing briengs on key
policy issues, the status of those issues,
what was going on with regulators, and
how the IVD industry was engaged
with regulators and policymakers in
each of their respective marketplaces.
Clearly one of the key takeaways
from that discussion is that we are
all facing essentially the same issues,
said Fish. And that is the need for
regulatory reform to ensure faster and
timely patient access to new tests and
technologies as well as the need for
reimbursement reform to more fully
recognize the full value of diagnostics.
Beyond those core policy areas, we
also continue to underscore our mutual
recognition that it is incumbent on all
of us as industry representatives to con-
tinue our work around educating poli-
cymakers and other stakeholders about
the technologies and the value of the
technologies that we all employ, and to
continue to expand those eorts to sup-
port our overall advocacy work.
Fish also said that AdvaMedDx
and its sister IVD associations con-
tinue to recognize that not all policy-
makers are as versed in diagnostics as
they should be.
We all have individually and
increasingly collectively taken on this
task of educating policymakers about
how IVDs contribute to all major
healthcare systems, both for indi-
vidual patients and to healthcare as a
whole, said Fish. So we recognize
that in order to maximize our value as
advocates for this industry, we need to
make sure that the policymakers were
talking to are as educated as possible
about our products. Weve all taken
that on individually, and increasingly
were sharing ideas and good practices
for doing that.
In addition, Fish said what all of
the IVD associations have identied
was that they each have their own
individual plans for continued advo-
cacy work, resting in part on a robust
public aairs outreach.
I can speak more specically to
both EDMA and AdvaMedDx hav-
ing well formed plans for continued
engagement with a number of stake-
holders as we look ahead to the com-
ing year, which would include both
increasing engagement with patient
advocacy organizations as well as direct
briengs for policymakers, said Fish.
So we didnt so much identify addi-
tional activities for all of us to engage
in as a group of associations but rather
identied that were all working on
the same kinds of activities within our
own spheres. What we did agree to
was to continue to share the kinds of
information that were all developing
to support our overall public aairs and
advocacy work. For example, contin-
ued health economics studies that may
come out of one region or another,
case examples of particular technolo-
gies and the impact that theyre having
on healthcare, and so forth.
Information about AdvaMedDx
can be accessed at www.advameddx.
org. Information about EDMA can
be accessed at www.edma-ivd.be.
Richard Park
Industry associations discuss
mutually important issues
In September of last year, Sony
Corp. acquired venture corporation
Micronics Inc. (Redmond, WA)
through its wholly owned subsidiary,
Sony Corp. of America. Sony bought
Micronics to boost its own R&D in
the area of point-of-care diagnostic
equipment and to accelerate commer-
cialization of these products.
We dont have a specic busi-
ness plan to announce at this time,
says Mack Araki, public aairs, Sony
Corp. of America. Our hope is that
the acquisition of Micronics will
accelerate commercialization of our
point-of-care devices.
Sony, well known worldwide for
everything from consumer electron-
ics to hospital equipment, has so far
dabbled in IVD research only. It has
not commercialized any IVD tech-
nology. Our goal is to commercial-
ize point-of-care diagnostic devices
based on both Micronics and Sonys
technologies, says Araki. Micronics
has globally recognized microuid-
ics technology and has an impressive
patent portfolio, he adds. Te com-
pany has also accumulated a wealth of
expertise through its comprehensive
product development for third-party
clients.
Araki says that Micronics was the
rst company to obtain FDA clear-
ance for a microuidics device for
rapid blood typing, the ABORhCard.
It is a closed-system, sample-to-result
test that provides both ABO and Rh
blood type from a ngerstick blood
sample. Once the blood sample is
applied, the test is performed in less
than one minute. Tat device was
cleared in April 2010.
Another product Micronics is
focused on, which may be of high
interest to Sony, is its PanNAT
molecular diagnostic platform and
the related assays. Te PanNAT
instrument is a battery- or main-
powered device capable of processing
discrete cartridges, each designed
to perform a single or multiplexed
nucleic acid amplication assay.
Each assay is fully integrated into
the disposable cartridge and includes
all necessary reagents. A small vol-
ume of biological sample is required,
and there is no sample prep, accord-
ing to a product description on
Micronics Web site. Te system
provides a sample-on/result-o
answer in 30 minutes and is cong-
ured for use in decentralized envi-
ronments. PanNAT assays currently
in development include malaria and
Shiga-toxin-producing E. coli.
Micronics also holds two patents
Sony buys Micronics, extends
IVD reach
http://us.gbo.com/bioscience
*OBCJOE
(SFJOFS#JP0OF.JDSPQMBUFT
Greiner Bio-One
800.884.4703 Phone | 800.726.0052 Fax | offce@us.gbo.com
Reliable and reproducible binding
of proteins
For transmission, fuorescence and
luminescence
Guaranteed consistent and uniform
binding properties
ELlSA strip well and 96, 384, 1536 well
microplate formats
Conserve materials and cost in 96 well
Half Area and 384 well Small volume
for a rapid thermocycling methodol-
ogy for molecular diagnostics. Te
second patent is called System and
method for heating, cooling and heat
cycling on a microuidic device and
has broad utility across the life sci-
ences sector, with particular applica-
tion in point-of-care molecular diag-
nostics, the company says.
Further Extending Its Life Sci-
ences Reach. In a move that appears
to support Arakis contention that
Sony is serious about working to
extend its reach into diagnostics,
on December 5, 2011, the company
announced that Sony DADC Biosci-
ences was collaborating with Maven
biotechnologies on the development
and manufacture of smart consum-
ables for Mavens LFIRE detection
platform. LFIRE, which stands for
label-free internal reection ellip-
sometry, is a real-time imaging
technology for performing quantita-
tive, label-free, cell-based assays and
multiplexed biomarker detection.
In 2010, the National Institute of
Health awarded Maven a nearly
$2-million grant to commercialize
the technology. In a press release on
this particular endeavor, Ali Tinalzli,
PhD, director of business develop-
ment & sales North America for
Sony DADC said that this collabo-
ration provides a perfect example
of how Sony DADC can translate
its experience in micro-structured
engineering, gained through its pio-
neering optical disc work, to the
needs of the life sciences industry.
We are particularly pleased, he
said, to work with Maven at such an
early stage, which ensures solutions
that will be scalable and traceable, to
smooth the way to future regulatory
approvals in the clinical space.
First TVs, Ten Medical Equip-
ment, Now Molecular Diagnostics?
In a press release about the Micron-
ics acquisition, Keiji Kimura, EVP
and executive o cer, said, For some
time, Sony has applied its consumer
electronics technology to contrib-
ute to research and development in
the medical and healthcare elds.
We believe that the combination of
Micronics development capabili-
ties in the medical diagnosis domain
and our consumer electronics and IT
technologies, such as in optical discs,
will enable us to oer innovative
solutions that are responsive to the
rapidly escalating needs of point-of-
care diagnostics worldwide.
Araki points out that Sony has
quite a presence in the medical-
electronics market already, with
products such as printers, recorders,
OLED displays, and imagers. For
example, he says, our image sensors
have been widely used for consumer
and professional cameras, and our
OLED display was rst introduced
as a television for general consumer
use. Maureen Kingsley
Ortho Clinical Diagnostics
(OCD), in partnership with the
National Association of Chronic
Disease Directors (NACDD), pub-
lished consumer-survey results and
a report revealing the state of blood
test health literacy in the United
States, with strategies to support
patient education and empowerment.
Te survey and report are part of
the Know Your Numbers campaign,
which was launched in conjunc-
tion with National Health Literacy
Month this past year.
Among the surveys ndings were
that nearly 90 percent of people
would prefer to discuss blood test
results during a doctor visit, yet
only about 40 percent have actually
discussed results in person. And,
although eight in ten people who
reported having a recent blood test
said they understood the results,
roughly half of those people did not
know their own cholesterol levels.
Nearly two-thirds of them, or 65
percent, did not know their blood-
glucose level.
Te Know Your Numbers cam-
paign seeks to help patients realize
the importance of blood test results
in maintaining their health and
encourage them to take a more active
role in engaging with their health-
care providers to understand those
results. Key to achieving the goals of
the campaign, says OCD, is ensur-
ing that laboratories can get results
directly to patients and their health-
care providerscurrently a limiting
factor in most states.
Getting Started. Stephanie Fagan,
vice president of communications,
OCD, explains the impetus for the
campaign this way: When we at
OCD stepped back and asked what
our role was in improving health lit-
eracy, it was really striking because
we, along with other manufacturers
of blood tests, are the starting point
for healthcare decisions for both the
physician and the consumer. And
its the information contained in our
tests that is either the starting point
for wellness or the starting point for
understanding sickness and what to
do about it. We asked, How do we
make inroads to health literacy with
the work that we do in healthcare?
Taking Steps Toward Change.
Te campaign, she says, can so far be
viewed as three steps: Te rst was
doing the survey and understanding
the results. Te second was holding
a Fundamental to Wellness summit
in the early part of 2011 that brought
together many of the stakeholders
who touch the healthcare con-
tinuum, Fagan says. Tese included
industry representatives, physicians,
nurse practitioners, and members
of organizations that serve minority
populations. We brought together
OCDs Know Your Numbers
campaign pushes forward
this diverse group of stakeholders,
Fagan says, to take a look at those
survey results and determine the bar-
riers to health literacy as it relates
to people understanding their own
blood tests. We compiled the dis-
cussion points and guidelines into a
summit report. OCD is making that
report available to a diverse group of
healthcare stakeholders to rst bring
awareness and then hopefully foster
understanding, Fagan says.
Te third step was to make some
educational materials available to
consumers. We wanted to give con-
sumers a simple call to action, says
Fagan. Tat call to action is as fol-
lows: Make sure you have an annual
health exam. As part of that exam,
make sure your blood test results are
captured, and make sure that there
is follow-up with your healthcare
provider to have a conversation about
those results. We know from the
survey that [consumers receiving test
results and discussing them] was the
missing link, Fagan says.
Future Plans. Now that the survey
results are in and have been examined
by the relevant stakeholders, OCD
is working on future plans. We are
working to come up with a measur-
able denition of success for the
campaign, Fagan says. One option is,
now that weve held the summit, done
market research, talked with various
stakeholders, do we go into disadvan-
taged communities next? Do we pick
one or two, for example, in the United
States and do some sort of market-
research community-based project
where we partner with nurses and
physicians in a community setting?
And take the tools that weve devel-
oped so far and put them to action?
She asks, What might we see, for
example, in a community clinic if
patients get their lab tests done rst?
Do we see an improvement in out-
comes? What do we see if we also have
a control arm that doesnt do that?
OCD is now looking at ways to put
the data it has to use to see what kind
of dierences it can make in health-
care settings when blood tests are top
of mind and become an integral part
of the provider-patient conversation,
Fagan says.
Whats really exciting about
this, she adds, is taking healthcare
information that typically has been
relegated to the lab and nding a
new voice for it by getting consumers
involved.
Ultimately this campaign will be
a success, Fagan says, if OCD can
get consumers to turn their blood-
test results into action and make a
dierence in their own healthcare.
If they know a number and they
know enough to take control of a
glucose or cholesterol level and avoid
a path to chronic disease, thats the
ultimate goal, she says.Maureen
Kingsley IVD
Medical Design & Manufacturing Trade Shows
C A L E N D A R O F E V E N T S
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Minneapolis, MNt.JOOFBQPMJT$POWFOUJPO$FOUFS
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December 14-15, 211 East Edition
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REGULATIONS & STANDARDS
Bio Name, PhD, Bio text, bio text, bio text, bio
text, bio text, bio text, bio text, bio text, bio text,
bio text, bio text, bio text, bio text, bio text, bio
bio text, bio text, bio text, bio text, bio text, bio
bio text, bio text.
IVDs are extremely important healthcare
products for which performance evaluation studies can
provide necessary evidence on safety and performance. Part
1 of this two-part column discusses European require-
ments related to performance evaluation studies. Part 2 will
discuss issues to consider when planning studies, in which
results will be used not only for CE marking but also for
clearance or approval in the United States.
European denitions and implications
Article 1(e) of the European In Vitro Diagnostic
Medical Devices Directive (IVDD; 98/79/EC) denes
a device for performance evaluation as any device
intended by the manufacturer to be subject to one or
more performance evaluation studies in laboratories for
medical analyses or in other appropriate environments
outside his own premises.
