BioMatters SPRING/SUMMER 2014
A MichBio Publication Showcasing Michigan’s Biosciences Industry
Michigan at Forefront of Medtech Innovation
FEATURED
9 UNIVERSITY OF MICHIGAN
3-D Printing Saves Young Lives
11 BEAUMONT HEALTH SYSTEM
Cardiovascular Innovation: Good for Health of Patients and Region
R&D, INC. IN2BEING 15 DETROIT 20 Novel Where Innovation
Diagnostics, Drug Screening Tools
Meets Reality
A job engine for Michigan. Life-saving medicines for the world. 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.
Together with our customers, we are driven to make healthcare better. www.stryker.com
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BioMatters | Spring/Summer 2014
LET’S WORK TOGETHER TO
GROW IDEAS INTO BUSINESS
SUCCESS STORIES. Y
ou 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 idea MSU Technologies offers the best MSU ideas ready for commercial licensing Spartan Innovations creates investment-ready businesses from MSU ideas Learn more today: www.innovation.msu.edu
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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.
PRESIDENT’S MESSAGE
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.
STAFF Stephen T. Rapundalo, PhD President & CEO srapundalo@michbio.org 734.527.9144 Katie Trevathan Director, Marketing & Communications katie@michbio.org 734.527.9147
As a result, company growth continues unabated and successful exits are becoming
David McGuire
routine.
Director,
BioMatters™ helps MichBio fulfill its mission in “driving bio-industry growth” by
Operations & Membership
educating you about the discoveries, technologies, and products being researched,
david@michbio.org
developed, and manufactured here in Michigan, and the many resources available to
734.527.9150
support those activities. As a whole, the economic impact of Michigan’s bio-industry is sizeable and its reach global.
Nancy Marcotte
Manager, Finance
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
nancy@michbio.org
Michigan’s outstanding biosciences community. Read how University of Michigan
734.527.9145
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
CONTACT INFORMATION
be treated with conventional approaches (p. 11). Or follow the growth of various companies in the chemical, device, bio-analytic, genetic, and diagnostic technology
Physical Address
areas as they pursue global markets with innovative products and services. Understand
3520 Green Court, Suite 175
how expert providers assist start-ups and established companies in Michigan—and
Ann Arbor, Michigan 48105-1175
around the world—with product development and communications strategies targeted toward health providers and patients. Lastly, familiarize yourself with the State of
Mailing Address
Michigan’s innovative BioTrust for Health through which residual newborn blood spots
P.O. Box 130199
are made available for important medical and public health research (p. 30).
Ann Arbor, Michigan 48113-0199
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
Phone
support network, and markets. Learn how so many of the vital components of the
734.527.9150
bio-industry can be so easily accessed right here in Michigan. Fax 734.302.4933 Website www.michbio.org
Stephen Rapundalo, PhD President & CEO
MichBio
info@michbio.org
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BioMatters | Spring/Summer 2014
PREMIUM MEMBERS
GOLD
OFFICERS & DIRECTORS
EXECUTIVE OFFICERS Chairman Stephen Munk, PhD Ash Stevens, Inc., President and CEO
SILVER
Vice Chairman Kevin McCurren Grand Valley State University, Executive Director, Center for Entrepreneurship and Innovation President and CEO Stephen T. Rapundalo, PhD MichBio, President and CEO Secretary Tina Rogers, PhD, MBA, DABT Midwest Life Science Advisors LLC, CEO and Founder
BRONZE
Stephen Munk, PhD Ash Stevens, Inc. President and CEO Stephen T. Rapundalo, PhD MichBio, President and CEO
DIRECTORS
John J.H. Schwarz, MD Battle Creek Family Health Center, Physician, Former U.S. Representative
Dale Grogan Michigan Accelerator Fund I, Managing Director Sanjay Gupta Wellness + Prevention, Inc. (a J&J Company), President A LIFE SCIENCE CONNEC T BRAND
Tim Mayleben Esperion Therapeutics, President and CEO
A LIFE SCIENCE CONNEC T BRAND
MichBio | www.michbio.org
Paul Morris AlixPartners LLP, Finance Director, Enterprise Improvement
Tina Rogers, PhD, MBA, DABT Midwest Life Science Advisors LLC, CEO and Founder
Doug Gage, PhD Michigan State University, Director, BioEconomy Network
MEDIA
Kevin McLeod Michigan Medical Device Accelerator, Managing Director
Treasurer Matthew L. McColl Ernst & Young LLP, Partner
Arik Anderson Terumo Cardiovascular Systems Corp., Vice President, Global R&D and Marketing
PATRON
Kevin McCurren Grand Valley State University, Executive Director, Center for Entrepreneurship and Innovation
4
Ned Staebler Wayne State University, Vice President, Economic Development Christopher J. Stein Ferndale Pharma Group Inc., Executive Vice President and COO George Wilson Beaumont Health System, Chief of Radiation Biology, Scientific Director, Beaumont Biobank David Zimmermann Kalexsyn, Inc., CEO
BioMatters TABLE OF CONTENTS
6 9 11 13 15
17
Michigan Biosciences by the Numbers University of Michigan 3-D Printing Saves Young Lives
Local Michigan Suppliers Help Develop World Markets
PREDICT & PROTECT EARLY Y-STAGE STAGE
MID-STAGE MID STAGE
LATE-STAGE LATE STAGE
INCREASING VASCULAR AGE Cardiovascular risk factors
Plaque formation Calcium build-up
Result in: Lower %FMD
Result in: V Vessel l stiffening tiff i and narrowing
Blood clots form Eventual blockage Res in: Result Che est pain Chest
Hea art attack Heart Stro oke Stroke
TM
25
HEALTHY HE EALTHY THY Y ENDOTHELIUM EN NDOTH TH HELIUM
DYSFUNCTIONAL DYSF FUNCT TIONAL L ENDOTHELIUM ENDO OTHEL L LIUM
DAMAGED ENDOTHELIUM
19
Beaumont Health System Cardiovascular Innovation: Good for Health of Patients and Region
20
Cayman Chemical The Evolution of Ann Arbor’s Cayman Chemical
23
Detroit R&D Novel Diagnostics and Drug-Screening Tools
GraMedica A Life-Changing Device Company Transformed
in2being Where Innovation Meets Reality
JB Ashtin Group, Inc. Helping Clients Publish and Publicize Medical Research
28 30 32
MPI Research Taking the Forward View: Advancing Bioanalytical Testing
Rubicon Genomics Translating Human Genetics into Real-Time Medicine
State of Michigan BioTrust Leads Nation as Resource for Public Health Research
Versicor Medical Device Technology that Serves the Greater Good
If you are interested in submitting an article or an advertisement for the next issue of BioMatters, email katie@michbio.org. Want to receive BioMatters? Visit www.michbio.org/subscribe.
ADVERTISERS Bank of Ann Arbor....................... 2 EFP Corporation ........................ 2 Healthmark ............................. 1 Hylant ...................................27 MichBio ............................. 8, BC
Michigan State University Innovation Center....................... 2 MPI Research ...........................27 PhRMA ..................................IFC Stryker ................................... 1
5
Terumo Cardiovascular Systems.......27 VWR ................................... IBC Western Michigan University Homer Stryker MD School of Medicine........................... IBC
BioMatters | Spring/Summer 2014
Michigan Biosciences
BY THE NUMBERS 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 billion Economic Impact:
$9.5 billion Total 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 & INCENTIVES Life Sciences Corridor Fund – 21st Century Jobs Fund:
>$350 million
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 world 2012 Winner – Algal Scientific 2011 Winner – DeNovo Sciences 2010 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:
Total VC Capital Available:
Convertible note ≤ $250,000 with 100% match; pre-seed loan is up to $50,000
(2013)
Accelerator Fund Program:
(1999-2011)
$538 million
Total Bioscience VC Investment: * (2009-2013)
$505 million
* Battelle/BIO State Bioscience Industry Development, 2014. † National Science Board, Science and Engineering Indicators, 2014.
