BioMatters - Spring 2014

BioMattersA MichBio Publication Showcasing Michigan’s Biosciences Industry

SPRING/SUMMER 2014

UNIVERSITY OF MICHIGAN

3-D Printing Saves Young Lives

BEAUMONT HEALTH SYSTEM

Cardiovascular Innovation: Good for Health of Patients and Region

DETROIT R&D, INC.

Novel Diagnostics, Drug Screening Tools

IN2BEING

Where Innovation Meets Reality

FEATURED

9 11 15 20

Michigan at Forefront of

Medtech Innovation

From Alpena to Ypsilanti, scientists working at the

nation’s biopharmaceutical companies are currently

researching and developing life saving medicines.

In collaboration with the state’s university medical

schools, science centers, local hospitals and contract

research organizations, nearly 3,500 clinical trials have

been conducted for new prescription drugs. These

have led to remarkable discoveries inspiring hope and

improving the quality of life for patients and their families.

For the people of Michigan, biopharmaceutical research

companies have also been an important source of jobs,

tax revenue and research spending.

A study found that in 2011 the industry supported

nearly 75,000 jobs include life sciences researchers,

management executives, office and administrative

support workers, engineers, architects, computer

and math experts and sales representatives.

We thank the people of Michigan and their communities

for their collaboration, support and kindness. Right now,

nearly 400 tests of new medicines for the six most

debilitating chronic diseases in America is underway

all over the state and they need patient volunteers.

A job engine for Michigan.Life-saving medicines for the world.

BioMatters | Spring/Summer 20141

Together with our customers, we are driven to make healthcare better.

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MichBio | www.michbio.org 2

LET’S WORK TOGETHER TO GROW IDEAS

INTO BUSINESSSUCCESS STORIES.

Marcos Dantus is the MSU Innovation

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A MSU Chemistry Department professor

and prolific inventor, Dantus launched

Biophotonic Solutions, a start-up company

with a successful line of Multiphoton

intrapulse interference phase scan (MIIPS) laser pulse shapers.You might be surprised at what you find at the MSU

Innovation Center: Access to nearly 5,000 researchers, $500 million in annual R&D expenditures, and 642 research and instructional buildings, scale-up facilities, pilot plants and lab space.

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Business-CONNECT links the right people and resources to develop your ideaMSU Technologies offers the best MSU ideas ready for commercial licensingSpartan Innovations creates investment-ready businesses from MSU ideasLearn more today: www.innovation.msu.edu


Welcome to Michigan’s Thriving Biosciences Industry! We are pleased to present the ninth issue of BioMatters™,

the only in-depth publication showcasing the range and vitality

of Michigan’s biosciences industry.

This is a dynamic time in Michigan’s economy, and sharing

information about our state’s health and biosciences industry is critical as we work

to build upon our already significant strengths and define a new future.

Michigan’s bioscience community is vibrant and robust, with strengths and assets

along the continuum—world-renowned academic research, emerging technology,

medical device and diagnostic companies, global pharmaceuticals, mature bio-industry,

and a strong support network. The state’s bioscience entrepreneurial ecosystem is

rapidly evolving and bursting with innovation, growing investment, and superb talent.

As a result, company growth continues unabated and successful exits are becoming

routine.

BioMatters™ helps MichBio fulfill its mission in “driving bio-industry growth” by

educating you about the discoveries, technologies, and products being researched,

developed, and manufactured here in Michigan, and the many resources available to

support those activities. As a whole, the economic impact of Michigan’s bio-industry

is sizeable and its reach global.

This issue highlights the innovation emerging from large and small companies—

as well as our academic and clinical research centers—and serves as a snapshot of

Michigan’s outstanding biosciences community. Read how University of Michigan

researchers and doctors are leading the creation and application of life-saving

3D-printed devices (p. 9). Learn how Beaumont, one of our state’s premier health

systems, is developing new cardiovascular technologies to help patients who can’t

be treated with conventional approaches (p. 11). Or follow the growth of various

companies in the chemical, device, bio-analytic, genetic, and diagnostic technology

areas as they pursue global markets with innovative products and services. Understand

how expert providers assist start-ups and established companies in Michigan—and

around the world—with product development and communications strategies targeted

toward health providers and patients. Lastly, familiarize yourself with the State of

Michigan’s innovative BioTrust for Health through which residual newborn blood spots

are made available for important medical and public health research (p. 30).

Discover more about Michigan’s bio-industry at www.michbio.org, and let

MichBio connect you to the state’s bioscience companies, business services and

support network, and markets. Learn how so many of the vital components of the

bio-industry can be so easily accessed right here in Michigan.

Stephen Rapundalo, PhD

President & CEO

MichBio

PRESIDENT’S MESSAGE

STAFF

CONTACT INFORMATION

Stephen T. Rapundalo, PhD

President & CEO

[email protected]

734.527.9144

Katie Trevathan

Director,

Marketing & Communications

[email protected]

734.527.9147

David McGuire

Director,

Operations & Membership

[email protected]

734.527.9150

Nancy Marcotte

Manager, Finance

[email protected]

734.527.9145

Physical Address

3520 Green Court, Suite 175

Ann Arbor, Michigan 48105-1175

Mailing Address

P.O. Box 130199

Ann Arbor, Michigan 48113-0199

Phone

734.527.9150

Fax

734.302.4933

Website

www.michbio.org

Email

[email protected]


PREMIUM MEMBERS

GOLD

SILVER

BRONZE

OFFICERS & DIRECTORS

EXECUTIVE OFFICERSChairmanStephen Munk, PhDAsh Stevens, Inc., President and CEO

Vice ChairmanKevin McCurrenGrand Valley State University,Executive Director, Center for Entrepreneurship and Innovation

President and CEOStephen T. Rapundalo, PhDMichBio, President and CEO

Secretary Tina Rogers, PhD, MBA, DABTMidwest Life Science Advisors LLC,CEO and Founder

Treasurer Matthew L. McCollErnst & Young LLP, Partner

DIRECTORSArik AndersonTerumo Cardiovascular Systems Corp.,Vice President, Global R&D and Marketing

Doug Gage, PhDMichigan State University,Director, BioEconomy Network

Dale GroganMichigan Accelerator Fund I,Managing Director

Sanjay GuptaWellness + Prevention, Inc. (a J&J Company), President

Tim MaylebenEsperion Therapeutics,President and CEO

Kevin McCurrenGrand Valley State University,Executive Director, Center for Entrepreneurship and Innovation

Kevin McLeodMichigan Medical Device Accelerator,Managing Director

Paul MorrisAlixPartners LLP, Finance Director, Enterprise Improvement

Stephen Munk, PhDAsh Stevens, Inc. President and CEO

Stephen T. Rapundalo, PhDMichBio, President and CEO

Tina Rogers, PhD, MBA, DABTMidwest Life Science Advisors LLC,CEO and Founder

John J.H. Schwarz, MDBattle Creek Family Health Center,Physician, Former U.S. Representative

Ned StaeblerWayne State University, Vice President, Economic Development

Christopher J. SteinFerndale Pharma Group Inc., Executive Vice President and COO

George WilsonBeaumont Health System,Chief of Radiation Biology, Scientific Director, Beaumont Biobank

David ZimmermannKalexsyn, Inc., CEO

MEDIA

PATRON

A LIFE SCIENCE CONNEC T BRAND

A LIFE SCIENCE CONNEC T BRAND


TABLE OF CONTENTS

ADVERTISERS

Bank of Ann Arbor ...................... 2

EFP Corporation ....................... 2

Healthmark ............................. 1

Hylant ..................................27

MichBio ............................ 8, BC

Terumo Cardiovascular Systems ......27

VWR .................................. IBC

Western Michigan University Homer Stryker MD School of Medicine .......................... IBC

Michigan State University Innovation Center ...................... 2

MPI Research ..........................27

PhRMA .................................IFC

Stryker .................................. 1

If you are interested in submitting an article or an advertisement for the next issue of BioMatters, email [email protected] to receive BioMatters? Visit www.michbio.org/subscribe.

9 University of Michigan3-D Printing Saves Young Lives

Michigan Biosciences by the Numbers

13 Cayman ChemicalThe Evolution of Ann Arbor’s Cayman Chemical

28 Rubicon GenomicsTranslating Human Genetics into Real-Time Medicine

20 in2beingWhere Innovation Meets Reality

6 25 MPI ResearchTaking the Forward View: Advancing Bioanalytical Testing

17 Local Michigan Suppliers Help Develop World Markets

State of MichiganBioTrust Leads Nation as Resource for Public Health Research

Detroit R&DNovel Diagnostics and Drug-Screening Tools

15

JB Ashtin Group, Inc.Helping Clients Publish and Publicize Medical Research

23

GraMedicaA Life-Changing Device Company Transformed

19Beaumont Health SystemCardiovascular Innovation: Good for Health of Patients and Region

11

30

BioMatters

EARLY-STAGE MID-STAGE LATE-STAGE

PREDICT & PROTECT

HEALTHY ENDOTHELIUM

DYSFUNCTIONALENDOTHELIUM

DAMAGEDENDOTHELIUM

EARLY STAGE MID STAGE LATE STAGE

INCREASING VASCULAR AGE

Blood clots formEventualblockage

Result in:Chest painHeart attackStroke

Cardiovascular risk factors

Result in: Lower %FMD

Plaque formationCalcium build-up

Result in:Vessel stiffening and narrowing

TM

Y EALTHYY HEHELIUMNDOTHTHEN

DYSFENDO

DAMAGEDENDOTHELIUM

blockage

Result in:est painart attackoke

Lower %FMDResult in:V l tiff i

THYY

ResCheHeaStro

Lower %FMD Vessel stiffening and narrowing

FUNCTOTHEL

DAMAGED

TL

LIONALLIUM

32 VersicorMedical Device Technology that Serves the Greater Good

MI BIO-INDUSTRY QUICK FACTS# Bio Companies & Organizations:

1,760*

# Bioscience Jobs:

41,892*

Total Employment Impact:

205,952*

Average Bioscience Salary:

$81,296*

Total Payroll:

$2.5 billionEconomic Impact:

$9.5 billionTotal Bioscience Start-Ups Since 2002:

164

ACADEMIC BIO-RESEARCH†

Total R&D:

$2.09 billion (#6 in nation, 2010)

Bioscience R&D:

$1.2 billion (#10 in nation)

# of Science/Engineering Degrees:

14,238 (#8 in nation, 2011)

# of Science/Engineering Patents:

4,598(#6 in nation, 2012)

BIO-INDUSTRY INVESTMENT, COMMERCIALIZATION RESOURCES & INCENTIVESLife Sciences Corridor Fund – 21st Century Jobs Fund:

>$350 million(1999-2011)

Total VC Capital Available:

$538 million(2013)

Total Bioscience VC Investment:

$505 million* (2009-2013)

21st Century Investment Fund:$120 million fund-to-funds$46 million to biosciences www.Michigan21stCenturyInvestmentFund.com

InvestMichigan! Fund:$300 million fund www.InvestMichiganFund.com

Venture Michigan Fund I & II:$95 million fund-to-funds www.VentureMichiganFund.com(2007-2009)

Accelerate MI Innovative Competition: $1 million in cash prizes; largest business plan competition in the world2012 Winner – Algal Scientific2011 Winner – DeNovo Sciences2010 Winner – Armune Biosciences

Angel Investment Group Seed Program: $500 for each Angel group member; $25,000 for administrative fees for 50+ members

EB-5 Investment & Visa Program: Permanent U.S. resident status based on EB-5 eligibility to investors of $1 million in a new commercial enterprise

Emerging Technology Fund: Matching fund for SBIR/STTR awards; up to 25% of SBIR/STTR with maximum of $25,000 for Phase I and up to $125,000 for Phase 2

Great Lakes Entrepreneurs Quest: $100,000 to prizes for annual business plan competition

MI Pre-Seed Fund 2.0:Convertible note ≤ $250,000 with 100% match; pre-seed loan is up to $50,000

Accelerator Fund Program:The Accelerator Fund Program seeded two new early stage venture capital funds with a total of $12 million.n Michigan Accelerator Fund In Huron River Ventures

Pure Michigan Venture Match Fund: $350,000-500,000 match on $700,000-$3 million investmentwww.MichiganAdvantage.org

Michigan Biosciences

BY THE NUMBERS

Testing/ Medical Labs

* Battelle/BIO State Bioscience Industry Development, 2014.

