biomatters - spring 2014
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BioMattersA MichBio Publication Showcasing Michigan’s Biosciences Industry
SPRING/SUMMER 2014
UNIVERSITY OF MICHIGAN
3-D Printing Saves Young Lives
BEAUMONT HEALTH SYSTEM
Cardiovascular Innovation: Good for Health of Patients and Region
DETROIT R&D, INC.
Novel Diagnostics, Drug Screening Tools
IN2BEING
Where Innovation Meets Reality
FEATURED
9 11 15 20
Michigan at Forefront of
Medtech Innovation
From Alpena to Ypsilanti, scientists working at the
nation’s biopharmaceutical companies are currently
researching and developing life saving medicines.
In collaboration with the state’s university medical
schools, science centers, local hospitals and contract
research organizations, nearly 3,500 clinical trials have
been conducted for new prescription drugs. These
have led to remarkable discoveries inspiring hope and
improving the quality of life for patients and their families.
For the people of Michigan, biopharmaceutical research
companies have also been an important source of jobs,
tax revenue and research spending.
A study found that in 2011 the industry supported
nearly 75,000 jobs include life sciences researchers,
management executives, office and administrative
support workers, engineers, architects, computer
and math experts and sales representatives.
We thank the people of Michigan and their communities
for their collaboration, support and kindness. Right now,
nearly 400 tests of new medicines for the six most
debilitating chronic diseases in America is underway
all over the state and they need patient volunteers.
A job engine for Michigan.Life-saving medicines for the world.
BioMatters | Spring/Summer 20141
Together with our customers, we are driven to make healthcare better.
www.stryker.com
MichBio | www.michbio.org 2
LET’S WORK TOGETHER TO GROW IDEAS
INTO BUSINESSSUCCESS STORIES.
Marcos Dantus is the MSU Innovation
Center’s 2013 Innovator of the Year.
A MSU Chemistry Department professor
and prolific inventor, Dantus launched
Biophotonic Solutions, a start-up company
with a successful line of Multiphoton
intrapulse interference phase scan (MIIPS) laser pulse shapers.You might be surprised at what you find at the MSU
Innovation Center: Access to nearly 5,000 researchers, $500 million in annual R&D expenditures, and 642 research and instructional buildings, scale-up facilities, pilot plants and lab space.
We have the world-class ingredients that entrepreneurs, investors, and inventors are looking for, all in one place:
Business-CONNECT links the right people and resources to develop your ideaMSU Technologies offers the best MSU ideas ready for commercial licensingSpartan Innovations creates investment-ready businesses from MSU ideasLearn more today: www.innovation.msu.edu
BioMatters | Spring/Summer 20143
Welcome to Michigan’s Thriving Biosciences Industry! We are pleased to present the ninth issue of BioMatters™,
the only in-depth publication showcasing the range and vitality
of Michigan’s biosciences industry.
This is a dynamic time in Michigan’s economy, and sharing
information about our state’s health and biosciences industry is critical as we work
to build upon our already significant strengths and define a new future.
Michigan’s bioscience community is vibrant and robust, with strengths and assets
along the continuum—world-renowned academic research, emerging technology,
medical device and diagnostic companies, global pharmaceuticals, mature bio-industry,
and a strong support network. The state’s bioscience entrepreneurial ecosystem is
rapidly evolving and bursting with innovation, growing investment, and superb talent.
As a result, company growth continues unabated and successful exits are becoming
routine.
BioMatters™ helps MichBio fulfill its mission in “driving bio-industry growth” by
educating you about the discoveries, technologies, and products being researched,
developed, and manufactured here in Michigan, and the many resources available to
support those activities. As a whole, the economic impact of Michigan’s bio-industry
is sizeable and its reach global.
This issue highlights the innovation emerging from large and small companies—
as well as our academic and clinical research centers—and serves as a snapshot of
Michigan’s outstanding biosciences community. Read how University of Michigan
researchers and doctors are leading the creation and application of life-saving
3D-printed devices (p. 9). Learn how Beaumont, one of our state’s premier health
systems, is developing new cardiovascular technologies to help patients who can’t
be treated with conventional approaches (p. 11). Or follow the growth of various
companies in the chemical, device, bio-analytic, genetic, and diagnostic technology
areas as they pursue global markets with innovative products and services. Understand
how expert providers assist start-ups and established companies in Michigan—and
around the world—with product development and communications strategies targeted
toward health providers and patients. Lastly, familiarize yourself with the State of
Michigan’s innovative BioTrust for Health through which residual newborn blood spots
are made available for important medical and public health research (p. 30).
Discover more about Michigan’s bio-industry at www.michbio.org, and let
MichBio connect you to the state’s bioscience companies, business services and
support network, and markets. Learn how so many of the vital components of the
bio-industry can be so easily accessed right here in Michigan.
Stephen Rapundalo, PhD
President & CEO
MichBio
PRESIDENT’S MESSAGE
STAFF
CONTACT INFORMATION
Stephen T. Rapundalo, PhD
President & CEO
734.527.9144
Katie Trevathan
Director,
Marketing & Communications
734.527.9147
David McGuire
Director,
Operations & Membership
734.527.9150
Nancy Marcotte
Manager, Finance
734.527.9145
Physical Address
3520 Green Court, Suite 175
Ann Arbor, Michigan 48105-1175
Mailing Address
P.O. Box 130199
Ann Arbor, Michigan 48113-0199
Phone
734.527.9150
Fax
734.302.4933
Website
www.michbio.org
MichBio | www.michbio.org 4
PREMIUM MEMBERS
GOLD
SILVER
BRONZE
OFFICERS & DIRECTORS
EXECUTIVE OFFICERSChairmanStephen Munk, PhDAsh Stevens, Inc., President and CEO
Vice ChairmanKevin McCurrenGrand Valley State University,Executive Director, Center for Entrepreneurship and Innovation
President and CEOStephen T. Rapundalo, PhDMichBio, President and CEO
Secretary Tina Rogers, PhD, MBA, DABTMidwest Life Science Advisors LLC,CEO and Founder
Treasurer Matthew L. McCollErnst & Young LLP, Partner
DIRECTORSArik AndersonTerumo Cardiovascular Systems Corp.,Vice President, Global R&D and Marketing
Doug Gage, PhDMichigan State University,Director, BioEconomy Network
Dale GroganMichigan Accelerator Fund I,Managing Director
Sanjay GuptaWellness + Prevention, Inc. (a J&J Company), President
Tim MaylebenEsperion Therapeutics,President and CEO
Kevin McCurrenGrand Valley State University,Executive Director, Center for Entrepreneurship and Innovation
Kevin McLeodMichigan Medical Device Accelerator,Managing Director
Paul MorrisAlixPartners LLP, Finance Director, Enterprise Improvement
Stephen Munk, PhDAsh Stevens, Inc. President and CEO
Stephen T. Rapundalo, PhDMichBio, President and CEO
Tina Rogers, PhD, MBA, DABTMidwest Life Science Advisors LLC,CEO and Founder
John J.H. Schwarz, MDBattle Creek Family Health Center,Physician, Former U.S. Representative
Ned StaeblerWayne State University, Vice President, Economic Development
Christopher J. SteinFerndale Pharma Group Inc., Executive Vice President and COO
George WilsonBeaumont Health System,Chief of Radiation Biology, Scientific Director, Beaumont Biobank
David ZimmermannKalexsyn, Inc., CEO
MEDIA
PATRON
A LIFE SCIENCE CONNEC T BRAND
A LIFE SCIENCE CONNEC T BRAND
BioMatters | Spring/Summer 20145
TABLE OF CONTENTS
ADVERTISERS
Bank of Ann Arbor ...................... 2
EFP Corporation ....................... 2
Healthmark ............................. 1
Hylant ..................................27
MichBio ............................ 8, BC
Terumo Cardiovascular Systems ......27
VWR .................................. IBC
Western Michigan University Homer Stryker MD School of Medicine .......................... IBC
Michigan State University Innovation Center ...................... 2
MPI Research ..........................27
PhRMA .................................IFC
Stryker .................................. 1
If you are interested in submitting an article or an advertisement for the next issue of BioMatters, email [email protected] to receive BioMatters? Visit www.michbio.org/subscribe.
9 University of Michigan3-D Printing Saves Young Lives
Michigan Biosciences by the Numbers
13 Cayman ChemicalThe Evolution of Ann Arbor’s Cayman Chemical
28 Rubicon GenomicsTranslating Human Genetics into Real-Time Medicine
20 in2beingWhere Innovation Meets Reality
6 25 MPI ResearchTaking the Forward View: Advancing Bioanalytical Testing
17 Local Michigan Suppliers Help Develop World Markets
State of MichiganBioTrust Leads Nation as Resource for Public Health Research
Detroit R&DNovel Diagnostics and Drug-Screening Tools
15
JB Ashtin Group, Inc.Helping Clients Publish and Publicize Medical Research
23
GraMedicaA Life-Changing Device Company Transformed
19Beaumont Health SystemCardiovascular Innovation: Good for Health of Patients and Region
11
30
BioMatters
EARLY-STAGE MID-STAGE LATE-STAGE
PREDICT & PROTECT
HEALTHY ENDOTHELIUM
DYSFUNCTIONALENDOTHELIUM
DAMAGEDENDOTHELIUM
EARLY STAGE MID STAGE LATE STAGE
INCREASING VASCULAR AGE
Blood clots formEventualblockage
Result in:Chest painHeart attackStroke
Cardiovascular risk factors
Result in: Lower %FMD
Plaque formationCalcium build-up
Result in:Vessel stiffening and narrowing
TM
Y EALTHYY HEHELIUMNDOTHTHEN
DYSFENDO
DAMAGEDENDOTHELIUM
blockage
Result in:est painart attackoke
Lower %FMDResult in:V l tiff i
THYY
ResCheHeaStro
Lower %FMD Vessel stiffening and narrowing
FUNCTOTHEL
DAMAGED
TL
LIONALLIUM
32 VersicorMedical Device Technology that Serves the Greater Good
MI BIO-INDUSTRY QUICK FACTS# Bio Companies & Organizations:
1,760*
# Bioscience Jobs:
41,892*
Total Employment Impact:
205,952*
Average Bioscience Salary:
$81,296*
Total Payroll:
$2.5 billionEconomic Impact:
$9.5 billionTotal Bioscience Start-Ups Since 2002:
164
ACADEMIC BIO-RESEARCH†
Total R&D:
$2.09 billion (#6 in nation, 2010)
Bioscience R&D:
$1.2 billion (#10 in nation)
# of Science/Engineering Degrees:
14,238 (#8 in nation, 2011)
# of Science/Engineering Patents:
4,598(#6 in nation, 2012)
BIO-INDUSTRY INVESTMENT, COMMERCIALIZATION RESOURCES & INCENTIVESLife Sciences Corridor Fund – 21st Century Jobs Fund:
>$350 million(1999-2011)
Total VC Capital Available:
$538 million(2013)
Total Bioscience VC Investment:
$505 million* (2009-2013)
21st Century Investment Fund:$120 million fund-to-funds$46 million to biosciences www.Michigan21stCenturyInvestmentFund.com
InvestMichigan! Fund:$300 million fund www.InvestMichiganFund.com
Venture Michigan Fund I & II:$95 million fund-to-funds www.VentureMichiganFund.com(2007-2009)
Accelerate MI Innovative Competition: $1 million in cash prizes; largest business plan competition in the world2012 Winner – Algal Scientific2011 Winner – DeNovo Sciences2010 Winner – Armune Biosciences
Angel Investment Group Seed Program: $500 for each Angel group member; $25,000 for administrative fees for 50+ members
EB-5 Investment & Visa Program: Permanent U.S. resident status based on EB-5 eligibility to investors of $1 million in a new commercial enterprise
Emerging Technology Fund: Matching fund for SBIR/STTR awards; up to 25% of SBIR/STTR with maximum of $25,000 for Phase I and up to $125,000 for Phase 2
Great Lakes Entrepreneurs Quest: $100,000 to prizes for annual business plan competition
MI Pre-Seed Fund 2.0:Convertible note ≤ $250,000 with 100% match; pre-seed loan is up to $50,000
Accelerator Fund Program:The Accelerator Fund Program seeded two new early stage venture capital funds with a total of $12 million.n Michigan Accelerator Fund In Huron River Ventures
Pure Michigan Venture Match Fund: $350,000-500,000 match on $700,000-$3 million investmentwww.MichiganAdvantage.org
Michigan Biosciences
BY THE NUMBERS
Testing/ Medical Labs
* Battelle/BIO State Bioscience Industry Development, 2014.