The Accelerator Fund Program seeded two new early stage venture capital funds with a total of $12 million. n Michigan Accelerator Fund I n Huron River Ventures
Pure Michigan Venture Match Fund: $350,000-500,000 match on $700,000-$3 million investment www.MichiganAdvantage.org
DISTRIBUTION OF MICHIGAN BIO-COMPANIES BY SECTOR
A SAMPLE OF BIOSCIENCE COMPANIES IN MICHIGAN
Pharma & Therapeutics
21%
n Amway
n Lycera
Medical Devices/Equipment
41%
n Ash Stevens
n Medbio
Research & Development
13%
n Asterand
n MPI Research
Testing/Medical Labs
3%
n Atek Medical
n NanoBio
Information Technology
9%
n Bayer CropScience
n Neogen
AgBio & Industrial Biotech
13%
n BD
n Orchid Orthopedic Solutions
n Beckman Coulter
n Oxford Biomedical
n Dow Chemical
n Perrigo
n Dow Corning
n Pfizer
n Emergent BioSolutions
n Rockwell Medical
n Enzo Life Sciences
n RTI Surgical
n Esperion Therapeutics
n SRI International
n Everist Genomics
n Stryker
n Ferndale Pharma Group
n Terumo Cardiovascular
n Housey Pharmaceuticals
n ThermoFisher
n Jasper Clinic
n Velesco Pharmaceutical
n JHP Pharmaceuticals
Services
n Kalexsyn
n Wellness & Prevention Inc.
n Kalsec
(a J&J company)
n Kellogg
n Zoetis
AgBio & Industrial Biotech Pharma & Therapeutics Information Technology
Testing/ Medical Labs
Research & Development
Medical Devices/ Equipment
Biosciences
IS BIG BUSINESS in Michigan
25 BioMatters | Spring/Summer 2014
SAVE With The MichBio
Preferred Purchasing Program 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.
LABORATORY AND OFFICE PRODUCTS used lab supplies and equipment
BUSINESS OPERATIONS
INTELLIGENCE AND DEVELOPMENT
news distribution/press releases
reagents/PCR
professional training
shipping
risk and insurance protection
market research/ intel reports
industrial and medical gases
government affairs and grants cold shipping
office supplies and furniture
relocation and moving
insurance brokerage
eLearning and development
computers/technology
lab supplies and equipment
MichBio | www.michbio.org
cloud storage and virtual solutions
8
scientific intel and reports
UNIVERSITY OF MICHIGAN
GARRETT PETERSON AND HIS MOTHER, NATALIE PETERSON, AT C.S. MOTT CHILDREN’S HOSPITAL.
3-D Printing Saves Young Lives
By Rick Haglund
2,200 children. Green said they likely
Garrett Peterson spent the first 18
months of his life fighting for nearly
would have died without the surgery.
every breath.
act of turning his head could make him
Born with a rare condition that
Garrett was so fragile that just the
caused his airways to collapse, Peterson
stop breathing.
was tethered to a ventilator from birth.
He spent 16 months in the intensive
his head from side to side, because of
“When the nurses would just move
his compromised airways, he would just
care unit of a Utah hospital, often heavily sedated. He twice was placed
surgery at U-M, in sewing the splints in
turn blue—like instantly,” said Natalie
in a medically induced coma to keep
Garrett’s airways to keep them open.
Peterson, Garrett’s mother, in a video
him alive.
The splints will reabsorb into his body
produced by U-M.
within three years.
of Michigan’s C.S. Mott Children’s
the first time like that. That was hard,”
Hospital implanted 3-D printed splints
in the world to get the implants, which
she said, her voice cracking.
in Garrett’s airways in January, he was
were created by using a sophisticated 3-D
able to return home with his parents
printer. Some experts say 3-D printing
engineering professor at U-M, is a
last month.
could revolutionize manufacturing for
pioneer in the development of medical
medical and many other applications.
3-D printing, a process somewhat
intravenous medications. He’s doing
similar to document printing.
the best he’s ever done in life,” said Dr.
at U-M on Kaiba Gionfriddo, a 20-month
Glenn Green, one of two surgeons who
old Ohio boy, in 2012.
of thin material, usually some type of
performed the surgery.
plastic, and are shaped into an object
But after surgeons at the University
“He’s doing well. He has no
Green assisted Dr. Richard G. Ohye, the head of pediatric cardiovascular
Garrett was just the second person
The first surgery also was performed
Both boys developed tracheobroncho-
malacia, a softening of the windpipe
“I will never forget seeing him for
Scott Hollister, a biomedical
3-D printers lay down many layers
using lasers. They have been used to
cartilage that affects about one in
9
BioMatters | Spring/Summer 2014
make a variety of prototypes
The price of manufacturing an
and products, ranging from guns
airways splint fell from $200,000
to guitars.
for Kaiba’s surgery in 2012 to
$40,000 for Garrett’s surgery
Hollister created the splints
this year, Green said.
used in Kaiba and Garrett’s airways from CT scans of their tracheas and bronchi, and 3-D modeling of their airways.
Manufacturing and implanting
A BIOPOLYMER AIRWAY IMPLANT MADE FROM A 3-D PRINTER.
the splints, plus the cost of hospitalization in the intensive care unit is about $300,000, he
Green and Hollister obtained
emergency clearance from the Food
and Drug Administration to perform
including printer sales, materials and
average $1.2 million cost of treating
both surgeries. They are in negotiations
services, is expected to grow from
tracheobronchomalacia without using
with the FDA for approval of clinic
$3.8 billion this year to $16.2 billion
3-D printed splints.
trials, which Green said might start
in 2018, according to market research
by the end of this year.
firm Canalys in Palo Alto, CA.
Green said.
“U-M is definitely a leader in this
The global market for 3-D printing,
Hollister said he thinks the medical
said. But that’s $900,000 less than the
“The costs are dropping rapidly,” But there are a variety of technical
area,” Green said. “But many others
market for 3-D printing could reach
and regulatory issues surrounding 3-D
are interested in doing this. I get emails
“the low billions of dollars” over the
printing for medical use.
from major medical centers at least
next 10 to 15 years.
once a month inquiring about how we
to use biomaterials for a variety of
use 3-D printing.”
advantages over other types of
medical applications, as U-M is doing,
3-D printing has cost and speed
Adapting a commercial 3-D printer
manufacturing processes, Hollister said.
“remains one of the technical hurdles,”
as well. Garrett Peterson’s parents
Hollister said.
called Green after reading about
surgery, Green suggested a design
Kaiba Gionfriddo’s successful surgery.
modification in the airways splints to
entrants into the medical implant field,
Green and Ohye say they are regularly
Hollister, who was able to redesign and
creating concerns about regulation and
contacted by other parents from around
make the new splints in two days.
manufacturing quality.
the country, asking if their children
might be candidates for the surgery.
might have required weeks or months
how do you regulate this?” Hollister
There is much patient interest
Days before Garrett Peterson’s
Traditional manufacturing processes
3-D printing also allows many new
“One of the broader questions is
to make the design change.
said. “It’s the beginning of a new
“We’ve all started to have the feeling
paradigm. You can make custom parts
that once the technology becomes
making that large of a change in a
and you don’t need a big medical
readily available, it’s going to be used
design with other kinds of manufacturing
device company to do it.”
more than we thought.”
techniques,” Hollister said.
“It’s pretty gratifying,” Ohye said.
“You would never conceive of
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 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.
MichBio | www.michbio.org
10
in front of you is overwhelming,” Hollister said.
BEAUMONT HEALTH SYSTEM
ELEVATED OBSERVATION ROOM AT THE TYNER CENTER FOR CARDIOVASCULAR INTERVENTIONS WHERE PHYSICIANS AND TRAINEES CAN VIEW HEART SURGERIES IN REAL TIME.