† National Science Board, Science and Engineering Indicators, 2014.


25

DISTRIBUTION OF MICHIGAN BIO-COMPANIES BY SECTORPharma & Therapeutics 21%

Medical Devices/Equipment 41%

Research & Development 13%

Testing/Medical Labs 3%

Information Technology 9%

AgBio & Industrial Biotech 13%

n Amway

n Ash Stevens

n Asterand

n Atek Medical

n Bayer CropScience

n BD

n Beckman Coulter

n Dow Chemical

n Dow Corning

n Emergent BioSolutions

n Enzo Life Sciences

n Esperion Therapeutics

n Everist Genomics

n Ferndale Pharma Group

n Housey Pharmaceuticals

n Jasper Clinic

n JHP Pharmaceuticals

n Kalexsyn

n Kalsec

n Kellogg

n Lycera

n Medbio

n MPI Research

n NanoBio

n Neogen

n Orchid Orthopedic Solutions

n Oxford Biomedical

n Perrigo

n Pfizer

n Rockwell Medical

n RTI Surgical

n SRI International

n Stryker

n Terumo Cardiovascular

n ThermoFisher

n Velesco Pharmaceutical

Services

n Wellness & Prevention Inc.

(a J&J company)

n Zoetis

A SAMPLE OF BIOSCIENCE COMPANIES IN MICHIGAN

Biosciences IS BIG BUSINESS in Michigan

Pharma & Therapeutics

Medical Devices/Equipment

Research & Development

Testing/ Medical Labs

AgBio & Industrial Biotech

Information Technology


Every MichBio member organization can take advantage of the Preferred Purchasing Program, which offers exceptional savings, discounts, and opportunities from key industry providers.

Find out how to save up to 75% on goods and services: www.michbio.org/preferred-purchasing.

SAVE With The MichBio Preferred Purchasing Program

LABORATORY AND OFFICE PRODUCTS

used lab supplies and equipment

reagents/PCR

industrial and medical gases

computers/technology

office supplies and furniture

lab supplies and equipment

INTELLIGENCE AND DEVELOPMENT

professional training

market research/intel reports

eLearning and development

scientific intel and reports

BUSINESS OPERATIONS

news distribution/press releases

risk and insurance protection

shipping

cold shipping

government affairs and grants

cloud storage and virtual solutions

relocation and moving insurance brokerage


3-D Printing Saves Young Lives

UNIVERSITY OF MICHIGAN

By Rick Haglund

Garrett Peterson spent the first 18

months of his life fighting for nearly

every breath.

Born with a rare condition that

caused his airways to collapse, Peterson

was tethered to a ventilator from birth.

He spent 16 months in the intensive

care unit of a Utah hospital, often

heavily sedated. He twice was placed

in a medically induced coma to keep

him alive.

But after surgeons at the University

of Michigan’s C.S. Mott Children’s

Hospital implanted 3-D printed splints

in Garrett’s airways in January, he was

able to return home with his parents

last month.

“He’s doing well. He has no

intravenous medications. He’s doing

the best he’s ever done in life,” said Dr.

Glenn Green, one of two surgeons who

performed the surgery.

Green assisted Dr. Richard G. Ohye,

the head of pediatric cardiovascular

surgery at U-M, in sewing the splints in

Garrett’s airways to keep them open.

The splints will reabsorb into his body

within three years.

Garrett was just the second person

in the world to get the implants, which

were created by using a sophisticated 3-D

printer. Some experts say 3-D printing

could revolutionize manufacturing for

medical and many other applications.

The first surgery also was performed

at U-M on Kaiba Gionfriddo, a 20-month

old Ohio boy, in 2012.

Both boys developed tracheobroncho-

malacia, a softening of the windpipe

cartilage that affects about one in

2,200 children. Green said they likely

would have died without the surgery.

Garrett was so fragile that just the

act of turning his head could make him

stop breathing.

“When the nurses would just move

his head from side to side, because of

his compromised airways, he would just

turn blue—like instantly,” said Natalie

Peterson, Garrett’s mother, in a video

produced by U-M.

“I will never forget seeing him for

the first time like that. That was hard,”

she said, her voice cracking.

Scott Hollister, a biomedical

engineering professor at U-M, is a

pioneer in the development of medical

3-D printing, a process somewhat

similar to document printing.

3-D printers lay down many layers

of thin material, usually some type of

plastic, and are shaped into an object

using lasers. They have been used to

GARRETT PETERSON AND HIS MOTHER, NATALIE PETERSON, AT C.S. MOTT CHILDREN’S HOSPITAL.

Every MichBio member organization can take advantage of the Preferred Purchasing Program, which offers exceptional savings, discounts, and opportunities from key industry providers.

Find out how to save up to 75% on goods and services: www.michbio.org/preferred-purchasing.

SAVE With The MichBio Preferred Purchasing Program

LABORATORY AND OFFICE PRODUCTS

used lab supplies and equipment

reagents/PCR

industrial and medical gases

computers/technology

office supplies and furniture

lab supplies and equipment

INTELLIGENCE AND DEVELOPMENT

professional training

market research/intel reports

eLearning and development

scientific intel and reports

BUSINESS OPERATIONS

news distribution/press releases

risk and insurance protection

shipping

cold shipping

government affairs and grants

cloud storage and virtual solutions

relocation and moving insurance brokerage


make a variety of prototypes

and products, ranging from guns

to guitars.

Hollister created the splints

used in Kaiba and Garrett’s

airways from CT scans of their

tracheas and bronchi, and 3-D

modeling of their airways.

Green and Hollister obtained

emergency clearance from the Food

and Drug Administration to perform

both surgeries. They are in negotiations

with the FDA for approval of clinic

trials, which Green said might start

by the end of this year.

“U-M is definitely a leader in this

area,” Green said. “But many others

are interested in doing this. I get emails

from major medical centers at least

once a month inquiring about how we

use 3-D printing.”

There is much patient interest

as well. Garrett Peterson’s parents

called Green after reading about

Kaiba Gionfriddo’s successful surgery.

Green and Ohye say they are regularly

contacted by other parents from around

the country, asking if their children

might be candidates for the surgery.

“It’s pretty gratifying,” Ohye said.

“We’ve all started to have the feeling

that once the technology becomes

readily available, it’s going to be used

more than we thought.”

The global market for 3-D printing,

including printer sales, materials and

services, is expected to grow from

$3.8 billion this year to $16.2 billion

in 2018, according to market research

firm Canalys in Palo Alto, CA.

Hollister said he thinks the medical

market for 3-D printing could reach

“the low billions of dollars” over the

next 10 to 15 years.

3-D printing has cost and speed

advantages over other types of

manufacturing processes, Hollister said.

Days before Garrett Peterson’s

surgery, Green suggested a design

modification in the airways splints to

Hollister, who was able to redesign and

make the new splints in two days.

Traditional manufacturing processes

might have required weeks or months

to make the design change.

“You would never conceive of

making that large of a change in a

design with other kinds of manufacturing

techniques,” Hollister said.

The price of manufacturing an

airways splint fell from $200,000

for Kaiba’s surgery in 2012 to

$40,000 for Garrett’s surgery

this year, Green said.

Manufacturing and implanting

the splints, plus the cost of

hospitalization in the intensive

care unit is about $300,000, he

said. But that’s $900,000 less than the

average $1.2 million cost of treating

tracheobronchomalacia without using

3-D printed splints.

“The costs are dropping rapidly,”

Green said.

But there are a variety of technical

and regulatory issues surrounding 3-D

printing for medical use.

Adapting a commercial 3-D printer

to use biomaterials for a variety of

medical applications, as U-M is doing,

“remains one of the technical hurdles,”

Hollister said.

3-D printing also allows many new

entrants into the medical implant field,

creating concerns about regulation and

manufacturing quality.

“One of the broader questions is

how do you regulate this?” Hollister

said. “It’s the beginning of a new

paradigm. You can make custom parts

and you don’t need a big medical

device company to do it.”

U-M physicians and researchers see

a variety of new uses for 3-D printing,

including nose and ear constructs, and

other nonmoving human parts.

Hollister said U-M’s dental school has

been working with dentists in Italy to a

make implants for jawbones damaged by

periodontal disease, using 3-D printing.

3-D printing also can manufacture

more realistic heart models that can aid

in teaching medical students, Ohye said.

But it is the aspect of saving more

lives through the use of this developing

technology that most excites the U-M

physicians and researchers.

“We believe there are many other

applications for these techniques, but

to see the impact living and breathing

in front of you is overwhelming,”

Hollister said. DRS. RICHARD OHYE AND GLENN GREEN (FROM LEFT) AND BIOMEDICAL ENGINEER SCOTT HOLLISTER DESIGNED AND IMPLANTED 3-D PRINTED SPLINTS IN THE AIRWAYS OF GARRETT PETERSON, SEATED ON GREEN’S LAP, ALLOWING HIM TO BREATH NORMALLY AND LIKELY SAVING HIS LIFE.

A BIOPOLYMER AIRWAY IMPLANT MADE FROM A 3-D PRINTER.


Beaumont Health System’s

Center for Innovation and Research

in Cardiovascular Diseases (CIRC)

is focused on developing new

cardiovascular technologies to help

patients who can’t be treated with

conventional heart procedures or

therapies.

But the benefit of CIRC goes well

beyond the important work of helping

patients without hope receive new,

innovative treatments.

CIRC is helping to make southeast

Michigan a major destination center for

cardiovascular research and innovation,

and for the commercialization of new

cardiovascular devices and therapies.

So, the economic health of the

region and state benefits as well.

Unlike other innovation centers,

CIRC is designed to interact with

inventors, medical device startup

companies, and large medical device

corporations at all stages of device

development leading up to approval

and market release. This includes

concept and design, pre-human testing,

clinical trials preceding FDA approval,

and physician training and education

after FDA and Medicare approval.

“Our approach of offering one-

stop-shopping for medical device

development encourages companies to

make a longer-term commitment to

doing business in this region,” explains

Robert Safian, MD, Beaumont CIRC

director and a Harvard-trained,

world-renowned cardiologist.

