Advanced Strategies and Tactics for Using the De Novo Pathway

Advanced Strategies and Tactics
for Using the De Novo Pathway™
Presented by:
Michael Drues, Ph.D.
President, Vascular Sciences
Grafton, Massachusetts
and
Adjunct Professor of Regulatory Science, Medicine,
Biomedical Engineering and Biotechnology
For questions or more information, contact me at
(508) 887 – 9486 or mdrues@vascularsci.com or
join me on LinkedIn at www.linkedin.com/in/michaeldrues
GreenLight.Guru Webinar (December 7, 2017)
http://blog.greenlight.guru/topic/mike-drues
Taken from: Designing Medical Products Seminar Series
For additional information, call (508) 887-9486 or e-mail mdrues@vascularsci.com
© Copyright 2017 by Vascular Sciences and Michael Drues, Ph.D. All rights reserved.

For additional information, contact Dr. Drues directly at (508) 887-9486, e-mail mdrues@vascularsci.com
or via LinkedIn at www.linkedin.com/in/michaeldrues.
© Copyright 2018 by Vascular Sciences. All rights reserved.
THE DE NOVO PATHWAY: Strategies and Tactics
presented by: Michael Drues, Ph.D.
There are many pathways medical device manufacturers may use to bring devices to market. Some, like the 510K
and PMA, are commonly used while others like the de novo are not. Although the de novo has not been frequently
used in the past, recent changes in regulation have made this pathway more attractive to many device
manufacturers for the future. While all areas of medical device technology may benefit, the de novo is particularly
attractive in the areas of mobile medical apps, imaging and in vitro/companion diagnostics. In many ways, the de
novo is the simplest pathway to market, even simpler than the 510k! Taken further, the de novo may be used as a
competitive regulatory strategy not only to bring a device to market but also to create a barrier to entry to the
competition! Using the case study approach, participants will learn:
• what is the de Novo pathway and when can I use it?
• what were the recent changes in regulation and how can they be used today?
• how do I design my de novo submission to maximize my probability of success?
• how can I use the de novo pathway to my competitive advantage?
Bottom line: there are many pathways to market medical device manufacturers can use to bring their products to
market but unless you understand all of the different pathways, not just the ones commonly used, and the
advantages and disadvantages to each, then how can you do your job? What to know more? See:
Workshop: When the De Novo Pathway is the Simplest Way to Market (MDM/Anaheim, Feb, 2018) here.
Workshop: The De Novo Pathway: Tips for Success and Traps to Avoid (MassMEDIC, Feb, 2015) here.
Secrets of the De Novo (I): Why Aren't More Device Makers Using It? (MedDeviceOnline, 2/5/14) available here.
Secrets of the De Novo (II): Is De Novo Right For Your Device? (MedDeviceOnline, 2/18/14) available here.
The De Novo Pathway to Market (Journal of Medical Device Regulation, March, 2015) here (available upon request).
Instructor Biography
Michael Drues, Ph.D., is President of Vascular Sciences, an education, training,
& consulting company offering a broad range of services to medical device,
pharmaceutical & biotechnology companies including (but not limited to):
stimulating & innovative educational programing, brain-storming sessions,
prototype design, product development, benchtop & animal testing, regulatory
strategy, intelligence & clinical trial design, FDA presentation preparation &
defense, reimbursement, clinical acceptance, business development &
technology assessment.
Dr. Drues received his B.S., M.S., and Ph.D. degrees in Biomedical Engineering
from Iowa State University in Ames, Iowa. He has worked for and consulted with leading medical device, pharmaceutical
and biotechnology companies ranging in size from start-ups to Fortune 100 companies. He also works on a regular basis
for the U.S. Food and Drug Administration (FDA), Health Canada, the US and European Patent Offices, the Centers for
Medicare and Medicaid Services (CMS) and other regulatory and governmental agencies around the world.
Dr. Drues is an internationally recognized expert and featured keynote speaker on cutting-edge medical technologies and
regulatory affairs. He conducts seminars and short-courses for medical device, pharmaceutical and biotechnology
companies, the U.S. Food and Drug Administration (FDA), Health Canada, the US and European Patent Offices, the US
Centers for Medicare and Medicare Services (CMS) and other regulatory and governmental agencies around the world.
Finally, Dr. Drues is an Adjunct Professor of Medicine, Biomedical Engineering & Biotechnology at several universities and
medical schools. He regularly teaches graduate courses in Regulatory Affairs and Clinical Trials, Clinical Trial Design,
Medical Device Regulatory Affairs and Product Development, Combination Products, Pathophysiology, Medical
Technology, Translational Medicine and Biotechnology.

Published in the Journal of Medical Device Regulation (May 30, 2015) available here.
The de novo pathway – strategies and tactics to use and avoid
by Michael Drues, Ph.D., author of Guerilla Regulatory Strategy
Publication Date: May, 2015 Page 1 Copyright 2015 by J Med Dev Reg and Michael Drues, Ph.D. All rights reserved.