CARDIOVASCULAR INNOVATION:
Good for Health of Patients and Region
Beaumont Health System’s
• A Simulation Lab, providing
Center for Innovation and Research
hands-on training in the
in Cardiovascular Diseases (CIRC)
management of clinical scenarios
is focused on developing new
using computerized manikins (still under development).
cardiovascular technologies to help
patients who can’t be treated with
• A Digital Camera Studio for web-based physician training
conventional heart procedures or
concept and design, pre-human testing,
therapies.
clinical trials preceding FDA approval,
and physician training and education
beyond the important work of helping
after FDA and Medicare approval.
components of the 9,000-square-foot
patients without hope receive new,
Suzanne and Herbert Tyner Center for
innovative treatments.
stop-shopping for medical device
Cardiovascular Interventions, which
But the benefit of CIRC goes well
“Our approach of offering one-
(still under development). In addition, CIRC clients can utilize
development encourages companies to
opened in December 2012. The center
Michigan a major destination center for
make a longer-term commitment to
includes a 1,600-square-foot, state-
cardiovascular research and innovation,
doing business in this region,” explains
of-the-art hybrid operating room
and for the commercialization of new
Robert Safian, MD, Beaumont CIRC
for procedures that blend minimally
cardiovascular devices and therapies.
director and a Harvard-trained,
invasive heart surgeries with procedures
world-renowned cardiologist.
performed through catheters, for
treating structural heart disease.
CIRC is helping to make southeast
So, the economic health of the
region and state benefits as well.
Unlike other innovation centers,
The unique components of CIRC include: • A one-of-a-kind, 950-square-foot
Adjacent to the hybrid operating suite
CIRC is designed to interact with
Bio Skills Lab for hands-on
is a large, elevated observation room
inventors, medical device startup
training for physicians in the
where physicians and trainees can view
companies, and large medical device
use of new, advanced
procedures in real-time, and a classroom
corporations at all stages of device
cardiovascular medical
where training courses can be broadcast
development leading up to approval
technologies. The lab includes
to locations around the world.
and market release. This includes
16 plug-and-play stations for hands-on device manipulation. 11
BioMatters | Spring/Summer 2014
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 physiciansin-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 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.
Most commercialization centers
alone brought in revenue close to
typically lead medical startup
$1 billion. Revenue projections for
companies to the point of acquisition
2015 are just over $3 billion and in
by a larger medical device company,
2020 are projected to reach $9 billion.
usually just prior to first-in-man
Beaumont is positioning CIRC to be a
studies. Of the 65 innovation centers
leading driver for this market.
in the nation, none are exactly like
CIRC, which leads companies through
solidify Beaumont’s world-wide
the entire commercialization process.
reputation as a destination center for
cardiovascular treatment firsts, and as a
Any inventors, physicians, medical
At the same time, CIRC helps to
institutions, hospitals, academic
leader in medical training and education.
institutions, medical device companies,
This in turn, attracts cardiovascular
or government entities can use CIRC.
medicine’s best and brightest physicians
and researchers to Beaumont.
Dr. Safian says the response of
medical device companies to CIRC’s
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
comprehensive approach has been
southeast Michigan’s economy while
uniformly positive. Major device
providing hope to patients suffering
industry leaders such as Boston
from cardiovascular conditions that
Scientific, Abbott, St. Jude Medical,
are beyond conventional treatments.”
Medtronic, Kona, and InfraRedX have
committed to use the services of CIRC
To learn more about CIRC, including
ways to support the program through
to commercialize devices for valve
philanthropy, call 248.898.4176.
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
MichBio | www.michbio.org
ROBERT SAFIAN
12
CAYMAN CHEMICAL
The Evolution
of Ann Arbor’s Cayman Chemical
Adam Uzieblo speaks with a thick
By the early 2000s, Cayman
Polish accent and has a bristling gray
recognized the need to move beyond
crew-cut. An accomplished medicinal
its bioactive lipid brand and develop
chemist, he is also a survivor. He
new product lines to sustain the growth
endured years of separation from his
of the company. Cayman invested
wife and young son when he fled to
heavily in new facilities and personnel,
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
ADAM UZIEBLO AT THE LAB BENCH SYNTHESIZING AN EICOSANOID.
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
Cayman Islands. This was the starting
taking advantage of the closure of
from a brightly lit synthetic chemistry
material that led to the establishment
the Pfizer research facility in Ann
laboratory that is part of Cayman’s
of Cayman Chemical. Cayman
Arbor to hire experienced medicinal
4-building, 14-acre, 170,000 ft2 campus
developed an extensive product
chemists. Cayman’s Chemistry division
in Ann Arbor, MI. He and Andrei Kornilov,
line focused on its signature brand,
capitalized on its experience with
another scientific ex-patriot from
rapidly becoming the industry leader
endogenous cannabinoids to begin
Eastern Europe, discovered a series of
in the production and distribution
manufacturing an extensive line of
compounds that can help to grow new
of bioactive lipid reagents. Cayman
market-leading reference standards
human bone. This discovery added a
chemists synthesized an extensive array
that forensics scientists use in the fight
second new drug development project
of bioactive lipid products including
against illegal, designer drugs of abuse,
to Cayman’s portfolio, which at this time
numerous eicosanoids (prostaglandins,
including synthetic cannabinoids (K2,
includes a novel set of prostaglandin
leukotrienes, and thromboxanes),
Spice, etc.). The analytical chemistry
inhibitors that show promise in treating
inositol phosphates, cannabinoids, and
group achieved ISO certification for its
muscular dystrophy and some features
steroids. At the same time, Cayman
mass spectrometry services, ensuring
of asthma and inflammation.
biochemists developed the antibodies
its customers receive the highest
and immunoassays used to detect the
quality in analytical service. As it grew,
BUILDING ON THE PAST
various bioactive lipids in cell culture
Cayman expanded internationally,
medium, serum, and plasma. Cayman
opening large-scale chemical synthesis
grams of prostaglandin A2 from
grew to $10 million in catalog sales and
facilities in Prague (Czech Republic)
an eight-pound sample of coral he
100 employees in its Ann Arbor research
and Tallin (Estonia).
harvested while scuba diving in the
facilities by the mid-1990s.
In 1981, Kirk Maxey isolated 30
13
BioMatters | Spring/Summer 2014
DISCOVERING THE FUTURE
Cayman’s Biochemistry
division also evolved beyond
In March of 2014, Cayman
the generation of lipid function
took the next step in the
assays and ELISA kits to add
evolution of a complete drug
recombinant protein cloning
discovery organization by
and expression, monoclonal antibody production, cell-based
ADAM UZIEBLO
officially naming two of its
KIRK MAXEY
scientists, Stephen Barrett and
assays, and protein structure/
analytical standards for sale in the
Jim Mobley, to the new positions of
x-ray crystallization. It developed an
catalog or by contributing to a large-
Director of Drug Discovery Chemistry
impressive array of proteins and high-
scale cGMP/API manufacturing contract.
and Director of Drug Discovery Biology,
throughput screening assays that are
An analytical chemist might be asked
respectively. With this organizational
used in epigenetics research, making
to perform a LC/MS analysis of drug
structure in place, Cayman is poised to
Cayman a major player in this area.
levels in the plasma of dosed mice on
perform all aspects of drug discovery,
The Cayman Biochemistry division grew
Monday and spend the rest of the week
including selection of a therapeutic
from 20 employees (one PhD) in the
performing quality analysis of forensics
area and drugable biological target,
mid-1990s to 55 employees, including
standards. A cell biologist might take
lead discovery chemistry, lead
12 PhD scientists, by 2012.
a day or two per month testing the
optimization, structure-based drug
Cayman had gathered the skills,
activity of Cayman Drug Discovery
design, in vitro screening, and in
capabilities, and facilities necessary to
compounds for receptor binding on
vivo efficacy testing. As the scope
undertake a legitimate drug discovery
cells in vitro and use the remainder of
of Cayman’s drug discovery effort
effort. Entry into the biopharmaceutical
the month to develop a new cell-based
expands, so will its funding options,
realm advanced Cayman beyond catalog
assay kit for catalog sale.
including writing SBIR grants, forming
sales and contract services and into the
strategic partnerships with biotech
risky but potentially more lucrative area
discovery makes Cayman unique in
and pharmaceutical organizations, and
of discovering novel small-molecule
all of Michigan. It’s efficient and
securing venture capital to support
therapies.