The unique components of CIRC include:

• A one-of-a-kind, 950-square-foot

Bio Skills Lab for hands-on

training for physicians in the

use of new, advanced

cardiovascular medical

technologies. The lab includes

16 plug-and-play stations for

hands-on device manipulation.

• A Simulation Lab, providing

hands-on training in the

management of clinical scenarios

using computerized manikins

(still under development).

• A Digital Camera Studio for

web-based physician training

(still under development).

In addition, CIRC clients can utilize

components of the 9,000-square-foot

Suzanne and Herbert Tyner Center for

Cardiovascular Interventions, which

opened in December 2012. The center

includes a 1,600-square-foot, state-

of-the-art hybrid operating room

for procedures that blend minimally

invasive heart surgeries with procedures

performed through catheters, for

treating structural heart disease.

Adjacent to the hybrid operating suite

is a large, elevated observation room

where physicians and trainees can view

procedures in real-time, and a classroom

where training courses can be broadcast

to locations around the world.

CARDIOVASCULAR INNOVATION:

Good for Health of Patients and Region

ELEVATED OBSERVATION ROOM AT THE TYNER CENTER FOR CARDIOVASCULAR INTERVENTIONS WHERE PHYSICIANS AND TRAINEES CAN VIEW HEART SURGERIES IN REAL TIME.

BEAUMONT HEALTH SYSTEM

MichBio | www.michbio.org

Most commercialization centers

typically lead medical startup

companies to the point of acquisition

by a larger medical device company,

usually just prior to first-in-man

studies. Of the 65 innovation centers

in the nation, none are exactly like

CIRC, which leads companies through

the entire commercialization process.

Any inventors, physicians, medical

institutions, hospitals, academic

institutions, medical device companies,

or government entities can use CIRC.

Dr. Safian says the response of

medical device companies to CIRC’s

comprehensive approach has been

uniformly positive. Major device

industry leaders such as Boston

Scientific, Abbott, St. Jude Medical,

Medtronic, Kona, and InfraRedX have

committed to use the services of CIRC

to commercialize devices for valve

replacement without surgery; stroke

prevention; treatment-resistant high

blood pressure; for opening chronically

occluded arteries; and for direct imaging

of cholesterol in heart vessel plaque to

assess stroke and heart attack risk.

Medical device development is

a lucrative part of the economy. In

2010, interventional cardiology devices

alone brought in revenue close to

$1 billion. Revenue projections for

2015 are just over $3 billion and in

2020 are projected to reach $9 billion.

Beaumont is positioning CIRC to be a

leading driver for this market.

At the same time, CIRC helps to

solidify Beaumont’s world-wide

reputation as a destination center for

cardiovascular treatment firsts, and as a

leader in medical training and education.

This in turn, attracts cardiovascular

medicine’s best and brightest physicians

and researchers to Beaumont.

CIRC’s Bio Skills Lab is another

unusual component of the center that

was funded by a gift from a local family.

“Once technologies gain Food and

Drug Administration and Medicare

approval, there’s an important need

to train physicians to use them,”

says Dr. Safian. “Through the Bio Skills

Lab, we are partnering with medical

device companies to train physicians-

in-practice how to transfer new

technologies to their patients.”

Currently, most physicians receive

training in the use of new medical

devices in hotel rooms from medical

device company representatives.

The opportunity to learn from

clinicians involved in the research

and testing of newly approved medical

devices, in a high-tech, hospital-based

setting, is a first that is especially

important as devices become more

sophisticated.

And by training other physicians in

the use of new technologies in the Bio

Skills Lab, the innovative treatments

that CIRC offers Beaumont patients

are extended to patients regionally,

nationally, and around the

world. “CIRC will encourage

entrepreneurialism, create high paying

jobs for talented people in medicine,

science, business and engineering, bring

the giants of the medical industry to

our region, teach physicians new ways

to save lives, and disseminate that

knowledge around the world,” says Dr.

Safian. “All of this will help drive

southeast Michigan’s economy while

providing hope to patients suffering

from cardiovascular conditions that

are beyond conventional treatments.”

To learn more about CIRC, including

ways to support the program through

philanthropy, call 248.898.4176.

DURING A BOSTON SCIENTIFIC TRAINING ON APRIL 18, BEAUMONT CATHETERIZATION LAB STAFF RECEIVED HANDS-ON SIMULATION TRAINING IN THE USE OF NEW MEDICAL DEVICES FOR ANGIOPLASTY AND STENT PROCEDURES IN RENAL AND CAROTID ARTERIES.

ROBERT SAFIAN

12


Adam Uzieblo speaks with a thick

Polish accent and has a bristling gray

crew-cut. An accomplished medicinal

chemist, he is also a survivor. He

endured years of separation from his

wife and young son when he fled to

the west during the Gdansk uprising

of 1980. A few years after coming

to the Midwest, Adam teamed up

with Kirk Maxey, a medical student

at the University of Michigan who

was struggling to build a small

biochemical company he called Cayman

Chemical. Named for the Caribbean

island where the potent biological

materials underlying its product line

originated, Cayman sold a handful of

prostaglandin standards to academic

and pharmaceutical research scientists.

In the more than 30 years since being

founded in a basement laboratory,

Cayman has grown to offer more than

6,000 biochemical standards, assay kits,

antibodies, and recombinant proteins.

Today, Adam is focused on a new

and remarkable project — he’s helping

to develop a new drug. Adam works

from a brightly lit synthetic chemistry

laboratory that is part of Cayman’s

4-building, 14-acre, 170,000 ft2 campus

in Ann Arbor, MI. He and Andrei Kornilov,

another scientific ex-patriot from

Eastern Europe, discovered a series of

compounds that can help to grow new

human bone. This discovery added a

second new drug development project

to Cayman’s portfolio, which at this time

includes a novel set of prostaglandin

inhibitors that show promise in treating

muscular dystrophy and some features

of asthma and inflammation.

BUILDING ON THE PAST In 1981, Kirk Maxey isolated 30

grams of prostaglandin A2 from

an eight-pound sample of coral he

harvested while scuba diving in the

Cayman Islands. This was the starting

material that led to the establishment

of Cayman Chemical. Cayman

developed an extensive product

line focused on its signature brand,

rapidly becoming the industry leader

in the production and distribution

of bioactive lipid reagents. Cayman

chemists synthesized an extensive array

of bioactive lipid products including

numerous eicosanoids (prostaglandins,

leukotrienes, and thromboxanes),

inositol phosphates, cannabinoids, and

steroids. At the same time, Cayman

biochemists developed the antibodies

and immunoassays used to detect the

various bioactive lipids in cell culture

medium, serum, and plasma. Cayman

grew to $10 million in catalog sales and

100 employees in its Ann Arbor research

facilities by the mid-1990s.

By the early 2000s, Cayman

recognized the need to move beyond

its bioactive lipid brand and develop

new product lines to sustain the growth

of the company. Cayman invested

heavily in new facilities and personnel,

taking advantage of the closure of

the Pfizer research facility in Ann

Arbor to hire experienced medicinal

chemists. Cayman’s Chemistry division

capitalized on its experience with

endogenous cannabinoids to begin

manufacturing an extensive line of

market-leading reference standards

that forensics scientists use in the fight

against illegal, designer drugs of abuse,

including synthetic cannabinoids (K2,

Spice, etc.). The analytical chemistry

group achieved ISO certification for its

mass spectrometry services, ensuring

its customers receive the highest

quality in analytical service. As it grew,

Cayman expanded internationally,

opening large-scale chemical synthesis

facilities in Prague (Czech Republic)

and Tallin (Estonia).

The Evolution of Ann Arbor’s Cayman Chemical

CAYMAN CHEMICAL

ADAM UZIEBLO AT THE LAB BENCH SYNTHESIZING AN EICOSANOID.


Cayman’s Biochemistry

division also evolved beyond

the generation of lipid function

assays and ELISA kits to add

recombinant protein cloning

and expression, monoclonal

antibody production, cell-based

assays, and protein structure/

x-ray crystallization. It developed an

impressive array of proteins and high-

throughput screening assays that are

used in epigenetics research, making

Cayman a major player in this area.

The Cayman Biochemistry division grew

from 20 employees (one PhD) in the

mid-1990s to 55 employees, including

12 PhD scientists, by 2012.

Cayman had gathered the skills,

capabilities, and facilities necessary to

undertake a legitimate drug discovery

effort. Entry into the biopharmaceutical

realm advanced Cayman beyond catalog

sales and contract services and into the

risky but potentially more lucrative area

of discovering novel small-molecule

therapies.

For most of Michigan’s fledgling

biotechnology companies, the

challenge to build a successful drug

discovery program from scratch would

necessitate obtaining vast amounts of

venture capital or grant funding to rent

lab space, purchase equipment and

supplies, and pay salaries — startups

can burn through millions of dollars

per year this way. Cayman had the

resources to fund its burgeoning drug

discovery program by relying on the

ongoing financial success of its catalog

business. To ensure its continued

success, Cayman created a unique

system in which every Cayman scientist

involved in drug discovery, like Adam

and Andrei, also contributed to the

manufacture and development of

catalog products and to the fulfillment

of custom products and services.

While the medicinal chemists are

developing novel, patentable chemicals

for Cayman Drug Discovery, they

offset their overhead by synthesizing

new inhibitors, lipid mediators, and

analytical standards for sale in the

catalog or by contributing to a large-

scale cGMP/API manufacturing contract.

An analytical chemist might be asked

to perform a LC/MS analysis of drug

levels in the plasma of dosed mice on

Monday and spend the rest of the week

performing quality analysis of forensics

standards. A cell biologist might take

a day or two per month testing the

activity of Cayman Drug Discovery

compounds for receptor binding on

cells in vitro and use the remainder of

the month to develop a new cell-based

assay kit for catalog sale.

This method of financing drug

discovery makes Cayman unique in

all of Michigan. It’s efficient and

economical, making the maximum

use of the skills and time of Cayman’s

scientists. Not only does this method

provide revenue-producing jobs to do

when not actively involved in drug

discovery, it produces a pipeline of

innovative catalog products.

It’s fitting that Cayman’s initial drug

discovery project took advantage of its

knowledge of the product that launched

the company, prostaglandin A2. Cayman

was contacted by the New London,

Connecticut-based biotech company

Myometrics, LLC for the discovery and

development of small molecule agonists

of the EP4 receptor, one of the four

cellular receptors of the multifunctional

prostaglandin PGE2. EP4 agonists have

several functions described in scientific

literature, including promoting new

bone growth, anti-inflammatory

activities, and effects on blood

pressure. Myometrics wanted to use

them in therapeutic conditions where

new bone growth was required, such as

spinal fusion surgery or the promotion

of bone fracture repair. IND filing is

expected in 2015.