Te term performance evaluation is not dened in
the IVDD; however, it is dened in the European har-
monized standard, EN 13612:2002, Performance evalu-
ation of in vitro diagnostic medical devices. Te standard
states that performance evaluation means investiga-
tion of the performance of an in vitro diagnostic medical
device based upon data already available, scientic litera-
ture and/or performance evaluation studies. Te stan-
dard denes performance evaluation studies as inves-
tigation of an in vitro diagnostic medical device intended
to validate the performance claims under the anticipated
conditions of use.
Tese are useful denitions that help manufacturers
determine whether they are conducting in-house design
validation or performance evaluation studies, which are
also part of design validation. Te purpose of design vali-
dation is to ensure that a product is capable of meeting the
requirements for a specied application or intended use.
For example, some companies believe they are conduct-
ing performance evaluation studies when, in fact, they are
conducting in-house design validation studies, which may
be su cient. Tat is, analytical testing with IVD reagents,
instruments, controls or calibrators in the manufacturers
facilities should not be considered performance evaluation,
but in-house design validation. Performance evaluation
studies are intended to validate the performance claims of
the device under anticipated conditions of usethat is,
how actual users are expected to use the device.
Evidence of performance claims
Section 3, indent 11 of Annex III, EC Declaration
of Conformity, of the IVDD states that device techni-
cal documentation must include adequate performance
evaluation data showing the performances claimed by
the manufacturer and supported by a reference measure-
ment system (when available), with information on the
reference methods, the reference materials, the known
reference values, the accuracy and measurement units
used; such data should originate from studies in a clinical
or other appropriate environment or result from relevant
biographical references.
In addition, section 6 of Annex III species require-
ments for self-testing devices, including the need to lodge
an application for examination of the design of the device
Understanding European requirements for performance-evaluation studies is
crucial for marketing devices in European nations. MARIA E. DONAWA
IVD Performance
Evaluation Studies: Part 1
Maria E. Donawa is a physician, pathologist, and
pharmacist with more than 30 years regulatory
experience. She can be reached at medonawa@
donawa.com.
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REGULATIONS & STANDARDS
with a notied body. Section 6.1 requires, among other
information, that test reports be submitted with the appli-
cation including, where appropriate, results of studies car-
ried out with lay persons and data showing the handling
suitability of the device in view of its intended purpose for
self-testing.
Section 3.2(c) of Annex IV, Full Quality Assurance
System, requires that the quality system include all docu-
mentation referred to in Annex III, section 3, indents 3 to
13, which, of course, includes indent 11, mentioned above.
Section 3 of Annex V, EC Type-Examination, requires
that the same documentation be included in the application
to the notied body for type examination.
Tus, evidence of performance claims is required for all
IVD devices; however, the particular IVD device and the
risks associated with its use will determine whether the
evaluation is based upon data already available, scientic
literature, and/or performance evaluation studies.
Requirements for performance evaluation
studies
When manufacturers wish to conduct performance
evaluation studies, they must comply with Article 9(4) of
the IVDD, which requires that they follow the procedure
referred to in Annex VIII, Statement and Procedures Con-
cerning Devices for Performance Evaluation, and draw up
the statement set out in that Annex before such devices are
made available for the studies.
Te IVDD does not require notication of the com-
petent authorities in the countries where performance
evaluation studies are being performed; however, national
requirements for such a notication may exist, such as in
Germany. Manufacturers should determine the existence
of any national requirements for notication before study
initiation. Instead of notication, the IVDD, in section 4
of Annex VIII, requires that devices for performance evalu-
ation be registered with the competent authority of the
country in which the manufacturer or authorized represen-
tative is established.
Essential requirement 8.4(f) of Annex I of the IVDD
species that the label of devices for performance evaluation
must include the words for performance evaluation only.
Manufacturers may wish to use the symbol for devices for
performance evaluation as specied in the European har-
monized standard, EN 980, Symbols for use in the labeling
of medical devices, which will avoid the need for transla-
tions of for performance evaluation only into national
languages.
Harmonized standards and technical
specications
As in the case of medical devices subject to the
Medical Devices Directive (MDD; 93/42/EEC) and the
Active Implantable Medical Devices Directive (AIMDD;
90/385/EEC), under Article 5, Reference to standards of
the IVDD, member states must presume compliance with
the essential requirements in Annex I of the IVDD for
IVD devices in conformity with applicable European har-
monized standards. Te relevant harmonized standard for
performance evaluation studies is EN 13612:2002, which
will be discussed in more detail in Part 2 of this article.
Article 5 also requires that member states must pre-
sume compliance with the essential requirements for
devices in conformity with common technical specica-
tions (CTS) drawn up for the devices in List A of Annex
II and, where necessary, the devices in List B of Annex
II. At present, CTS have been developed only for devices
in List A. CTS, which can be found on the European
Commission Web site (http://ec.europa.eu/consum-
ers/sectors/medical-devices/documents/index_en.htm),
establish performance evaluation and re-evaluation crite-
ria, batch release criteria, reference methods, and refer-
ence materials. Tus, CTS that have been developed for
a particular device should be taken into consideration
during the development of the performance evaluation
study plan.
Statement for performance evaluations
studies
Before initiating a performance evaluation study, the
manufacturer or manufacturers authorized representa-
tive must draw up a statement containing the information
specied in section 2 of Annex VIII and ensure that any
relevant provisions of the IVDD are met.
Section 2 of Annex VIII requires the statement to contain:
Data allowing identication of the device in question;
An evaluation plan stating the purpose, scientic, tech-
nical or medical grounds, scope of the evaluation, and
number of devices concerned;
A list of laboratories or other institutions taking part in
the evaluation study;
Te starting date and scheduled duration of the evalua-
tions and, in the case of devices for self-testing, the loca-
tion and number of lay persons involved;
A statement that the device in question conforms to the
requirements of the directive, apart from the aspects cov-
ered by the evaluation and apart from those specically
itemized in the statement, and that every precaution has
been taken to protect the health and safety of the patient,
user, and other persons.
Other requirements in Annex VIII concern the reten-
tion of documentation that can be checked by competent
authorities, and the required retention time, which is at
least ve years after the end of the performance evaluation.
Registration requirements
Section 4 of Annex VIII requires that certain provisions
of Article 10, Registration of manufacturers and devices,
must also be met for devices intended to be used for per-
formance evaluation studies. Tese provisions are found in
i vdt echnol ogy. com
paragraphs 1, 3, and 5 of Article 10.
Paragraph 1 of Article 10 requires that any manufacturer
who places devices on the market under its own name shall
notify the competent authorities of the member state in
which it has its registered place of business. Readers should
refer to the article for the complete text of the require-
ments; however, some of the information that must be
notied includes:
Te address of the manufacturers registered place of
business;
Information relating to the reagents, reagent products,
and calibration and control materials in terms of common
technological characteristics and/or analytes, and of any
signicant change thereto, including discontinuation of
placement on the market; for other devices, the appropri-
ate indications;
In the case of devices covered by Annex II and of devices
for self-testing, all data allowing for identication of
such devices and other specied information includ-
ing the outcome of performance evaluation pursuant to
Annex VIII.
Paragraph 3 of Article 10 requires that where a manu-
facturer who places devices on the market under its own
name does not have a registered place of business in a
member state, it shall designate an authorized representa-
tive. Te authorized representative shall notify the com-
petent authorities of the member state in which it has its
registered place of business of the information referred to in
paragraph 1.
Paragraph 5 of Article 10 is addressed to member
states, which are required to take all necessary measures
to ensure that the notications referred to in paragraphs
1 and 3 are registered immediately in the European
databank. Some member states, such as the UK Medi-
cines and Healthcare products Regulatory Agency, have
issued guidance on the IVD registration process for IVDs
intended for performance evaluation. (See the online ver-
sion of this article at ivdtechnology.com for links to the
guidance documents.)
Performance evaluation study strategy
A performance evaluation study strategy should be based
on the intended safety and performance claims of the IVD
medical device, its technical and analytical characteristics,
the risks associated with the use of the device, intended
sales conguration, the manufacturers business and mar-
keting objectives, and perhaps other factors depending on
the particular study project. Te latter might include target
population or laboratory practices.
If an IVD will be marketed not only in Europe but
also in the United States, early consideration of require-
ments in both jurisdictions is necessary to avoid the risk
of having to repeat IVD studies to meet FDA require-
ments. (To be continued next month, in Part II of this
two-part series.) IVD
IN PERSON
Developing an amplied molecu-
lar instrument is challenging. It is a
time-consuming and costly endeavor
for manufacturers, and the end result
must be a highly reliable, robust
instrument. Add in the regulatory
hurdles and issues related to marketing
the product worldwide, and the task
seems almost insurmountable.
To learn more about how such
challenges are overcome and why the
benets of developing such instru-
ments are worth the costs, IVD Tech-
nology editor Richard Park spoke with
Brad Blake, vice president, research &
development for Gen-Probe. Te full-
length interview is available online at
www.ivdtechnology.com.
IVD Technology: What have
been the biggest technological
advances in IVD instrumentation
development recently?
Brad Blake: Amplied molecular
methods are at the top of the list. I
have been in instrument diagnostics
for over 25 years, and to me, the
biggest advancement is the ampli-
ed methods where you amplify the
genetic target and enable sample
detection with very low copy levels.
Tis is a profound improvement over
standard signal amplied technologies
like immunoassay and chemistry. A
good analogy is nding the proverbial
needle in a haystack. In non-amplied
methods, you have to process every
single piece of hay, hoping that the
lone needle will pass by your sensor
and be detected. And then, even if
that needle does pass by your sensor, it
most likely will be at such a low signal
level that your sensors will not detect
it above the noise of the machine.
Tis can result in a situation where the
instrument reports no needle is pres-
ent, when in fact they were present
but went undetected.
In comparison, for amplied
molecular assays, a needle-amplifying
reagent is added to the hay, which
then duplicates the single needle into
two needles. Tis process continues by
duplicating the two needles into four
needles, then 8, then 16, then 32, and
on until you have millions of needles.
So if zero needles were present in the
original sample, you have zero needles.
If there was one needle present, you
end up with millions of needles.
Tis technology enables you to
detect very low copy levels of your tar-
get cell, which can mean much earlier
diagnosis and treatment for the patient
and improved clinical outcomes. Tis
kind of true amplication is important
not only in diagnostics, but in blood
supply testing as well, where we and
our partner, Novartis, maintain more
than 80% of the US market.
With the new molecular methods,
the blood supply has been made much
safer for people around the world. For
example, in South Africa, where 20
to 30 percent of the adult population
has the virus that causes AIDS, there
has not been a single documented case
where an individual has contracted
AIDS from transfused blood in the
several years since molecular blood
testing began. So the biggest advance-
ment I see is molecular testing, and it
keeps on delivering more value as we
move forward.
What development efforts were
required to make molecular diag-
nostics more automated?
Tat is a really great question. I
have led the development of many
diagnostics instrumentshematology,
immunoassay, chemistry, liquid-base
Pap, high-resolution imaging device,
et cetera. Developing a molecular
automated system is signicantly
more di cult than these other sys-
tems, and thats why you see very few
fully automated molecular instru-
Despite advances in point of care, mid- to large-volume IVD instruments
remain cost-eective and highly reliable choices for labs. Although they are
complex and expensive to develop, these instruments answer a global need
and retain several advantages over their smaller, more-portable counterparts.
Developing IVD Instruments:
Complex But Rewarding
Brad Blake is
vice president,
research &
development,
Gen-Probe. He
has more than
twenty years
experience
in instrument
development.
He can be
reached via
Alyssa Eggum
at
alyssa.eggum@gen-probe.com.
is no need to batch or write what test
needs to be runyou can simply load
samples on the y, while the system is
running. You can also change reagents
on the y.
We think Panther has achieved
that same degree of automation as the
chemistry and immunoassay instru-
ments. Panther was designed and built
to be a major improvement in molecu-
lar lab productivity.
What are the primary obstacles
that IVD manufacturers encounter
when developing their IVD instru-
ments and in doing business in
this area?
Dealing with the tremendous
complexity of these instruments. Tey
have to process thousands of samples
without a problem, work with over
six dierent sample types, and achieve
very high levels of sensitivity and
ments in the marketplace.
It took Gen-Probe more than
10 years and millions of dollars to
develop the know-how to create
Tigris, because molecular processing
can take some 40 to 80 steps. Each
step has to be done very precisely,
with very tight temperature controls
and with very small aspiration and
dispense volumes of sample and
reagents, all while having to address
the di cult problem of contamina-
tion. To ensure each one of these
steps is done correctly, your process
controls have to be extremely robust.