economical, making the maximum
late-stage development efforts. Just as
use of the skills and time of Cayman’s
Cayman grew from its modest start in
biotechnology companies, the
scientists. Not only does this method
a basement in 1981, its Drug Discovery
challenge to build a successful drug
provide revenue-producing jobs to do
division will grow to play a significant
discovery program from scratch would
when not actively involved in drug
role in Cayman’s ongoing efforts to
necessitate obtaining vast amounts of
discovery, it produces a pipeline of
advance human and animal health and
venture capital or grant funding to rent
innovative catalog products.
help make research possible.
lab space, purchase equipment and
supplies, and pay salaries — startups
discovery project took advantage of its
Chemical can be found on our website
can burn through millions of dollars
knowledge of the product that launched
www.caymanchem.com or by calling
per year this way. Cayman had the
the company, prostaglandin A2. Cayman
800.364.9897.
resources to fund its burgeoning drug
was contacted by the New London,
discovery program by relying on the
Connecticut-based biotech company
ongoing financial success of its catalog
Myometrics, LLC for the discovery and
business. To ensure its continued
development of small molecule agonists
success, Cayman created a unique
of the EP4 receptor, one of the four
system in which every Cayman scientist
cellular receptors of the multifunctional
involved in drug discovery, like Adam
prostaglandin PGE2. EP4 agonists have
and Andrei, also contributed to the
several functions described in scientific
manufacture and development of
literature, including promoting new
catalog products and to the fulfillment
bone growth, anti-inflammatory
of custom products and services.
activities, and effects on blood
pressure. Myometrics wanted to use
For most of Michigan’s fledgling
While the medicinal chemists are
This method of financing drug
It’s fitting that Cayman’s initial drug
developing novel, patentable chemicals
them in therapeutic conditions where
for Cayman Drug Discovery, they
new bone growth was required, such as
offset their overhead by synthesizing
spinal fusion surgery or the promotion
new inhibitors, lipid mediators, and
of bone fracture repair. IND filing is expected in 2015.
MichBio | www.michbio.org
14
More information about Cayman
DR. LEVI BLAZER AND DR. DAN BOCHAR DISCUSS THE RESULTS OF A HIGH THROUGHPUT SCREENING ASSAY.
DETROIT R&D
BREAST CANCER TISSUE LABELED WITH DETROIT R&D ANTIBODIES THAT RECOGNIZE A SPECIFIC MODIFIED PROTEIN.
Novel Diagnostics and Drug-Screening Tools
Founded in 1997 by Dr. Hyesook
Unfortunately, the cause of
Kim, Detroit R&D has been steadily
hypertension is presently unknown in
establishing itself as a worldwide source
about 90 percent of reported cases.
for novel diagnostic and drug-screening
Currently, reducing blood pressure
products. The Detroit R&D laboratories
in hypertensive patients is served by a number of different drugs such as
and offices are located inside the newly renamed Block at Cass Park Building on
and tissue. Hypertension affects nearly
calcium blockers and ACE inhibitors, just
Second Avenue in the heart of a new
50 million individuals in the USA and
to name a few. These varied approaches
redevelopment district in the city of
about 1 billion people worldwide, and is
to treating hypertension illustrate the
Detroit, Michigan. The historic building
an under-diagnosed condition because
difficulty of finding a single drug that
(formerly the Metropolitan Center for
the underlying damage to the body
effectively lowers blood pressure.
High Technology) is already the home
occurs with only mild or no symptoms.
With over 75 different medications in
of many small businesses and has ample
In 2009, heart disease and stroke
several different categories, physicians
laboratory space to attract additional
accounted for 27,794 deaths in the
are often faced with a bewildering set
small biotech and start-up companies.
state of Michigan (MDCH statistics) and
of treatment options, resulting in a
hypertension during pregnancy is one
‘roulette wheel’ approach to patient
to develop an easy and inexpensive
of the major risk factors in pregnancy-
care. The ability to measure a biomarker
hypertension kit for measuring novel
related mortality.
of hypertension, as can be accomplished
The company’s original project was
with the kits developed at Detroit R&D,
fatty acid biomarkers in blood, urine,
would be advantageous in several ways:
15
BioMatters | Spring/Summer 2014
• It could serve as an early prediction
Now 10 years later, Detroit R&D
markets nearly 100 products directly or
study, Detroit R&D produced antibodies
pressure and associated
through more than twenty distributors
that recognize important proteins with
cardiovascular events including
to customers in the U.S. and worldwide.
very specific sugar groups attached to their protein backbone. Detection of
stroke, and this prediction would have enormous value in the
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.
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
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
2030. According to the Michigan
worldwide. During a recent NCI SBIR
of the onset of elevated blood
Department of Community Health,
In addition to hypertension kits, the
cell death as compared to non-cancerous
high blood pressure costs in Michigan
company portfolio includes kits for
cells. In addition, the company has a
were estimated at $1.5 billion
measuring biomarkers of diabetes,
pending patent disclosing a method to
in 2007, so choosing the correct
prostate cancer, septic shock, oxidative
screen synthetic and natural anti-cancer
medication earlier would lower the
stress, and environmental contaminants.
drug candidates using antibodies for
chance of developing cardiovascular
Several of the technologies developed
these modified proteins.
diseases and could result in
at Detroit R&D have been patented
substantial cost savings.
(7 issued and 6 pending patents),
developing innovative technologies
mainly as the result of research and
to help researchers understand the
monitor the effectiveness of drug
development supported by 17 National
underlying causes of many worldwide
candidates undergoing pre-clinical
Institutes of Health (NIH) Small Business
health problems. This company has
and clinical trials and possibly
Innovative Research (SBIR) grants
the talent, insight, and drive to grow
could be used to develop a new
awarded to Detroit R&D (>$9 million in
substantially and is poised to expand
• It would also provide a tool to
In summary, Detroit R&D is
anti-hypertensive therapy. Thus FREE + GLUCURONIDATED 14,15-DHET (NG/MG CREATININE)
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
140
**
120 100 80 60 40 20
HYPERTENSIVE Preeclamptic n=7 ** Significantly different
NORMOTENSIVE Healthy n=9
RESULTS OF A STUDY OF HYPERTENSION IN PREGNANT WOMEN USING DETROIT R&D HYPERTENSION KIT.
of these biomarker levels may
total). Currently, Detroit R&D is working
into the clinical and therapeutic
be detected before noticeable
on two Phase I and Phase II National
markets. Detroit R&D welcomes
elevations in blood pressure.
Cancer Institute (NCI) SBIR awards.
collaborations and licensing inquiries.
The company is now exploring
even simpler and faster dip-stick
cancer diagnostic products has recently
Detroit R&D visit their website at
techniques to measure this
become a major focus of research
www.detroitrandd.com or call
biomarker under non-laboratory
and development for Detroit R&D,
313.961.1606.
conditions.
and it is attracting outside attention
MichBio | www.michbio.org
Developing new and innovative
16
For more information about
EVERIST HEALTH
ANGIODEFENDER
Local Michigan Suppliers Help Develop World Markets
at risk for developing heart disease and
Not so long ago, Michigan-based
Everist Health was working with
vascular dementia. The device is low
suppliers from all over the United
cost, non-invasive, and simple to use.
States—manufacturers in California and
The AngioDefender measures the fitness
India, web designers and public relations
of the endothelial cells that line the
companies based in New York, and
arteries of the body. These cells produce nitric oxide that instructs the arteries
attorneys in California. Today, virtually
to expand and contract to allow blood
all of the medical device company’s
partners are within a short drive of
supplies locally, they are seeing plenty
to flow to every organ of the body as
Everist Health’s Ann Arbor headquarters.
of opportunity to sell around the
needed.