DISCOVERING THE FUTURE In March of 2014, Cayman

took the next step in the

evolution of a complete drug

discovery organization by

officially naming two of its

scientists, Stephen Barrett and

Jim Mobley, to the new positions of

Director of Drug Discovery Chemistry

and Director of Drug Discovery Biology,

respectively. With this organizational

structure in place, Cayman is poised to

perform all aspects of drug discovery,

including selection of a therapeutic

area and drugable biological target,

lead discovery chemistry, lead

optimization, structure-based drug

design, in vitro screening, and in

vivo efficacy testing. As the scope

of Cayman’s drug discovery effort

expands, so will its funding options,

including writing SBIR grants, forming

strategic partnerships with biotech

and pharmaceutical organizations, and

securing venture capital to support

late-stage development efforts. Just as

Cayman grew from its modest start in

a basement in 1981, its Drug Discovery

division will grow to play a significant

role in Cayman’s ongoing efforts to

advance human and animal health and

help make research possible.

More information about Cayman

Chemical can be found on our website

www.caymanchem.com or by calling

800.364.9897.

DR. LEVI BLAZER AND DR. DAN BOCHAR DISCUSS THE RESULTS OF A HIGH THROUGHPUT SCREENING ASSAY.

ADAM UZIEBLO KIRK MAXEY


Founded in 1997 by Dr. Hyesook

Kim, Detroit R&D has been steadily

establishing itself as a worldwide source

for novel diagnostic and drug-screening

products. The Detroit R&D laboratories

and offices are located inside the newly

renamed Block at Cass Park Building on

Second Avenue in the heart of a new

redevelopment district in the city of

Detroit, Michigan. The historic building

(formerly the Metropolitan Center for

High Technology) is already the home

of many small businesses and has ample

laboratory space to attract additional

small biotech and start-up companies.

The company’s original project was

to develop an easy and inexpensive

hypertension kit for measuring novel

fatty acid biomarkers in blood, urine,

and tissue. Hypertension affects nearly

50 million individuals in the USA and

about 1 billion people worldwide, and is

an under-diagnosed condition because

the underlying damage to the body

occurs with only mild or no symptoms.

In 2009, heart disease and stroke

accounted for 27,794 deaths in the

state of Michigan (MDCH statistics) and

hypertension during pregnancy is one

of the major risk factors in pregnancy-

related mortality.

Unfortunately, the cause of

hypertension is presently unknown in

about 90 percent of reported cases.

Currently, reducing blood pressure

in hypertensive patients is served by

a number of different drugs such as

calcium blockers and ACE inhibitors, just

to name a few. These varied approaches

to treating hypertension illustrate the

difficulty of finding a single drug that

effectively lowers blood pressure.

With over 75 different medications in

several different categories, physicians

are often faced with a bewildering set

of treatment options, resulting in a

‘roulette wheel’ approach to patient

care. The ability to measure a biomarker

of hypertension, as can be accomplished

with the kits developed at Detroit R&D,

would be advantageous in several ways:

BREAST CANCER TISSUE LABELED WITH DETROIT R&D ANTIBODIES THAT RECOGNIZE A SPECIFIC MODIFIED PROTEIN.

Novel Diagnostics and Drug-Screening Tools

DETROIT R&D


• It could serve as an early prediction

of the onset of elevated blood

pressure and associated

cardiovascular events including

stroke, and this prediction would

have enormous value in the

individualization of treatment

for cardiovascular patients. The

American Heart Association estimates

that the cost of cardiovascular

diseases and stroke in the U.S. alone

were nearly $475 billion in 2009

and will increase to $818 billion in

2030. According to the Michigan

Department of Community Health,

high blood pressure costs in Michigan

were estimated at $1.5 billion

in 2007, so choosing the correct

medication earlier would lower the

chance of developing cardiovascular

diseases and could result in

substantial cost savings.

• It would also provide a tool to

monitor the effectiveness of drug

candidates undergoing pre-clinical

and clinical trials and possibly

could be used to develop a new

anti-hypertensive therapy. Thus

it could be an attractive target

for pharmaceutical companies

facing the challenges of patent

expirations and rising research

and development costs.

• Studies utilizing the Detroit R&D

hypertension kit with coded human

urine specimens obtained from

hypertensive (pre-eclamptic) and

healthy women have confirmed that

this fatty acid is an exceptionally

specific and sensitive biomarker

of hypertension. This is the only

technology currently available

to measure hypertension outside

of the use of mechanical blood

pressure monitors and alteration

of these biomarker levels may

be detected before noticeable

elevations in blood pressure.

The company is now exploring

even simpler and faster dip-stick

techniques to measure this

biomarker under non-laboratory

conditions.

Now 10 years later, Detroit R&D

markets nearly 100 products directly or

through more than twenty distributors

to customers in the U.S. and worldwide.

In addition to hypertension kits, the

company portfolio includes kits for

measuring biomarkers of diabetes,

prostate cancer, septic shock, oxidative

stress, and environmental contaminants.

Several of the technologies developed

at Detroit R&D have been patented

(7 issued and 6 pending patents),

mainly as the result of research and

development supported by 17 National

Institutes of Health (NIH) Small Business

Innovative Research (SBIR) grants

awarded to Detroit R&D (>$9 million in

total). Currently, Detroit R&D is working

on two Phase I and Phase II National

Cancer Institute (NCI) SBIR awards.

Developing new and innovative

cancer diagnostic products has recently

become a major focus of research

and development for Detroit R&D,

and it is attracting outside attention

worldwide. During a recent NCI SBIR

study, Detroit R&D produced antibodies

that recognize important proteins with

very specific sugar groups attached to

their protein backbone. Detection of

these modified proteins will serve as

novel biomarkers for breast and prostate

cancer and possibly other cancers, as

well. During this study Detroit R&D also

discovered an anti-breast cancer drug

candidate that will become the focus

of further projects. The drug candidate

prevented breast cancer cell metastasis

and dramatically increased breast cancer

cell death as compared to non-cancerous

cells. In addition, the company has a

pending patent disclosing a method to

screen synthetic and natural anti-cancer

drug candidates using antibodies for

these modified proteins.

In summary, Detroit R&D is

developing innovative technologies

to help researchers understand the

underlying causes of many worldwide

health problems. This company has

the talent, insight, and drive to grow

substantially and is poised to expand

into the clinical and therapeutic

markets. Detroit R&D welcomes

collaborations and licensing inquiries.

For more information about

Detroit R&D visit their website at

www.detroitrandd.com or call

313.961.1606.

Developing new and innovative cancer diagnostic products has recently become a major focus of research and development for Detroit R&D, and it is attracting outside attention worldwide.

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100

80

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HYPERTENSIVEPreeclamptic

n=7** Significantly different

NORMOTENSIVEHealthy

n=9

**

RESULTS OF A STUDY OF HYPERTENSION IN PREGNANT WOMEN USING DETROIT R&D HYPERTENSION KIT.


Not so long ago, Michigan-based

Everist Health was working with

suppliers from all over the United

States—manufacturers in California and

India, web designers and public relations

companies based in New York, and

attorneys in California. Today, virtually

all of the medical device company’s

partners are within a short drive of

Everist Health’s Ann Arbor headquarters.

This includes Detroit-based attorneys

Dykema, Ann Arbor-based web designers

Stone Interactive, and Canton-based

manufacturer Miller Technical Services.

“Many of our original suppliers came

to us because we had worked with

them in previous ventures,” explains

Chief Operating Officer Matt Bartlam,

“however, over time we have found that

we could access almost every service

we needed locally, and the quality of

service from our local suppliers has been

cost effective and outstanding.”

While the company is sourcing

supplies locally, they are seeing plenty

of opportunity to sell around the

world. “At the moment, we have zero

business in the United States because

we are still going through the process

of FDA trials,” explains Matt, “however,

we have regulatory approval to sell

the technology in other markets, and

our devices are in over 30 locations

worldwide—India, Middle East, Europe,

and Canada.”

Everist Health’s device, known as

the AngioDefender, deals with core

health problems such as diagnosing,

as early as possible while there is still

time to take remedial action, people

at risk for developing heart disease and

vascular dementia. The device is low

cost, non-invasive, and simple to use.

The AngioDefender measures the fitness

of the endothelial cells that line the

arteries of the body. These cells produce

nitric oxide that instructs the arteries

to expand and contract to allow blood

to flow to every organ of the body as

needed.

The AngioDefender produces a score

which can be used with the Everist

Vascular Age Calculator to determine

the vascular age of the individual. “You

may be 45 but have a vascular age of

35 or 65,” explains Matt. “If your heart

age is older than it should be, there are

many things you can do to improve your

vascular health such as quitting smoking,

improving your diet and exercise, lower

stress, and improving sleep patterns.

In certain cases where individuals have

a family history of heart problems,

medication may be prescribed.”

Local Michigan Suppliers Help Develop World Markets

ANGIODEFENDER

EVERIST HEALTH


“Heart disease is the number one

killer in the western world,” says Matt.

“At the same time, dementia is reaching

crisis proportions. For example, in the

UK, an estimated 800,000 people suffer

from dementia and that number is

expected to grow to 1.6 million by 2030.

Currently, one in four hospital beds in the

UK are occupied by dementia patients.

Therefore, the market for technology like

AngioDefender that helps predict people

at risk, is potentially huge.”

Health experts around the world

recognize that this made-in-Michigan

technology is a genuine innovation that

can lower healthcare costs and improve

the health of populations by providing

early warning of disease risk to permit

people to take action before they suffer

a potentially fatal heart attack or

develop irreversible vascular dementia.

The UK National Health Service

was sufficiently impressed with the

technology to invite Everist to exhibit

at its National Health Innovation

Conference, and the AngioDefender

has also been featured at a national

cardiology conference in Bangalore,

India, and at the Arab Health Congress.

Researchers in London, Ontario,

Canada are beginning trials this spring.

Everist Health believes the

AngioDefender will appeal to a wide

range of health outlets beyond just

hospitals which are set up to deal with

problems after they have occurred.

Everist Health already has primary care

doctors using AngioDefender as part

of wellness programs. Corporations

are also using the AngioDefender to

encourage employees who are engaged

in sedentary work to adopt healthy

living habits. A major rehabilitation

heart center in Canada is planning to

use AngioDefender to show recovering

patients the value of increased exercise,

and in the United Kingdom, a pharmacy

chain plans to offer AngioDefender

testing, along with other tests, to

measure blood pressure and cholesterol.

In India, a major inflammatory disease

clinic is using AngioDefender to test

patients because for example, people

with rheumatoid arthritis have a 50%

higher risk of developing heart problems

than the rest of the population.

The AngioDefender may also have

application for diagnosing people who

have no obvious heart health symptoms

such as fit young men and women.

“We see a major world market

for this predictive test,” says Matt,

“it is worth noting that our company

has received financial support from

the Michigan Economic Development

Corporation (MEDC). The company is

aiming to obtain FDA approval to market

the device in the United States within

the next year. The support of the MEDC,

together with our other investors may

well create a large number of jobs for

local suppliers and manufacturers for a

device that will be made in Michigan and

sold around the world.”

More information about Everist

Health can be found on our website

www.everisthealth.com or by calling

855.383.7478.