† National Science Board, Science and Engineering Indicators, 2014.
BioMatters | Spring/Summer 2014
25
DISTRIBUTION OF MICHIGAN BIO-COMPANIES BY SECTORPharma & Therapeutics 21%
Medical Devices/Equipment 41%
Research & Development 13%
Testing/Medical Labs 3%
Information Technology 9%
AgBio & Industrial Biotech 13%
n Amway
n Ash Stevens
n Asterand
n Atek Medical
n Bayer CropScience
n BD
n Beckman Coulter
n Dow Chemical
n Dow Corning
n Emergent BioSolutions
n Enzo Life Sciences
n Esperion Therapeutics
n Everist Genomics
n Ferndale Pharma Group
n Housey Pharmaceuticals
n Jasper Clinic
n JHP Pharmaceuticals
n Kalexsyn
n Kalsec
n Kellogg
n Lycera
n Medbio
n MPI Research
n NanoBio
n Neogen
n Orchid Orthopedic Solutions
n Oxford Biomedical
n Perrigo
n Pfizer
n Rockwell Medical
n RTI Surgical
n SRI International
n Stryker
n Terumo Cardiovascular
n ThermoFisher
n Velesco Pharmaceutical
Services
n Wellness & Prevention Inc.
(a J&J company)
n Zoetis
A SAMPLE OF BIOSCIENCE COMPANIES IN MICHIGAN
Biosciences IS BIG BUSINESS in Michigan
Pharma & Therapeutics
Medical Devices/Equipment
Research & Development
Testing/ Medical Labs
AgBio & Industrial Biotech
Information Technology
MichBio | www.michbio.org 8
Every MichBio member organization can take advantage of the Preferred Purchasing Program, which offers exceptional savings, discounts, and opportunities from key industry providers.
Find out how to save up to 75% on goods and services: www.michbio.org/preferred-purchasing.
SAVE With The MichBio Preferred Purchasing Program
LABORATORY AND OFFICE PRODUCTS
used lab supplies and equipment
reagents/PCR
industrial and medical gases
computers/technology
office supplies and furniture
lab supplies and equipment
INTELLIGENCE AND DEVELOPMENT
professional training
market research/intel reports
eLearning and development
scientific intel and reports
BUSINESS OPERATIONS
news distribution/press releases
risk and insurance protection
shipping
cold shipping
government affairs and grants
cloud storage and virtual solutions
relocation and moving insurance brokerage
BioMatters | Spring/Summer 20149
3-D Printing Saves Young Lives
UNIVERSITY OF MICHIGAN
By Rick Haglund
Garrett Peterson spent the first 18
months of his life fighting for nearly
every breath.
Born with a rare condition that
caused his airways to collapse, Peterson
was tethered to a ventilator from birth.
He spent 16 months in the intensive
care unit of a Utah hospital, often
heavily sedated. He twice was placed
in a medically induced coma to keep
him alive.
But after surgeons at the University
of Michigan’s C.S. Mott Children’s
Hospital implanted 3-D printed splints
in Garrett’s airways in January, he was
able to return home with his parents
last month.
“He’s doing well. He has no
intravenous medications. He’s doing
the best he’s ever done in life,” said Dr.
Glenn Green, one of two surgeons who
performed the surgery.
Green assisted Dr. Richard G. Ohye,
the head of pediatric cardiovascular
surgery at U-M, in sewing the splints in
Garrett’s airways to keep them open.
The splints will reabsorb into his body
within three years.
Garrett was just the second person
in the world to get the implants, which
were created by using a sophisticated 3-D
printer. Some experts say 3-D printing
could revolutionize manufacturing for
medical and many other applications.
The first surgery also was performed
at U-M on Kaiba Gionfriddo, a 20-month
old Ohio boy, in 2012.
Both boys developed tracheobroncho-
malacia, a softening of the windpipe
cartilage that affects about one in
2,200 children. Green said they likely
would have died without the surgery.
Garrett was so fragile that just the
act of turning his head could make him
stop breathing.
“When the nurses would just move
his head from side to side, because of
his compromised airways, he would just
turn blue—like instantly,” said Natalie
Peterson, Garrett’s mother, in a video
produced by U-M.
“I will never forget seeing him for
the first time like that. That was hard,”
she said, her voice cracking.
Scott Hollister, a biomedical
engineering professor at U-M, is a
pioneer in the development of medical
3-D printing, a process somewhat
similar to document printing.
3-D printers lay down many layers
of thin material, usually some type of
plastic, and are shaped into an object
using lasers. They have been used to
GARRETT PETERSON AND HIS MOTHER, NATALIE PETERSON, AT C.S. MOTT CHILDREN’S HOSPITAL.
Every MichBio member organization can take advantage of the Preferred Purchasing Program, which offers exceptional savings, discounts, and opportunities from key industry providers.
Find out how to save up to 75% on goods and services: www.michbio.org/preferred-purchasing.
SAVE With The MichBio Preferred Purchasing Program
LABORATORY AND OFFICE PRODUCTS
used lab supplies and equipment
reagents/PCR
industrial and medical gases
computers/technology
office supplies and furniture
lab supplies and equipment
INTELLIGENCE AND DEVELOPMENT
professional training
market research/intel reports
eLearning and development
scientific intel and reports
BUSINESS OPERATIONS
news distribution/press releases
risk and insurance protection
shipping
cold shipping
government affairs and grants
cloud storage and virtual solutions
relocation and moving insurance brokerage
MichBio | www.michbio.org 10
make a variety of prototypes
and products, ranging from guns
to guitars.
Hollister created the splints
used in Kaiba and Garrett’s
airways from CT scans of their
tracheas and bronchi, and 3-D
modeling of their airways.
Green and Hollister obtained
emergency clearance from the Food
and Drug Administration to perform
both surgeries. They are in negotiations
with the FDA for approval of clinic
trials, which Green said might start
by the end of this year.
“U-M is definitely a leader in this
area,” Green said. “But many others
are interested in doing this. I get emails
from major medical centers at least
once a month inquiring about how we
use 3-D printing.”
There is much patient interest
as well. Garrett Peterson’s parents
called Green after reading about
Kaiba Gionfriddo’s successful surgery.
Green and Ohye say they are regularly
contacted by other parents from around
the country, asking if their children
might be candidates for the surgery.
“It’s pretty gratifying,” Ohye said.
“We’ve all started to have the feeling
that once the technology becomes
readily available, it’s going to be used
more than we thought.”
The global market for 3-D printing,
including printer sales, materials and
services, is expected to grow from
$3.8 billion this year to $16.2 billion
in 2018, according to market research
firm Canalys in Palo Alto, CA.
Hollister said he thinks the medical
market for 3-D printing could reach
“the low billions of dollars” over the
next 10 to 15 years.
3-D printing has cost and speed
advantages over other types of
manufacturing processes, Hollister said.
Days before Garrett Peterson’s
surgery, Green suggested a design
modification in the airways splints to
Hollister, who was able to redesign and
make the new splints in two days.
Traditional manufacturing processes
might have required weeks or months
to make the design change.
“You would never conceive of
making that large of a change in a
design with other kinds of manufacturing
techniques,” Hollister said.
The price of manufacturing an
airways splint fell from $200,000
for Kaiba’s surgery in 2012 to
$40,000 for Garrett’s surgery
this year, Green said.
Manufacturing and implanting
the splints, plus the cost of
hospitalization in the intensive
care unit is about $300,000, he
said. But that’s $900,000 less than the
average $1.2 million cost of treating
tracheobronchomalacia without using
3-D printed splints.
“The costs are dropping rapidly,”
Green said.
But there are a variety of technical
and regulatory issues surrounding 3-D
printing for medical use.
Adapting a commercial 3-D printer
to use biomaterials for a variety of
medical applications, as U-M is doing,
“remains one of the technical hurdles,”
Hollister said.
3-D printing also allows many new
entrants into the medical implant field,
creating concerns about regulation and
manufacturing quality.
“One of the broader questions is
how do you regulate this?” Hollister
said. “It’s the beginning of a new
paradigm. You can make custom parts
and you don’t need a big medical
device company to do it.”
U-M physicians and researchers see
a variety of new uses for 3-D printing,
including nose and ear constructs, and
other nonmoving human parts.
Hollister said U-M’s dental school has
been working with dentists in Italy to a
make implants for jawbones damaged by
periodontal disease, using 3-D printing.
3-D printing also can manufacture
more realistic heart models that can aid
in teaching medical students, Ohye said.
But it is the aspect of saving more
lives through the use of this developing
technology that most excites the U-M
physicians and researchers.
“We believe there are many other
applications for these techniques, but
to see the impact living and breathing
in front of you is overwhelming,”
Hollister said. DRS. RICHARD OHYE AND GLENN GREEN (FROM LEFT) AND BIOMEDICAL ENGINEER SCOTT HOLLISTER DESIGNED AND IMPLANTED 3-D PRINTED SPLINTS IN THE AIRWAYS OF GARRETT PETERSON, SEATED ON GREEN’S LAP, ALLOWING HIM TO BREATH NORMALLY AND LIKELY SAVING HIS LIFE.
A BIOPOLYMER AIRWAY IMPLANT MADE FROM A 3-D PRINTER.
BioMatters | Spring/Summer 201411
Beaumont Health System’s
Center for Innovation and Research
in Cardiovascular Diseases (CIRC)
is focused on developing new
cardiovascular technologies to help
patients who can’t be treated with
conventional heart procedures or
therapies.
But the benefit of CIRC goes well
beyond the important work of helping
patients without hope receive new,
innovative treatments.
CIRC is helping to make southeast
Michigan a major destination center for
cardiovascular research and innovation,
and for the commercialization of new
cardiovascular devices and therapies.
So, the economic health of the
region and state benefits as well.
Unlike other innovation centers,
CIRC is designed to interact with
inventors, medical device startup
companies, and large medical device
corporations at all stages of device
development leading up to approval
and market release. This includes
concept and design, pre-human testing,
clinical trials preceding FDA approval,
and physician training and education
after FDA and Medicare approval.
“Our approach of offering one-
stop-shopping for medical device
development encourages companies to
make a longer-term commitment to
doing business in this region,” explains
Robert Safian, MD, Beaumont CIRC
director and a Harvard-trained,
world-renowned cardiologist.