This includes Detroit-based attorneys
world. “At the moment, we have zero
Dykema, Ann Arbor-based web designers
business in the United States because
which can be used with the Everist
Stone Interactive, and Canton-based
we are still going through the process
Vascular Age Calculator to determine
manufacturer Miller Technical Services.
of FDA trials,” explains Matt, “however,
the vascular age of the individual. “You
we have regulatory approval to sell
may be 45 but have a vascular age of
to us because we had worked with
the technology in other markets, and
35 or 65,” explains Matt. “If your heart
them in previous ventures,” explains
our devices are in over 30 locations
age is older than it should be, there are
Chief Operating Officer Matt Bartlam,
worldwide —India, Middle East, Europe,
many things you can do to improve your
“however, over time we have found that
and Canada.”
vascular health such as quitting smoking,
we could access almost every service
improving your diet and exercise, lower
we needed locally, and the quality of
the AngioDefender, deals with core
stress, and improving sleep patterns.
service from our local suppliers has been
health problems such as diagnosing,
In certain cases where individuals have
cost effective and outstanding.”
as early as possible while there is still
a family history of heart problems,
time to take remedial action, people
medication may be prescribed.”
“Many of our original suppliers came
While the company is sourcing
Everist Health’s device, known as
17
The AngioDefender produces a score
BioMatters | Spring/Summer 2014
“Heart disease is the number one
doctors using AngioDefender as part
killer in the western world,” says Matt.
of wellness programs. Corporations
Health can be found on our website
“At the same time, dementia is reaching
are also using the AngioDefender to
www.everisthealth.com or by calling
crisis proportions. For example, in the
encourage employees who are engaged
855.383.7478.
UK, an estimated 800,000 people suffer
in sedentary work to adopt healthy
from dementia and that number is
living habits. A major rehabilitation
expected to grow to 1.6 million by 2030.
heart center in Canada is planning to
PREDICT & PROTECT EARLY Y-STAGE STAGE
MID STAGE MID-STAGE
TM
LATE-STAGE LATE STAGE
INCREASING VASCULAR AGE Cardiovascular risk factors
Plaque formation Calcium build-up
Result in: Lower %FMD
Result in: V Vessel l stiffening tiff i and narrowing
Blood clots form Eventual blockage Res in: Result Che est pain Chest Hea art attack Heart Stro oke Stroke
HE HEALTHY EALTHY THY Y ENDOTHELIUM EN NDOTH TH HELIUM
DAMAGED ENDOTHELIUM
Currently, one in four hospital beds in the
use AngioDefender to show recovering
UK are occupied by dementia patients.
patients the value of increased exercise,
Therefore, the market for technology like
and in the United Kingdom, a pharmacy
AngioDefender that helps predict people
chain plans to offer AngioDefender
at risk, is potentially huge.”
testing, along with other tests, to
measure blood pressure and cholesterol.
Health experts around the world
recognize that this made-in-Michigan
In India, a major inflammatory disease
technology is a genuine innovation that
clinic is using AngioDefender to test
can lower healthcare costs and improve
patients because for example, people
the health of populations by providing
with rheumatoid arthritis have a 50%
early warning of disease risk to permit
higher risk of developing heart problems
people to take action before they suffer
than the rest of the population.
a potentially fatal heart attack or
develop irreversible vascular dementia.
application for diagnosing people who
have no obvious heart health symptoms
The UK National Health Service
The AngioDefender may also have
was sufficiently impressed with the
such as fit young men and women.
technology to invite Everist to exhibit
at its National Health Innovation
for this predictive test,” says Matt,
Conference, and the AngioDefender
“it is worth noting that our company
has also been featured at a national
has received financial support from
cardiology conference in Bangalore,
the Michigan Economic Development
India, and at the Arab Health Congress.
Corporation (MEDC). The company is
Researchers in London, Ontario,
aiming to obtain FDA approval to market
Canada are beginning trials this spring.
the device in the United States within
the next year. The support of the MEDC,
Everist Health believes the
“We see a major world market
AngioDefender will appeal to a wide
together with our other investors may
range of health outlets beyond just
well create a large number of jobs for
hospitals which are set up to deal with
local suppliers and manufacturers for a
problems after they have occurred.
device that will be made in Michigan and
Everist Health already has primary care
sold around the world.”
MichBio | www.michbio.org
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
DYSFUNCTIONAL DYSF FUNCT TIONAL L ENDOTHELIUM ENDO OTHEL L LIUM
© 2014 EVERIST HEALTH. ALL RIGHTS RESERVED.
More information about Everist
18
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
GRAMEDICA
A Life-Changing Device Company Transformed By Karen M. Sandlin and Jean Stroster
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
HYPROCURE® SURGEON TRAINING AT CLEMI LABS IN BOGOTÁ, COLOMBIA
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
40 countries, including in Africa, Asia, Europe, and Latin America.
to pain and damage not only to the ankle and feet, but to the knees
GraMedica’s team of employees enjoys knowing that the work they
and hips. Unhappy with the results of previously available products
do improves the quality of life for people everywhere. In December
intended to treat the condition, Dr. Graham invented HyProCure
2013, GraMedica announced the selection of Dr. Anthony Weinert,
®
a renowned foot surgeon with offices in Troy and
specifically to improve treatment outcomes.
Warren, Michigan, as the first Michigan HyProCure®
A recent study by N. Shibuya et al in the Journal
of Foot & Ankle Surgery showed that 18 percent of its
Center of Excellence. And in early in 2014, Al Seef
study patients had a functional flatfoot deformity, a
Hospital, Kuwait was announced as the first Middle
common symptom of misaligned feet. Foot and ankle
East HyProCure® International Center of Excellence.
surgeons estimate that 10 to 30 percent of the general
The Center of Excellence designation recognizes
public suffers from this same congenital deformity and
expert physicians, medical groups, and healthcare
the related secondary effects. The brief HyProCure procedure, typically
centers accomplished at performing HyProCure® Extra-Osseous
only 20-minutes long, permanently corrects foot and ankle alignment with
TaloTarsal Stabilization (EOTTS) procedures and providing consummate
life-changing results. For example, a child who was not able to walk is now
post-operative care.
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.
International Implant Institute® (GIII) is committed to research,
®
HyProCure works by preventing excessive pronation of the ankle’s ®
GraMedica’s sister educational organization, the Graham
training, certification, and support on implantology for foot surgeons
subtalar joint. During a minimally invasive procedure at a hospital, surgery
worldwide. Recently, GIII and GraMedica sponsored a minimally
center, or physician’s office, the stent is placed in a naturally occurring
invasive foot and ankle surgery symposium in Bogotá, Colombia.
space in the ankle. The stent stabilizes the ankle bone on the heel bone,
Forty surgeons from seven countries were trained to identify and treat
eliminating excessive internal pressures and inward rolling of the foot —
patients with flexible flat foot using HyProCure®. GIII and GraMedica
while enabling full, normal range of foot motion.
are expected to continue this training in North
HyProCure ’s patented design and medical-grade
America, Asia, Europe, and the Middle East in 2014.
®
titanium make it a permanent solution with a unique
In addition to HyProCure®, GraMedica is
classification that outperforms older implants that
currently developing additional high-quality,
tried to accomplish the same thing.
innovative product lines to support their mission
of “changing lives, one step at a time.” To learn
While still a small company of less than 20
employees, GraMedica has become recognized for
more about HyProCure® and other GraMedica
its innovation in foot care solutions. Almost ten
products, visit the company’s website at
years after receiving its first product clearance
www.GraMedica.com. Additional requests for
to market, GraMedica has grown dynamically
information can be made by calling GraMedica’s
and now has products available in more than
office at 586.677.9600.
MICHAEL E. GRAHAM
BioMatters | Spring/Summer 2014
IN2BEING
Where Innovation Meets Reality
Lessons learned in the start-up
minimal learning curve requirement for
trenches are invaluable. Founded in
user acceptance? How will the device be
2010, in2being brings this knowledge and
regulated?
experience to emerging medical and life-
science device companies. Gene Parunak
classification is the starting point for
and Aaron Kehrer, veterans of HandyLab
determining the level of regulatory
and Accuri Cytometers, lead the nine-
For clinical applications, device
control, the process of marketing
person, Saline-based medical device
that will be used in a regulated clinical
approval or clearance, and the data
design and development firm.
setting as opposed to a research setting.
required to submit a marketing
application to the FDA.