EARLY-STAGE MID-STAGE LATE-STAGE

PREDICT & PROTECT

HEALTHY ENDOTHELIUM

DYSFUNCTIONALENDOTHELIUM

DAMAGEDENDOTHELIUM

EARLY STAGE MID STAGE LATE STAGE

INCREASING VASCULAR AGE

Blood clots formEventualblockage

Result in:Chest painHeart attackStroke

Cardiovascular risk factors

Result in: Lower %FMD

Plaque formationCalcium build-up

Result in:Vessel stiffening and narrowing

TM

Y EALTHYY HEHELIUMNDOTHTHEN

DYSFENDO

DAMAGEDENDOTHELIUM

blockage

Result in:est painart attackoke

Lower %FMDResult in:V l tiff i

THYY

ResCheHeaStro

Lower %FMD Vessel stiffening and narrowing

FUNCTOTHEL

DAMAGED

TL

LIONALLIUM

© 2014 EVERIST HEALTH. ALL RIGHTS RESERVED.

EVERIST HEALTH’S LOCAL SUPPLIERS: CriTech Research, Inc. — Saline, MI Software Verification & Validation

In2being, LLC — Saline, MI Medical Product Development and Consulting

Karthik Ganesan — Ann Arbor, MI Software Developer Consultant

Quality Management & Consulting — Saline, MI QMS Consultant/Auditor

Weathervane Software — Ann Arbor, MI Software Developer Consultant

Miller Technical Services — Canton, MI OEM

Urgent Plastic Services — Troy, MI Plastic Mold Manufacturer

Inspec, Inc. — Canton, MI Calibration of Instruments

MMS Holdings, Inc. — Canton, MI Data Management/CRO

Evolution Enterprises — Milan, MI Data Analysis

Dykema — Detroit, MI Attorney, General Business, and Patents

Hile Creative — Ann Arbor, MI Marketing Literature/Video

Stone Interactive Group — Ann Arbor, MI Website Development

George Cesario — Plymouth, MI IT Consultant

Rick Matovina — Canton, MI Quality System Consultant

Parvin Panahi — Whitmore Lake, MI Design Consultant

Brent Truex — Ann Arbor, MI Software Developer

A Life-Changing Device Company Transformed

On a quest to improve his patients’ quality of life, Dr. Michael E.

Graham, an accomplished foot and ankle surgeon, transformed rapidly

from physician to start-up CEO when his innovative titanium stent,

called HyProCure®, was cleared by the U.S. Food and Drug Administration

(FDA) in 2004. After 10 years of world-wide lecturing and physician

education, GraMedica®, the former start-up, has also transformed

into a successful, global medical device company with headquarters

in Macomb, Michigan. Committed to his mission of “changing lives,

one step at time,” Dr. Graham says, “it’s been a wild ride, but satisfying.

I’ve been able to help more people than I ever expected.”

The first HyProCure® placement took place September 2004. Since

then, HyProCure® has been used in tens of thousands of procedures

worldwide. HyProCure®’s unique design permanently corrects misaligned

feet. Since most of a person’s weight rests on the ankle bone,

misalignment can cause the ankles to turn inward, eventually leading

to pain and damage not only to the ankle and feet, but to the knees

and hips. Unhappy with the results of previously available products

intended to treat the condition, Dr. Graham invented HyProCure®

specifically to improve treatment outcomes.

A recent study by N. Shibuya et al in the Journal

of Foot & Ankle Surgery showed that 18 percent of its

study patients had a functional flatfoot deformity, a

common symptom of misaligned feet. Foot and ankle

surgeons estimate that 10 to 30 percent of the general

public suffers from this same congenital deformity and

the related secondary effects. The brief HyProCure® procedure, typically

only 20-minutes long, permanently corrects foot and ankle alignment with

life-changing results. For example, a child who was not able to walk is now

able to ski a year after the procedure; a nurse who used to end her days

with tremendous foot pain can comfortably work a 12-hour shift.

HyProCure® works by preventing excessive pronation of the ankle’s

subtalar joint. During a minimally invasive procedure at a hospital, surgery

center, or physician’s office, the stent is placed in a naturally occurring

space in the ankle. The stent stabilizes the ankle bone on the heel bone,

eliminating excessive internal pressures and inward rolling of the foot —

while enabling full, normal range of foot motion.

HyProCure®’s patented design and medical-grade

titanium make it a permanent solution with a unique

classification that outperforms older implants that

tried to accomplish the same thing.

While still a small company of less than 20

employees, GraMedica has become recognized for

its innovation in foot care solutions. Almost ten

years after receiving its first product clearance

to market, GraMedica has grown dynamically

and now has products available in more than

40 countries, including in Africa, Asia, Europe, and Latin America.

GraMedica’s team of employees enjoys knowing that the work they

do improves the quality of life for people everywhere. In December

2013, GraMedica announced the selection of Dr. Anthony Weinert,

a renowned foot surgeon with offices in Troy and

Warren, Michigan, as the first Michigan HyProCure®

Center of Excellence. And in early in 2014, Al Seef

Hospital, Kuwait was announced as the first Middle

East HyProCure® International Center of Excellence.

The Center of Excellence designation recognizes

expert physicians, medical groups, and healthcare

centers accomplished at performing HyProCure® Extra-Osseous

TaloTarsal Stabilization (EOTTS) procedures and providing consummate

post-operative care.

GraMedica’s sister educational organization, the Graham

International Implant Institute® (GIII) is committed to research,

training, certification, and support on implantology for foot surgeons

worldwide. Recently, GIII and GraMedica sponsored a minimally

invasive foot and ankle surgery symposium in Bogotá, Colombia.

Forty surgeons from seven countries were trained to identify and treat

patients with flexible flat foot using HyProCure®. GIII and GraMedica

are expected to continue this training in North

America, Asia, Europe, and the Middle East in 2014.

In addition to HyProCure®, GraMedica is

currently developing additional high-quality,

innovative product lines to support their mission

of “changing lives, one step at a time.” To learn

more about HyProCure® and other GraMedica

products, visit the company’s website at

www.GraMedica.com. Additional requests for

information can be made by calling GraMedica’s

office at 586.677.9600.

By Karen M. Sandlin and Jean Stroster

HYPROCURE® SURGEON TRAINING AT CLEMI LABS IN BOGOTÁ, COLOMBIA

MICHAEL E. GRAHAM

A Life-Changing Device Company Transformed

GRAMEDICA



Lessons learned in the start-up

trenches are invaluable. Founded in

2010, in2being brings this knowledge and

experience to emerging medical and life-

science device companies. Gene Parunak

and Aaron Kehrer, veterans of HandyLab

and Accuri Cytometers, lead the nine-

person, Saline-based medical device

design and development firm.

IF YOU DREAM IT Medical device design and

development is a custom-tailored

process, not a simple check list. Product

dreams can become reality once a

company’s unique path is understood and

implemented. Upfront visioning exercises

play an invaluable role in determining a

product’s individual pathway.

Based on user input, and resulting

in design requirements, visioning helps

define the product pathway at an early

stage. This is critical since documentation

requirements vary greatly for a device

that will be used in a regulated clinical

setting as opposed to a research setting.

The process of visioning describes a

product concept 2-5 years in the future

after successful market placement. The

exercise clarifies the “product story,”

consolidates stake holders’ visions, and

defines device requirements in terms of

user groups, their unique interactions

with the device and implementation

environments.

For example, is the product intended

for use only in a controlled laboratory

setting or also in field applications

that require additional durability? Is

the device replacing a traditionally-

accepted product and procedure in

the marketplace, in turn mandating a

minimal learning curve requirement for

user acceptance? How will the device be

regulated?

For clinical applications, device

classification is the starting point for

determining the level of regulatory

control, the process of marketing

approval or clearance, and the data

required to submit a marketing

application to the FDA.

A 510(k) filing for a Class II device

typically requires identification of a

predicate device and demonstration of

substantial equivalence. Alternately,

if the application is accepted by the

FDA as a 510(k) de novo submission,

substantial equivalence does not apply,

but significant compliance effort remains.

Seemingly innocuous class I devices,

often exempt from the 510(k) process,

are nevertheless often subject to Good

Manufacturing Practices (GMP).

Understanding the device uses allows

selection of the correct standards,

which must be designed to and tested

to, and are an often overlooked, and

misunderstood, part of the development

process. Additionally, clinical devices

must fit profitably into a reimbursement

category, a frequent oversight in new

device development.

Once visioning is complete, in many

cases, a conceptual design, proposed

architecture identifying the major

product subsystems and potential design

challenges, and a sample bill of materials

(BOM) can be generated. Putting

straw-men, such as these, forward

throughout the process provide tangible

items for stake holders to react to, keeps

everyone on the same page, correcting

misinterpretations along the way.

GENE PARUNAK AND AARON KEHRER LEAD IN2BEING, A NINE-PERSON, SALINE-BASED MEDICAL DEVICE DESIGN AND DEVELOPMENT FIRM.

Where InnovationMeets Reality

IN2BEING


THE FOUR FORCES Many great products never

make it to market because of

unbalanced, competing forces.

A compass rose helps visualize

these forces, which must be

kept in alignment for successful

development.

The four primary forces

for medical device design and

development are (1) the regulatory

process, (2) the technical

development possibilities, (3) the

intellectual property landscape,

and (4) the market requirements. These

forces are further subdivided into two

major groups; the group that rewards

novelty and the group that penalizes it.

A strong competitive strategy

demands a robust intellectual property

portfolio; the United States Patent

and Trademark Office (USPTO) rewards

novelty and non-obviousness. A successful

market plan frequently requires that

the product deliver superior results and

benefits but not necessarily be more

complex to operate than existing devices.

Achieving this often requires novelty.

As discussed, the 510(k) process for

Class II medical devices is based on the

concept of demonstrating substantial

equivalence to a predicate device; with

the proper expertise, this conflict with

the patent process can be minimized.

The amount of novel technology

built into a product can negatively

affect the speed of the design and

development process. Increasing

product complexity most often

means increasing iterations during

product development. The potential

for increased troubleshooting costs,

increased maintenance costs, and lower

mean time between failures is warning

enough to be wary of unneeded novelty.

EVERYTHING IS A TESTBED Conceptual designs, sample BOMs,

and other testbeds allow better decision-

making to take place earlier in the design

process (see table at right).

Prototypes, commonly understood

as an integrated device for an alpha

or beta customer release, signal to

investors that the product is ready for

market. Everyone wants one, but going

directly to this stage, which typically

comes just before design transfer to

manufacturing, can be a dangerous

and costly leap of faith.

Used as proof of concept for specific

technically-challenging elements of the

product, testbeds reduce the number

of variables under evaluation. They are

used to produce repeatable outcomes

from individual components of the

device, and to illustrate functioning

device subsystems. Even seemingly

simple products can be broken

down into value-add testbeds.

A testbed can be as simple as

a conceptual design, a drawing or

3D print, to show potential users

for product-definition confirmation.

Or to prove at a rough level that

a concept is likely to work, finite

element analysis, modeling of

products and systems in a virtual

environment, can be performed.

Rapid prototyping, using

fused deposition modeling (FDM),

selective laser sintering (SLS), or

stereolithography (SLA), is another

type of testbed. A final example is

the assembly of the entire product,

or a subsystem, using off-the-shelf

components to prove functionality even

if components may need redesign for the

final build. The goal is to avoid major

expense, like designing and purchasing

injection molds, before the product is

reasonably optimized.

THE ACCELERATION POINT Generically, the acceleration

point, when the burn rate increases

due to investment in tooling, fixture

assemblies, and materials, occurs after

design questions are answered and the

techniques to build the products are

understood.