Taking all these factors into
account, making an amplied molecu-
lar instrument is denitely the most
di cult challenge in the diagnostics
space. It is very, very di cult. It is very
expensive, and it takes a great deal of
know-how and system knowledge to
create these instruments. Tigris has
been in the market since 2004 and
it has no strong competitors, in part
because of the di culties in bringing
this type of instrumentation to market.
What are the new trends emerg-
ing in IVD instrumentation devel-
opment?
Te next step is to get the auto-
mation of molecular instruments to
the same level as that of chemistry
and immunoassay systems. Te goal
is to eliminate the need for specially
trained operators to perform these
unique processing steps in order to
get a good result.
What would it take to bring molec-
ular up to the same level of auto-
mation as the assay systems?
We just released the Panther Sys-
tem in Europe, which we strongly
believe achieves that end. Panther has
random sample loading. We have host
query, so the customer really just loads
the sample onto Panther and it does
all the work for them. Panther goes
up to the host via the LIS and queries
the host on what test needs to be run.
It then runs that test and sends the
result back to the host, so the operator
has no need to interact with it. Tere
2011 Web Industries, Inc. All rights reserved.

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IN PERSON
specicity. Te entire development
process takes a large group of very
talented people with diverse back-
grounds and talents who must work
cooperatively together in the same
directionnot an easy task.
Additionally, there are always the
regulatory approval challenges to work
outFDA, EU, Health Canada, et
cetera. You must have a best-in-class
development team to be successful in
creating these instruments.
How do IVD companies go about
overcoming such challenges?
First, by following a systematic
development process. We use a phase-
gate development process, in which
development is broken up into sepa-
rate stages. Ten you have to hire very
knowledgeable people in these various
areas, looking at it from a system point
of view. Gen-Probe has some of the
best system engineers in the world.
Although it took us more than 10
years to develop Tigris, Panther took
only three-and-a-half years. Tat dem-
onstrates that companies need to invest
in the systematic knowledge that is
needed to create these instruments.
And once you start, it does get
easier but it is never truly easy. Once
you complete one instrument, you
can do a second and third, but its
critical to have that solid infrastruc-
ture of software engineers, system
engineers, hardware engineers, assay
scientists all of whom must have
the expertise needed.
You also need a systematic and
controlled development process.
For instance, our software follows a
spiral model. Tis was developed by
Carnegie Mellon and is viewed as a
superior process for developing soft-
ware for complex instruments. We
also use automatic requirements pro-
cessing software, so when we write
our requirements, they ow through
all our development stages, right
down to our test cases. Gen-Probe
has also developed simulators that
replicate all the hardware functional-
ity before any hardware modules are
designed and built, so we can ne-
tune designs quickly and easily.
Using all these automated tools
makes the development processes
easier, because again the processes are
so complex, you must move beyond
the proverbial notes on the back of
the napkin and some smart people
in a room. You still need those smart
people, but they have to be well-man-
aged and well-coordinated with these
automated tools. With our software
verication and validation, we use
automated tools to test all our external
interfaces and do extensive simulation
that stress our software to ensure we
have a robust product.
Te key is using this whole suite of
the latest development tools to help
create a winning product.
When developing IVD instruments,
what model do IVD companies
tend to follow?
First, we spend a great deal of eort
understanding what our customers will
want as a next product, what our cus-
tomers key requirements are that will
improve their business, so they will be
delighted with our product. We then
look at how we can best address those
needs. Tis is a very complex process.
We look at multiple pathways and
options until we are satised we have
found the best one that addresses our
customer needs. Tis is a place where
we do not rush. It is critical to deter-
mine up front what product you need
to robustly meet your customer needs.
If you design the wrong product, you
lose. If midway through development,
you determine the need to change
your design, it is very costly, time
consuming, and problematicagain,
you lose. Simply, it very important
to spend the time and eort up front
to ensure you are designing the right
product for your customers.
Determining if you should design
a product from scratch or modify an
existing design (a derivative product)
is based on the product requirements,
time to-market, cost, et cetera. If
you can meet the product require-
ment with a derivative product, that
is great. It speeds up the time-to-
market and by utilizing design that
has been proven, you increase product
reliability. Tis is good for both the
company and our customers. Cus-
tomers get a great product that meets
their needs sooner.
Sometimes, customer requirements
dictate a completely new design that
will robustly meet those needs. In
these cases, a completely new, from-
scratch design is created, which typi-
cally increases the time to market.
When you do build a completely
new instrument, what goes into
developing it? When would you
see a need to build a completely
new IVD instrument?
You can divide it into at least two
areas. Te rst is if the technology
is old and getting near the end of its
useful life, there is a need to move to
a new technology to stay competi-
tive. Te second case is when you
have good technology, but you really
want to make a quantum leap and
take it to a new market where it may
not have been the most appropriate.
Ten you need to make a major jump
in technology.
But normally, you keep evolving
your technologykeep it fresh and up
to date, keep improving it in steps so
you stay ahead of your competition.
Tis approach is often better for cus-
tomers, because developing a whole
new technology takes longer.
To summarize, the goal is to
develop a product that best meets the
customers needs. Typically, if you
keep evolving your technology so it
stays ahead of competition, you will
have a winning product using that
technology. However, there are cases
when the best solution is to use a new
technology, but that is more rare.
What role has connectivity
played in IVD instrumentation
development?
Connectivity plays a large role. As
we have discussed, labs are looking
for more and more automation. Labs
are desperate for more automation
for three important reasons: One, it is
Clearly, point-of-care systems are
getting better, but the mid- to large-
volume systems are here to stay.
Look at LabCorp or Quest, and you
see the huge number of tests that
they run and the value they provide
to customers. Point-of-care instru-
ments just cannot oer this level of
e ciency, for many reasons. If you
just look at it from the cost perspec-
tive, typical point-of-care tests are
much more expensive than mid- to
large-volume systems. Unit-dose
consumables can cost you ve, six, or
ten times what assays on a mid- to
high-volume system cost. Consider-
ing this cost model, mid- to high-
volume systems have the advantage.
And typically, the sensitivity and
specicity of large-volume systems
are better than those of the point-of-
care systems.
IVD
more and more di cult to nd skilled
laboratorians; two, labs are under
constant competitive pressures and
are looking to increase productivity of
their workers; three, people make a
great deal more mistakes than instru-
ments. Te more manual steps that
humans have to perform, the more
likely a mistake will be made. Tis is
costly, decreases productivity, and in
some cases, leads to incorrect results.
Labs are looking for a host
query where you load the racks on
the instrument and press a button
that says go. Tat request will go
through the LIS connectivity to the
host and ask what test needs to be
run, then the instrument will run that
test and report the results back to
the LIS. Te operator has no need to
interact with the sample, except for
placing it on the system.
Another place where I see connec-
tivity is in remote service and diagnos-
tics. Tis is becoming more important
as it allows your service person or call
center sta to remotely dial in to the
instrument to gather information to
help x problems. Sometimes the call
center can x the problem right over
the phone, saving a eld service engi-
neer (FSE) visit. If an FSE is needed,
the technician will know in advance
which part to bring along to resolve
the problem, which again saves time.
In all, instrument uptime is increased.
We have remote service and diag-
nostics on both our Panther and Tigris
systems. Connectivity is playing a big
role in helping to improve the quality,
reliability, and customer experience of
our instruments.
How has point-of-care testing
affected IVD instrumentation
development?
Another great question. For years,
industry analysts have predicted that
point of care is going to take a large
percent of the market. Years back,
Abbotts handheld blood analyzer,
iSTAT, was going to be the dominant
player in the market, but iSTAT has
never really achieved those market
predictions.
Dive deeper.
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2011 Millipore Corporation. All rights reserved.

B
lood is the only uid
that ows throughout
the entire human body.
Blood analysis can detect
a wide range of com-
mon physiological problems such as
anemia, diabetes, autoimmune de-
ciencies, infections, and cancers. It
can also expose genetic information,
viruses, organ deciencies, etc.
Hematology is the study of blood
cells. Hematology analyzer instru-
ments can take the form of a relatively
simple handheld unit, a more sophisti-
cated point-of-care diagnostic instru-
ment, or a highly complex clinical
laboratory analyzer. While all blood
analyzers are designed to be accurate
and reliable, the primary factors that
set these three types of instrumenta-
tion apart from each other are sample
throughput rate and the number of
blood parameters measured.
Te most common blood test is a
complete blood count (CBC). Tis
test can help to detect blood dis-
eases and disorders such as anemia,
infections, clotting problems, blood
cancers, and immune system disor-
ders. Te specic blood components
counted are the following:
Red blood cells carry oxygen from
the lungs throughout the human
body. Abnormalities in this reading
could indicate conditions such as
anemia, dehydration, or bleeding.
White blood cells are the part of the
immune system that ghts infection
and disease. Abnormal levels could
indicate infection, blood cancer, or
an immune system disorder.
Platelets are blood cell fragments
that aid in clotting. Abnormal
levels could indicate a bleeding dis-
order, such as hemophilia, in which
blood is slow to clot, or a throm-
botic disorder, which exhibits too
much clotting.
Hemoglobin is an iron-rich protein
in the red blood cell that carries
oxygen. Abnormal levels could indi-
cate anemia, sickle cell anemia, or
other blood disorders.
Hematocrit is a measure of how
much space red blood cells take up
in the blood. A high level might
indicate dehydration. A low level
might indicate anemia. Abnormal
readings may also be a sign of a
blood or bone marrow disorder.
Other common blood tests include
the following:
Blood chemistry tests or basic meta-
bolic panel measure dierent chemi-
cals in the blood, such as glucose,
calcium, and electrolytes.
Blood enzyme tests measure
enzymes such as troponin and
creatine kinase, which can help to
identify whether patients have had a
heart attack.
Blood tests to aid in assessing the
risk of heart disease. Such tests mea-
sure cholesterol and triglycerides.
Anatomy of a Hematology
Instrument
Hematology analyzers count,
measure, and characterize blood cells
and their components by collecting
and calculating results from electrical
impedance and/or light-scattering
data. Comprised of pumps, motors,
syringes, tubing, optics, electronics,
and software, the analyzer performs
an intricate and delicate task. Mul-
tidisciplinary skills in mechanics,
chemistry, electronics, software,
optics, and uidics are necessary to
engineer and develop such an instru-
ment (see Figure 1).
Design and Mechanics. A
hematology analyzer contains basic
mechanical parts: pumps, syringes,
motors, and tubing. Tese mechani-
Hematology instrumentation developers must be equipped to meet
technology challenges coupled with IVD manufacturers demands for speed-
to-market and cost e ciency. BY HENRI CHAMPSEIX AND ERIC JOLAIN
The challenges of developing
hematology instruments
S
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E
M
E
N
S

H
E
A
L
T
H
C
A
R
E

D
I
A
G
N
O
S
T
I
C
S
cal parts operate in conjunction with
reagents, optics, and software to
deliver the appropriate test results to
clinicians. In order to produce success-
fully such an instrument, a developer
must have an intimate knowledge of
the underpinnings of the system, how
that system works, and what results it
must deliver. Only by having a solid
knowledge in place can one develop
cost-eective, innovative solutions
with maximum optimization for all
of the involved technologies. Engi-
neering teams need to work with the
latest CAD tools, which enable inter-
net data exchange in many dierent
standards including management of a
database of software updates and ver-
sion upgrades.
Technical specications of the
hematology analyzer are dened
jointly between the customer and the
developing teams. At the beginning
of the project, the teams strive to nd
the best mechanical design solutions
to improve the manufacturing process
and reduce future maintenance costs.
Models, prototypes, work pieces,
assembling process, and tools are
designed and digitized using CAD
software, and then developed using
either quick prototyping or machining
techniques. Te mounting and assem-
bly of modules or complete instru-
ments is performed in order to check
and validate the overall design.
Fluidics. Precise uidics is crucial
to the accurate operation of a hema-
tology analyzer. Blood specimens
travel throughout the instrument,
being pushed or pulled through tub-
ing by pumps. Specialized techniques
must be used to prevent pushing or
pulling too hard or too quickly, which
could destroy or alter the blood com-
ponents, thereby causing faulty and
inaccurate results.
