Photo courtesy Jake Evill (3D Exoskeleton) A Pathway to ... courtesy Jake Evill ... The goal is to...

April 2014 | ManufacturingEngineeringMedia.com 89

Additive manufacturing is now

producing all manner of medical

devices, and new ideas for the

process—ranging from printed

surgical tools and bone replace-

ments to human tissue—are

coming from designers and engineers daily.

Even the best idea, though, has little value in the

United States unless the Food and Drug Adminis-

tration gives its go-ahead for putting the device on

the market.

A Pathway to Approval for Additive-Made DevicesDevices made with additive manufacturing techniques often replace a similar, or predicate, device made in a different manner

Ilene WolffContributing Editor

Additive Manufacturing

Photo courtesy Jake Evill (3D Exoskeleton)

Jake Evill’s Cortex is a recyclable plastic exoskeleton that

would replace a fiberglass or plaster cast for a broken limb.

April 2014 f3 Additive.indd 89 3/21/14 10:39 AM

Because many new devices made with additive manufac-

turing techniques are, essentially, replacing similar devices

simply made with different manufacturing techniques, there is

often an easier “predicate” device pathway to federal regula-

tory approval.

This article examines three medical devices manufactured

with 3D technology, one of which obtained government ap-

proval in 2013: The OsteoFab Patient-Specifi c Cranial Device.

Scott DeFelice, president and CEO of Oxford Performance Ma-

terials (South Windsor, CT), which manufactures the device,

shares his experience working with the FDA.

“Essentially, say, ‘Here’s my device,and here’s a predicate device. Mydevice has the same intended useand it shares the same technical

characteristics as this previous device.’ ”

OsteoFab is Oxford’s brand name for polyethylene ketone

ketone, or PEKK.

We also look at two other, as-yet unapproved devices. One

is less intrusive than the OsteoFab skull patch, and would be

worn as an exoskeleton on the outside of the body to immo-

bilize and support a broken limb. The other is more intrusive,

and would create a prosthesis for a missing nose or ear from

a bioresorbable scaffold and a person’s own stem cells. Two

experts weigh in on what the FDA may require before approv-

ing these devices.

Patching the Skull

Oxford Performance Medical made headlines in early

2013 when its patient-specifi c cranial device, or skull prosthe-

sis, became the fi rst FDA-cleared, 3D-manufactured polymer

implant. The company produces the one-off devices that are

custom fi t for individual patients using PEKK-based OsteoFab,

its own product, and an EOSINT P 800 laser sintering 3D

printer in a computer-aided design process.

DeFelice said Oxford has made the skull prostheses for

more than 200 people in the year since gaining government

clearance to market the device. The devices are shipped within

fi ve days of receiving an order to locations in Europe, the Mid-

dle East and South America, in addition to the United States.

Oxford was due to break into the Japanese market in January.

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“We do them every week now,” he said of the devices.

Oxford obtained clearance to market the device within the

FDA’s self-imposed time frame of 90 days, he said, because

the government agency already had extensive data on the

biocompatibility and purity of the proprietary raw material,

OsteoFab; all processes were developed internally; and the

company controls the entire supply chain.

“In our cranial device, where things got complicated is that

we do patient-specific devices,” said DeFelice.

He explained that the FDA already had addressed the

patient-specific issue with metal skull prostheses, so the agen-

cy knew what to look for and that moved the process along.

“What it basically means at the end of the day is the FDA

will evaluate your ability to design and produce your product,”

he said.

Oxford had already done about 30 skull prostheses outside

of the United States before submitting its request for clear-

ance to the FDA. DeFelice declined to go into detail regarding

clinical trials.

His company recently submitted for approval a mid-face

implant (for the bone around the eye and cheek) A device for

spine fusion is in the works.

“So, it’s a very broad platform [for OsteoFab],” he said.

Going Independent

While DeFelice has in-house advisers to help with the

regulatory process, not everyone is so fortunate. For them,

there are independent consultants, some of whom previously

worked for the FDA.

One such consultant is Dennis Moore, of The FDA Group

(Westborough, MA), who has 30 years’ experience with the

government agency, both as an employee and an adviser.

“One thing that people should keep in mind is that it’s not

a very well-defined process,” he said. “Nothing is absolute.

I’ve seen exceptions to every rule.”

That said, Moore offers his three-step process for FDA

510(k) clearance (for Class II devices) or pre-market approval

(for Class III devices).