A COMPASS ROSE HELPS VISUALIZE COMPETING FORCES, WHICH MUST BE KEPT IN ALIGNMENT FOR SUCCESSFUL DEVELOPMENT.

SOME VIRTUAL TESTBEDSFEA (Finite Element Analysis) • Fluids • Mechanics • Dynamics • Heat • Magnetic Flux • Reactions • ESF (Electrostatic Force) • Auditory

Other Virtual Simulation • Electrical • Movement Path • Optical • Sensor Networks

SOME PHYSICAL TESTBEDSSubsystems (or full prototype candidates) for: • Biocompatibility Testing • Durability/Repeatability Verification • User Feedback • Proof of Principle • Electrical Test • Iteration of Specific Design Elements • Manufacturability Verification • Solution Comparison • Clinical Testing

TESTBED EXAMPLES


A growing body of scientific research supports that cancerous tumors

release cells into the blood stream, at levels that are nearly undetectable.

DeNovo Sciences has developed a microfluidic-based system for enrichment

and molecular characterization of these rare circulating tumor cells (CTC)

from whole blood. Primary clinical benefits include the early detection of

metastasis, and the generation of molecular information on the cancer for

therapy selection and assessment.

Developing a cutting-edge platform, composed of hardware, software,

reagents and kits, is challenging from a resource point of view, especially

if the goal is to get the product to market quickly, as the current funding

environment favors product commercialization, not technology development.

Product design and development requires the right skill sets, preferably

from individuals who have experienced the rigor of developing devices. An

emerging company, DeNovo Sciences has 7 full-time employees, half of them

biochemists. The company’s development strategy was to utilize their internal

personnel for the portions of the platform that required daily interaction

between the biochemists and engineers, and to outsource the development

of the imaging module, a more-defined project, to in2being.

“We try to do immensely difficult tasks at DeNovo Sciences. In a little over two

years, we have developed the first version of our platform and will begin launching

it this spring,” commented Dr. Kalyan “Handy” Handique, DeNovo’s CEO.

“A medical device company needs to satisfy the needs of the diagnostic

marketplace, and in2being is well versed in the regulatory landscape, as well

as very knowledgeable about the entire development process. They had the

right expertise from their HandyLab tenure, and I had absolute confidence

that they would do a high-quality job, providing the best solutions, in a tight

timeframe. In2being has been an excellent complement to our internal team;

they have been very responsive to our needs and evolving milestones.”

In the Trenches with DeNovo Sciences The development process should be

focused on solving the technical hurdles

before manufacturing. Starting the

acceleration process too early leads,

inevitably, to product failure and is

usually accompanied by an increase in

the burn rate as the company attempts

to compensate for the mishap.

Pushing the process too quickly, can

lead to a situation where every device

coming off of the manufacturing floor

is hand built, at some level, by the

development engineers, increasing the

cost of goods. Manufacturing will bring

its own set of issues to resolve, but

they should not be issues that violate

the core product assumptions.

Think of a product’s defined limits

and marketing expectations as guard

rails on a highway. The guard rails keep

the driver from going off the road; the

driver needs control over their own

process and vehicle to stay on the road.

During the development process,

the design should be driven to a

point where it works within the

expected outputs. Continually trying

to manufacture a product that keeps

running into the guard rails can be

very challenging, and potentially

monetarily destructive. Learning

earlier in the design and development

process how to keep everything within

limits will provide a more rewarding

manufacturing experience.

CONCLUSION Medical device design and

development is a custom-tailored

process; each product has a unique

pathway. To reach the end goal, a

solid foundation built on good data

is required. Careful planning defines

the user groups and implementation

environments, balances the four forces,

and establishes the design pathway

along with meaningful testbeds.

in2being is located at the crossroads

in downtown Saline, MI, and can be

contacted at www.in2being.com or

734.316.2623.

CIRCULATING TUMOR CELLS (CTC) REMAIN ONE OF THE MOST PROMISING AREAS OF CANCER RESEARCH FOR GUIDING PATIENT TREATMENT AND PREDICTING CANCER PROGRESSION. THE JETTA DEVELOPED BY DENOVO SCIENCES PERFORMS CTC ISOLATION AND CELL ANALYSIS USING DENOVO’S CUSTOMIZED CONSUMABLES.


Are you surrounded by a mound

of unpublished data and suffering

from writer’s block? The pressure

to publish clinical trial results can

feel overwhelming and often induces

anxiety in clinical development teams

across the pharmaceutical/biotech

industries. Compounding this angst

is the need for companies to meet

FDA-mandated timetables, which can

add to the pressure, especially for

smaller companies that may lack the

experience and resources to navigate

the publishing process.

The JB Ashtin Group, Inc.

(JB Ashtin) is a local scientific

communications agency that supports

biopharmaceutical, medical device, and

medical diagnostic companies with the

strategic dissemination of clinical trial

results. “Fifteen years ago, I started

my company because I enjoyed working

with pharmaceutical clients and being

able to use my medical writing and drug

information background. What started

as a small consulting business grew into

a full-service communications company

with the goal of being an extension of

biopharma teams,” says Joan Bradley,

PharmD, who is president and CEO of

the Plymouth, Michigan-based agency.

Dr. Bradley states that, “Scientific

writing and content development

are services we provide, but these

services come bundled with our deep

understanding of the regulatory

environment, a thorough knowledge

of best publication practices, and the

strategic awareness to know where and

how best to communicate our clients’

trial information.”

The rules that govern all aspects of

the pharmaceutical/biotech industries

are growing increasingly complex. The

same level of scrutiny and oversight that

governs the clinical trial process extends

into the dissemination of results.

To stay at the forefront of these

evolving regulations, JB Ashtin

encourages employees to join

professional organizations. ISMPP

offers a Certified Medical Publication

Professional (CMPP) credential, which

indicates an individual has advanced

proficiency in good publication practices

and a commitment to ethical and

By Lori J. Bainbridge

Helping Clients Publish and Publicize Medical Research

Select your target journal carefully.Determine:N Are you reporting signi�cant or novel results?N Who is your target audience?N Where are the best papers in your �eld being published?N What factors are important to you? Consider: Journal reputation/impact factor, circulation, visibility, speed of handling/publication, publication costs, subscription/open access

Determine authorshipN Agree on who is the primary author, corresponding author, name order (position is indeed important)N Determine who has responsibility for the integrity of the work. General rule: all individuals named as authors should qualify for authorship and all those who do qualify should be listedN Follow International Committee of Medical Journal Editors (ICMJE [Vancouver]) guidelinesN Keep an accurate record of who did what during the study

Prepare the manuscriptN Ensure your manuscript is complete, well written, well presented, and organized according to the journal’s requirementsN Ensure that all �gures are of good quality to publishN Prepare a detailed, well-written cover letter for submission to the journal of your choiceN Know how, where, and when to submit

After you’ve identi�ed your journaland before you write:N Read the journal’s Instructions for Authors very carefully: Highlight important aspects Know the journal’s policy requirementsN Collect your paperwork early – all necessary signatures, copyright permissions, ethics committee approvals, etcN Handle all ethical issues. Request guidance when necessary

Manage the review processN Respond quickly to all communications/requests by reviewers and editorsN Always be courteous and professional. Reviewers are people, tooN Share any new or relevant information you may have

5 Fundamental Tips for Getting Science Published

5 Fundamental Tips for Getting Science Published

JB ASHTIN GROUP, INC

© 2014 THE JB ASHTIN GROUP, INC.

transparent data dissemination standards. Most JB Ashtin

writers have this certification, or are pursuing it.

While no two clients are alike, all the companies

JB Ashtin support have one thing in common: the necessity to

communicate scientific information and the desire to improve

the health of patients. “We work with companies at all

phases of drug development,” explains executive director of

scientific services Lamara Shrode, PhD. “Some of our clients

have robust pipelines that require very large publication plans

that may include multiple scientific posters, abstracts, and

manuscripts, while other organizations may be in a start-up

mode and, therefore, have different needs.”

Recently, JB Ashtin added several Michigan-based

companies to their growing client roster, including Rockwell

Medical (Wixom) and Esperion Therapeutics (Plymouth).

“The ability to help companies in our own backyard gives our

staff a real sense of pride. Most of our writers are PharmDs

or PhDs who earned their degrees here in Michigan,” notes

Amy Horton, PharmD, a U-M alumna herself, who has been

with JB Ashtin since the early days of the organization and

serves as vice president of the scientific services team. A

few staff members even serve as adjunct faculty for the

University of Michigan College of Pharmacy.

Frequently, Dr. Bradley and her team are invited to speak at

industry events and offer advice on publication strategies.

JB Ashtin regularly has local pharmacy students who spend a drug information externship in their office and then go on to accept full-time employment with them. Shelly Asiala, PharmD, an alumna of Alma College and U-M, joined the agency after her rotation in 2012 and has become the principal scientific writer for a global skincare brand account the firm manages. “When I graduated, I knew that I didn’t want to follow the traditional career path of a pharmacist, such as a community pharmacy practice or a residency in pharmacy,” explains Dr. Asiala. “When I came to JB Ashtin, I discovered a new option that allowed me to stay connected to hard science and also exposed me to exciting aspects of drug discovery, development, and commercialization.” For information about careers with JB Ashtin, contact Cheryl Stone at [email protected].

JB Ashtin Hires Homegrown Talent

Several local companies have discovered the advantages of

partnering with a scientific communications agency. “Typically

our clients have a diverse set of responsibilities within their

organizations and are often pulled in many directions. When you

couple a heavy workload with a busy travel schedule, it becomes

increasingly difficult to manage the day-to-day responsibilities of a

communications plan,” explains Dr. Bradley.

“As a small biotechnology company, we rely on external

consultants and contractors with specific levels of expertise to help

us get things done,” reports Marianne Andreach, vice president,

strategic marketing and product planning at Esperion Therapeutics.

“We realized that we needed an experienced team to support our

own efforts with getting several manuscripts written and submitted

for timely publication, and we reached out to JB Ashtin.”

Raymond Pratt, MD, FACP, also sees the value of partnering

with an agency. He serves as chief medical officer at Rockwell

Medical and oversees the clinical development and FDA regulatory

process for Rockwell. “I’ve had the pleasure of working with the JB

Ashtin team now and when I was with a previous company. Their

professional and objective approach to the publications process has

been a great help with getting our clinical trial data published and

presented in a timely fashion.”

Writing, editing, and data verification are essential elements

of manuscript creation, but almost as time-consuming are the

administrative details. The ability to document the manuscript

development process and to provide audit-ready files is an essential

good publication practice.

“The FDA is looking at everything, especially if a company is

under a corporate integrity agreement,” cautions Dr. Horton. “Each

author’s participation in manuscript generation should be agreed to

in writing and documented throughout development.” Tracking this

kind paperwork and keeping on top of the manuscript submission

packages and the review process falls on the desk of the agency’s

publication managers.

In addition to providing writing and editorial services, JB Ashtin

collaborates with clients’ internal teams on strategic direction and

timing of publications, which helps to ensure that information will

reach the appropriate healthcare providers. The ultimate goal of

any publication plan is to provide clinicians with the information

they need to make better healthcare decisions for their patients.

For more information about the services JB Ashtin provides,

visit www.jbashtin.com or contact Joan Bradley, PharmD, at

734.459.3144.