Electronics. Dierent measure-
ment techniques are used to classify
cells. Light-scattering events are
translated into electrical pulses by
opto-electrical devices, and thousands
of measurements are performed each
second (see Figure 2). Specic capa-
bilities needed to design, prototype,
and manufacture embedded system
Figure 1. Comprised of pumps,
motors, syringes, tubing, optics,
electronics, and software, this
hematology analyzer, developed and
manufactured by BIT C2 Diagnos-
tics, performs an intricate and deli-
cate task. Multidisciplinary skills in
mechanics, chemistry, electronics,
software, optics, and fuidics are
necessary to engineer and develop
such an instrument.
KNF NEUBERGER, INC.
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Liquid Pump Selection Guide
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Liquid DiaphragmPump
For dosing, transfer, wasteremoval, recirculation
Compact 1.5x1.5x1.25in. Lowpower consumption
Maintenance-free, varietyof motors available
Speedcontrol andtachpulsefeedback available
Corrosion-resistant material options
KNFwelcomes your uniqueOEMrequirements
This highly-efficient micro-diaph agmpump offers a high-pressure solution

for reliably dosing or transferring liquids or liquid-gas mixtures. It features
precision valves and diaphragmtechnology to realize high levels of
efficiency. It can run dry, mounts in any position and is maintenance-free.
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145 PSIG Pressure Long Lifetime Quiet
5-60 ml/min adj. flow
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P U M P S
products include the fol-
lowing: programmable logic
design, expertise in VHDL
(FGPA, CPLD), 8 to 32 bits
embedded processor boards
for RTOS, analog and digital
board design, low noise data
acquisition and signal con-
ditioning, low EMI design,
motion and positioning sys-
tems, and PCB layout.
Reagents. Reagents are
solutions used to either dilute
the blood that is being tested
or dierentiate or mark vari-
ous cell components in the
blood sample, which enables
the further electrical and optical analy-
ses. Other reagents are used to clean
the device between sample analyses to
prevent cross-contamination of sam-
ples. Reagents are consumables that
dier from IVD manufacturer to IVD
manufacturer. Each manufacturer uses
or designs its instrument to work with
dierent reagents, and these reagents
are often integrated into an instru-
ments unique design.
Optics. Precision optics are an
integral part of a hematology ana-
lyzer. Te blood cells characterization
relies on optical systems that measure
scattering properties of individual
cells. Sophisticated software enables
the counting and identifying of vari-
ous types of blood cells. In practice,
a dilute suspension of cells passes
through tubing past a laser beam.
Light scatter from each cell is analyzed
by the software, and the resulting
numerical representation is interpreted
by clinicians. In this manner, cell pop-
ulations are described, quantied, and
classied. Fluorescent techniques may
also be used to improve cell identica-
tion (see Figure 3).
Software. Te software in a hema-
tology instrument performs multiple
functions. It interprets and carries out
the orders of the instrument operator.
It monitors and drives the operation of
the instruments working components.
It collects and analyzes the resulting
data. Essentially, the software pilots
everything. In addition, the software
works in conjunction with the graphi-
cal user interface (GUI), which is dif-
ferent for every customer and depends
on the measurement techniques and
parameters measured by the device.
Menus with selections are used by
the administrator of the instrument
to control the underlying processes.
Te graphical menus serve to enrich
the user experience and help to reduce
operator error.
Basic functions of a common clini-
cal analyzer might include pipetting
(i.e., moving uid from one place to
another), mixing and adding reagents,
and incubating the nal mixture for
a determined amount of time. Te
software coding for such basic func-
tions controls the speed of the motor,
the operation of the pumps, and the
direction and precise movement of the
loaders and stepper motors in order
to minimize jostling of the uids.
In addition, software controls the
pipetting function, higher level incu-
bation, and the action of picking up a
sample and dropping it o somewhere
else inside the instrument for more
processing.
For an instrument developer,
the handling competencies required
for full IVD automation manage-
ment include the following: design
of embedded systems with real-time
requirements; motor driving (continu-
ous or step-by-step), inputs, outputs,
and system control; data acquisition
and signal processing; ergonomic and
international GUI (languages, alpha-
bets, unities); data transmission; mod-
ules and release downloading; software
for verication and validation; and
production and control tools.
From a programming perspec-
tive, IVD instruments are very com-
plex. Te more tasks an instrument
performs, the more software code is
required. And the more code there
is, the greater the chance for software
bugs to emerge. Programmers often
think they can write pages of code in
a day. But after debugging and mak-
ing that code functional, the amount
of code written is reduced to only a
few lines per day. Given the time and
expense needed to identify the bugs
and eradicate them, it is critical to
reuse clean code that has already been
validated and certied. Tis is possible
through Software Platform Technol-
ogy, an innovative approach to IVD
instrumentation development in
which developers can utilize a layered
system: building advanced features
on top of a solid, tested foundation of
codes dictating fundamental processes.
Organizing a library of proven code
sequences for reuse can eectively
expedite a bug-free design of an IVD
instrument (see Figure 4).
Business of Hematology
Instrumentation Development
Automated blood analyzers,
point-of-care instrumentation, and
patient-operated handheld units have
TIME
LIGHT INTENSITY
SAMPLE FLOW
WBC CELL
OPTICAL DETECTION AREA
Figure 2. Electronic measurement techniques are used to classify cells. Light-scattering
events are translated into electrical pulses by opto-electrical devices, and thousands of
measurements are performed each second.
become high-tech and complex in
operation yet simple to use. Research
advancements have led to profes-
sional demands for more capabilities
in the testing units. Te business of
developing and manufacturing such
precise, exible technologies quickly
and within budget has become a
specialized discipline. Hematology
instrumentation developers must be
equipped to meet the challenges of
high technology coupled with custom-
ers demands for speed-to-market and
cost e ciency. Research advancements
continually drive IVD manufactur-
ers to enhance designs, adding new
features and capabilities while making
the units easier to use and service.
Since speed-to-market and com-
petitive cost structures are primary
drivers when it comes to outsourcing
the development of diagnostic instru-
ments, more IVD manufacturers are
considering platform technology. BIT
Companies has found that by exploit-
ing the fact that many instruments
share the basic building blocks with
regard to both hardware and software,
a manufacturer can repurpose a foun-
dation that is proven and validated,
and spend development dollars on the
proprietary technologies and features
that make the instrument unique.
With the availability of a virtual library
of basic certied components that
are scalable and updateable, platform
technology has changed the way many
IVD manufacturers do business.
With the development process
time measured in years, and the aver-
age cost in the millions of dollars,
IVD manufacturers are eager to fast-
forward their projects by repurpos-
ing fundamental, proven technology
in the shape of existing, validated
platform modules. Platform modules
are previously designed, developed
components that have been tested,
proven, certied, and used in other
IVD systems over time. Tey are
composed of selections from a devel-
opers portfolio of existing hardware,
electronics, and software systems that
can be scaled up or down to suit the
purpose. All of the components com-
prising the platform module are spe-
cically designed for operation within
a complex medical diagnostic instru-
ment, and all systems are developed
on the lowest level possible to allow
for the highest vertical and horizontal
integration.
High-End Hematology
Analyzer Market
In the high-end hematology
analyzer market, there are ve to six
major corporate players. A high-end
blood analyzer can analyze more
than one hundred samples per hour
and measure a multitude of param-
eters. Such automated instruments
are very complex and usually take
more than seven years to develop,
validate, and release to market. IVD
manufacturers nearly always choose
to develop these instruments inter-
nally within their companies rather
than outsource the development to
an outside IVD instrumentation
development rm.
However, these same IVD manu-
facturers usually oer both low- and
mid-range models of blood analyz-
ers which, although using similar
technologies as the high-end models,
oer lower throughput rates and
fewer parameters measured (see
Figure 5). Mid-range models gener-
ally provide a sample throughput
rate of 60-80 samples per hour and
are equipped with or without an
autosampler. Low-range models
provide a sample throughput rate of
fewer than 50-60 samples per hour.
Due to the lower throughput rates
and parameter oerings (and therefore
lower price and prot margin), IVD
Figure 4. The graphical user
interface (GUI) provides menus with
selections used by the administra-
tor of the instrument to control the
underlying processes. The graphi-
cal menus serve to enrich the user
experience and help to reduce
operator error.
ALL
FSC
BOSINOPHILES
BASOPHILES
LYMPHOCYTES
NEUTROPHILES
MONOCYTES
Figure 3. A blood cells characterization relies on optical systems that mea-
sure scattering properties of individual cells. The y-axis represents axis loss
light (ALL), and the x-axis represents forward side scatter (FSC).
manufacturers nd it more e cient
and more cost-eective to outsource
the low- and mid-range hematology
instruments to companies that special-
ize in IVD instrumentation develop-
ment and manufacturing. Te technol-
ogies used in the low- and mid-range
models oer the same reliability as the
high-end models and are often based
on the same underlying technologies
(i.e. the same measurement techniques
and reagents). However, as opposed
to the high-end models seven-year
development period, the slower, sim-
pler models can be developed and
released to market in about two years.
Due to the competitive nature
among the major corporate players
in the high-end hematology instru-
ment segment, it is rare for a contract
manufacturer to develop a line of
instrumentation for more than one of
the large IVD manufacturers.
Low- and Mid-Range
Hematology Analyzer Market
Te IVD manufacturers specializ-
ing in marketing low- and mid-range
hematology analyzers include 10-15
major players. Some of these compa-
nies employ their own design teams
to work in conjunction with contract
manufacturers to produce the instru-
ments, while others outsource all
design, development, and manufactur-
ing and simply market the instrument.
Since all blood analyzer instru-
ments currently operate on the same
basic principles developed more than
fty years ago, the IVD manufacturers
compete on the basis of unique mea-
surement techniques, reagents used,
and the number of parameters oered
for the best price, style, and service.
While the low-range instruments are
easier and quicker to market, there are
lower barriers to entry, and therefore
there are more competitors. Tere
is always pressure on the developer
to reduce the price of development
and manufacturing, and speed up the
launch of the instrument to market.
Contract manufacturers must move
quickly, be innovative, and have a
fountain of knowledge, experience,
and specialized skills. Prevalidated,
proven components and software,
which are modied to adapt to the
needs of a specic system, can save the
developer valuable time. As the impe-
tus for hematology instruments to be
smaller continues to grow, a specialty
in injected plastic parts helps to reduce
costs because smaller size translates
directly into manufacturing cost sav-
ings. For example, ten years ago, an
optical bench measured up to 50-60
centimeters long and 10 centimeters
in diameter and was very expensive.
Today, due to the creation of special-
ized injected plastic parts resulting
from the drive toward miniaturiza-
tion, that same optical bench measures
10-15 centimeters long and 3 centi-
meters in diameter.
Reagents also play a key role in
hematology instrument development.
Driven by economy of scale and a
desire to recoup high-end segment
instrument investment costs, IVD
manufacturers often require that the
same reagents used in their high-end
analyzers also be used in the low- and
mid-range systems. Tis requirement
can present a challenge to develop-
ers as they simultaneously strive to
respond to demands by implementing
new techniques to increase reliability
and reduce price. In such cases, the
secret to success may lie in the process
of reagent development and integra-
tion (i.e., the method by which a com-
pound mixture is blended, the timing,
the temperature, etc.). Such valuable
know-how is ercely protected. How-
ever, due to the revealing nature of the
patent process, developers do not often
apply for patents on this technology.
Future Demands and
Advancements
Te customers unrelenting
demands to reduce the size, cost, and
development time of hematology
instruments while increasing value
through reliability, exibility, ease of
use, and the number of parameters
tested requires developers to be inno-
vative and highly specialized in mul-
tiple areas with systems and processes
that are streamlined and organized
for e ciency.
Tere has recently been a move-
ment in the IVD industry to re-invent
the technology for analyzing blood
samples. If successful, this signicant
undertaking will revolutionize the
industry by increasing the ability to
measure more parameters in blood
with greater precision and reliability at
a lower cost. With the last great tech-
nology leap occurring more than fty
years ago, such an advancement would
present great changes and new oppor-
tunities in the hematology analyzer
business.
IVD
Figure 5. Low-range segment mod-
els of blood analyzers use technol-
ogy similar to the high-end models
but offer lower throughput rates and
fewer parameters measured.
Henri Champseix is Chief
Technology Offcer and
Director of Research and
Development at BIT C2
Diagnostics, a BIT Company
located in Montpellier,
France. He can be reached
at h.champseix@bit-c2d.
com.
Eric Jolain is Chief Operat-
ing Offcer of BIT C2 Diag-
nostics, a BIT Company,
located in Montpellier,
France. He can be reached
at e.jolain@bit-c2d.com.