The unique components of CIRC include:
• A one-of-a-kind, 950-square-foot
Bio Skills Lab for hands-on
training for physicians in the
use of new, advanced
cardiovascular medical
technologies. The lab includes
16 plug-and-play stations for
hands-on device manipulation.
• A Simulation Lab, providing
hands-on training in the
management of clinical scenarios
using computerized manikins
(still under development).
• A Digital Camera Studio for
web-based physician training
(still under development).
In addition, CIRC clients can utilize
components of the 9,000-square-foot
Suzanne and Herbert Tyner Center for
Cardiovascular Interventions, which
opened in December 2012. The center
includes a 1,600-square-foot, state-
of-the-art hybrid operating room
for procedures that blend minimally
invasive heart surgeries with procedures
performed through catheters, for
treating structural heart disease.
Adjacent to the hybrid operating suite
is a large, elevated observation room
where physicians and trainees can view
procedures in real-time, and a classroom
where training courses can be broadcast
to locations around the world.
CARDIOVASCULAR INNOVATION:
Good for Health of Patients and Region
ELEVATED OBSERVATION ROOM AT THE TYNER CENTER FOR CARDIOVASCULAR INTERVENTIONS WHERE PHYSICIANS AND TRAINEES CAN VIEW HEART SURGERIES IN REAL TIME.
BEAUMONT HEALTH SYSTEM
MichBio | www.michbio.org
Most commercialization centers
typically lead medical startup
companies to the point of acquisition
by a larger medical device company,
usually just prior to first-in-man
studies. Of the 65 innovation centers
in the nation, none are exactly like
CIRC, which leads companies through
the entire commercialization process.
Any inventors, physicians, medical
institutions, hospitals, academic
institutions, medical device companies,
or government entities can use CIRC.
Dr. Safian says the response of
medical device companies to CIRC’s
comprehensive approach has been
uniformly positive. Major device
industry leaders such as Boston
Scientific, Abbott, St. Jude Medical,
Medtronic, Kona, and InfraRedX have
committed to use the services of CIRC
to commercialize devices for valve
replacement without surgery; stroke
prevention; treatment-resistant high
blood pressure; for opening chronically
occluded arteries; and for direct imaging
of cholesterol in heart vessel plaque to
assess stroke and heart attack risk.
Medical device development is
a lucrative part of the economy. In
2010, interventional cardiology devices
alone brought in revenue close to
$1 billion. Revenue projections for
2015 are just over $3 billion and in
2020 are projected to reach $9 billion.
Beaumont is positioning CIRC to be a
leading driver for this market.
At the same time, CIRC helps to
solidify Beaumont’s world-wide
reputation as a destination center for
cardiovascular treatment firsts, and as a
leader in medical training and education.
This in turn, attracts cardiovascular
medicine’s best and brightest physicians
and researchers to Beaumont.
CIRC’s Bio Skills Lab is another
unusual component of the center that
was funded by a gift from a local family.
“Once technologies gain Food and
Drug Administration and Medicare
approval, there’s an important need
to train physicians to use them,”
says Dr. Safian. “Through the Bio Skills
Lab, we are partnering with medical
device companies to train physicians-
in-practice how to transfer new
technologies to their patients.”
Currently, most physicians receive
training in the use of new medical
devices in hotel rooms from medical
device company representatives.
The opportunity to learn from
clinicians involved in the research
and testing of newly approved medical
devices, in a high-tech, hospital-based
setting, is a first that is especially
important as devices become more
sophisticated.
And by training other physicians in
the use of new technologies in the Bio
Skills Lab, the innovative treatments
that CIRC offers Beaumont patients
are extended to patients regionally,
nationally, and around the
world. “CIRC will encourage
entrepreneurialism, create high paying
jobs for talented people in medicine,
science, business and engineering, bring
the giants of the medical industry to
our region, teach physicians new ways
to save lives, and disseminate that
knowledge around the world,” says Dr.
Safian. “All of this will help drive
southeast Michigan’s economy while
providing hope to patients suffering
from cardiovascular conditions that
are beyond conventional treatments.”
To learn more about CIRC, including
ways to support the program through
philanthropy, call 248.898.4176.
DURING A BOSTON SCIENTIFIC TRAINING ON APRIL 18, BEAUMONT CATHETERIZATION LAB STAFF RECEIVED HANDS-ON SIMULATION TRAINING IN THE USE OF NEW MEDICAL DEVICES FOR ANGIOPLASTY AND STENT PROCEDURES IN RENAL AND CAROTID ARTERIES.
ROBERT SAFIAN
12
BioMatters | Spring/Summer 201413
Adam Uzieblo speaks with a thick
Polish accent and has a bristling gray
crew-cut. An accomplished medicinal
chemist, he is also a survivor. He
endured years of separation from his
wife and young son when he fled to
the west during the Gdansk uprising
of 1980. A few years after coming
to the Midwest, Adam teamed up
with Kirk Maxey, a medical student
at the University of Michigan who
was struggling to build a small
biochemical company he called Cayman
Chemical. Named for the Caribbean
island where the potent biological
materials underlying its product line
originated, Cayman sold a handful of
prostaglandin standards to academic
and pharmaceutical research scientists.
In the more than 30 years since being
founded in a basement laboratory,
Cayman has grown to offer more than
6,000 biochemical standards, assay kits,
antibodies, and recombinant proteins.
Today, Adam is focused on a new
and remarkable project — he’s helping
to develop a new drug. Adam works
from a brightly lit synthetic chemistry
laboratory that is part of Cayman’s
4-building, 14-acre, 170,000 ft2 campus
in Ann Arbor, MI. He and Andrei Kornilov,
another scientific ex-patriot from
Eastern Europe, discovered a series of
compounds that can help to grow new
human bone. This discovery added a
second new drug development project
to Cayman’s portfolio, which at this time
includes a novel set of prostaglandin
inhibitors that show promise in treating
muscular dystrophy and some features
of asthma and inflammation.
BUILDING ON THE PAST In 1981, Kirk Maxey isolated 30
grams of prostaglandin A2 from
an eight-pound sample of coral he
harvested while scuba diving in the
Cayman Islands. This was the starting
material that led to the establishment
of Cayman Chemical. Cayman
developed an extensive product
line focused on its signature brand,
rapidly becoming the industry leader
in the production and distribution
of bioactive lipid reagents. Cayman
chemists synthesized an extensive array
of bioactive lipid products including
numerous eicosanoids (prostaglandins,
leukotrienes, and thromboxanes),
inositol phosphates, cannabinoids, and
steroids. At the same time, Cayman
biochemists developed the antibodies
and immunoassays used to detect the
various bioactive lipids in cell culture
medium, serum, and plasma. Cayman
grew to $10 million in catalog sales and
100 employees in its Ann Arbor research
facilities by the mid-1990s.
By the early 2000s, Cayman
recognized the need to move beyond
its bioactive lipid brand and develop
new product lines to sustain the growth
of the company. Cayman invested
heavily in new facilities and personnel,
taking advantage of the closure of
the Pfizer research facility in Ann
Arbor to hire experienced medicinal
chemists. Cayman’s Chemistry division
capitalized on its experience with
endogenous cannabinoids to begin
manufacturing an extensive line of
market-leading reference standards
that forensics scientists use in the fight
against illegal, designer drugs of abuse,
including synthetic cannabinoids (K2,
Spice, etc.). The analytical chemistry
group achieved ISO certification for its
mass spectrometry services, ensuring
its customers receive the highest
quality in analytical service. As it grew,
Cayman expanded internationally,
opening large-scale chemical synthesis
facilities in Prague (Czech Republic)
and Tallin (Estonia).
The Evolution of Ann Arbor’s Cayman Chemical
CAYMAN CHEMICAL
ADAM UZIEBLO AT THE LAB BENCH SYNTHESIZING AN EICOSANOID.
MichBio | www.michbio.org 14
Cayman’s Biochemistry
division also evolved beyond
the generation of lipid function
assays and ELISA kits to add
recombinant protein cloning
and expression, monoclonal
antibody production, cell-based
assays, and protein structure/
x-ray crystallization. It developed an
impressive array of proteins and high-
throughput screening assays that are
used in epigenetics research, making
Cayman a major player in this area.
The Cayman Biochemistry division grew
from 20 employees (one PhD) in the
mid-1990s to 55 employees, including
12 PhD scientists, by 2012.
Cayman had gathered the skills,
capabilities, and facilities necessary to
undertake a legitimate drug discovery
effort. Entry into the biopharmaceutical
realm advanced Cayman beyond catalog
sales and contract services and into the
risky but potentially more lucrative area
of discovering novel small-molecule
therapies.
For most of Michigan’s fledgling
biotechnology companies, the
challenge to build a successful drug
discovery program from scratch would
necessitate obtaining vast amounts of
venture capital or grant funding to rent
lab space, purchase equipment and
supplies, and pay salaries — startups
can burn through millions of dollars
per year this way. Cayman had the
resources to fund its burgeoning drug
discovery program by relying on the
ongoing financial success of its catalog
business. To ensure its continued
success, Cayman created a unique
system in which every Cayman scientist
involved in drug discovery, like Adam
and Andrei, also contributed to the
manufacture and development of
catalog products and to the fulfillment
of custom products and services.
While the medicinal chemists are
developing novel, patentable chemicals
for Cayman Drug Discovery, they
offset their overhead by synthesizing
new inhibitors, lipid mediators, and
analytical standards for sale in the
catalog or by contributing to a large-
scale cGMP/API manufacturing contract.
An analytical chemist might be asked
to perform a LC/MS analysis of drug
levels in the plasma of dosed mice on
Monday and spend the rest of the week
performing quality analysis of forensics
standards. A cell biologist might take
a day or two per month testing the
activity of Cayman Drug Discovery
compounds for receptor binding on
cells in vitro and use the remainder of
the month to develop a new cell-based
assay kit for catalog sale.
This method of financing drug
discovery makes Cayman unique in
all of Michigan. It’s efficient and
economical, making the maximum
use of the skills and time of Cayman’s
scientists. Not only does this method
provide revenue-producing jobs to do
when not actively involved in drug
discovery, it produces a pipeline of
innovative catalog products.
It’s fitting that Cayman’s initial drug
discovery project took advantage of its
knowledge of the product that launched
the company, prostaglandin A2. Cayman
was contacted by the New London,
Connecticut-based biotech company
Myometrics, LLC for the discovery and
development of small molecule agonists
of the EP4 receptor, one of the four
cellular receptors of the multifunctional
prostaglandin PGE2. EP4 agonists have
several functions described in scientific
literature, including promoting new
bone growth, anti-inflammatory
activities, and effects on blood
pressure. Myometrics wanted to use
them in therapeutic conditions where
new bone growth was required, such as
spinal fusion surgery or the promotion
of bone fracture repair. IND filing is
expected in 2015.
DISCOVERING THE FUTURE In March of 2014, Cayman
took the next step in the
evolution of a complete drug
discovery organization by
officially naming two of its
scientists, Stephen Barrett and
Jim Mobley, to the new positions of
Director of Drug Discovery Chemistry
and Director of Drug Discovery Biology,
respectively. With this organizational
structure in place, Cayman is poised to
perform all aspects of drug discovery,
including selection of a therapeutic
area and drugable biological target,
lead discovery chemistry, lead
optimization, structure-based drug
design, in vitro screening, and in
vivo efficacy testing. As the scope
of Cayman’s drug discovery effort
expands, so will its funding options,
including writing SBIR grants, forming
strategic partnerships with biotech
and pharmaceutical organizations, and
securing venture capital to support
late-stage development efforts. Just as
Cayman grew from its modest start in
a basement in 1981, its Drug Discovery
division will grow to play a significant
role in Cayman’s ongoing efforts to
advance human and animal health and
help make research possible.