Supporting Local Pharma is a Source of Pride

SHELLY ASIALA


The marketplace today has very high

expectations for their analyses that are

delivered with the highest of quality

and at a low cost.

Fortunately, that limitation is being

challenged in the life sciences realm.

As researchers develop increasingly

complex and potent new compounds,

the ability to analyze them quickly,

accurately, and cost effectively is

keeping pace, thanks to innovative

technologies and processes in

bioanalytical testing.

MPI Research, a clinical research

organization (CRO) headquartered in

Mattawan, Michigan, has conducted

thousands of drug safety, discovery,

surgery, medical device evaluation,

bioanalytical, and analytical studies.

Skilled scientists in a large-capacity,

state-of-the-art laboratory perform a

range of analytical services that meet

specialized needs in pharmaceutical,

chemical, and environmental science.

At the same time, the team is always

on the lookout for new and better ways

to assess the medicines of tomorrow.

COMPREHENSIVE SERVICE Bioanalytical testing determines the

quantity of a drug or metabolite in a

biological sample, i.e., blood, serum,

plasma, urine, tissue, or skin. Using

a wide array of tools, these tests are

applied to both small molecules and

biopharmaceuticals under GLP (Good

Laboratory Practices) requirements.

Increasingly, pharmaceutical

companies are outsourcing bioanalytical

testing to CROs. The right partner

can deliver quality results under tight

timeframes, thus allowing sponsors

to make key decisions on candidate

drugs earlier in development. A

successful enterprise means providing

scientific expertise and hand-in-

glove collaboration. Ensuring well-

designed, well-validated, and precise

analytical methodologies is central to

that commitment and critical to data

integrity.

CROs that offer robust solutions

possess the following core competencies:

• Preclinical and clinical bioanalytical

capabilities using LC-MS/MS for

small molecules, peptides, and

proteins and immunochemistry

expertise for the bioanalysis of

protein therapeutics

• Dose formulation and analysis for

early drug development studies

Beyond providing a full slate of

services is the ever-rising standard

of quality. Facilities, equipment,

methods, practices, and records must

meet— and exceed where possible — the

requirements of regulatory authorities

and, in the case of CROs, also those of

the sponsor. Likewise, compliance with

study protocols and standard operating

procedures is not just a measure of

success, but an expectation throughout

the life sciences realm.

MPI RESEARCH BIOANALYTICAL AND ANALYTICAL GYROLAB SOLUTIONS.

Taking the Forward View: ADVANCING

BIOANALYTICAL TESTING By Roger Hayes, PhD

MPI RESEARCH


CONSTANT EVALUATION The complexity of new chemical

entities presents significant challenges

to developing and validating

bioanalytical methods. Testing

capabilities—whether in-house

or through a CRO—need constant

evaluation and improvement. In taking

this forward view, MPI Research focuses

on five essential actions:

Investing in equipment to improve capabilities. As drug potency increases,

the ability to determine the level

of analyte in a sample challenges

the limits of instrument sensitivity.

Fortunately, new and more sensitive

instrument platforms are available,

including ultra-high performance liquid

chromatography (UHPLC) interfaced

with modern liquid chromatography

tandem mass spectrometry (LC-MS/MS).

Looking at new technologies. Many laboratories and CROs still use

conventional ELISA (enzyme linked

immunosorbent assay) methods for

immunoassay analysis. While 96-well

plate ELISA has its place, it’s being

challenged by new platforms, such as the

Gyrolab workstation and its CD format

that can conduct immunoassays using

only nanoliters of sample. These systems

are highly automated and offer a wider

analytical range, meaning faster analysis,

higher efficiency, and lower costs.

Assessing the impact of rising dose trials on patient safety. When

it comes to ensuring a medicine is

safe, the bar continues to rise. This

is especially true for rising dose trials

and first-to-file generic drugs, where

clinical bioanalysis requires high-

throughput with rapid turnaround of

results. Chemists turn to automated

liquid handlers to achieve productivity

on the order of 1,500 to 2,000 samples

per day. This strengthens evaluation of

safety and shrinks timelines—especially

helpful for Clinical Summary Reports in

first-to-file opportunities.

Using the most appropriate platform. The standard approach

isn’t always the best. LC-MS/MS is

the go-to platform for conventional

small molecules, but as new classes

are defined, other analytical tools

may prove to be a better option. In

addition to LC-MS/MS, the bioanalytical

team at MPI Research employs gas

chromatography-mass spectrometry

(GC-MS/MS) and inductively coupled

plasma-mass spectrometry (ICP-MS).

In short, it’s about using the right tool

for the right job.

Staying abreast of bioanalytical regulatory challenges. Reporting

analytical data reliably is at the core of

any successful bioanalytical operation.

Laboratories that perform regulated

analysis are routinely inspected

by worldwide regulatory agencies.

Each country’s authority has its own

requirements for method validation

and how methods are applied. These

requirements change regularly, so it’s

important to be connected through

forums such as the Global Bioanalysis

Consortium and the Global CRO Council.

FORWARD VIEW With the pressures of reducing

costs, improving timelines, and keeping

pace with increasingly complex

compounds, no company can afford

to take the easy path to analytical

testing—that is, doing things the way

they’ve always been done. While new

technologies and processes may present

challenges of their own, managing the

bottom line of drug development makes

looking for improved approaches to

testing worth the effort.

MPI Research is committed to

continuously moving forward. The

stringent scientific demands of the

pharmaceutical, animal health,

biotechnology, medical device,

environmental, and chemical industries

call for sophisticated and highly

sensitive bioanalytical/analytical

testing using both standard methods

and customized methodologies. MPI

Research offers analytical services

that are systematically designed and

structured, and which are grounded

in sound scientific principles to

provide data of the highest quality.

As collaborative, responsive partners

we provide flexibility in everything

from our scientific approach to our

scheduling. While we analyze the

typical biological matrices such as

plasma and urine, our bioanalytical

experience with all tissue and organ

types, along with a variety of other

unique requests, runs the gamut from

stents to retinas. In our large-capacity,

state-of-the-art laboratory, our skilled

scientific team performs a full range

of analytical services such as GC/MS

for volatiles, ICP-MS for elements and

metals, LC-MS/MS for small molecules,

and LBA for protein therapeutics to

meet the specialized needs of our

sponsors in a regulated environment.

MPI Research is ready to support

bioanalysis/analysis needs during

all phases of discovery, development,

or formulated finished product.

MPI RESEARCH BIOANALYTICAL AND ANALYTICAL LABORATORY SOLUTIONS.


MPI Research is more than an early stage CRO.

We continually think strategically beyond discovery and preclinical research to how our vast compound experience and scienti� c expertise can in� uence all phases to bring safer drugs to market faster and more e� ciently. With broad therapeutic coverage and a deep understanding of market forces that a� ect Sponsors, we share knowledge that’s beyond data to make a real di� erence in healthcare.

Beyond Expectations.

GO BEYOND

For more information, visit www.mpiresearch.com

That willingness to take the forward view is a

hallmark of the Michigan life sciences industry and

another reason why the state’s industry and MPI

Research continues to deliver solutions quickly, cost

effectively, and with the highest quality.

Roger Hayes, PhD, is vice president and general manager

of Laboratory Sciences at MPI Research. He has held

numerous leadership positions in the global life

sciences industry and academia, leading teams in

the development of state-of-the-art bioanalytical

and analytical techniques. With global headquarters

in Mattawan, Michigan, MPI Research serves the

biopharmaceutical, medical device, animal health,

and chemical industries with discovery research and

preclinical development services. www.mpiresearch.com

ROGER HAYES

Terumo® is a registered trademark of Terumo Corporation. ©2014 Terumo Cardiovascular Systems Corporation 851541

Terumo Cardiovascular Group and Terumo Heart, Inc., are Proud Sponsors of MichBio and Michigan’s

Growing Biosciences Industry

www.terumo-cvgroup.com | www.terumoheart.com

Life Science

Focus.

We understand your risks and unique issues!

At Hylant, our experienced advisors specialize in Life Science organizations so you can collaborate with a team who understands your business and bottom line.

Medical Devices | Clinical Research | Clinical Trials | Pharmaceuticals Biotechnology | Product and Technology Development

hylant.com

24 Frank Lloyd Wright Drive, Suite J4100 | Ann Arbor, MI 48105 | P 734-741-0044


Driven by the goal of advancing

the translation of human genetics

“lab knowledge” into practical medical

applications, University of Michigan

Professors John Langmore, PhD and

Vladimir Makarov, PhD founded Rubicon

Genomics in May of 2000. The founders

were dedicated to supporting the

economy of Michigan so there was no

hesitation in establishing headquarters

in Ann Arbor to maintain roots in the

community. More than a dozen years

later as Rubicon expands its footprint

around the globe, the state of Michigan

continues to play an important role in

the company’s growth as more than half

of its current staff has received degrees

from native universities.

Rubicon’s breakthrough product is

based on its PicoPLEX™ technology, used

worldwide for pre-implantation genetic

screening and diagnosis. PicoPLEX is

part of an assay that helps to detect

chromosomal anomalies and genetic

copy variations that may cause birth

defects, helping medical professionals

to select the most predictably viable

embryos for implantation. Rubicon’s

ThruPLEX® technology enables the

study of fragmented or small pieces

of DNA. Currently used for research

purposes, ThruPLEX supports the study

of specific samples such as plasma

that had previously not been possible.

This is enabling physicians to monitor

such events as the treatment of

USING RUBICON GENOMICS’ LATEST HIGH THROUGHPUT KIT, SCIENTISTS DOMINIQUE WILSON AND MAUREEN CAREY PREPARE DNA LIBRARIES FOR NEXT GENERATION DNA SEQUENCING.

Translating Human Genetics into Real-Time Medicine

RUBICON GENOMICS

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PICOPLEX™ DNA-SEQ KIT

individual cancer patients while they

are undergoing therapies. Rubicon’s

TransPLEX® technology is applied in

the study of cDNA, RNA that has been

converted to DNA in order to stabilize

it for analysis. TransPLEX is currently

incorporated into the Symphony™

suite of breast cancer diagnostic tests

manufactured by Agendia. Each of

Rubicon’s technologies consistently

provides reliable, unambiguous

results from small or degraded sample

material. Rubicon technologies are

currently contributing across the in-

vitro fertilization, infectious disease

testing, and cancer platforms.

But the small company’s story

wasn’t always rosy. In late 2009, after

nearly a decade of success, Rubicon

was stumbling in the faltering economy.

Dire economic straits gutted the

organization by November of that year,

leaving only four full-time employees

in place; all of whom are still part of

the company today. Enter CEO Dr. Jim

Koziarz and CFO Betsy Long. Regarding

the decision to take on the struggling

start-up, CEO Jim Koziarz said, “Betsy

and I looked at the technologies of

Rubicon Genomics and saw something

worth saving. That’s when we rolled up

our sleeves and made a commitment

to bring this company back with new

life.” Within two years Jim’s vision,

along with a small infusion of capital to

expand staff and develop new products,

landed the organization on solid ground

and it has not looked back.