His step No. 1 is to determine what already-approved

item—a predicate device—most resembles your bright idea.

“And that’s not always an easy task,” Moore said.

The goal is to closely define what your device is by its

intended use.

“A toothpick becomes a device when you say it removes

plaque,” Moore explained. “A cotton swab may be a cosmetic

product until it’s used to clean a wound bed.

“The whole game is to ramp down your claim so you can

get clearance.”

Attorney James Lawrence, of the Coats & Bennett law firm

in the Research Triangle Park area of North Carolina, said of

the predicate device process: “Essentially, say, 'Here’s my

device, and here’s a predicate device.

“My device has the same intended use and it shares the

same technical characteristics as this previous device.’ ”

Lawrence, who has an undergraduate biomedical engineer-

ing degree in addition to his law degree, interned at the FDA.

He offers an insider tip about the predicate device process.

“FDA reviewers are wary of ‘predicate creep,’ where sub-

missions veer further and further away from something that’s

been approved,” Lawrence said.

Moore recommends making a blind call to the FDA’s Divi-

sion of Small Manufacturers Assistance line (1-800-638-2041

or 301-796-7100) and saying, “We’ve got this widget, what

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your device and the FDA will tell you where its staff thinks it fi ts. The process takes

30–60 days, Moore said.

It can pay off to match your invention to a predicate device carefully, he warns.

“If approached correctly and you can tone down the claim enough you can

sometimes avoid a clinical trial,” said Moore. Clinical trials typically require a mini-

mum of 50 patients, and each patient’s costs can tally $10,000 or more, he said.

Some makers get a toehold in foreign markets, where regulatory hurdles are

lower, before trying to get their device approved in the United States. This offers the

advantage of having patient usage data that can be included in an FDA submission.

“In some cases you can leverage that to a degree,” said Moore.

Lawrence is more optimistic.

“You can rely on data from trials that were conducted outside the US,” said

Lawrence. “You just have to make sure it complies with the laws in the country

of origin.”

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Oxford Performance Medical’s patient-specifi c cranial device, or skull prosthesis,

became the fi rst FDA-cleared, 3D-manufactured polymer implant.

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After figuring out what your predicate device is, Moore said

the next hurdle is to strategize the steps you need to take, and

itemize your costs. A white board and sticky notes—one for

each step—come in handy.

“You don’t want to get hit with an unexpected electrical

safety test that can cost $100,000,” he warned.

Moore’s Step No. 3 is to file a submission with the FDA

and answer any objections brought up by its reviewers. The

clock on the government’s 90-day timeframe stops ticking

while the applicant works on his answers.

The Emergo Group Inc., global consultants for medical

devices, got scientific about how long it takes the FDA to com-

plete the 510(k) process and has done periodic analyses.

“On average, it takes five months for the FDA to review

and clear a medical device 510(k) application,” wrote Scott

Schorre, vice president of global marketing for Emergo in

his 2014 analysis of 24,000 applications cleared from 2006

through 2013. “About two-thirds of all 510(k) submissions are

cleared within six months.”

Moore offers a warning.

“The FDA loves to get you wrapped in pre-submission

meetings, and there’s no timer on those,” he said. “Pre-

submission meetings are not required. If you feel you have

enough data to file a submission, then go ahead.”

Lawrence offers tips on what goes into that submission.

“The agency wants to see that in the history of designing

and trying to get your device on the market that you’ve gone

through a rigorous design process,” he said. “You have to

prove you have internal controls so designs are vetted and

peer-reviewed, tested and validated.”

Keep track of all changes to the device’s design, he said.

“At the end of the day your design history file will show the

evaluation of the designs from the beginning to the end,” said

Lawrence. “It’s not something foreign to the way engineering

is typically done.”

It’s always better to do your homework before submitting,

even going so far as to talk with the people who will be review-

ing your device.

You can even go one step further hire an FDA-authorized

third-party reviewer who can expedite the process for a price,

said Emergo’s Schorre, but the FDA still has final say-so.

“Do the math to see if it makes sense for your situation,”

he said.

What to do if the FDA rejects your submission?

“You can challenge those determinations by the FDA and

companies have tried to do that,” said Lawrence. “You can

appeal up the agency’s chain of command, and as a last

resort argue [in court] that the FDA made an arbitrary and

capricious decision.

“[But] courts are typically

very deferential to the scientific

expertise of federal agencies.”