PRODUCT DEVELOPMENT
M
any of the worlds
greatest inventions
have often drawn
inspiration from
other diverse indus-
tries. For example, two-dimensional
color ow Doppler imaging, a major
breakthrough in cardiac diagnostics,
came about through military radar
engineers teaming up with Japanese
physicians. Te Coulter Counter,
which revolutionized hematology by
enabling the counting of blood cells,
was invented as a result of technical
experience gained through exposure
to a number of global industries.
Tis approach of fuelling innovation
through cross-pollination from diverse
industries may hold the key for many
IVD companies to gain a jump on
their competitors and reshape markets.
If done well, innovation comes
about through neither luck nor ser-
endipity. Rather, it is the result of a
thoughtfully composed team working
on clearly identied challenges using a
carefully managed process. Tis article
explores and illustrates principles of
how to build and manage development
teams capable of drawing on trends
from a variety of seemingly unrelated
elds to deliver breakthrough ideas in
IVDs that can capture a market.
Looking for Fish Leads to
Cardiac IVDs
Te development of ultrasound
technology in Japan began when Hei-
ichii Nukiyama returned to Tohoku
University in 1919 after spending
two years at Harvard studying electric
transduction. He was instrumental in
founding the faculty of engineering at
Tohoku and ensuring that ultrasonics
was part of the curriculum. His stu-
dents went on to develop ultrasound
for a range of purposes including
underwater detection systems and
non-destructive metal testing. In addi-
tion, they took the study of ultrasonics
into the engineering programs at other
major Japanese universities, creating
a broad technology skill base among
Japans graduating engineers.
In the 1940s, Kenji Tanaka, a
professor of neurosurgery at Juntendo
University in Tokyo, wondered if
the ultrasound waves that are used to
detect the discontinuities in acoustic
impedance in the sea around schools of
sh could also be used to detect similar
acoustic boundaries surrounding brain
tumors. He contacted the Japan Radar
Company (JRC), a manufacturer of
marine detection systems, and estab-
lished a cross-functional collaboration
between Toshio Wagai, a resident
neurosurgeon at Juntendo; Yoshimitsu
Kikuchi, an ultrasonic engineer from
Sendai University; and Rokuro Uchida,
the chief engineer at JRC. Tey began
work on the use of ultrasound in the
diagnosis of intracranial lesions, and
their eorts proved so successful that
by 1950, JRC had renamed itself
Aloka and refocused the business onto
ultrasonic applications.
Aloka continued to harness the
power of cross-functional teams,
accessing their experience in military
radar to develop Doppler ultrasound
for blood-ow detection. Tis presaged
the use of phase detection and auto-
correlation, both well known in radar
applications, in the 1984 invention of
real-time 2-D color ow mapping for
cardiac diagnosis. Tis breakthrough
By using product development teams with experience gained from industries
beyond the IVD world, IVD companies can draw on trends from seemingly
unrelated elds to deliver breakthrough ideas that enable them to leap ahead
of their competitors and redene markets. BY JARI PALANDER
Knowledge and experience
diversity for IVD innovation
Figure 1. The TearLab Osmolar-
ity System, a point-of-care system
that diagnoses dry eye syndrome,
imported ideas, skills, and experi-
ence from the parallel worlds of
nanotechnology, IVD instrument
development, and consumer product
innovation.
PRODUCT DEVELOPMENT
marked the culmination of a powerful
set of steps that began with a search
for sh and were all built on skills and
technology from well beyond the realm
of diagnostic medicine.
1
Varied Knowledge Sparks
Modern Hematology
At the age of 22, Wallace H.
Coulters college education in electron-
ics was cut short by the Great Depres-
sion. Undeterred, he joined General
Electric X-Ray in Chicago as a sales
and service engineer for medical equip-
ment. In this role, Coulter gained
insights into hospital lab testing pro-
cedures, and when a rare opportunity
to work in Asia arose, he grabbed the
chance to extend his experience.
In the lead-up to and during World
War II, Coulters business travels
took him to medical facilities in Hong
Kong, Macao, Canton, Shanghai, and
Singapore, where he gained familiarity
with a wide range of medical traditions
and standards. By the end of the war,
Coulter returned to the United States
and worked in electronic development
for Press Wireless in New York and
later participated in electro-medical
instrumentation development for Ray-
theon Manufacturing Co.
Returning home to Chicago,
Coulter continued his passion for
electronics, taking on roles at several
major electronics companies. Not
fully extended by his work, he began
experimenting with applications of
optics and electronics in the basement
of his home. While under contract
to the United States Navy in the late
1940s, Coulter developed a technology
for counting and sizing particles using
impedance measurements.
With this accomplishment and
motivated by the events that ended the
war, Coulter used his knowledge and
varied technical experience to nd a
way to simplify and improve blood cell
analysis to enable large populations to
be screened quickly. In 1947, he had
his rst major breakthrough. Using
his own blood and a hole in a sheet of
cellophane, he discovered a variance
between the electrical impedance on
one side of the cellophane and that on
the other side as red blood cells passed
through the hole. Leveraging years of
experience, Coulter determined that
an electrical charge could be used to
determine the size and number of
microscopic particles in a solution, and
he went on to develop the rst Coulter
Counter, revolutionizing the hematol-
ogy industry.
T-Shaped Professional
Wallace Coulter exemplied what
has now come to be known as the
T-shaped professional: one who pos-
sesses a great depth of knowledge in
a particular eld coupled with broad
exposure to a number of other elds.
2

In Coulters case, this was his lifelong
passion for electronics combined with
his experience in medicine, Asian tra-
ditions, and international hospital lab-
oratory practices. T-shaped profession-
als are valuable in innovation teams for
their ability to knit together diverse
experiences to produce unique solu-
tions from known elements. T-shaped
professionals are also well placed to
access the already existing solutions
that produce a breakthrough invention
in a new sphere of application.
T-Shaped Teams
Stephen Shapiro of Innocentive is
a veteran of innovation initiatives. He
takes the T idea for fueling innova-
tion one step further to advocate the
T-shaped team, the same kind of team
Tanaka put together for the intracra-
nial ultrasound development work at
JRC. By way of illustration, Shapiro
suggests that adding one more aero-
space engineer to a large team of rocket
scientists at NASA may be far less
eective than adding a concert musi-
cian.
3
With this approach, it is possible
to manage the mix of experience in
choosing which of the parallel worlds
to draw on for innovative inspiration.
Even at the national level, diversity
management is the keystone for inno-
vation strategies. For example, Japan
faces a nationwide need to break out
of a strong tradition of conformity.
Within Japanese corporate culture,
people who think creatively are often
called deru kui (the nail that sticks up).
4

Te fate of these nails has very often
been to be hammered back into line. In
postwar Japan, Honda, Sony, Aloka,
and others were corporations in which
the deru kui were nurtured and our-
ished to produce valuable innovations
for their companies.
Today, Wako Pure Chemicals is
pursuing a strategy to foster diversity
and the development of T-shaped
professionals at research facilities
in Mountain View, CA and Osaka,
Japan. At these two locations, the best
of Japanese and American industrial
practices are being carefully nurtured
to produce IVD innovations. U.S.
appointments to the team are carefully
selected for lateral thinking ability,
curiosity, and the ability to engage. In
combination with Japanese strengths in
detail management, quality engineer-
ing, and continuous improvement, a
powerful synergy is generated and put
to work. In the process, skilled individ-
uals are exposed to new perspectives so
Figure 2. The Coca-Cola Freestyle
fountain dispenser uses technology
adapted from the medical industry
to deliver accurately more than 100
beverages.
that along with the products,
the individuals also undergo signicant
development.
Managing Team Diversity to
Optimize Innovation
For IVD companies embarked on
the overall process of bringing prod-
ucts to market, it is easy to think of
innovation as just one discrete event in
the long sequence of activities needed
to capture a market successfully. Such
thinking can consign innovation pro-
cesses to a cyclical pattern of use that is
seen as peripheral to the core business.
Tere is a clear space here for pure
innovation houses where manage-
ment of innovation is the business.
5

Innovation team members are care-
fully selected, and teams themselves
are recomposed throughout a project
to ensure domain expertise (the deep
knowledge in a particular eld) is on
hand at the right moments in the
development cycle, while maintaining
the broad experience and diversity to
inspire sought-after breakthroughs.
Careful management of diversity is
essential to guarantee the best results
for an innovation project. It requires
mutual respect and the ability to rec-
ognize a good idea no matter where
it comes from and to collect it at the
right moment so that it can be acted
upon. Managing the process and
controlling the eects of diversity is
its own skill set. Research shows that
diversity in teams that lack skilled
management can lead to miscom-
munication and extended time cycles,
especially when attempts to insert
innovative ideas into a project occur
out of sync with the investment in
the development, leading to signi-
cant departures from project plans.
6,7

Successful innovation management
requires so much more than just pull-
ing together a diverse team and waiting
for inspiration to arrive.
Nanouidics Join Consumer
Goods to Advance IVDs
TearLabs research into dry eye
syndrome had already produced a
breakthrough in formulating a fast
turnaround diagnostic test, and they
were on the verge of being able to
turn an idea into a viable IVD instru-
ment. However, with the companys
core expertise grounded in medical
research and clinical trial manage-
ment, they needed external help to
realize a user-friendly CLIA-waived
test as well as nanouidics expertise
to manage reliably samples of tear
uid as small as 50 nl.
Tear Lab teamed up with a number
of innovation companies to import
ideas, skills, and experiences from the
parallel worlds of nanotechnology,
IVD instrumentation, and fast mov-
ing consumer goods (FMCG) product
development.
Expertise in IVD instrumentation
was an essential skill in this develop-
ment project, and TearLab was able
to benet from FDA- and QSR-
compliant development processes
rened on previous instrument devel-
opment projects. Further expertise
garnered from work on lab-on-a-chip
applications and nanouidics simpli-
ed and improved the reliability of
sample collection and integrated the
test platform.
Te instrument ultimately produced
was built on expertise from at least ve
parallel worlds: nanotechnology, IVD
instrumentation, FMCG, ophthalmol-
ogy, and clinical trials (see Figure 1).
Crucial contributions from these elds
included the following:
Nanoliter sample size eliminates the
need for provoking tear production
to collect a testable sample.
Nanotechnology test card prevents
evaporation and volume, and mini-
mizes diagnostic variability.
Disposable test cards incorporate
packaging and manufacturing fea-
tures common to FMCG products.
Ease-of-use considerations, vital
to product success in the FMCG
world, were imported and used in
achieving CLIA waiver status.
Managing communications among
these diverse contributing areas was
key to the successful outcome.
Beverage Delivery Benets
from IVD Instruments
Te Coca-Cola Co. is in the midst
of revolutionizing the delivery of
carbonated beverages with the intro-
duction of the Coca-Cola Freestyle
fountain dispenser (see Figure 2). Te
Coca-Cola Freestyle uses proprietary
PurePour Technology that enables
accurate dispensing with much higher
levels of concentrated ingredients. Te
dispenser uses technology adapted
from the medical industry to deliver
the beverages accurately.
8
Coca-Cola engaged a number of
technology partners to help bring
the Freestyle concept to fruition. Its
development partners included an
innovation company that leveraged
its diversity of skills in microuidics,
footprint reduction, and user interface
development. Such skills were honed
on such IVD projects as Bio-Rads
BioPlex 2200 and bioMerieuxs Previ
Isola. Te development partner also
used a project manager who had 17
years experience developing kiosks
Figure 3. Coca-
Colas develop-
ment partners
leveraged their
diversity of skills
in microfuidics, footprint
reduction, and user interface
development that were honed
on such IVD projects as Bio-
Rads BioPlex 2200.
PRODUCT DEVELOPMENT
Build T-shaped teams that amplify
the creativity of a group.
Do not rely on luck. Manage the
people and the process to direct their
eorts and harvest ideas.
Today, companies like Wako Pure
Chemicals are cleverly combining
eclectic cultures, including the best of
U.S. and Japanese engineers, to drive
innovation. Bio-Rad, Coca-Cola, and
TearLab all successfully borrowed
ideas from parallel worlds to turbo-
charge their product development and
leap ahead of their competitors.