The process of visioning describes a
IF YOU DREAM IT
product concept 2-5 years in the future
after successful market placement. The
typically requires identification of a
development is a custom-tailored
exercise clarifies the “product story,”
predicate device and demonstration of
process, not a simple check list. Product
consolidates stake holders’ visions, and
substantial equivalence. Alternately,
dreams can become reality once a
defines device requirements in terms of
if the application is accepted by the
company’s unique path is understood and
user groups, their unique interactions
FDA as a 510(k) de novo submission,
implemented. Upfront visioning exercises
with the device and implementation
substantial equivalence does not apply,
play an invaluable role in determining a
environments.
but significant compliance effort remains.
product’s individual pathway.
Seemingly innocuous class I devices,
for use only in a controlled laboratory
often exempt from the 510(k) process,
in design requirements, visioning helps
setting or also in field applications
are nevertheless often subject to Good
define the product pathway at an early
that require additional durability? Is
Manufacturing Practices (GMP).
stage. This is critical since documentation
the device replacing a traditionally-
requirements vary greatly for a device
accepted product and procedure in
selection of the correct standards,
the marketplace, in turn mandating a
which must be designed to and tested
Medical device design and
Based on user input, and resulting
For example, is the product intended
A 510(k) filing for a Class II device
Understanding the device uses allows
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.
MichBio | www.michbio.org
20
THE FOUR FORCES
simple products can be broken
down into value-add testbeds.
Many great products never
make it to market because of
unbalanced, competing forces.
a conceptual design, a drawing or
A compass rose helps visualize
3D print, to show potential users
these forces, which must be
for product-definition confirmation.
kept in alignment for successful
Or to prove at a rough level that
development.
a concept is likely to work, finite
element analysis, modeling of
The four primary forces
A testbed can be as simple as
for medical device design and
products and systems in a virtual
development are (1) the regulatory
environment, can be performed.
process, (2) the technical
development possibilities, (3) the
fused deposition modeling (FDM),
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.
A COMPASS ROSE HELPS VISUALIZE COMPETING FORCES, WHICH MUST BE KEPT IN ALIGNMENT FOR SUCCESSFUL DEVELOPMENT.
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
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.
The amount of novel technology
built into a product can negatively
TESTBED EXAMPLES
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
Rapid prototyping, using
Conceptual designs, sample BOMs,
and other testbeds allow better decisionmaking to take place earlier in the design process (see table at right).
SOME VIRTUAL TESTBEDS
SOME PHYSICAL TESTBEDS
FEA (Finite Element Analysis) • Fluids • Mechanics • Dynamics • Heat • Magnetic Flux • Reactions • ESF (Electrostatic Force) • Auditory
Subsystems (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
Other Virtual Simulation • Electrical • Movement Path • Optical • Sensor Networks
21
BioMatters | Spring/Summer 2014
In the Trenches with DeNovo Sciences
A growing body of scientific research supports that cancerous tumors
The development process should be
focused on solving the technical hurdles before manufacturing. Starting the acceleration process too early leads,
release cells into the blood stream, at levels that are nearly undetectable.
inevitably, to product failure and is
DeNovo Sciences has developed a microfluidic-based system for enrichment
usually accompanied by an increase in
and molecular characterization of these rare circulating tumor cells (CTC)
the burn rate as the company attempts
from whole blood. Primary clinical benefits include the early detection of
to compensate for the mishap.
metastasis, and the generation of molecular information on the cancer for
therapy selection and assessment.
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
Developing a cutting-edge platform, composed of hardware, software,
they should not be issues that violate
reagents and kits, is challenging from a resource point of view, especially
the core product assumptions.
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
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.
biochemists. The company’s development strategy was to utilize their internal
personnel for the portions of the platform that required daily interaction
the design should be driven to a
between the biochemists and engineers, and to outsource the development
point where it works within the
of the imaging module, a more-defined project, to in2being.
expected outputs. Continually trying
During the development process,
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 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.
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
“We try to do immensely difficult tasks at DeNovo Sciences. In a little over two
is required. Careful planning defines
years, we have developed the first version of our platform and will begin launching
the user groups and implementation
it this spring,” commented Dr. Kalyan “Handy” Handique, DeNovo’s CEO.
environments, balances the four forces,
and establishes the design pathway
“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.”
MichBio | www.michbio.org
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.
JB ASHTIN GROUP, INC
Helping Clients Publish and Publicize Medical Research By Lori J. Bainbridge
Are you surrounded by a mound
Dr. Bradley states that, “Scientific
of unpublished data and suffering
writing and content development
from writer’s block? The pressure
are services we provide, but these
to publish clinical trial results can
services come bundled with our deep
feel overwhelming and often induces
understanding of the regulatory
anxiety in clinical development teams
environment, a thorough knowledge
across the pharmaceutical/biotech
of best publication practices, and the
industries. Compounding this angst
strategic awareness to know where and
is the need for companies to meet
how best to communicate our clients’
FDA-mandated timetables, which can
trial information.”
add to the pressure, especially for smaller companies that may lack the
5 Fundamental Tips for Getting Science Published Select your target journal carefully. Determine: N N N N
Are you reporting significant or novel results? Who is your target audience? Where are the best papers in your field being published? What factors are important to you? Consider: Journal reputation/impact factor, circulation, visibility, speed of handling/publication, publication costs, subscription/open access
After you’ve identified your journal and before you write:
experience and resources to navigate
N Read the journal’s Instructions for Authors very carefully: Highlight important aspects Know the journal’s policy requirements N Collect your paperwork early – all necessary signatures,
the publishing process.
N Handle all ethical issues. Request guidance when
copyright permissions, ethics committee approvals, etc necessary
The JB Ashtin Group, Inc.
Determine authorship
(JB Ashtin) is a local scientific The rules that govern all aspects of
N Agree on who is the primary author, corresponding
communications agency that supports
biopharmaceutical, medical device, and
the pharmaceutical/biotech industries
medical diagnostic companies with the
are growing increasingly complex. The
strategic dissemination of clinical trial
same level of scrutiny and oversight that
results. “Fifteen years ago, I started
governs the clinical trial process extends
my company because I enjoyed working
into the dissemination of results.
Prepare the manuscript
with pharmaceutical clients and being
N Ensure your manuscript is complete, well written,
able to use my medical writing and drug
evolving regulations, JB Ashtin
information background. What started
encourages employees to join
as a small consulting business grew into
professional organizations. ISMPP
a full-service communications company
offers a Certified Medical Publication
with the goal of being an extension of
Professional (CMPP) credential, which
biopharma teams,” says Joan Bradley,
indicates an individual has advanced
N Always be courteous and professional. Reviewers
PharmD, who is president and CEO of
proficiency in good publication practices
N Share any new or relevant information you may have
the Plymouth, Michigan-based agency.
and a commitment to ethical and
To stay at the forefront of these
23
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 listed N Follow International Committee of Medical Journal Editors (ICMJE [Vancouver]) guidelines N Keep an accurate record of who did what during the study
well presented, and organized according to the journal’s requirements
N Ensure that all figures are of good quality to publish N Prepare a detailed, well-written cover letter for
submission to the journal of your choice
N Know how, where, and when to submit
Manage the review process N Respond quickly to all communications/requests by
reviewers and editors are people, too
© 2014 THE JB ASHTIN GROUP, INC.
BioMatters | Spring/Summer 2014
Supporting Local Pharma is a Source of Pride
transparent data dissemination standards. Most JB Ashtin writers have this certification, or are pursuing it.
Several local companies have discovered the advantages of
While no two clients are alike, all the companies
JB Ashtin support have one thing in common: the necessity to
partnering with a scientific communications agency. “Typically
communicate scientific information and the desire to improve
our clients have a diverse set of responsibilities within their
the health of patients. “We work with companies at all
organizations and are often pulled in many directions. When you
phases of drug development,” explains executive director of
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
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.”
consultants and contractors with specific levels of expertise to help
us get things done,” reports Marianne Andreach, vice president,
companies to their growing client roster, including Rockwell
strategic marketing and product planning at Esperion Therapeutics.
Medical (Wixom) and Esperion Therapeutics (Plymouth).
“We realized that we needed an experienced team to support our
“The ability to help companies in our own backyard gives 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
Recently, JB Ashtin added several Michigan-based
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
Medical and oversees the clinical development and FDA regulatory
few staff members even serve as adjunct faculty for the
process for Rockwell. “I’ve had the pleasure of working with the JB
University of Michigan College of Pharmacy.