More information about Cayman
Chemical can be found on our website
www.caymanchem.com or by calling
800.364.9897.
DR. LEVI BLAZER AND DR. DAN BOCHAR DISCUSS THE RESULTS OF A HIGH THROUGHPUT SCREENING ASSAY.
ADAM UZIEBLO KIRK MAXEY
BioMatters | Spring/Summer 201415
Founded in 1997 by Dr. Hyesook
Kim, Detroit R&D has been steadily
establishing itself as a worldwide source
for novel diagnostic and drug-screening
products. The Detroit R&D laboratories
and offices are located inside the newly
renamed Block at Cass Park Building on
Second Avenue in the heart of a new
redevelopment district in the city of
Detroit, Michigan. The historic building
(formerly the Metropolitan Center for
High Technology) is already the home
of many small businesses and has ample
laboratory space to attract additional
small biotech and start-up companies.
The company’s original project was
to develop an easy and inexpensive
hypertension kit for measuring novel
fatty acid biomarkers in blood, urine,
and tissue. Hypertension affects nearly
50 million individuals in the USA and
about 1 billion people worldwide, and is
an under-diagnosed condition because
the underlying damage to the body
occurs with only mild or no symptoms.
In 2009, heart disease and stroke
accounted for 27,794 deaths in the
state of Michigan (MDCH statistics) and
hypertension during pregnancy is one
of the major risk factors in pregnancy-
related mortality.
Unfortunately, the cause of
hypertension is presently unknown in
about 90 percent of reported cases.
Currently, reducing blood pressure
in hypertensive patients is served by
a number of different drugs such as
calcium blockers and ACE inhibitors, just
to name a few. These varied approaches
to treating hypertension illustrate the
difficulty of finding a single drug that
effectively lowers blood pressure.
With over 75 different medications in
several different categories, physicians
are often faced with a bewildering set
of treatment options, resulting in a
‘roulette wheel’ approach to patient
care. The ability to measure a biomarker
of hypertension, as can be accomplished
with the kits developed at Detroit R&D,
would be advantageous in several ways:
BREAST CANCER TISSUE LABELED WITH DETROIT R&D ANTIBODIES THAT RECOGNIZE A SPECIFIC MODIFIED PROTEIN.
Novel Diagnostics and Drug-Screening Tools
DETROIT R&D
MichBio | www.michbio.org 16
• It could serve as an early prediction
of the onset of elevated blood
pressure and associated
cardiovascular events including
stroke, and this prediction would
have enormous value in the
individualization of treatment
for cardiovascular patients. The
American Heart Association estimates
that the cost of cardiovascular
diseases and stroke in the U.S. alone
were nearly $475 billion in 2009
and will increase to $818 billion in
2030. According to the Michigan
Department of Community Health,
high blood pressure costs in Michigan
were estimated at $1.5 billion
in 2007, so choosing the correct
medication earlier would lower the
chance of developing cardiovascular
diseases and could result in
substantial cost savings.
• It would also provide a tool to
monitor the effectiveness of drug
candidates undergoing pre-clinical
and clinical trials and possibly
could be used to develop a new
anti-hypertensive therapy. Thus
it could be an attractive target
for pharmaceutical companies
facing the challenges of patent
expirations and rising research
and development costs.
• Studies utilizing the Detroit R&D
hypertension kit with coded human
urine specimens obtained from
hypertensive (pre-eclamptic) and
healthy women have confirmed that
this fatty acid is an exceptionally
specific and sensitive biomarker
of hypertension. This is the only
technology currently available
to measure hypertension outside
of the use of mechanical blood
pressure monitors and alteration
of these biomarker levels may
be detected before noticeable
elevations in blood pressure.
The company is now exploring
even simpler and faster dip-stick
techniques to measure this
biomarker under non-laboratory
conditions.
Now 10 years later, Detroit R&D
markets nearly 100 products directly or
through more than twenty distributors
to customers in the U.S. and worldwide.
In addition to hypertension kits, the
company portfolio includes kits for
measuring biomarkers of diabetes,
prostate cancer, septic shock, oxidative
stress, and environmental contaminants.
Several of the technologies developed
at Detroit R&D have been patented
(7 issued and 6 pending patents),
mainly as the result of research and
development supported by 17 National
Institutes of Health (NIH) Small Business
Innovative Research (SBIR) grants
awarded to Detroit R&D (>$9 million in
total). Currently, Detroit R&D is working
on two Phase I and Phase II National
Cancer Institute (NCI) SBIR awards.
Developing new and innovative
cancer diagnostic products has recently
become a major focus of research
and development for Detroit R&D,
and it is attracting outside attention
worldwide. During a recent NCI SBIR
study, Detroit R&D produced antibodies
that recognize important proteins with
very specific sugar groups attached to
their protein backbone. Detection of
these modified proteins will serve as
novel biomarkers for breast and prostate
cancer and possibly other cancers, as
well. During this study Detroit R&D also
discovered an anti-breast cancer drug
candidate that will become the focus
of further projects. The drug candidate
prevented breast cancer cell metastasis
and dramatically increased breast cancer
cell death as compared to non-cancerous
cells. In addition, the company has a
pending patent disclosing a method to
screen synthetic and natural anti-cancer
drug candidates using antibodies for
these modified proteins.
In summary, Detroit R&D is
developing innovative technologies
to help researchers understand the
underlying causes of many worldwide
health problems. This company has
the talent, insight, and drive to grow
substantially and is poised to expand
into the clinical and therapeutic
markets. Detroit R&D welcomes
collaborations and licensing inquiries.
For more information about
Detroit R&D visit their website at
www.detroitrandd.com or call
313.961.1606.
Developing new and innovative cancer diagnostic products has recently become a major focus of research and development for Detroit R&D, and it is attracting outside attention worldwide.
FREE
+ G
LUCU
RON
IDAT
ED 1
4,15
-DH
ET
(N
G/M
G C
REAT
ININ
E)
140
120
100
80
60
40
20
HYPERTENSIVEPreeclamptic
n=7** Significantly different
NORMOTENSIVEHealthy
n=9
**
RESULTS OF A STUDY OF HYPERTENSION IN PREGNANT WOMEN USING DETROIT R&D HYPERTENSION KIT.
BioMatters | Spring/Summer 201417
Not so long ago, Michigan-based
Everist Health was working with
suppliers from all over the United
States—manufacturers in California and
India, web designers and public relations
companies based in New York, and
attorneys in California. Today, virtually
all of the medical device company’s
partners are within a short drive of
Everist Health’s Ann Arbor headquarters.
This includes Detroit-based attorneys
Dykema, Ann Arbor-based web designers
Stone Interactive, and Canton-based
manufacturer Miller Technical Services.
“Many of our original suppliers came
to us because we had worked with
them in previous ventures,” explains
Chief Operating Officer Matt Bartlam,
“however, over time we have found that
we could access almost every service
we needed locally, and the quality of
service from our local suppliers has been
cost effective and outstanding.”
While the company is sourcing
supplies locally, they are seeing plenty
of opportunity to sell around the
world. “At the moment, we have zero
business in the United States because
we are still going through the process
of FDA trials,” explains Matt, “however,
we have regulatory approval to sell
the technology in other markets, and
our devices are in over 30 locations
worldwide—India, Middle East, Europe,
and Canada.”
Everist Health’s device, known as
the AngioDefender, deals with core
health problems such as diagnosing,
as early as possible while there is still
time to take remedial action, people
at risk for developing heart disease and
vascular dementia. The device is low
cost, non-invasive, and simple to use.
The AngioDefender measures the fitness
of the endothelial cells that line the
arteries of the body. These cells produce
nitric oxide that instructs the arteries
to expand and contract to allow blood
to flow to every organ of the body as
needed.
The AngioDefender produces a score
which can be used with the Everist
Vascular Age Calculator to determine
the vascular age of the individual. “You
may be 45 but have a vascular age of
35 or 65,” explains Matt. “If your heart
age is older than it should be, there are
many things you can do to improve your
vascular health such as quitting smoking,
improving your diet and exercise, lower
stress, and improving sleep patterns.
In certain cases where individuals have
a family history of heart problems,
medication may be prescribed.”
Local Michigan Suppliers Help Develop World Markets
ANGIODEFENDER
EVERIST HEALTH
MichBio | www.michbio.org 18
“Heart disease is the number one
killer in the western world,” says Matt.
“At the same time, dementia is reaching
crisis proportions. For example, in the
UK, an estimated 800,000 people suffer
from dementia and that number is
expected to grow to 1.6 million by 2030.
Currently, one in four hospital beds in the
UK are occupied by dementia patients.
Therefore, the market for technology like
AngioDefender that helps predict people
at risk, is potentially huge.”
Health experts around the world
recognize that this made-in-Michigan
technology is a genuine innovation that
can lower healthcare costs and improve
the health of populations by providing
early warning of disease risk to permit
people to take action before they suffer
a potentially fatal heart attack or
develop irreversible vascular dementia.
The UK National Health Service
was sufficiently impressed with the
technology to invite Everist to exhibit
at its National Health Innovation
Conference, and the AngioDefender
has also been featured at a national
cardiology conference in Bangalore,
India, and at the Arab Health Congress.
Researchers in London, Ontario,
Canada are beginning trials this spring.
Everist Health believes the
AngioDefender will appeal to a wide
range of health outlets beyond just
hospitals which are set up to deal with
problems after they have occurred.
Everist Health already has primary care
doctors using AngioDefender as part
of wellness programs. Corporations
are also using the AngioDefender to
encourage employees who are engaged
in sedentary work to adopt healthy
living habits. A major rehabilitation
heart center in Canada is planning to
use AngioDefender to show recovering
patients the value of increased exercise,
and in the United Kingdom, a pharmacy
chain plans to offer AngioDefender
testing, along with other tests, to
measure blood pressure and cholesterol.
In India, a major inflammatory disease
clinic is using AngioDefender to test
patients because for example, people
with rheumatoid arthritis have a 50%
higher risk of developing heart problems
than the rest of the population.
The AngioDefender may also have
application for diagnosing people who
have no obvious heart health symptoms
such as fit young men and women.
“We see a major world market
for this predictive test,” says Matt,
“it is worth noting that our company
has received financial support from
the Michigan Economic Development
Corporation (MEDC). The company is
aiming to obtain FDA approval to market
the device in the United States within
the next year. The support of the MEDC,
together with our other investors may
well create a large number of jobs for
local suppliers and manufacturers for a
device that will be made in Michigan and
sold around the world.”
More information about Everist
Health can be found on our website
www.everisthealth.com or by calling
855.383.7478.