References
1. J Woo, A Short History of the Development
of Diagnostic Ultrasound in Japan, available
from Internet: www.ob-ultrasound.net/japan_
ultrasonics.html
2. D Ing, T-Shaped Professionals, T-Shaped
Skills, Hybrid Managers, September 6, 2008;
Available from Internet: coevolving.com/blogs/
index.php/archive/t-shaped-professionals-t-
shaped-skills-hybrid-managers
3. S Shapiro, Tree Innovation Distinctions, avail-
able from Internet: www.24-7innovation.com
4. K Yoshida, Japans Innovation Strategy:
Necessitating a Change in Value, July 12,
2007, Center for Strategic and International
Studies (Washington, DC).
5. A Hargadon, How Breakthroughs Happen:
Te Surprising Truth about How Companies
Innovate, Harvard Business School Press,
Boston, 2003.
6. D Gebert, S Boerner, and E Kearney, Cross-
Functionality and Innovation in New Product
Development Teams: A Dilemmatic Structure
and its Consequences for the Management
of Diversity, European Journal of Work and
Organizational Psychology 15, no. 4 (2006):
431 458.
7. MHJ Park, JW Lim, and PH Birnbaum-More,
Te Eect of Multiknowledge Individuals on
Performance in Cross-Functional New Prod-
uct Development Teams, Journal of Product
Innovation Management 26 (2009): 8696.
8. The Coca-Cola Company Press Kit, The
Coca-Cola Company Invites Consumers to
Experience Freestyle, Atlanta, April 28, 2009;
available from Internet: www.thecoca-cola-
company.com/dynamic/press_center/2009/04/
the-coca-cola-coompany-invites-consumers-
to-experience-freestyle.html
IVD
and ATM equipment for the banking
sector. Te next-generation fountain
beverage dispenser is the beneciary
of this eclectic mix of technology and
development skills from a number of
parallel worlds.
Mosquito Repellent Device
Informs IVD Consumable
Design
In a recent example, a world-lead-
ing IVD company wanted to reduce as
much cost as possible from its consum-
ables without compromising quality. In
order to nd a way to do this, the com-
pany turned to its outsourced innova-
tion partner, which subsequently called
on its recent experience in designing
a mosquito repellant device for the
consumer market. Te skills used to
design the mosquito repellant device,
which used a capillary action through
a ceramic wick to deliver consistent,
small uid volumes to a heated mat,
were transferred to produce a highly
eective IVD consumable with the
required shelf life and climate robust-
ness. Most importantly, the intense
design focus on unit cost that was
learned in the consumer product world
paid o handsomely by signicantly
reducing the cost of the IVD consum-
ables that are intended for use in high-
throughput pathology labs.
Conclusion
Tere are countless examples of how
diverse experiences have fuelled inno-
vations, which have led to industry-
changing breakthroughs. By tracing
the history of color ow Doppler for
cardiac diagnosis and modern hematol-
ogy, it can be seen that the diversity of
skills in people and teams has provided
the genesis to changing the game.
Te key messages for IVD com-
panies looking to redene markets
include the following:
Use T-shaped professionals who
posses both breadth and depth of
experience.
Jari Palander is executive
vice president at Invetech
(Melbourne, Australia).
He can be reached at jari.
palander@invetech.us.
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partner 4U B.V.
Esdoennlaan 13 n 3951 DB Maarn n The Netherlands
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OUTSOURCING
C
linical patient samples
are an essential but
often overlooked tool in
numerous clinical and
medical applications.
In the IVD industry, they are widely
used during the various stages of test
kit development, including marker
discovery, eld trials, product valida-
tion, and preparation for regulatory
approval. Tey are essential to ensure
the scientic relevance and specicity
in the clinical application of a novel
IVD test or instrument before it can
be launched into the marketplace.
Clinical patient samples can include
any body uid ranging from saliva to
cerebrospinal uid. However, blood-
based samples such as serum and
plasma are by far the most common
types of samples used for developing
commercial IVD tests.
It was not until 1976 that FDA
dierentiated between medical
devices and drugs, and an elaborate
and detailed scheme to regulate
medical devices was established in
the United States. Legislation passed
in 1976 dictated that simple clini-
cal patient samples with a measured
analyte level were su cient during
product validation. Since then, FDA
requirements have been modied
numerous times. However, unless a
device has been identied for pre-
market approval (PMA) or special
controls have been requested by
FDA, very little premarket analysis
is required. Figure 1 highlights the
key modications to FDA legislation
during the past 80 years.
Te recent report submitted to
FDA by the Institute of Medicine
(IOM), Medical Devices and the
Publics Health: Te FDA Clearance
Process at 35 years, has recom-
mended that an integrated pre-
market and postmarket regulatory
framework should be introduced. If
such a framework is implemented,
it would enhance the demands on
IVD manufacturers to show evidence
of a products safety and eective-
ness before it is launched onto the
marketplace. IVD industry develop-
ments, such as companion diagnostics
and the requirements for evidence-
based medicine, are also fuelling this
demand for improved premarket
analysis. Inevitably, this will aect the
amount of resources IVD manufac-
turers will have to dedicate to sourc-
ing clinical patient samples to meet
these requirements in the future.
For IVD manufacturers, sourc-
ing high-quality blood-based clinical
samples can often be problematic.
Numerous considerations have to be
taken into account when selecting a
cohort of samples to validate a novel
IVD test, ranging from the pre-
analytical status to ensuring a back-up
supply for future work.
A review of current issues encountered when sourcing blood-based clinical
patient samples and the future outlook for IVD manufacturers. BY SIMON PACKER,
KELI STOCKBRIDGE, AND PHILIP JEWESS
Sourcing clinical patient
samples for IVD development
Automatic sampling systems allow for effcient storage and handling of a
diverse range of clinical samples.
OUTSOURCING
Using Clinical Samples and
Their Requirements
Developing an IVD test can take
many years, from the initial biomarker
discovery to a successful commercial
launch. During the complete develop-
ment process, clinical patient samples
play a key role. In the marker discov-
ery and initial research phase, small
quantities of samples with a clinical
diagnosis or elevated analyte levels
are required to demonstrate proof of
concept. Such samples tend to require
minimal patient information and are
generally fairly simple to source. At
this stage, if samples are too di cult
to source, insu ciently robust, or not
representative of the nal application,
the IVD cannot be developed any fur-
ther for day-to-day clinical use.
If the research stage proves suc-
cessful, lab and eld trials can be
initiated. At this point, the require-
ments for the clinical patient samples
become more tightly dened, and
more time and resources have to be
allocated. Currently in the United
States, all new IVD tests must be
registered with FDA and fall into one
of the three medical device classes
detailed below. Tis classication will
dene the premarket testing proce-
dures and clinical evidence required
for that particular device.
Class I: A device of which the
general postmarketing controls
would be su cient to provide
reasonable assurance of safety and
eectiveness.
Class II: A device which cannot
be placed into Class I because the
general controls are not su cient
by themselves to provide reasonable
assurance of safety and eective-
ness, but on which there is suf-
cient information to establish a
performance standard to provide
reasonable assurance.
Class III: A device that is repre-
sented as being for use in support-
ing or sustaining life (or in prevent-
ing impairment of health) or that
creates a potential unreasonable risk
of illness or injury and that cannot
be placed into Class I or Class II.
For Class I and Class II devices, an
IVD manufacturer is usually required
to submit its diagnostic test for 510(k)
premarket notication before being
launched on the market. For Class III
devices, the manufacturer is required
to submit a PMA application. All
three classes require the manufacturer
to submit data that demonstrates clin-
ical performance compared to existing
products on the market.
If the IVD is targeting a novel
biomarker, and there is no direct com-
parison method on the market, it will
likely be classied as Class III, or alter-
natively Class II with an FDA request
for special controls. In this case, a
larger amount of supporting data may
be required to demonstrate the test
kits clinical eectiveness. Such data
require a large number of clinical sam-
ples with in-depth patient information
in order to establish an evidence-based
assessment of clinical utility.
Current Issues in Sourcing
Samples
IVD manufacturers have at their
disposal two widely used methods to
source clinical patient samples: com-
mercial outlets and direct collection
centers. Whichever supply route a
manufacturer chooses, both types
of suppliers will be faced with some
common issues discussed below.
Reference Method
When deciding which cohort of
patient samples to use, one of the rst
considerations is the selection of the
reference method. Choosing the refer-
ence method for comparing a novel test
is vital to establishing the validity of
the data produced. If there is an inter-
nationally accepted reference method
(e.g., the peptide digest method used
in the IFCC standardization of the
HbA1c standard), the method used
for comparison should be directly
traceable to it. In some instances,
there will be no such accepted ref-
erence method, in which case, the
investigator must use the clinical
information to judge the most relevant
comparative diagnostic criterion.
Biomarker Values
Te values of the biomarker in ques-
tion in the sample cohort are important
in selecting a relevant test sample panel.
Te range should reect the biomarker
values that clinicians will be looking
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Figure 1. FDA legislation developments during the past 80 years.
for when ordering a test for that spe-
cic marker. Hence, the sample panel
should include samples in or around
the reference range, and up to the assay
cut-o point for a positive diagnosis.
Te panel should also include samples
that go from the minimum detectable
biomarker value (sensitivity challenge)
up to the highest biomarker levels.
Within the panel, the number of
samples at each biomarker level should
reect the patient ratios expected in the
relevant testing populations.
Reference Range
Establishing a reference range for
an assay is often done after introduc-
ing the assay at a local level, which is
still a very important exercise under-
taken by individual testing laborato-
ries. However, when validating a test
kit, it is important to conduct suf-
cient testing of a normal population
dened from the testing criteria and
for potential dierences in the sam-
ples clinical information, which will
provide a baseline for the IVD test.
Racial, geographic, and dietary dier-
ences may aect the reference range,
and clinical cut-o levels should be
established as soon as possible.
Test Interferences
All IVD tests are potentially sus-
ceptible to test interferences, which
should be assessed within the relevant
sample cohort. Te potential interfer-
ence samples used should reect the
likely interference factors within the
testing population and should include
common interfering substances such
as hemolytic and lipemic samples.
Specic rare interfering factors such
as HAMA and closely related cross-
reacting biomarkers should also be
considered. Such interfering factors
should ideally be native samples with
varying levels of the target biomarker
to challenge the testing methods per-
formance and specicity.
Pre-Analytical Status
When carrying out in-depth
510(k) reviews or submitting PMAs,
IVD manufacturers should consider
the pre-analytical status of the clini-
cal sample. To obtain the best results,
it is essential that all test material
has been handled in a consistent
manner appropriate to maintaining
sample integrity, which includes col-
lection methods, time-to-freezing,
and sample storage. Information
on these aspects of the sample can
often be extremely di cult to obtain
since they are not standardized from
hospital to hospital. Unless specic
requirements are known at the early
collection stage, it is nearly impos-
sible to control.
An example of where control of
the pre-analytical status of samples is
important is in commercial Troponin
I assays. Falsely elevated troponin I
levels are observed if brin is found
in the sample. Fibrin formation can
occur from inadequate tube mixing on
collection, inadequate clotting time,
and cold activation of clotting factors.
When it is possible, IVD manufac-
turers should follow a standardized
sample collection protocol that denes
all of the key variables from the pre-
analytical phase (e.g., time and
method of specimen collection, stor-
age at every stage) to the analytical
phase and the time taken from sample
collection to sample analysis.
Tracking, Stability, and
Quality Assurance
IVD manufacturers should also
consider storage, relative stability, and
shelf-life of dierent sample types
when utilizing clinical patient sam-
ples. When a large number of samples
are required but will be used over an
extended period of time, this raises
the issue of where and how they will
be stored, especially if they are being
stored by the end user. Many sample
suppliers can store clinical samples in
their biorepositories and then send
them to the manufacturer as needed.
Manufacturers must assess the sample
suppliers to ensure they have robust
systems in place for tracking patient
sample collection and for guarantee-
ing the continuity of the sample sup-
ply. Te storage system used for the
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OUTSOURCING
samples should be relevant for the
sample and monitored to assure the
sample integrity.
Another important factor to con-
sider is the accuracy of the clinical data
and ensuring that the data is relevant
to the samples provided and viable for
direct correlation to the nal IVD kit
application. Using a biorepository or
supplier with a proven track record,
a well-dened quality system, and
well-established standard operating
procedures is one way of ensuring the
samples used will have the integrity
required for most regulatory bodies.
IVD manufacturers can monitor the
integrity of the specimens stored at
a biorepository by including aliquots
of some specimens in the repository,
which have been tested at the same
laboratory responsible for generating
the data that will be submitted to gain
approval of the biomarker for clinical
use. Te aliquots act as controls that
are stored on site and are analyzed at
the time of specimen testing.