Ashtin team now and when I was with a previous company. Their
professional and objective approach to the publications process has
industry events and offer advice on publication strategies.
Frequently, Dr. Bradley and her team are invited to speak at
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.
JB Ashtin Hires Homegrown Talent JB Ashtin regularly has local pharmacy students who spend a drug information SHELLY ASIALA 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 cstone@jbasthin.com.
MPI RESEARCH
MPI RESEARCH BIOANALYTICAL AND ANALYTICAL GYROLAB SOLUTIONS.
Taking the Forward View:
ADVANCING BIOANALYTICAL TESTING By Roger Hayes, PhD
glove collaboration. Ensuring well-
The marketplace today has very high
expectations for their analyses that are
designed, well-validated, and precise
delivered with the highest of quality
analytical methodologies is central to
and at a low cost.
that commitment and critical to data
integrity.
Fortunately, that limitation is being
challenged in the life sciences realm.
CROs that offer robust solutions
As researchers develop increasingly
possess the following core competencies: • Preclinical and clinical bioanalytical
complex and potent new compounds, the ability to analyze them quickly,
COMPREHENSIVE SERVICE
capabilities using LC-MS/MS for
accurately, and cost effectively is
small molecules, peptides, and
keeping pace, thanks to innovative
quantity of a drug or metabolite in a
proteins and immunochemistry
technologies and processes in
biological sample, i.e., blood, serum,
expertise for the bioanalysis of
bioanalytical testing.
plasma, urine, tissue, or skin. Using
MPI Research, a clinical research
Bioanalytical testing determines the
a wide array of tools, these tests are
protein therapeutics • Dose formulation and analysis for early drug development studies
organization (CRO) headquartered in
applied to both small molecules and
Mattawan, Michigan, has conducted
biopharmaceuticals under GLP (Good
thousands of drug safety, discovery,
Laboratory Practices) requirements.
services is the ever-rising standard
surgery, medical device evaluation,
of quality. Facilities, equipment,
bioanalytical, and analytical studies.
companies are outsourcing bioanalytical
methods, practices, and records must
Skilled scientists in a large-capacity,
testing to CROs. The right partner
meet— and exceed where possible — the
state-of-the-art laboratory perform a
can deliver quality results under tight
requirements of regulatory authorities
range of analytical services that meet
timeframes, thus allowing sponsors
and, in the case of CROs, also those of
specialized needs in pharmaceutical,
to make key decisions on candidate
the sponsor. Likewise, compliance with
chemical, and environmental science.
drugs earlier in development. A
study protocols and standard operating
At the same time, the team is always
successful enterprise means providing
procedures is not just a measure of
on the lookout for new and better ways
scientific expertise and hand-in-
success, but an expectation throughout
Increasingly, pharmaceutical
Beyond providing a full slate of
the life sciences realm.
to assess the medicines of tomorrow.
25
BioMatters | Spring/Summer 2014
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 MPI RESEARCH BIOANALYTICAL AND ANALYTICAL LABORATORY SOLUTIONS.
challenges of their own, managing the bottom line of drug development makes looking for improved approaches to
CONSTANT EVALUATION
safe, the bar continues to rise. This
The complexity of new chemical
is especially true for rising dose trials
entities presents significant challenges
and first-to-file generic drugs, where
to developing and validating
clinical bioanalysis requires high-
bioanalytical methods. Testing
throughput with rapid turnaround of
capabilities—whether in-house
results. Chemists turn to automated
or through a CRO—need constant
liquid handlers to achieve productivity
evaluation and improvement. In taking
on the order of 1,500 to 2,000 samples
this forward view, MPI Research focuses
per day. This strengthens evaluation of
on five essential actions:
safety and shrinks timelines—especially
Investing in equipment to improve
helpful for Clinical Summary Reports in
capabilities. As drug potency increases,
first-to-file opportunities.
the ability to determine the level
of analyte in a sample challenges
platform. The standard approach
the limits of instrument sensitivity.
isn’t always the best. LC-MS/MS is
Fortunately, new and more sensitive
the go-to platform for conventional
instrument platforms are available,
small molecules, but as new classes
including ultra-high performance liquid
are defined, other analytical tools
chromatography (UHPLC) interfaced
may prove to be a better option. In
with modern liquid chromatography
addition to LC-MS/MS, the bioanalytical
tandem mass spectrometry (LC-MS/MS).
team at MPI Research employs gas
Using the most appropriate
Looking at new technologies.
chromatography-mass spectrometry
Many laboratories and CROs still use
(GC-MS/MS) and inductively coupled
conventional ELISA (enzyme linked
plasma-mass spectrometry (ICP-MS).
immunosorbent assay) methods for
In short, it’s about using the right tool
immunoassay analysis. While 96-well
for the right job.
plate ELISA has its place, it’s being
challenged by new platforms, such as the
regulatory challenges. Reporting
Gyrolab workstation and its CD format
analytical data reliably is at the core of
that can conduct immunoassays using
any successful bioanalytical operation.
only nanoliters of sample. These systems
Laboratories that perform regulated
are highly automated and offer a wider
analysis are routinely inspected
analytical range, meaning faster analysis,
by worldwide regulatory agencies.
higher efficiency, and lower costs.
Each country’s authority has its own
Staying abreast of bioanalytical
Assessing the impact of rising
requirements for method validation
dose trials on patient safety. When
and how methods are applied. These
it comes to ensuring a medicine is
requirements change regularly, so it’s
MichBio | www.michbio.org
26
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.
c S e Lif
F
ROGER HAYES
c n ie
c o
e
. s u
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
We understand your risks and unique issues!
Research continues to deliver solutions quickly, cost effectively, and with the highest quality.
At Hylant, our experienced advisors specialize in Life Science organizations so you can collaborate with a team who understands your business and bottom line.
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
hylant.com
biopharmaceutical, medical device, animal health, and chemical industries with discovery research and
24 Frank Lloyd Wright Drive, Suite J4100 | Ann Arbor, MI 48105 | P 734-741-0044 Medical Devices | Clinical Research | Clinical Trials | Pharmaceuticals Biotechnology | Product and Technology Development
preclinical development services. www.mpiresearch.com
GO BEYOND Beyond Expectations. 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 scientific expertise can influence all phases to bring safer drugs to market faster and more efficiently. With broad therapeutic coverage and a deep understanding of market forces that affect Sponsors, we share knowledge that’s beyond data to make a real difference in healthcare.
Terumo Cardiovascular Group and Terumo Heart, Inc., are Proud Sponsors of MichBio and Michigan’s Growing Biosciences Industry
For more information, visit www.mpiresearch.com
www.terumo-cvgroup.com | www.terumoheart.com Terumo® is a registered trademark of Terumo Corporation. ©2014 Terumo Cardiovascular Systems Corporation 851541
27
BioMatters | Spring/Summer 2014
USING RUBICON GENOMICS’ LATEST HIGH THROUGHPUT KIT, SCIENTISTS DOMINIQUE WILSON AND MAUREEN CAREY PREPARE DNA LIBRARIES FOR NEXT GENERATION DNA SEQUENCING.
PHOTO: MICROBIOLOGY TECHS
RUBICON GENOMICS
Translating Human Genetics into Real-Time Medicine
Driven by the goal of advancing
part of an assay that helps to detect
the translation of human genetics
chromosomal anomalies and genetic
“lab knowledge” into practical medical
copy variations that may cause birth
applications, University of Michigan
defects, helping medical professionals
Professors John Langmore, PhD and
to select the most predictably viable
Vladimir Makarov, PhD founded Rubicon
embryos for implantation. Rubicon’s
Genomics in May of 2000. The founders
continues to play an important role in
ThruPLEX® technology enables the
were dedicated to supporting the
the company’s growth as more than half
study of fragmented or small pieces
economy of Michigan so there was no
of its current staff has received degrees
of DNA. Currently used for research
hesitation in establishing headquarters
from native universities.
purposes, ThruPLEX supports the study
in Ann Arbor to maintain roots in the
of specific samples such as plasma
community. More than a dozen years
based on its PicoPLEX™ technology, used
that had previously not been possible.
later as Rubicon expands its footprint
worldwide for pre-implantation genetic
This is enabling physicians to monitor
around the globe, the state of Michigan
screening and diagnosis. PicoPLEX is
such events as the treatment of
MichBio | www.michbio.org
Rubicon’s breakthrough product is
28
individual cancer patients while they
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.