EARLY-STAGE MID-STAGE LATE-STAGE
PREDICT & PROTECT
HEALTHY ENDOTHELIUM
DYSFUNCTIONALENDOTHELIUM
DAMAGEDENDOTHELIUM
EARLY STAGE MID STAGE LATE STAGE
INCREASING VASCULAR AGE
Blood clots formEventualblockage
Result in:Chest painHeart attackStroke
Cardiovascular risk factors
Result in: Lower %FMD
Plaque formationCalcium build-up
Result in:Vessel stiffening and narrowing
TM
Y EALTHYY HEHELIUMNDOTHTHEN
DYSFENDO
DAMAGEDENDOTHELIUM
blockage
Result in:est painart attackoke
Lower %FMDResult in:V l tiff i
THYY
ResCheHeaStro
Lower %FMD Vessel stiffening and narrowing
FUNCTOTHEL
DAMAGED
TL
LIONALLIUM
© 2014 EVERIST HEALTH. ALL RIGHTS RESERVED.
EVERIST HEALTH’S LOCAL SUPPLIERS: CriTech Research, Inc. — Saline, MI Software Verification & Validation
In2being, LLC — Saline, MI Medical Product Development and Consulting
Karthik Ganesan — Ann Arbor, MI Software Developer Consultant
Quality Management & Consulting — Saline, MI QMS Consultant/Auditor
Weathervane Software — Ann Arbor, MI Software Developer Consultant
Miller Technical Services — Canton, MI OEM
Urgent Plastic Services — Troy, MI Plastic Mold Manufacturer
Inspec, Inc. — Canton, MI Calibration of Instruments
MMS Holdings, Inc. — Canton, MI Data Management/CRO
Evolution Enterprises — Milan, MI Data Analysis
Dykema — Detroit, MI Attorney, General Business, and Patents
Hile Creative — Ann Arbor, MI Marketing Literature/Video
Stone Interactive Group — Ann Arbor, MI Website Development
George Cesario — Plymouth, MI IT Consultant
Rick Matovina — Canton, MI Quality System Consultant
Parvin Panahi — Whitmore Lake, MI Design Consultant
Brent Truex — Ann Arbor, MI Software Developer
A Life-Changing Device Company Transformed
On a quest to improve his patients’ quality of life, Dr. Michael E.
Graham, an accomplished foot and ankle surgeon, transformed rapidly
from physician to start-up CEO when his innovative titanium stent,
called HyProCure®, was cleared by the U.S. Food and Drug Administration
(FDA) in 2004. After 10 years of world-wide lecturing and physician
education, GraMedica®, the former start-up, has also transformed
into a successful, global medical device company with headquarters
in Macomb, Michigan. Committed to his mission of “changing lives,
one step at time,” Dr. Graham says, “it’s been a wild ride, but satisfying.
I’ve been able to help more people than I ever expected.”
The first HyProCure® placement took place September 2004. Since
then, HyProCure® has been used in tens of thousands of procedures
worldwide. HyProCure®’s unique design permanently corrects misaligned
feet. Since most of a person’s weight rests on the ankle bone,
misalignment can cause the ankles to turn inward, eventually leading
to pain and damage not only to the ankle and feet, but to the knees
and hips. Unhappy with the results of previously available products
intended to treat the condition, Dr. Graham invented HyProCure®
specifically to improve treatment outcomes.
A recent study by N. Shibuya et al in the Journal
of Foot & Ankle Surgery showed that 18 percent of its
study patients had a functional flatfoot deformity, a
common symptom of misaligned feet. Foot and ankle
surgeons estimate that 10 to 30 percent of the general
public suffers from this same congenital deformity and
the related secondary effects. The brief HyProCure® procedure, typically
only 20-minutes long, permanently corrects foot and ankle alignment with
life-changing results. For example, a child who was not able to walk is now
able to ski a year after the procedure; a nurse who used to end her days
with tremendous foot pain can comfortably work a 12-hour shift.
HyProCure® works by preventing excessive pronation of the ankle’s
subtalar joint. During a minimally invasive procedure at a hospital, surgery
center, or physician’s office, the stent is placed in a naturally occurring
space in the ankle. The stent stabilizes the ankle bone on the heel bone,
eliminating excessive internal pressures and inward rolling of the foot —
while enabling full, normal range of foot motion.
HyProCure®’s patented design and medical-grade
titanium make it a permanent solution with a unique
classification that outperforms older implants that
tried to accomplish the same thing.
While still a small company of less than 20
employees, GraMedica has become recognized for
its innovation in foot care solutions. Almost ten
years after receiving its first product clearance
to market, GraMedica has grown dynamically
and now has products available in more than
40 countries, including in Africa, Asia, Europe, and Latin America.
GraMedica’s team of employees enjoys knowing that the work they
do improves the quality of life for people everywhere. In December
2013, GraMedica announced the selection of Dr. Anthony Weinert,
a renowned foot surgeon with offices in Troy and
Warren, Michigan, as the first Michigan HyProCure®
Center of Excellence. And in early in 2014, Al Seef
Hospital, Kuwait was announced as the first Middle
East HyProCure® International Center of Excellence.
The Center of Excellence designation recognizes
expert physicians, medical groups, and healthcare
centers accomplished at performing HyProCure® Extra-Osseous
TaloTarsal Stabilization (EOTTS) procedures and providing consummate
post-operative care.
GraMedica’s sister educational organization, the Graham
International Implant Institute® (GIII) is committed to research,
training, certification, and support on implantology for foot surgeons
worldwide. Recently, GIII and GraMedica sponsored a minimally
invasive foot and ankle surgery symposium in Bogotá, Colombia.
Forty surgeons from seven countries were trained to identify and treat
patients with flexible flat foot using HyProCure®. GIII and GraMedica
are expected to continue this training in North
America, Asia, Europe, and the Middle East in 2014.
In addition to HyProCure®, GraMedica is
currently developing additional high-quality,
innovative product lines to support their mission
of “changing lives, one step at a time.” To learn
more about HyProCure® and other GraMedica
products, visit the company’s website at
www.GraMedica.com. Additional requests for
information can be made by calling GraMedica’s
office at 586.677.9600.
By Karen M. Sandlin and Jean Stroster
HYPROCURE® SURGEON TRAINING AT CLEMI LABS IN BOGOTÁ, COLOMBIA
MICHAEL E. GRAHAM
A Life-Changing Device Company Transformed
GRAMEDICA
BioMatters | Spring/Summer 2014
MichBio | www.michbio.org 20
Lessons learned in the start-up
trenches are invaluable. Founded in
2010, in2being brings this knowledge and
experience to emerging medical and life-
science device companies. Gene Parunak
and Aaron Kehrer, veterans of HandyLab
and Accuri Cytometers, lead the nine-
person, Saline-based medical device
design and development firm.
IF YOU DREAM IT Medical device design and
development is a custom-tailored
process, not a simple check list. Product
dreams can become reality once a
company’s unique path is understood and
implemented. Upfront visioning exercises
play an invaluable role in determining a
product’s individual pathway.
Based on user input, and resulting
in design requirements, visioning helps
define the product pathway at an early
stage. This is critical since documentation
requirements vary greatly for a device
that will be used in a regulated clinical
setting as opposed to a research setting.
The process of visioning describes a
product concept 2-5 years in the future
after successful market placement. The
exercise clarifies the “product story,”
consolidates stake holders’ visions, and
defines device requirements in terms of
user groups, their unique interactions
with the device and implementation
environments.
For example, is the product intended
for use only in a controlled laboratory
setting or also in field applications
that require additional durability? Is
the device replacing a traditionally-
accepted product and procedure in
the marketplace, in turn mandating a
minimal learning curve requirement for
user acceptance? How will the device be
regulated?
For clinical applications, device
classification is the starting point for
determining the level of regulatory
control, the process of marketing
approval or clearance, and the data
required to submit a marketing
application to the FDA.
A 510(k) filing for a Class II device
typically requires identification of a
predicate device and demonstration of
substantial equivalence. Alternately,
if the application is accepted by the
FDA as a 510(k) de novo submission,
substantial equivalence does not apply,
but significant compliance effort remains.
Seemingly innocuous class I devices,
often exempt from the 510(k) process,
are nevertheless often subject to Good
Manufacturing Practices (GMP).
Understanding the device uses allows
selection of the correct standards,
which must be designed to and tested
to, and are an often overlooked, and
misunderstood, part of the development
process. Additionally, clinical devices
must fit profitably into a reimbursement
category, a frequent oversight in new
device development.
Once visioning is complete, in many
cases, a conceptual design, proposed
architecture identifying the major
product subsystems and potential design
challenges, and a sample bill of materials
(BOM) can be generated. Putting
straw-men, such as these, forward
throughout the process provide tangible
items for stake holders to react to, keeps
everyone on the same page, correcting
misinterpretations along the way.
GENE PARUNAK AND AARON KEHRER LEAD IN2BEING, A NINE-PERSON, SALINE-BASED MEDICAL DEVICE DESIGN AND DEVELOPMENT FIRM.
Where InnovationMeets Reality
IN2BEING
BioMatters | Spring/Summer 201421
THE FOUR FORCES Many great products never
make it to market because of
unbalanced, competing forces.
A compass rose helps visualize
these forces, which must be
kept in alignment for successful
development.
The four primary forces
for medical device design and
development are (1) the regulatory
process, (2) the technical
development possibilities, (3) the
intellectual property landscape,
and (4) the market requirements. These
forces are further subdivided into two
major groups; the group that rewards
novelty and the group that penalizes it.
A strong competitive strategy
demands a robust intellectual property
portfolio; the United States Patent
and Trademark Office (USPTO) rewards
novelty and non-obviousness. A successful
market plan frequently requires that
the product deliver superior results and
benefits but not necessarily be more
complex to operate than existing devices.
Achieving this often requires novelty.
As discussed, the 510(k) process for
Class II medical devices is based on the
concept of demonstrating substantial
equivalence to a predicate device; with
the proper expertise, this conflict with
the patent process can be minimized.
The amount of novel technology
built into a product can negatively
affect the speed of the design and
development process. Increasing
product complexity most often
means increasing iterations during
product development. The potential
for increased troubleshooting costs,
increased maintenance costs, and lower
mean time between failures is warning
enough to be wary of unneeded novelty.
EVERYTHING IS A TESTBED Conceptual designs, sample BOMs,
and other testbeds allow better decision-
making to take place earlier in the design
process (see table at right).
Prototypes, commonly understood
as an integrated device for an alpha
or beta customer release, signal to
investors that the product is ready for
market. Everyone wants one, but going
directly to this stage, which typically
comes just before design transfer to
manufacturing, can be a dangerous
and costly leap of faith.
Used as proof of concept for specific
technically-challenging elements of the
product, testbeds reduce the number
of variables under evaluation. They are
used to produce repeatable outcomes
from individual components of the
device, and to illustrate functioning
device subsystems. Even seemingly
simple products can be broken
down into value-add testbeds.
A testbed can be as simple as
a conceptual design, a drawing or
3D print, to show potential users
for product-definition confirmation.
Or to prove at a rough level that
a concept is likely to work, finite
element analysis, modeling of
products and systems in a virtual
environment, can be performed.
Rapid prototyping, using
fused deposition modeling (FDM),
selective laser sintering (SLS), or
stereolithography (SLA), is another
type of testbed. A final example is
the assembly of the entire product,
or a subsystem, using off-the-shelf
components to prove functionality even
if components may need redesign for the
final build. The goal is to avoid major
expense, like designing and purchasing
injection molds, before the product is
reasonably optimized.
THE ACCELERATION POINT Generically, the acceleration
point, when the burn rate increases
due to investment in tooling, fixture
assemblies, and materials, occurs after
design questions are answered and the
techniques to build the products are
understood.