Clinical Information
Another pressing issue for IVD kit
manufacturers is ensuring all the rel-
evant clinical data required are avail-
able for a patient sample, which is
especially true as the demand for evi-
dence-based medicine becomes more
prevalent. In this instance, there must
be evidence to demonstrate how an
IVD kit will actually assist in diagno-
sis and treatment, leading to a posi-
tive outcome. To achieve this, having
the clinical samples relevant patient
information such as age, sex, demo-
graphics, disease prognosis, clinical
stage, current and past treatments,
treatment response, and any other
relevant medical history is essential to
produce accurate testing data. Such
information can often be di cult to
obtain, especially as the majority of
samples that are readily available in
the marketplace are left over from
hospital pathology tests, without any
key patient information being made
available to the end user.
Sourcing a diverse range of clinical
samples can often be di cult if the
relevant marker is specic to one par-
ticular demographic or global region.
Samples used to assess a diagnostic
marker should ultimately reect the
population that the marker will be
used to test. However, the original
testing should also assess diagnostic
accuracy in as wide a range as pos-
sible, and therefore the cohort of
samples should include samples from
every demographic, age, and socio-
economic group. Samples should also
be related to the stages of disease.
For example, in the case of tumor
markers, samples can reect early
tumor development, each stage of
chemotherapy, and benign and highly
aggressive tumors.
Ethical Considerations
It is critical to ensure that Institu-
tional Review Board (IRB) approval
has been achieved and that evidence
of patient consent for a specic end
use is made available to the IVD
manufacturer. Tis factor is espe-
cially important since FDA liability
The Idea
: Marker dlsocvery
: Teohnclcgy
: Develcpments
: lnncvatlcn
Research
: Feaslblllty Studles
: Market Revlew
: Reagent ^vallablllty
Proof of Concept
: Reprcduolblllty
: Sensltlvlty
: Speolfolty
Lab & Field Trials
: Speolmen ^nalysls
: Rreferenoe System / Range
: lnterferenoe Revlew
Manufacture
: Scuroe Reagents
: Soale Up
Regulatory Approval
: lrcduot Classlfoatlcn
: lM^
: 510(k) Clearanoe
Patient Use
uantlty ^nalyte Ccno. Cllnloal lnfc
Figure 2. Consideration factors when selecting a clinical patient samples
provider.
manufacturers can set up agreements
with direct collection centers and
hospitals. Tis approach can be eec-
tive when only routine samples are
required and can sometimes be more
cost eective. However, the scope of
individual hospitals is localized and
limited, and dealing with them can be
time-consuming and resource-heavy
in the initial set-up stages.
Once an IVD manufacturer has
selected a sample supplier, other key
factors need to be considered to make
sure all requirements are met, includ-
ing price, collection completion tim-
escales, standardized collection pro-
cedures, supplier quality systems, and
customer service. If a manufacturer
uses a commercial supplier, establish-
ing a supplier agreement to ensure a
continuous supply of samples within
an allocated timeframe can be bene-
cial. Figure 2 shows the stages of test
development, along with the sample
requirements and key factors to con-
sider when selecting a supplier.
Future Outlook
In the future, IVD manufactur-
ers could face a number of potential
changes when sourcing clinical patient
samples. With greater demands for
more specic and accurate tests, as
well as the continuing emergence of
companion diagnostics and multi-
plex assays, there is an ever growing
demand for clinical patient samples
with better and more complete patient
information than ever before.
Te recent IOM report concluded
that the current 510(k) clearance pro-
cess for Class I and Class II devices
was not designed to evaluate a medi-
cal devices safety and eectiveness,
but rather only assesses its similarity
to commercially available devices
prior to 1976. Te report recom-
mended that an integrated premarket
and postmarket regulatory framework
be introduced to replace the 510(k)
clearance process. If such a frame-
work were implemented, it would
increase the requirements for IVD
for this rests with the manufacturer
rather than the sample provider.
Evidence of consent may be required
during an FDA audit, making it an
essential piece of information. Post-
approval launches of kits to market
may also prompt requests from
potential customers to demonstrate
compliance with ethical sample col-
lection procedures.
Sourcing Clinical Patient
Samples
Before sourcing a selection of
clinical samples, one of the most
important steps is to dene clearly
the individual requirements. Such
requirements can include the follow-
ing: the number of samples, analyte
levels required, patient information,
and evidence of patient consent.
Dening the required timeline
at this early development stage is
important in order to ensure no costly
delays in the process. Realistic time-
lines for sourcing a bulk number of
clinical samples can vary depending
on the specic requirements, but they
should be established at the outset of
any project. For commonly occurring
conditions in developed countries
(e.g., prostate cancer or kidney fail-
ure), many commercial outlets have
stocks of patient samples readily
available, which could be processed in
as little as 2-3 weeks. For rarer con-
ditions, and where extensive patient
information is required, the collection
times can extend from six months
up to a year to obtain a diverse range
of samples. It is essential that the
samples are stored and handled cor-
rectly during these extended periods
to ensure that no stability issues are
encountered.
Once the sample requirements are
clearly dened by the IVD manu-
facturer, the next step is to select
the most appropriate supplier. In
most cases, a commercial supplier is
selected since they will have a large
biorepository along with a number of
sources, allowing for a good collec-
tion rate and scope to accommodate
varying specications. Alternatively,
Cardiovascular Systems
Therapeutic Devices
Diagnostic Instruments
Implantable Devices
Monitoring Systems
FDA REGISTERED ISO 13485 CERTIFIED
www.minnetronix.com D
Engineering Exceptional Results
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Thinking Medical Systems
OUTSOURCING
manufacturers to show evidence of
a products safety and eectiveness
before being launched on the mar-
ketplace, which would require large
volumes of clinical samples with rel-
evant collection controls in place.
In the IVD market, demands
for IVD tests with greater accuracy
and specicity for elements such as
disease progression and prognosis
are increasing. Key research insti-
tutes are developing a wide variety
of novel markers that could provide
a vast range of possibilities for the
IVD market. Once a specic marker
has been selected for further devel-
opment and commercial launch,
generating evidence of its relevance
is essential.
One example is recent research
into the use of PSA isoforms as a
more accurate diagnosis of pros-
tate cancer, thereby reducing the
number of biopsies required. Initial
research has shown that PSA iso-
forms provide a higher predictive
value compared to traditional PSA
tests. However, they do not give an
indication about the aggressiveness
of the cancer. If the tests for specic
isoforms were to be developed into a
marketable device, an in-depth clini-
cal study would be required, and a
large range of clinical patient samples
with vast amounts of associated data
would be needed. Tis places sig-
nicant development and nancial
demands on IVD companies, and
restricts the desire to develop novel
but clinically desirable devices. Dur-
ing the next 510 years, the demand
for clinical samples with greater
patient information is expected to
increase rapidly and is likely to be
one of the most signicant changes
when sourcing samples in the future.
Other IVD advances will also
aect clinical patient sample require-
ments. Multiplex assays are now
more widely used than ever before,
prompted by the completion of the
human genome project, with growth
likely to continue during the coming
years. Since this type of assay looks
at hundreds of markers simultane-
ously, large and diverse ranges of
samples with a selection of marker
levels for each measured analyte
are required during the validation
phases. Te pre-analytical challenges
for each analyte in multiplex assays
also make their approval more prob-
lematic. Sourcing this type of sample
variety will require more investment
and resources during the validation
stages of development.
One of the key developments
expected during the next 510 years
is the collaboration between the
IVD and pharmaceutical industries
to develop companion diagnostics.
Although companion diagnostics
have seen a slow start, a few suc-
cess stories have meant that strate-
gic growth in this area is likely to
continue. With the collaborations
between pharmaceutical and IVD
companies, enhancing the product
analysis and generating medicine-
based data associated with both the
diagnostic test and the companion
drug are essential. Te regulatory
demands on the pharmaceutical and
biotechnology industries are very sig-
nicant. IVD companies will likely
have to elevate their abilities to meet
expectations and regulatory require-
ments, so more samples will be
required to provide extensive statisti-
cally relevant data.
In tandem with high-end kits,
there is also a signicant demand
for developing simple, cost-eective
IVD tests suitable for developing
third-world countries. As these
countries advance economically, this
trend is likely to continue in the
future. When developing and vali-
dating such tests, one of the most
common issues is sourcing good
clinical patient samples. Often the
diseases that are tested in third-
world nations only occur regularly
in a specic demographic area. Tey
are predominantly infectious diseases
such as malaria and HIV, along with
diseases that are now rarely seen in
developed countries such as polio
and tuberculosis. As demand for
IVD tests increases in these devel-
oping countries, more economical
solutions will reach the market. Tis
means greater demands for clini-
cal patient samples to validate these
economical alternatives and higher
investments in establishing a suit-
able supply chain for appropriate
samples.
Te future for IVD manufacturers
will hinge upon legislation-related
changes and scientic advances in
the industry. If the recommendation
to FDA for an integrated premarket
and postmarket regulatory frame-
work for medical devices is imple-
mented, clinical sample requirements
will likely be amplied in the future.
Moreover, with the development of
new technologies, novel biomarkers,
multiplex assays, and companion
diagnostics, IVD manufactures will
have to expand the time and
resources allocated for sourcing clini-
cal patient samples. IVD
Simon Packer is the tech-
nical director for Scipac
Ltd. He can be reached at
simon.packer@scipac.com.
Keli Stockbridge is the mar-
keting manager for Scipac
Ltd. She can be reached at
keli.stockbridge@scipac.
com.
Philip Jewess is a senior
scientist at Scipac Ltd. He
can be reached at phillip.
jewess@scipac.com.
Research
institutes are
developing a
variety of novel
markers that
could provide vast
possibilities for
the IVD market.
PRODUCTS & SERVICES
Electric rotary valves
A series of electric rotary valves delivers unobstructed, inert
uid paths with high ow rates and low dead volumes. Te
RV series of valves features three models for easy integra-
tion into OEM systems. Designed for such applications as
sample collection, loop injection, or ow-path selection,
the valves provide a lower pressure drop than conventional
solenoid mixing valves. Each models uid port connec-
tions and ow congurations were designed to match
the industry standard most commonly found in existing
systems. All valves use a unique PTFE uid path for maxi-
mum compatibility with aggressive solvents.
BIOCHEM FLUIDICS
www.biochemfuidics.com
Continuous-level sensors
A manufacturer of sensors, miniature solenoid valves, and uidic systems announced the
launch of the XT-1000 series of magnetostrictive continuous-level sensors for OEM
and end-user applications. Te XT-1000 series oers a line of robust stainless-steel sen-
sors with highly accurate continuous-level measurement in lengths from 8 in. to more
than 13 ft. Te XT-1000 measures liquid media levels using the complete probe length
and is largely unaected by temperature. Te sensor oers constant sensing of uid level
regardless of the physical state of the mediabubbles, foam, condensation, precipitation,
pressure, temperature or changes in density. Magnetostriction is well-suited to applica-
tions requiring extremely accurate indication. Te 4-20 mA sensor is compatible with a
variety of tank dimensions and oers an explosion-proof version.
GEMS SENSORS & CONTROLS
www.gemssensors.com
Machined Base Plates
Precision machined base plates provide a stable foundation for medical diag-
nostic equipment. Tese base plates eliminate exure or unintended move-
ment, which can cause damage to the machine or produce inaccurate test
results. Te manufacturer uses dedicated machinery to make its base plates for
the customer in a cost-eective manner. Te products are machined using a
Kitamura bridge manufacturing center with spindle speeds of 22,000 RPM,
which allow it to produce large, complex aluminum base plates while holding
very tight tolerances. Finished products are checked for accuracy with a Brown
& Sharp coordinate measuring machine utilizing PC-DIMIS software for
direct model comparison, to verify that they will meet customers requirements.
ACCUDYNAMICS LLC
www.accudynamics.com
Plasma treatment system
A plasma-processing technology company is introduc-
ing global availability of the MaxVIA plasma treat-
ment system that streamlines the printed circuit board
manufacturing process by quickly and uniformly treat-
ing a variety of panel sizes and types. Te MaxVIA
system provides
high throughput and
superior plasma uni-
formity in desmear
and etchback appli-
cations for high-
density interconnect,
exible, and rigid
circuit board manu-
facturing. Te treat-
ment system oers
an expanded plasma
chamber to accommodate large panel sizes of up to 24
x 42 in. and has a high-throughput capacity of 92 to
138 units per hour, depending on panel size.