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 invitro fertilization, infectious disease testing, and cancer platforms.
But the small company’s story
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
wasn’t always rosy. In late 2009, after
worldwide distribution network, and a
nearly a decade of success, Rubicon
The formation of a growing
was stumbling in the faltering economy.
global presence and network of
2014, Rubicon will move this summer
Dire economic straits gutted the
distributors has helped to fuel
to a fully renovated, 19,000+ square-
organization by November of that year,
Rubicon’s expansion. In back-to-back
foot facility less than a mile from its
leaving only four full-time employees
years Rubicon has participated in the
current location in Pittsfield Township.
in place; all of whom are still part of
Michigan State Trade Export Program
Co-founder and Chief Scientific Officer
the company today. Enter CEO Dr. Jim
(STEP), a program operated by the
Dr. John Langmore has strong feelings
Koziarz and CFO Betsy Long. Regarding
Michigan Economic Development
about keeping the company local,
the decision to take on the struggling
Corporation (MEDC) designed to help
“Rubicon was born in Michigan and
start-up, CEO Jim Koziarz said, “Betsy
small Michigan companies enter the
our roots are deep here. There was
and I looked at the technologies of
global marketplace. This program has
never any consideration of moving the
Rubicon Genomics and saw something
allowed Rubicon to attend international
company out of state and we’re here
worth saving. That’s when we rolled up
tradeshows in Paris and Munich, leading
for the duration.” Learn more about
our sleeves and made a commitment
to the development of key global
Rubicon at rubicongenomics.com or
to bring this company back with new
partnerships and distribution channels.
contact them at 734.677.4845.
plan for a 30% increase in headcount for
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.
PICOPLEX™ DNA-SEQ KIT
29
BioMatters | Spring/Summer 2014
PHOTO: MICROBIOLOGY TECHS
STATE OF MICHIGAN
BLOOD SPOTS ARE TAKEN SHORTLY AFTER DELIVERY FROM NEARLY EVERY INFANT TO PERFORM LIFE-SAVING NEWBORN SCREENING.
BioTrust Leads Nation as Resource for Public Health Research By Carrie Langbo
important role in advancing population
Recognizing the important role of
biorepositories in advancing medical
health research. Through the BioTrust
and public health research, the Michigan
program, we are eager to work
Department of Community Heath (MDCH)
with pioneering researchers while
has joined our state’s drive in biobanking
maintaining a commitment to uphold
expansion by allowing use of residual
the Department’s ethical and privacy
newborn screening blood spot specimens
standards.”
for health research through an innovative
program known as the Michigan
process of examining issues surrounding
BioTrust for Health (BioTrust). Following
blood spot retention and use more than
technological advances and steps to
two decades ago. Michigan’s public
improve preservation, use of residual
health code establishes the foundation
newborn screening blood spot samples
for storage and research use of residual
can make an important contribution to
blood spots, but numerous challenges
current and future research.
initially had to be addressed to ensure
adequate community education and
In 1965 newborn screening (NBS)
MDCH first began the stepwise
support. A legal expert roundtable was
for phenylketonuria marked the advent of what is now a vital public health
public health benefits from newborn
convened and determined that MDCH
program. Blood spots are collected
screening. While many state NBS
served as a trustee or steward having
annually from more than 99.5% of
programs still grapple with development
“qualified ownership” of residual blood
Michigan’s newborns to screen for
of policies regarding residual blood
spots. Multiple methods were also used
over 50 disorders. This has led to the
spot storage and research, Michigan is
to gauge community views and beliefs
identification and treatment of more
at the forefront with implementation
on issues such as individual autonomy
than 5,100 Michigan infants with serious
of the BioTrust. According to Director
versus public benefit, acceptable
disorders through the end of 2012.
James Haveman, “MDCH is optimistic
research guidelines and appropriate
Today, the BioTrust offers additional
that residual blood spots will play an
methods to inform individuals about
MichBio | www.michbio.org
30
participation. A BioTrust Community
making the specimens a vital resource.
Values Advisory Board was convened and
As technology continues to advance
continues to advise MDCH on BioTrust
and investigators become more aware
policies and methods to ensure on-going
of potential applications for blood
and open dialogue surrounding the
spot research, their use will become
often-complex ethical issues raised by
increasingly important. Since 2009,
biobanking endeavors.
Michigan’s blood spots have already
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
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
in over 200 community engagement and educational endeavors since 2010 to
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.
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
NEARLY 2 MILLION SAMPLES ARE STORED AT THE MICHIGAN NEONATAL BIOBANK.
been utilized in over 25 research
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 populationbased sample and provide a unique window for studying prenatal and neonatal environments—
31
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.
BioMatters | Spring/Summer 2014
VERSICOR
Medical Device Technology that Serves the Greater Good
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.
CAD DRAWINGS OF THE LIFT CHAIR THAT WILL BE INSTALLED IN THE SLATTERY HOME.
THE TECHNOLOGY
now wheelchair-bound. Versicor wanted to help the Slattery family
“Versicor works with both new medical device startups and
seasoned companies looking to make their ideas a reality,” says Christie
by working to create a wheelchair accessible home.
Coplen. Its robust hardware platform and model-based software enables
ideas to be transformed into reality. In fact, medical device products
for the family. The home will consist of an open floor plan to
The concept for the home is finding and defining a new “normal”
produced by Versicor are developed four times faster
accommodate the wheel chair, special cook
than traditional methods. Its platform also decreases
tops, pull down cabinets, a therapy pool, and
risk and reduces development cost for customers.
even a lift chair, created by Versicor that will
Versicor offers turnkey design to distribution with
allow Matthew to exercise in the safety of
capabilities ranging from controls development,
his own home. The Versicor team provided
electronics, mobile design and development, data
software development, electrical hardware, and
analytics and validation, and verification. Versicor is ISO 13485 compliant
mechanical components for the lift chair. With extensive materials
and stands with its customer through the FDA process.
research and consumer testing, Versicor translated the design concept
into a fully tested application.
A key element in improving care is expanding the ability to care for
patients outside of the standard hospital footprint. OEM’s and hospitals
By understanding the client’s needs, Versicor successfully converted
will have to begin working with companies that understand systems,
Ed’s idea into reality. The lift chair will be completed and installed in
connectivity, and communications that enable the transition occurring
May and the Slattery home should be completed in the next six months. Continuing its support for the community through technology,
in healthcare while integrating with historical systems. Versicor is providing a solution to this transition. Versicor is not only known for
Versicor is launching Ideas to Action, a nation-wide contest
its impressive services and expertise. The company also makes it its
designed to help medical device, clean-tech, and transportation
mission to serve its local community utilizing the
entrepreneurs transform their project ideas
technology it has available to serve community needs.
into products. Versicor will provide $250,000
SERVING THE COMMUNITY
worth of controls, electronics, and software
development services to contest recipients.
One such need came from Ed Slattery and his
For more information on how Versicor can
family, whose lives dramatically changed two years
help you turn your idea into a reality, visit
ago when a truck driver fell asleep behind the wheel,
www.goversicor.com or call 248.914.5582.
killing wife Susan and disabling son Matthew, who is
CHRISTIE COPLEN
MichBio | www.michbio.org
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BioMatters | Spring/Summer 2014
P.O. Box 130199 Ann Arbor, MI 48113-0199
STAYWITH CONNECTED MICHBIO NEW WEBSITE
LAUNCHED IN MAY www.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 CONFERENCE SEPTEMBER 30OCTOBER 1, 2014 www.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.
www.michbio.org/social-media Keep up to date on the Michigan bioscience industry by subscribing to our e-newsletter, biolink: www.michbio.org/subscribe.