A COMPASS ROSE HELPS VISUALIZE COMPETING FORCES, WHICH MUST BE KEPT IN ALIGNMENT FOR SUCCESSFUL DEVELOPMENT.
SOME VIRTUAL TESTBEDSFEA (Finite Element Analysis) • Fluids • Mechanics • Dynamics • Heat • Magnetic Flux • Reactions • ESF (Electrostatic Force) • Auditory
Other Virtual Simulation • Electrical • Movement Path • Optical • Sensor Networks
SOME PHYSICAL TESTBEDSSubsystems (or full prototype candidates) for: • Biocompatibility Testing • Durability/Repeatability Verification • User Feedback • Proof of Principle • Electrical Test • Iteration of Specific Design Elements • Manufacturability Verification • Solution Comparison • Clinical Testing
TESTBED EXAMPLES
MichBio | www.michbio.org
A growing body of scientific research supports that cancerous tumors
release cells into the blood stream, at levels that are nearly undetectable.
DeNovo Sciences has developed a microfluidic-based system for enrichment
and molecular characterization of these rare circulating tumor cells (CTC)
from whole blood. Primary clinical benefits include the early detection of
metastasis, and the generation of molecular information on the cancer for
therapy selection and assessment.
Developing a cutting-edge platform, composed of hardware, software,
reagents and kits, is challenging from a resource point of view, especially
if the goal is to get the product to market quickly, as the current funding
environment favors product commercialization, not technology development.
Product design and development requires the right skill sets, preferably
from individuals who have experienced the rigor of developing devices. An
emerging company, DeNovo Sciences has 7 full-time employees, half of them
biochemists. The company’s development strategy was to utilize their internal
personnel for the portions of the platform that required daily interaction
between the biochemists and engineers, and to outsource the development
of the imaging module, a more-defined project, to in2being.
“We try to do immensely difficult tasks at DeNovo Sciences. In a little over two
years, we have developed the first version of our platform and will begin launching
it this spring,” commented Dr. Kalyan “Handy” Handique, DeNovo’s CEO.
“A medical device company needs to satisfy the needs of the diagnostic
marketplace, and in2being is well versed in the regulatory landscape, as well
as very knowledgeable about the entire development process. They had the
right expertise from their HandyLab tenure, and I had absolute confidence
that they would do a high-quality job, providing the best solutions, in a tight
timeframe. In2being has been an excellent complement to our internal team;
they have been very responsive to our needs and evolving milestones.”
In the Trenches with DeNovo Sciences The development process should be
focused on solving the technical hurdles
before manufacturing. Starting the
acceleration process too early leads,
inevitably, to product failure and is
usually accompanied by an increase in
the burn rate as the company attempts
to compensate for the mishap.
Pushing the process too quickly, can
lead to a situation where every device
coming off of the manufacturing floor
is hand built, at some level, by the
development engineers, increasing the
cost of goods. Manufacturing will bring
its own set of issues to resolve, but
they should not be issues that violate
the core product assumptions.
Think of a product’s defined limits
and marketing expectations as guard
rails on a highway. The guard rails keep
the driver from going off the road; the
driver needs control over their own
process and vehicle to stay on the road.
During the development process,
the design should be driven to a
point where it works within the
expected outputs. Continually trying
to manufacture a product that keeps
running into the guard rails can be
very challenging, and potentially
monetarily destructive. Learning
earlier in the design and development
process how to keep everything within
limits will provide a more rewarding
manufacturing experience.
CONCLUSION Medical device design and
development is a custom-tailored
process; each product has a unique
pathway. To reach the end goal, a
solid foundation built on good data
is required. Careful planning defines
the user groups and implementation
environments, balances the four forces,
and establishes the design pathway
along with meaningful testbeds.
in2being is located at the crossroads
in downtown Saline, MI, and can be
contacted at www.in2being.com or
734.316.2623.
CIRCULATING TUMOR CELLS (CTC) REMAIN ONE OF THE MOST PROMISING AREAS OF CANCER RESEARCH FOR GUIDING PATIENT TREATMENT AND PREDICTING CANCER PROGRESSION. THE JETTA DEVELOPED BY DENOVO SCIENCES PERFORMS CTC ISOLATION AND CELL ANALYSIS USING DENOVO’S CUSTOMIZED CONSUMABLES.
BioMatters | Spring/Summer 201423
Are you surrounded by a mound
of unpublished data and suffering
from writer’s block? The pressure
to publish clinical trial results can
feel overwhelming and often induces
anxiety in clinical development teams
across the pharmaceutical/biotech
industries. Compounding this angst
is the need for companies to meet
FDA-mandated timetables, which can
add to the pressure, especially for
smaller companies that may lack the
experience and resources to navigate
the publishing process.
The JB Ashtin Group, Inc.
(JB Ashtin) is a local scientific
communications agency that supports
biopharmaceutical, medical device, and
medical diagnostic companies with the
strategic dissemination of clinical trial
results. “Fifteen years ago, I started
my company because I enjoyed working
with pharmaceutical clients and being
able to use my medical writing and drug
information background. What started
as a small consulting business grew into
a full-service communications company
with the goal of being an extension of
biopharma teams,” says Joan Bradley,
PharmD, who is president and CEO of
the Plymouth, Michigan-based agency.
Dr. Bradley states that, “Scientific
writing and content development
are services we provide, but these
services come bundled with our deep
understanding of the regulatory
environment, a thorough knowledge
of best publication practices, and the
strategic awareness to know where and
how best to communicate our clients’
trial information.”
The rules that govern all aspects of
the pharmaceutical/biotech industries
are growing increasingly complex. The
same level of scrutiny and oversight that
governs the clinical trial process extends
into the dissemination of results.
To stay at the forefront of these
evolving regulations, JB Ashtin
encourages employees to join
professional organizations. ISMPP
offers a Certified Medical Publication
Professional (CMPP) credential, which
indicates an individual has advanced
proficiency in good publication practices
and a commitment to ethical and
By Lori J. Bainbridge
Helping Clients Publish and Publicize Medical Research
Select your target journal carefully.Determine:N Are you reporting signi�cant or novel results?N Who is your target audience?N Where are the best papers in your �eld being published?N What factors are important to you? Consider: Journal reputation/impact factor, circulation, visibility, speed of handling/publication, publication costs, subscription/open access
Determine authorshipN Agree on who is the primary author, corresponding author, name order (position is indeed important)N Determine who has responsibility for the integrity of the work. General rule: all individuals named as authors should qualify for authorship and all those who do qualify should be listedN Follow International Committee of Medical Journal Editors (ICMJE [Vancouver]) guidelinesN Keep an accurate record of who did what during the study
Prepare the manuscriptN Ensure your manuscript is complete, well written, well presented, and organized according to the journal’s requirementsN Ensure that all �gures are of good quality to publishN Prepare a detailed, well-written cover letter for submission to the journal of your choiceN Know how, where, and when to submit
After you’ve identi�ed your journaland before you write:N Read the journal’s Instructions for Authors very carefully: Highlight important aspects Know the journal’s policy requirementsN Collect your paperwork early – all necessary signatures, copyright permissions, ethics committee approvals, etcN Handle all ethical issues. Request guidance when necessary
Manage the review processN Respond quickly to all communications/requests by reviewers and editorsN Always be courteous and professional. Reviewers are people, tooN Share any new or relevant information you may have
5 Fundamental Tips for Getting Science Published
5 Fundamental Tips for Getting Science Published
JB ASHTIN GROUP, INC
© 2014 THE JB ASHTIN GROUP, INC.
transparent data dissemination standards. Most JB Ashtin
writers have this certification, or are pursuing it.
While no two clients are alike, all the companies
JB Ashtin support have one thing in common: the necessity to
communicate scientific information and the desire to improve
the health of patients. “We work with companies at all
phases of drug development,” explains executive director of
scientific services Lamara Shrode, PhD. “Some of our clients
have robust pipelines that require very large publication plans
that may include multiple scientific posters, abstracts, and
manuscripts, while other organizations may be in a start-up
mode and, therefore, have different needs.”
Recently, JB Ashtin added several Michigan-based
companies to their growing client roster, including Rockwell
Medical (Wixom) and Esperion Therapeutics (Plymouth).
“The ability to help companies in our own backyard gives our
staff a real sense of pride. Most of our writers are PharmDs
or PhDs who earned their degrees here in Michigan,” notes
Amy Horton, PharmD, a U-M alumna herself, who has been
with JB Ashtin since the early days of the organization and
serves as vice president of the scientific services team. A
few staff members even serve as adjunct faculty for the
University of Michigan College of Pharmacy.
Frequently, Dr. Bradley and her team are invited to speak at
industry events and offer advice on publication strategies.
JB Ashtin regularly has local pharmacy students who spend a drug information externship in their office and then go on to accept full-time employment with them. Shelly Asiala, PharmD, an alumna of Alma College and U-M, joined the agency after her rotation in 2012 and has become the principal scientific writer for a global skincare brand account the firm manages. “When I graduated, I knew that I didn’t want to follow the traditional career path of a pharmacist, such as a community pharmacy practice or a residency in pharmacy,” explains Dr. Asiala. “When I came to JB Ashtin, I discovered a new option that allowed me to stay connected to hard science and also exposed me to exciting aspects of drug discovery, development, and commercialization.” For information about careers with JB Ashtin, contact Cheryl Stone at [email protected].
JB Ashtin Hires Homegrown Talent
Several local companies have discovered the advantages of
partnering with a scientific communications agency. “Typically
our clients have a diverse set of responsibilities within their
organizations and are often pulled in many directions. When you
couple a heavy workload with a busy travel schedule, it becomes
increasingly difficult to manage the day-to-day responsibilities of a
communications plan,” explains Dr. Bradley.
“As a small biotechnology company, we rely on external
consultants and contractors with specific levels of expertise to help
us get things done,” reports Marianne Andreach, vice president,
strategic marketing and product planning at Esperion Therapeutics.
“We realized that we needed an experienced team to support our
own efforts with getting several manuscripts written and submitted
for timely publication, and we reached out to JB Ashtin.”
Raymond Pratt, MD, FACP, also sees the value of partnering
with an agency. He serves as chief medical officer at Rockwell
Medical and oversees the clinical development and FDA regulatory
process for Rockwell. “I’ve had the pleasure of working with the JB
Ashtin team now and when I was with a previous company. Their
professional and objective approach to the publications process has
been a great help with getting our clinical trial data published and
presented in a timely fashion.”
Writing, editing, and data verification are essential elements
of manuscript creation, but almost as time-consuming are the
administrative details. The ability to document the manuscript
development process and to provide audit-ready files is an essential
good publication practice.
“The FDA is looking at everything, especially if a company is
under a corporate integrity agreement,” cautions Dr. Horton. “Each
author’s participation in manuscript generation should be agreed to
in writing and documented throughout development.” Tracking this
kind paperwork and keeping on top of the manuscript submission
packages and the review process falls on the desk of the agency’s
publication managers.
In addition to providing writing and editorial services, JB Ashtin
collaborates with clients’ internal teams on strategic direction and
timing of publications, which helps to ensure that information will
reach the appropriate healthcare providers. The ultimate goal of
any publication plan is to provide clinicians with the information
they need to make better healthcare decisions for their patients.
For more information about the services JB Ashtin provides,
visit www.jbashtin.com or contact Joan Bradley, PharmD, at
734.459.3144.