NORDSON MARCH
www.nordsonmarch.com
PRODUCTS & SERVICES
Laser Plastic Welding
Resource
A manufacturer of laser and elec-
tronic systems has launched a new
blog and resource site about laser
plastic welding. The Web site is an
extension of LPKF Laser & Elec-
tronics and educates both engineers
and designers about the latest laser
plastic welding information. The
intention of the site is to provide
a central resource for laser plastic
welding information, in the form of
webinars, white papers, videos, and
case studies. The Resources page is
populated with a range of content
and is updated regularly. Addition-
ally, this site provides a LPW 101
page for visitors who are new to the
industry.
LPKF LASER & ELECTRONICS
www.laserplasticwelding.com
Synthetic VDRL
antigen
The ASI Synthetic VDRL Antigen
is available. VDRL antigen is rou-
tinely used as a screening test for
syphilis. Only serum or cerebrospi-
nal fluid are appropriate specimens
for the VDRL tests. VDRL antigen
is also the key raw material for the
RPR (rapid plasma reagin) non-
treponemal test. The Centers for
Disease Control and Prevention
recommend syphilis serology
screening with the RPR or VDRL
tests to identify persons with pos-
sible untreated infection; this
screening is followed by confirma-
tion using one of several treponemal
tests. ASI Synthetic VDRL Anti-
gen incorporates patented, intellec-
tual property rights that provide
commercial and public benefits.
Using synthetic cardiolipin and lec-
ithin, the ASI Synthetic VDRL
Antigen may be used in rapid, sim-
ple, and inexpensive tests to aid in
detecting, diagnosing, and monitor-
ing the treatment of syphilis. Com-
parative analysis of Synthetic
VDRL and conventional Natural
VDRL antigen have demonstrated
increased sensitivity, a higher
degree of flocculation, improved
specificity, and RPR end-point
titers of one-half or one dilution
greater with Synthetic VDRL anti-
gen tests.
ARLINGTON SCIENTIFIC INC.
www.arlingtonscientifc.com
Barcode
congurator
A barcode configurator is an online
tool that provides an easy, conve-
nient way to design and order cus-
tom barcoded Nunc plates online.
With the ability to specify the num-
ber of digits, code type, prefixes,
or suffixes and label location via
a simple step-by-step online user
interface, site visitors can build a
barcoding label scheme to best suit
their application needs. Users of the
barcode configurator will benefit
from faster turnaround time and the
assurance of no repeats. Upon visit-
ing the site, users are asked to select
plate attributes, such as well num-
ber, well geometry and irradiation.
After selecting the desired quantity,
users can choose from numeric or
alphanumeric barcoding, with the
optional of adding human readable
print and color blocking. All codes
can also be prefixed and/or suffixed
with a sequence of characters for
easy identification of plate types.
Finally, users can specify the label
location and properties of the fin-
ished surface.
THERMO FISHER SCIENTIFIC
www.thermoscientifc.com/barcodecon-
fgurator
Medical Grade
Epoxy
Capable of tolerating the harsh envi-
ronments of the medical industry,
EP42HT-2ND2MED (black) fully
complies with the testing require-
ments of USP Class VI plastics. Tis
two-component epoxy resists recur-
rent autoclaving and sterilizations
including radiation, steam, ethylene
oxide, and chemical sterilants.
EP42HT-2ND2MED is a good
electrical insulator with a volume
resistivity of greater than 1012 ohm-
cm, a thermal expansion coe cient
of 35 to 40 in/in 10-6/C, a dielec-
tric constant of 3.8, and a tensile
strength exceeding 12,000 psi at
ambient temperatures. Heat resistant
up to 450F, it also withstands
chemicals such as inorganic and
organic acids, alkalis, organic sol-
vents, and aromatic hydrocarbons.
Tis epoxy cures at room tempera-
ture in 48 to 72 hours.
MASTER BOND INC.
www.masterbond.com IVD
INDEX TO ADVERTISERS
Receive free information from suppliers
For more information, call the phone number or use the online contact information provided.
When contacting these advertisers, please mention you saw their ad in IVD Technology.
AACC 43
800/892-1400 www.aacc.org
BBInternational (British Biocell Intl) 44
+44 2920 747 232 www.bbigold.com
Binding Site Inc. 7
800/633-4484 oem@bindingsite.co.uk
Biosearch Technologies 9
800/436-6631 www.biosearchtech.com
BIT Analytical Instruments 4
800/888-9285 www.group-bit.com
See us at MD&M West, Booth #2521
EMD Millipore 23
800/645-5476 www.millipore.com/probumin
Fluid Metering Inc. 10
800/223-3388 www.fmipump.com
Greiner Bio-One GmbH 13
704/261-7800 www.gbo.com/bioscience
Hamilton Co. 2, 35
800/648-5950 www.hamiltoncompany.com/oem
KMC/Elbit 19
603/886-7525 www.kmcsystems.com
KNF 25
609/890-8600 www.knf.com
Minnetronix Inc. 37
651/917-4060 www.minnetronix.com
Oyster Bay Pump Works, Inc. 15
516/933-4500 www.obpw.com
Poly-Pipets 25
201/894-8828 www.polypipets.com
Safe-Tec Clinical Products Inc. 32
800/356-6033 www.safe-tecinc.com
Spherotech 10
800/368-0822 www.spherotech.com
Virostat Inc. 3
207/856-6620 www.virostat-inc.com
Web Industries 21
800/932-3212 www.webindustries.com
www.MDEAwards.com
VISIT OUR WEB SITE FOR COMPLETE INFORMATION.
Transforming Healthcare
One Innovation at a Time
ENDORSED BY:
2
1
2
8
0
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E
_
M
D
E
A
1
2
PRESENTED BY:
Late Deadline: Janaury 13, 2011
FINAL THOUGHTS
Despite UN Secretary-General Ban Ki-moons
statement in March 2010 that in this day and age, no
one should be dying from TB, fatal cases of TB remain
a reality.
1
In 2009, an estimated 1.7 million people died
of TB380,000 of whom were co-infected with HIV.
2

Roughly one-third of the worlds population is infected
with TB, and 10 percent of infected people are likely to
develop active TB at some point in their lives.
2
Development of more-eective TB tests is critical. It
depends not only on the identication of new technologies
and improved engineering of diagnostic devices, but also on
the integration of these technologies into existing clinical
algorithms to simplify and expedite diagnosis or exclusion
of TB in TB-endemic countries.
With these objectives in mind, in 2009 the National
Institute of Allergy and Infectious Diseases (NIAID)
established the Tuberculosis Clinical Diagnostics Research
Consortium (CDRC; www.tbcdrc.org) under a contract
with Johns Hopkins University to promote the develop-
ment of improved diagnostics. Te goal of the CDRC is
to determine, early in the development process, whether
investigational diagnostics have the potential to impact the
current clinical and laboratory diagnostic algorithm in TB-
endemic countries.
Diagnostic developers are invited to submit concept
sheets to the CDRC to request evaluation of a technology
at clinical study sites in such countries. Data from these
studies can be used to inform developers on the next steps
for improving a technology and where the diagnostic can
be most appropriately positioned (for instance, in a refer-
ence hospital or at the point of care) to improve speed and
accuracy of TB diagnosis or the determination of drug
resistance.
Te CDRC evaluates experimental diagnostics not
solely in comparison to stand-alone gold standard
diagnostics tests; it also evaluates how these diagnostics
perform within a clinical algorithm. Tis is particularly
important since the gold standard currently used for TB
diagnosis (the acid fast stain) is an antiquated test with
limited specicity and sensitivity. Trough evaluation of
new diagnostic tests in combination with a clinical algo-
rithm, it is expected that the CDRC will demonstrate that
even diagnostic tests with limited sensitivity and specicity
may nevertheless show great utility when evaluated in the
context of a diagnostic process.
Technology holders with diagnostic platforms that
have performed well for diagnosis of other pathogens are
encouraged to consider developing these platforms for use
in TB diagnosis in collaboration with the CDRC. In gen-
eral, technologies that are well suited for CDRC studies
are those that have the potential to impact TB diagnostic
algorithms in endemic settings and also have existing
proof-of-principle data but have not undergone extensive
eld testing.
Te consortium conducts feasibility studies of new or
experimental diagnostics at four established clinical-study
sites in TB-endemic countries: Cape Town, South Africa;
Kampala, Uganda; Vitoria, Brazil; and Masan, South
Korea. Te CDRC does not perform interventional studies,
nor does it support the development of diagnostics. It does
not provide funds to support research at sites una liated
with the consortium.
More information about the CDRC program and appli-
cation information is available at www.tbcdrc.org.
References
1. UN Secretary-General Ban Ki-moons message for World Tuberculosis
Day, 24 March 2010.
2. Te World Health Organization/Stop TB Partnership Global Plan to Stop
TB 2006-2015. IVD
TB CDRC Fights TB with
Diagnostic Science
Jerrold Ellner, MD is Principal Investigator of the
TB CDRC, Professor of Medicine, and Chief of
Infectious Diseases at Boston University School
of Medicine and Boston Medical Center. He can
be reached via David Hom, Director of the TB
Clinical Diagnostics Research Consortium Coordi-
nating Center, at David.Hom@bmc.org.
Diagnostic developers are
invited to submit concept
sheets to the CDRC to
request evaluation of a
technology at clinical study
sites in TB-endemic countries.
44th

Annual
Emerging Technologies
for 21st Century
Clinical Diagnostics
April 19 & 20, 2012
San Jos, Calif.
Conference Program
Speakers
Nanopore Detectors
Mark Akeson
University of California-Santa Cruz
Droplet Flow and Merger in Microuidic
Channels
Bradley Stone
San Jos State University
Integrated Device for Molecular Detection
of Pathogens
Haim Bau
University of Pennsylvania
Top Down Proteomics
Neil L. Kelleher
Northwestern University
Mass Cytometry
Scott Tanner
DVS Sciences, Inc.
Molecular Imaging of Tissue Sections by MS
Richard Caprioli
Vanderbilt University
Informatics and Single-Molecule Detection
for Rapid Triage
Pejman Naraghi-Arani
Lawrence Livermore National Laboratory
Photo-induced Polymerization Detection of
Inuenza Virus
Erica Dawson
INDEVR, Inc.
Quantitative, Multiplex Applications of
Proximity-dependent DNA Ligation
Cor Schoen
Plant Research International
Understanding User Needs in
Low-Resource Settings
Matthew Steele
PATH
IVD Platforms for the Developing World
David Kelso
Northwestern University
A POC Test Platform for Lab-Quality
Nucleic Acid Testing
Eugen Ermantraut
Alere Technologies GmbH
Keynote Presentation
Integration of Automated
Biosensor Systems for Point-of-Use
Francis S. Ligler
The Center for Bio/Molecular Science and Engineering
Naval Research Laboratory, Washington, D.C.
A highly regard expert in biosensors and microuidics, Dr. Ligler has
published extensively and hold numerous patents. She is currently
the Navys Senior Scientist for Biosensors and Biomaterials and the
current Chair of the Bioengineering Section of the National Academy
of Engineering. In her keynote address, Dr. Ligler will present her
unique and lively perspective of optical biosensor technology as it
applies to homeland security and clinical diagnostics.
Four Sessions
O
Novel Lab-on-a-Chip Technologies for Clinical Diagnostics
O
Emerging Diagnostic Technologies using Mass Spectrometry
O
Innovative Technologies for Pathogen Diagnostics
O
New Point-of-Care Technologies for the Developing and
Developed World
In addition to the invited speakers, the conference will feature
oral presentations of selected abstracts, a poster session,
networking breaks, and a reception.
Same Fees as 2011!
Registration Fees (PID 6767)
Early Bird Regular
AACC Member $825 $950
Non-member $1,050 $1,175
Student/Emeritus Member $425 $550
To qualify for the early registration fee, full payment must be received
no later than March 26, 2012.
Not an AACC member? Become a member and save.
See the AACC website or ask Customer Service for details.
How to Register
Online: www.aacc.org (credit card or checks)
By Phone: (800) 892-1400 or (202) 857-0717
Select Customer Service (credit card only)
Accommodations
The special room rate at the Fairmont Hotel, San Jos, Calif. is $225.00
plus tax. Offer expires March 29, 2012 or when our block of rooms sells out.
Phone: (408) 998-1900.
1850 K Street, NW, Suite 625, Washington, DC 20006
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