The formation of a growing

global presence and network of

distributors has helped to fuel

Rubicon’s expansion. In back-to-back

years Rubicon has participated in the

Michigan State Trade Export Program

(STEP), a program operated by the

Michigan Economic Development

Corporation (MEDC) designed to help

small Michigan companies enter the

global marketplace. This program has

allowed Rubicon to attend international

tradeshows in Paris and Munich, leading

to the development of key global

partnerships and distribution channels.

COO Christine Haakenson is especially

grateful for these grants acknowledging

“these agreements reflect our strategy

of enhancing our existing global

distribution channels by partnering

with companies that know their local

markets and are able to provide a high

level of technical service and support.

They extend our reach in growing

sequencing markets around the globe

and enable our customers to access our

products without the additional cost

and complications of shipping from the

U.S. to global destinations.”

And Rubicon shows no signs of

slowing down. With an aggressive

new-product pipeline, rapidly growing

worldwide distribution network, and a

plan for a 30% increase in headcount for

2014, Rubicon will move this summer

to a fully renovated, 19,000+ square-

foot facility less than a mile from its

current location in Pittsfield Township.

Co-founder and Chief Scientific Officer

Dr. John Langmore has strong feelings

about keeping the company local,

“Rubicon was born in Michigan and

our roots are deep here. There was

never any consideration of moving the

company out of state and we’re here

for the duration.” Learn more about

Rubicon at rubicongenomics.com or

contact them at 734.677.4845.

Rubicon’s breakthrough product is based on its PicoPLEX™ technology, used worldwide for pre-implantation genetic screening and diagnosis. PicoPLEX is part of an assay that helps to detect chromosomal anomalies and genetic copy variations that may cause birth defects, helping medical professionals to select the most predictably viable embryos for implantation.


By Carrie Langbo

Recognizing the important role of

biorepositories in advancing medical

and public health research, the Michigan

Department of Community Heath (MDCH)

has joined our state’s drive in biobanking

expansion by allowing use of residual

newborn screening blood spot specimens

for health research through an innovative

program known as the Michigan

BioTrust for Health (BioTrust). Following

technological advances and steps to

improve preservation, use of residual

newborn screening blood spot samples

can make an important contribution to

current and future research.

In 1965 newborn screening (NBS)

for phenylketonuria marked the advent

of what is now a vital public health

program. Blood spots are collected

annually from more than 99.5% of

Michigan’s newborns to screen for

over 50 disorders. This has led to the

identification and treatment of more

than 5,100 Michigan infants with serious

disorders through the end of 2012.

Today, the BioTrust offers additional

public health benefits from newborn

screening. While many state NBS

programs still grapple with development

of policies regarding residual blood

spot storage and research, Michigan is

at the forefront with implementation

of the BioTrust. According to Director

James Haveman, “MDCH is optimistic

that residual blood spots will play an

important role in advancing population

health research. Through the BioTrust

program, we are eager to work

with pioneering researchers while

maintaining a commitment to uphold

the Department’s ethical and privacy

standards.”

MDCH first began the stepwise

process of examining issues surrounding

blood spot retention and use more than

two decades ago. Michigan’s public

health code establishes the foundation

for storage and research use of residual

blood spots, but numerous challenges

initially had to be addressed to ensure

adequate community education and

support. A legal expert roundtable was

convened and determined that MDCH

served as a trustee or steward having

“qualified ownership” of residual blood

spots. Multiple methods were also used

to gauge community views and beliefs

on issues such as individual autonomy

versus public benefit, acceptable

research guidelines and appropriate

methods to inform individuals about

BLOOD SPOTS ARE TAKEN SHORTLY AFTER DELIVERY FROM NEARLY EVERY INFANT TO PERFORM LIFE-SAVING NEWBORN SCREENING.

STATE OF MICHIGAN

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BioTrust Leads Nation as Resource for Public Health Research


participation. A BioTrust Community

Values Advisory Board was convened and

continues to advise MDCH on BioTrust

policies and methods to ensure on-going

and open dialogue surrounding the

often-complex ethical issues raised by

biobanking endeavors.

Ensuring individuals have the ability

to participate in the decision-making

process for their own or their child’s

blood spots has been an important

component of the BioTrust. There are

different methods to inform MDCH

about one’s choice depending on

the date the sample was collected.

Samples collected prior to July 1984

no longer exist, but those obtained

from July 1984 to the present day are

currently being stored in the BioTrust’s

designated biorepository, the Michigan

Neonatal Biobank, which affords optimal

temperature and humidity controls as

well as stringent privacy and security

measures. De-identified samples

collected prior to May 1, 2010, are

available for approved research under a

waiver of informed consent granted by

the MDCH Institutional Review Board. If

parents or individuals (≥18years of age)

are not comfortable with the potential

research use of blood spots, they can

contact MDCH and either request that

samples be destroyed or continue to

be stored but not made available for

research. MDCH staff has participated

in over 200 community engagement and

educational endeavors since 2010 to

increase awareness about the research

use of blood spots and parental options.

In 2010 Michigan became the first

state to implement a universal parental

consent process for research use of

residual newborn screening blood spots

as part of routine newborn screening

procedures following delivery. Samples

collected after April 30, 2010, are only

available for research if

parents grant consent

for the BioTrust or

for participation in a

particular research study.

Consented blood spot

samples are currently

available from about

60% of babies born since

May 2010. Historically,

blood spots from nearly

all babies born before

that time were available;

however, the more recent

consent process is a

necessary tradeoff to

ensure public support and

continued availability of

any specimens for health

research.

Residual newborn

screening blood spots

represent a population-

based sample and provide

a unique window for

studying prenatal and

neonatal environments—

making the specimens a vital resource.

As technology continues to advance

and investigators become more aware

of potential applications for blood

spot research, their use will become

increasingly important. Since 2009,

Michigan’s blood spots have already

been utilized in over 25 research

protocols investigating techniques

to improve newborn screening,

etiologies of childhood disorders as

well as associations with birth defects

and environmental agents or genetic

alterations. Dr. Rick Neitzel, a University

of Michigan researcher provides further

evidence stating, “The BioTrust has

been an incredible resource for my

work exploring the relationship between

heavy metals exposure and adverse

hearing outcomes among Michigan

newborns. Having access to a large

repository of newborn dried blood spots

supported by a tremendously helpful

staff has made my move into this area

of research substantially easier than it

would have been otherwise.”

MDCH looks forward to facilitating

the research use of residual newborn

screening blood spots and anticipating

the evolution of the BioTrust to meet

future research regulations. For

additional information regarding the

BioTrust including current policies and

procedures for approval of proposed

studies and privacy protection,

summaries of on-going research

and consent options please visit

www.michigan.gov/biotrust or contact

the Newborn Screening Program at

866.673.9939.

Blood spots are collected annually from more than 99.5% of Michigan’s newborns to screen for over 50 disorders. This has led to the identification and treatment of more than 5,100 Michigan infants with serious disorders through the end of 2012.

NEARLY 2 MILLION SAMPLES ARE STORED AT THE MICHIGAN NEONATAL BIOBANK.

30

Versicor is an electronics, controls, and software development

company based in Royal Oak, Michigan that is changing how medical

devices are developed. Versicor is made up of an eclectic team of

passionate entrepreneurs dedicated to filling the gaps in the medical

device industry through technological products that aim to serve

the community.

WHY VERSICOR Versicor solves tough problems for big thinkers. Versicor offers

turnkey design to distribution with capabilities ranging from controls

development, electronics, mobile design and development, big data,

and testing and validation. President Christie Coplen brings creative,

entrepreneurial problem solving and product development to Versicor

by utilizing her 15 years of leadership experience in progressive

management and product development roles. Versicor is a team of

engineers, entrepreneurs, and creative thinkers who are convinced

that innovation should be easier. Their combined experience has led

to improved product creation efforts, speed to market, increased

profitability, and maximized investment value.

THE TECHNOLOGY “Versicor works with both new medical device startups and

seasoned companies looking to make their ideas a reality,” says Christie

Coplen. Its robust hardware platform and model-based software enables

ideas to be transformed into reality. In fact, medical device products

produced by Versicor are developed four times faster

than traditional methods. Its platform also decreases

risk and reduces development cost for customers.

Versicor offers turnkey design to distribution with

capabilities ranging from controls development,

electronics, mobile design and development, data

analytics and validation, and verification. Versicor is ISO 13485 compliant

and stands with its customer through the FDA process.

A key element in improving care is expanding the ability to care for

patients outside of the standard hospital footprint. OEM’s and hospitals

will have to begin working with companies that understand systems,

connectivity, and communications that enable the transition occurring

in healthcare while integrating with historical systems. Versicor is

providing a solution to this transition. Versicor is not only known for

its impressive services and expertise. The company also makes it its

mission to serve its local community utilizing the

technology it has available to serve community needs.

SERVING THE COMMUNITY One such need came from Ed Slattery and his

family, whose lives dramatically changed two years

ago when a truck driver fell asleep behind the wheel,

killing wife Susan and disabling son Matthew, who is

now wheelchair-bound. Versicor wanted to help the Slattery family

by working to create a wheelchair accessible home.

The concept for the home is finding and defining a new “normal”

for the family. The home will consist of an open floor plan to

accommodate the wheel chair, special cook

tops, pull down cabinets, a therapy pool, and

even a lift chair, created by Versicor that will

allow Matthew to exercise in the safety of

his own home. The Versicor team provided

software development, electrical hardware, and

mechanical components for the lift chair. With extensive materials

research and consumer testing, Versicor translated the design concept

into a fully tested application.

By understanding the client’s needs, Versicor successfully converted

Ed’s idea into reality. The lift chair will be completed and installed in

May and the Slattery home should be completed in the next six months.

Continuing its support for the community through technology,

Versicor is launching Ideas to Action, a nation-wide contest

designed to help medical device, clean-tech, and transportation

entrepreneurs transform their project ideas

into products. Versicor will provide $250,000

worth of controls, electronics, and software

development services to contest recipients.

For more information on how Versicor can

help you turn your idea into a reality, visit

www.goversicor.com or call 248.914.5582.

Medical Device Technology that Serves the Greater Good

CAD DRAWINGS OF THE LIFT CHAIR THAT WILL BE INSTALLED IN THE SLATTERY HOME.

CHRISTIE COPLEN

VERSICOR



VWR_BIO_Consortium_7.5x4.875_final.indd 1 3/20/2014 10:34:18 AM

33

P.O. Box 130199Ann Arbor, MI 48113-0199

STAY CONNECTEDNEW WEBSITE LAUNCHED IN MAYwww.michbio.org

Features include:

Comprehensive Michigan Bioscience Directory

Expanded Preferred Purchasing Program

New MichBio Product Showcase (members can promote their goods and services)

A BioToolbox clearinghouse for bioscience industry resources

Member portal with access to online community, digital library, more

Enhanced news and events listings (members can now submit their own items)

Better social media integration

MICHBIO EXPO AND CONFERENCESEPTEMBER 30- OCTOBER1, 2014www.michbio.org/expo

This 10th annual event, to be held at the MotorCity Casino Hotel in Detroit, is Michigan’s premier bioscience gathering. The event will include local bioscience facility tours; a plenary speaker and keynote address; breakout sessions in human health, bioscience technology, and business growth tracks; bioscience and service provider exhibits; and more. Registration and exhibition details coming soon.

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.

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Documents

BioMatters - Spring 2014