Supporting Local Pharma is a Source of Pride
SHELLY ASIALA
BioMatters | Spring/Summer 201425
The marketplace today has very high
expectations for their analyses that are
delivered with the highest of quality
and at a low cost.
Fortunately, that limitation is being
challenged in the life sciences realm.
As researchers develop increasingly
complex and potent new compounds,
the ability to analyze them quickly,
accurately, and cost effectively is
keeping pace, thanks to innovative
technologies and processes in
bioanalytical testing.
MPI Research, a clinical research
organization (CRO) headquartered in
Mattawan, Michigan, has conducted
thousands of drug safety, discovery,
surgery, medical device evaluation,
bioanalytical, and analytical studies.
Skilled scientists in a large-capacity,
state-of-the-art laboratory perform a
range of analytical services that meet
specialized needs in pharmaceutical,
chemical, and environmental science.
At the same time, the team is always
on the lookout for new and better ways
to assess the medicines of tomorrow.
COMPREHENSIVE SERVICE Bioanalytical testing determines the
quantity of a drug or metabolite in a
biological sample, i.e., blood, serum,
plasma, urine, tissue, or skin. Using
a wide array of tools, these tests are
applied to both small molecules and
biopharmaceuticals under GLP (Good
Laboratory Practices) requirements.
Increasingly, pharmaceutical
companies are outsourcing bioanalytical
testing to CROs. The right partner
can deliver quality results under tight
timeframes, thus allowing sponsors
to make key decisions on candidate
drugs earlier in development. A
successful enterprise means providing
scientific expertise and hand-in-
glove collaboration. Ensuring well-
designed, well-validated, and precise
analytical methodologies is central to
that commitment and critical to data
integrity.
CROs that offer robust solutions
possess the following core competencies:
• Preclinical and clinical bioanalytical
capabilities using LC-MS/MS for
small molecules, peptides, and
proteins and immunochemistry
expertise for the bioanalysis of
protein therapeutics
• Dose formulation and analysis for
early drug development studies
Beyond providing a full slate of
services is the ever-rising standard
of quality. Facilities, equipment,
methods, practices, and records must
meet— and exceed where possible — the
requirements of regulatory authorities
and, in the case of CROs, also those of
the sponsor. Likewise, compliance with
study protocols and standard operating
procedures is not just a measure of
success, but an expectation throughout
the life sciences realm.
MPI RESEARCH BIOANALYTICAL AND ANALYTICAL GYROLAB SOLUTIONS.
Taking the Forward View: ADVANCING
BIOANALYTICAL TESTING By Roger Hayes, PhD
MPI RESEARCH
MichBio | www.michbio.org 26
CONSTANT EVALUATION The complexity of new chemical
entities presents significant challenges
to developing and validating
bioanalytical methods. Testing
capabilities—whether in-house
or through a CRO—need constant
evaluation and improvement. In taking
this forward view, MPI Research focuses
on five essential actions:
Investing in equipment to improve capabilities. As drug potency increases,
the ability to determine the level
of analyte in a sample challenges
the limits of instrument sensitivity.
Fortunately, new and more sensitive
instrument platforms are available,
including ultra-high performance liquid
chromatography (UHPLC) interfaced
with modern liquid chromatography
tandem mass spectrometry (LC-MS/MS).
Looking at new technologies. Many laboratories and CROs still use
conventional ELISA (enzyme linked
immunosorbent assay) methods for
immunoassay analysis. While 96-well
plate ELISA has its place, it’s being
challenged by new platforms, such as the
Gyrolab workstation and its CD format
that can conduct immunoassays using
only nanoliters of sample. These systems
are highly automated and offer a wider
analytical range, meaning faster analysis,
higher efficiency, and lower costs.
Assessing the impact of rising dose trials on patient safety. When
it comes to ensuring a medicine is
safe, the bar continues to rise. This
is especially true for rising dose trials
and first-to-file generic drugs, where
clinical bioanalysis requires high-
throughput with rapid turnaround of
results. Chemists turn to automated
liquid handlers to achieve productivity
on the order of 1,500 to 2,000 samples
per day. This strengthens evaluation of
safety and shrinks timelines—especially
helpful for Clinical Summary Reports in
first-to-file opportunities.
Using the most appropriate platform. The standard approach
isn’t always the best. LC-MS/MS is
the go-to platform for conventional
small molecules, but as new classes
are defined, other analytical tools
may prove to be a better option. In
addition to LC-MS/MS, the bioanalytical
team at MPI Research employs gas
chromatography-mass spectrometry
(GC-MS/MS) and inductively coupled
plasma-mass spectrometry (ICP-MS).
In short, it’s about using the right tool
for the right job.
Staying abreast of bioanalytical regulatory challenges. Reporting
analytical data reliably is at the core of
any successful bioanalytical operation.
Laboratories that perform regulated
analysis are routinely inspected
by worldwide regulatory agencies.
Each country’s authority has its own
requirements for method validation
and how methods are applied. These
requirements change regularly, so it’s
important to be connected through
forums such as the Global Bioanalysis
Consortium and the Global CRO Council.
FORWARD VIEW With the pressures of reducing
costs, improving timelines, and keeping
pace with increasingly complex
compounds, no company can afford
to take the easy path to analytical
testing—that is, doing things the way
they’ve always been done. While new
technologies and processes may present
challenges of their own, managing the
bottom line of drug development makes
looking for improved approaches to
testing worth the effort.
MPI Research is committed to
continuously moving forward. The
stringent scientific demands of the
pharmaceutical, animal health,
biotechnology, medical device,
environmental, and chemical industries
call for sophisticated and highly
sensitive bioanalytical/analytical
testing using both standard methods
and customized methodologies. MPI
Research offers analytical services
that are systematically designed and
structured, and which are grounded
in sound scientific principles to
provide data of the highest quality.
As collaborative, responsive partners
we provide flexibility in everything
from our scientific approach to our
scheduling. While we analyze the
typical biological matrices such as
plasma and urine, our bioanalytical
experience with all tissue and organ
types, along with a variety of other
unique requests, runs the gamut from
stents to retinas. In our large-capacity,
state-of-the-art laboratory, our skilled
scientific team performs a full range
of analytical services such as GC/MS
for volatiles, ICP-MS for elements and
metals, LC-MS/MS for small molecules,
and LBA for protein therapeutics to
meet the specialized needs of our
sponsors in a regulated environment.
MPI Research is ready to support
bioanalysis/analysis needs during
all phases of discovery, development,
or formulated finished product.
MPI RESEARCH BIOANALYTICAL AND ANALYTICAL LABORATORY SOLUTIONS.
BioMatters | Spring/Summer 201427
MPI Research is more than an early stage CRO.
We continually think strategically beyond discovery and preclinical research to how our vast compound experience and scienti� c expertise can in� uence all phases to bring safer drugs to market faster and more e� ciently. With broad therapeutic coverage and a deep understanding of market forces that a� ect Sponsors, we share knowledge that’s beyond data to make a real di� erence in healthcare.
Beyond Expectations.
GO BEYOND
For more information, visit www.mpiresearch.com
That willingness to take the forward view is a
hallmark of the Michigan life sciences industry and
another reason why the state’s industry and MPI
Research continues to deliver solutions quickly, cost
effectively, and with the highest quality.
Roger Hayes, PhD, is vice president and general manager
of Laboratory Sciences at MPI Research. He has held
numerous leadership positions in the global life
sciences industry and academia, leading teams in
the development of state-of-the-art bioanalytical
and analytical techniques. With global headquarters
in Mattawan, Michigan, MPI Research serves the
biopharmaceutical, medical device, animal health,
and chemical industries with discovery research and
preclinical development services. www.mpiresearch.com
ROGER HAYES
Terumo® is a registered trademark of Terumo Corporation. ©2014 Terumo Cardiovascular Systems Corporation 851541
Terumo Cardiovascular Group and Terumo Heart, Inc., are Proud Sponsors of MichBio and Michigan’s
Growing Biosciences Industry
www.terumo-cvgroup.com | www.terumoheart.com
Life Science
Focus.
We understand your risks and unique issues!
At Hylant, our experienced advisors specialize in Life Science organizations so you can collaborate with a team who understands your business and bottom line.
Medical Devices | Clinical Research | Clinical Trials | Pharmaceuticals Biotechnology | Product and Technology Development
hylant.com
24 Frank Lloyd Wright Drive, Suite J4100 | Ann Arbor, MI 48105 | P 734-741-0044
MichBio | www.michbio.org 28
Driven by the goal of advancing
the translation of human genetics
“lab knowledge” into practical medical
applications, University of Michigan
Professors John Langmore, PhD and
Vladimir Makarov, PhD founded Rubicon
Genomics in May of 2000. The founders
were dedicated to supporting the
economy of Michigan so there was no
hesitation in establishing headquarters
in Ann Arbor to maintain roots in the
community. More than a dozen years
later as Rubicon expands its footprint
around the globe, the state of Michigan
continues to play an important role in
the company’s growth as more than half
of its current staff has received degrees
from native universities.
Rubicon’s breakthrough product is
based on its PicoPLEX™ technology, used
worldwide for pre-implantation genetic
screening and diagnosis. PicoPLEX is
part of an assay that helps to detect
chromosomal anomalies and genetic
copy variations that may cause birth
defects, helping medical professionals
to select the most predictably viable
embryos for implantation. Rubicon’s
ThruPLEX® technology enables the
study of fragmented or small pieces
of DNA. Currently used for research
purposes, ThruPLEX supports the study
of specific samples such as plasma
that had previously not been possible.
This is enabling physicians to monitor
such events as the treatment of
USING RUBICON GENOMICS’ LATEST HIGH THROUGHPUT KIT, SCIENTISTS DOMINIQUE WILSON AND MAUREEN CAREY PREPARE DNA LIBRARIES FOR NEXT GENERATION DNA SEQUENCING.
Translating Human Genetics into Real-Time Medicine
RUBICON GENOMICS
PHO
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MIC
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BioMatters | Spring/Summer 201429
PICOPLEX™ DNA-SEQ KIT
individual cancer patients while they
are undergoing therapies. Rubicon’s
TransPLEX® technology is applied in
the study of cDNA, RNA that has been
converted to DNA in order to stabilize
it for analysis. TransPLEX is currently
incorporated into the Symphony™
suite of breast cancer diagnostic tests
manufactured by Agendia. Each of
Rubicon’s technologies consistently
provides reliable, unambiguous
results from small or degraded sample
material. Rubicon technologies are
currently contributing across the in-
vitro fertilization, infectious disease
testing, and cancer platforms.
But the small company’s story
wasn’t always rosy. In late 2009, after
nearly a decade of success, Rubicon
was stumbling in the faltering economy.
Dire economic straits gutted the
organization by November of that year,
leaving only four full-time employees
in place; all of whom are still part of
the company today. Enter CEO Dr. Jim
Koziarz and CFO Betsy Long. Regarding
the decision to take on the struggling
start-up, CEO Jim Koziarz said, “Betsy
and I looked at the technologies of
Rubicon Genomics and saw something
worth saving. That’s when we rolled up
our sleeves and made a commitment
to bring this company back with new
life.” Within two years Jim’s vision,
along with a small infusion of capital to
expand staff and develop new products,
landed the organization on solid ground
and it has not looked back.