Helping Bones Mend

Like DeFelice, Jake Evill also

has an idea for bone problems.

But his device would support,

rather than replace, bone that’s

been damaged. Its Cortex, an

exoskeleton made of recyclable

plastic that would replace plaster

or fiberglass casts. Plaster is

heavy, and both it and fiber-

glass are not water-resistant or

recyclable. Casts made of plaster

and fiberglass and are itchy and

smelly as well.

Cortex looks like a custom-fitted plastic web that fits over

an arm or leg: the device is more solid and less “webby” at

the site of the break to provide extra support. It opens like a

book, and snaps closed for one-time patient use. Once the

break is healed, Cortex can be tossed in the recycling bin.



The Emergo Group Inc. analyzed 24,000 510(k) applications cleared by the FDA from

2006 through 2013.

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“The Cortex exoskeletal cast provides a highly technical

and trauma zone localized support system that is fully ven-

tilated, super light, shower friendly, hygienic, recyclable and

stylish,” Evill wrote on his website.

To make Cortex, a patient would be X-rayed and 3D

scanned. Then computer-aided design would calculate the

device’s pattern for support in the area of the bone break, and

an algorithm would be used to 3D print the device.

Evill was an industrial design student in New Zealand

when he created Cortex. The James Dyson Foundation, estab-

lished by the creator of the Dyson vacuum cleaner, thought so

highly of Evill’s idea that it named him runner-up in its 2013

design engineering competition.

Attorney Lawrence said of Evill’s device: “That being out-

side the body it’s more akin to an arm sling or an orthopedic

brace. I have a hard time believing it wouldn’t be similar to a

predicate device.”

2-in-1 Devices

DeFelice and Evill aren’t the only ones making news with

their devices.

Two years ago, Dr. Scott Hollister, professor of biomedical

and mechanical engineering and associate professor of sur-

gery at the University of Michigan, used 3D printing to make a

life-saving device for a baby.

“FDA reviewers are wary of ‘predicate creep,’ where submissions veer further and further

away from something that’s been approved.”

Kaiba Gionfriddo, a 3-year-old from Ohio, passed the

two-year survival mark in February after receiving an emer-

gency experimental splint to keep his trachea open. Kaiba has

severe tracheobronchomalacia, a rare condition that causes

the airway to routinely collapse.

To make the splint, doctors at U-M CT scanned the affected

area of Kaiba’s respiratory tract, and used the images to design

and print the tube-shaped splint to help keep the area open.

When a pediatric otolaryngologist implanted it, Kaiba’s lungs

immediately started moving on their own in the operating room.

Unlike the skull prosthesis or broken limb exoskeleton,

though, Kaiba’s splint is expected to dissolve in his body as

his airway naturally matures. That’s because it’s made of

polycaprolactone, or PCL.

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Hollister explains that

it took him six mnths to

adapt PCL for use in his

EOS Formiga P 100 laser

sintering machine. Since

his success, he’s made

Kaiba’s splint as well as a

scaffold to regenerate bone

in the mandibule (jaw) for

an adult patient in 2013.

But there’s a twist in

the prosthesis for the adult

patient—a biologic growth

factor was adsorbed onto the PCL. The idea is that, as the

man’s own replacement bone grows, the PCL prosthesis will

dissolve, just like Kaiba’s splint.

So far in the United States, Hollister is using a PCL scaffold

seeded with stem cells and growth factor to grow replacement

ears and noses in pre-clinical research.

It’s possible to fashion a prosthesis from

a patient’s own bone and cartilage, but

often the soft tissue around the graft

breaks down. His idea would eliminate

another issue as well.

“You don’t need the surgeon to be

Michangelo in the operating room,”

said Hollister.

There are other issues still to be

resolved, but Hollister said the patient-

specific ears and noses would be clas-

sified two ways by the FDA: as a device

and as a biologic.

Attorney Lawrence predicts that as

scientists and clinicians make progress

in 3D biomedical engineering, the FDA

will increasingly encounter similar two-

in-one devices.

“This is a classic example,” he said.

“As far as regulation is concerned, it’s

probably [something] the Office of Com-

bined Products would look at.

“The question asked would be

what’s driving the overall therapeutic

effect? It’s something the agency deals

with fairly frequently.” ME

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Want More Information?

The Emergo Group periodically publishes analyses of FDA 510(k) clearance data.

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