BioMatters - Spring 2014

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

1

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

MichBio | www.michbio.org

2

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

Email

MichBio

info@michbio.org

3

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.