The formation of a growing
global presence and network of
distributors has helped to fuel
Rubicon’s expansion. In back-to-back
years Rubicon has participated in the
Michigan State Trade Export Program
(STEP), a program operated by the
Michigan Economic Development
Corporation (MEDC) designed to help
small Michigan companies enter the
global marketplace. This program has
allowed Rubicon to attend international
tradeshows in Paris and Munich, leading
to the development of key global
partnerships and distribution channels.
COO Christine Haakenson is especially
grateful for these grants acknowledging
“these agreements reflect our strategy
of enhancing our existing global
distribution channels by partnering
with companies that know their local
markets and are able to provide a high
level of technical service and support.
They extend our reach in growing
sequencing markets around the globe
and enable our customers to access our
products without the additional cost
and complications of shipping from the
U.S. to global destinations.”
And Rubicon shows no signs of
slowing down. With an aggressive
new-product pipeline, rapidly growing
worldwide distribution network, and a
plan for a 30% increase in headcount for
2014, Rubicon will move this summer
to a fully renovated, 19,000+ square-
foot facility less than a mile from its
current location in Pittsfield Township.
Co-founder and Chief Scientific Officer
Dr. John Langmore has strong feelings
about keeping the company local,
“Rubicon was born in Michigan and
our roots are deep here. There was
never any consideration of moving the
company out of state and we’re here
for the duration.” Learn more about
Rubicon at rubicongenomics.com or
contact them at 734.677.4845.
Rubicon’s breakthrough product is based on its PicoPLEX™ technology, used worldwide for pre-implantation genetic screening and diagnosis. PicoPLEX is part of an assay that helps to detect chromosomal anomalies and genetic copy variations that may cause birth defects, helping medical professionals to select the most predictably viable embryos for implantation.
MichBio | www.michbio.org 30
By Carrie Langbo
Recognizing the important role of
biorepositories in advancing medical
and public health research, the Michigan
Department of Community Heath (MDCH)
has joined our state’s drive in biobanking
expansion by allowing use of residual
newborn screening blood spot specimens
for health research through an innovative
program known as the Michigan
BioTrust for Health (BioTrust). Following
technological advances and steps to
improve preservation, use of residual
newborn screening blood spot samples
can make an important contribution to
current and future research.
In 1965 newborn screening (NBS)
for phenylketonuria marked the advent
of what is now a vital public health
program. Blood spots are collected
annually from more than 99.5% of
Michigan’s newborns to screen for
over 50 disorders. This has led to the
identification and treatment of more
than 5,100 Michigan infants with serious
disorders through the end of 2012.
Today, the BioTrust offers additional
public health benefits from newborn
screening. While many state NBS
programs still grapple with development
of policies regarding residual blood
spot storage and research, Michigan is
at the forefront with implementation
of the BioTrust. According to Director
James Haveman, “MDCH is optimistic
that residual blood spots will play an
important role in advancing population
health research. Through the BioTrust
program, we are eager to work
with pioneering researchers while
maintaining a commitment to uphold
the Department’s ethical and privacy
standards.”
MDCH first began the stepwise
process of examining issues surrounding
blood spot retention and use more than
two decades ago. Michigan’s public
health code establishes the foundation
for storage and research use of residual
blood spots, but numerous challenges
initially had to be addressed to ensure
adequate community education and
support. A legal expert roundtable was
convened and determined that MDCH
served as a trustee or steward having
“qualified ownership” of residual blood
spots. Multiple methods were also used
to gauge community views and beliefs
on issues such as individual autonomy
versus public benefit, acceptable
research guidelines and appropriate
methods to inform individuals about
BLOOD SPOTS ARE TAKEN SHORTLY AFTER DELIVERY FROM NEARLY EVERY INFANT TO PERFORM LIFE-SAVING NEWBORN SCREENING.
STATE OF MICHIGAN
PHO
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BioTrust Leads Nation as Resource for Public Health Research
BioMatters | Spring/Summer 201431
participation. A BioTrust Community
Values Advisory Board was convened and
continues to advise MDCH on BioTrust
policies and methods to ensure on-going
and open dialogue surrounding the
often-complex ethical issues raised by
biobanking endeavors.
Ensuring individuals have the ability
to participate in the decision-making
process for their own or their child’s
blood spots has been an important
component of the BioTrust. There are
different methods to inform MDCH
about one’s choice depending on
the date the sample was collected.
Samples collected prior to July 1984
no longer exist, but those obtained
from July 1984 to the present day are
currently being stored in the BioTrust’s
designated biorepository, the Michigan
Neonatal Biobank, which affords optimal
temperature and humidity controls as
well as stringent privacy and security
measures. De-identified samples
collected prior to May 1, 2010, are
available for approved research under a
waiver of informed consent granted by
the MDCH Institutional Review Board. If
parents or individuals (≥18years of age)
are not comfortable with the potential
research use of blood spots, they can
contact MDCH and either request that
samples be destroyed or continue to
be stored but not made available for
research. MDCH staff has participated
in over 200 community engagement and
educational endeavors since 2010 to
increase awareness about the research
use of blood spots and parental options.
In 2010 Michigan became the first
state to implement a universal parental
consent process for research use of
residual newborn screening blood spots
as part of routine newborn screening
procedures following delivery. Samples
collected after April 30, 2010, are only
available for research if
parents grant consent
for the BioTrust or
for participation in a
particular research study.
Consented blood spot
samples are currently
available from about
60% of babies born since
May 2010. Historically,
blood spots from nearly
all babies born before
that time were available;
however, the more recent
consent process is a
necessary tradeoff to
ensure public support and
continued availability of
any specimens for health
research.
Residual newborn
screening blood spots
represent a population-
based sample and provide
a unique window for
studying prenatal and
neonatal environments—
making the specimens a vital resource.
As technology continues to advance
and investigators become more aware
of potential applications for blood
spot research, their use will become
increasingly important. Since 2009,
Michigan’s blood spots have already
been utilized in over 25 research
protocols investigating techniques
to improve newborn screening,
etiologies of childhood disorders as
well as associations with birth defects
and environmental agents or genetic
alterations. Dr. Rick Neitzel, a University
of Michigan researcher provides further
evidence stating, “The BioTrust has
been an incredible resource for my
work exploring the relationship between
heavy metals exposure and adverse
hearing outcomes among Michigan
newborns. Having access to a large
repository of newborn dried blood spots
supported by a tremendously helpful
staff has made my move into this area
of research substantially easier than it
would have been otherwise.”
MDCH looks forward to facilitating
the research use of residual newborn
screening blood spots and anticipating
the evolution of the BioTrust to meet
future research regulations. For
additional information regarding the
BioTrust including current policies and
procedures for approval of proposed
studies and privacy protection,
summaries of on-going research
and consent options please visit
www.michigan.gov/biotrust or contact
the Newborn Screening Program at
866.673.9939.
Blood spots are collected annually from more than 99.5% of Michigan’s newborns to screen for over 50 disorders. This has led to the identification and treatment of more than 5,100 Michigan infants with serious disorders through the end of 2012.
NEARLY 2 MILLION SAMPLES ARE STORED AT THE MICHIGAN NEONATAL BIOBANK.
30
Versicor is an electronics, controls, and software development
company based in Royal Oak, Michigan that is changing how medical
devices are developed. Versicor is made up of an eclectic team of
passionate entrepreneurs dedicated to filling the gaps in the medical
device industry through technological products that aim to serve
the community.
WHY VERSICOR Versicor solves tough problems for big thinkers. Versicor offers
turnkey design to distribution with capabilities ranging from controls
development, electronics, mobile design and development, big data,
and testing and validation. President Christie Coplen brings creative,
entrepreneurial problem solving and product development to Versicor
by utilizing her 15 years of leadership experience in progressive
management and product development roles. Versicor is a team of
engineers, entrepreneurs, and creative thinkers who are convinced
that innovation should be easier. Their combined experience has led
to improved product creation efforts, speed to market, increased
profitability, and maximized investment value.
THE TECHNOLOGY “Versicor works with both new medical device startups and
seasoned companies looking to make their ideas a reality,” says Christie
Coplen. Its robust hardware platform and model-based software enables
ideas to be transformed into reality. In fact, medical device products
produced by Versicor are developed four times faster
than traditional methods. Its platform also decreases
risk and reduces development cost for customers.
Versicor offers turnkey design to distribution with
capabilities ranging from controls development,
electronics, mobile design and development, data
analytics and validation, and verification. Versicor is ISO 13485 compliant
and stands with its customer through the FDA process.
A key element in improving care is expanding the ability to care for
patients outside of the standard hospital footprint. OEM’s and hospitals
will have to begin working with companies that understand systems,
connectivity, and communications that enable the transition occurring
in healthcare while integrating with historical systems. Versicor is
providing a solution to this transition. Versicor is not only known for
its impressive services and expertise. The company also makes it its
mission to serve its local community utilizing the
technology it has available to serve community needs.
SERVING THE COMMUNITY One such need came from Ed Slattery and his
family, whose lives dramatically changed two years
ago when a truck driver fell asleep behind the wheel,
killing wife Susan and disabling son Matthew, who is
now wheelchair-bound. Versicor wanted to help the Slattery family
by working to create a wheelchair accessible home.
The concept for the home is finding and defining a new “normal”
for the family. The home will consist of an open floor plan to
accommodate the wheel chair, special cook
tops, pull down cabinets, a therapy pool, and
even a lift chair, created by Versicor that will
allow Matthew to exercise in the safety of
his own home. The Versicor team provided
software development, electrical hardware, and
mechanical components for the lift chair. With extensive materials
research and consumer testing, Versicor translated the design concept
into a fully tested application.
By understanding the client’s needs, Versicor successfully converted
Ed’s idea into reality. The lift chair will be completed and installed in
May and the Slattery home should be completed in the next six months.
Continuing its support for the community through technology,
Versicor is launching Ideas to Action, a nation-wide contest
designed to help medical device, clean-tech, and transportation
entrepreneurs transform their project ideas
into products. Versicor will provide $250,000
worth of controls, electronics, and software
development services to contest recipients.
For more information on how Versicor can
help you turn your idea into a reality, visit
www.goversicor.com or call 248.914.5582.
Medical Device Technology that Serves the Greater Good
CAD DRAWINGS OF THE LIFT CHAIR THAT WILL BE INSTALLED IN THE SLATTERY HOME.
CHRISTIE COPLEN
VERSICOR
MichBio | www.michbio.org
BioMatters | Spring/Summer 2014
VWR_BIO_Consortium_7.5x4.875_final.indd 1 3/20/2014 10:34:18 AM
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P.O. Box 130199Ann Arbor, MI 48113-0199
STAY CONNECTEDNEW WEBSITE LAUNCHED IN MAYwww.michbio.org
Features include:
Comprehensive Michigan Bioscience Directory
Expanded Preferred Purchasing Program
New MichBio Product Showcase (members can promote their goods and services)
A BioToolbox clearinghouse for bioscience industry resources
Member portal with access to online community, digital library, more
Enhanced news and events listings (members can now submit their own items)
Better social media integration
MICHBIO EXPO AND CONFERENCESEPTEMBER 30- OCTOBER1, 2014www.michbio.org/expo
This 10th annual event, to be held at the MotorCity Casino Hotel in Detroit, is Michigan’s premier bioscience gathering. The event will include local bioscience facility tours; a plenary speaker and keynote address; breakout sessions in human health, bioscience technology, and business growth tracks; bioscience and service provider exhibits; and more. Registration and exhibition details coming soon.
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