About the Author
Michael Drues, Ph.D., is President of Vascular Sciences,
an education, training, & consulting company offering a
broad range of services to medical device,
pharmaceutical & biotechnology companies including
(but not limited to): stimulating & innovative educational
programing, brain-storming sessions, prototype design,
product development, benchtop & animal testing,
regulatory strategy, intelligence & clinical trial design,
FDA presentation preparation & defense,
reimbursement, clinical acceptance, business
development & technology assessment.
Dr. Drues received his B.S., M.S., and Ph.D. degrees in Biomedical Engineering from Iowa State
University in Ames, Iowa. He has worked for and consulted with leading medical device,
pharmaceutical and biotechnology companies ranging in size from start-ups to Fortune 100
companies. He also works on a regular basis for the U.S. Food and Drug Administration (FDA), Health
Canada, the US and European Patent Offices, the Centers for Medicare and Medicaid Services (CMS)
and other regulatory and governmental agencies around the world.
Dr. Drues is an internationally recognized expert and featured keynote speaker on cutting-edge
medical technologies and regulatory affairs. He conducts seminars and short-courses for medical
device, pharmaceutical and biotechnology companies, the U.S. Food and Drug Administration (FDA),
Health Canada, the US and European Patent Offices, the US Centers for Medicare and Medicare
Services (CMS) and other regulatory and governmental agencies around the world.
Finally, Dr. Drues is an Adjunct Professor of Medicine, Biomedical Engineering & Biotechnology at
several universities and medical schools. He regularly teaches graduate courses in Regulatory Affairs
and Clinical Trials, Clinical Trial Design, Medical Device Regulatory Affairs and Product Development,
Combination Products, Pathophysiology, Medical Technology, Translational Medicine and
Biotechnology.
To learn more about the author, including his upcoming presentations and list of columns, podcasts
and webinars, visit his LinkedIn page here or contact him directly at::
Vascular Sciences
246 Magill Drive
Grafton, MA 01519
Phone: (508) 887-9486 / Fax: (508) 861-0205
E-mail: mdrues@vascularsci.com
URL: www.vascularsci.com
LinkedIn: www.linkedin.com/in/michaeldrues

1
Advanced Strategies and Tactics for Using the De Novo Pathway
For additional information, www.linkedin.com/in/michaeldrues,
call (508) 887-9486 or e-mail mdrues@vascularsci.com
Copyright 2018, Michael Drues, Ph.D.
© Copyright 2018 by Michael Drues, Ph.D. and Vascular Sciences. All rights reserved.De Novo Pathway: Strategies and Tactics 1
Advanced Strategies and Tactics for
Using the De Novo Pathway
presented by:
Michael Drues, Ph.D.
President, Vascular Sciences, Grafton, Massachusetts
and
Adjunct Professor of Regulatory Science, Medicine, and Biomedical Engineering
For questions or more information, contact me at or
(508) 887 – 9486 or mdrues@vascularsci.com
Join me on LinkedIn at www.linkedin.com/in/michaeldrues
De Novo Pathway: Strategies and Tactics © Copyright 2018 by Michael Drues, Ph.D. and Vascular Sciences. All rights reserved.2
Here’s what we’ll talk about…
✓ What is the de novo pathway?
✓ When to consider it and when not to?
✓ What are the advantages and disadvantages compared to
other pathways?
✓ How can we use the de novo to our competitive advantage?
✓ Why is risk mitigation important?
✓ How do we apply “regulatory logic,” i.e., case studies (most
important part!)
✓ Other interesting issues to ponder time permitting

2
First, an important disclaimer...
I can’t make you an expert in a few minutes!
I’m not even going to try but…
Remember my philosophy of education:
To teach you how to think not what to think!
Is it possible to think regulatory?
“Regulatory affairs is a way of
thinking much more than it is a body
of rules and regulations – or at least
it should be!”
Michael Drues (1964–)
Regulatory Strategist and Amateur Philosopher ☺
www.meddeviceonline.com/author/michael-drues
“Science is a way of thinking much
more than it is a body of knowledge.”
Carl Sagan (1934–1996)
American astronomer, author and science journalist
So how about this?
Maybe Carl Sagan would be proud!

3
Want
more?
Boring but free… basic mechanics, some tactics, absolutely no
strategy – that’s not FDA’s job, that’s your job!
https://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm582518.htm
Guest Editorial:
The de novo
pathway -
Strategies and
Tactics to Use
and Avoid
http://www.globalregulatorypress.com/
The De Novo Pathway (J Med Dev Reg, May, 2015)
Abstract available here.

4
Check it out!
Secrets Of The De Novo Pathway
(MedDeviceOnline, February, 2014)
Polling Question
How many were familiar with the de novo process (before today)?
How many have seriously considered the de novo pathway in
bring a medical device to the market?
How many have actually used the de novo pathway in bring a
medical device to the market?
Did you watch the recent CDRH De Novo webinar (11/21/17)?
Before we begin…

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The De Novo
Strategy, tactics and beyond…
When you think de novo,
what should you think of
Why?

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Could the de novo be
simpler than the 510k
Short answer: yes
Why?
What are the two most
important components of
a successful 510k
Substantial Equivalence Argument
and Risk Mitigation Strategy

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Is there a Governing Equation of the 510k?
Two fundamental equations of the 510k are:
1) 510k = SE + Risk
and
2) SE = Labeling + Technology
To simplify, combining 1) and 2) gives the Governing Equation of the 510k:
510k = (LabelingSE + TechnologySE) + Risk
Note: Risk = RiskBucket1 + RiskBucket2 + RiskBucket3
Simply put, any successful 510k has to solve the equation above i.e.,
valid and defensible solution  510k
no, invalid or indefensible solution  de novo, PMA…
In other words…
Don’t focus on what the regulation says – focus instead on
understanding the regulatory logic, i.e., thinking process,
which is infinitely more important than regulation!
What technology areas
are most applicable for
the de novo?
Many but here are the big three:
Mobile Medical Apps, Imaging and In Vitro Diagnostics (IVDs)
Bottom line:
If you’re working in of these, you should definitely consider the de novo!

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De Novo
“Process”
Question:
Which step is most
important? Why?
De Novo Classifications: FDA Drafts Guidance on Acceptance Reviews (RAPS, 27 October 2017) here / CDRH Guidance here
Is it possible to request a pre-
sub to discuss both a 510k and
de novo in the same pre-sub?
Question:
Is it two different devices OR same device with two different indications (one 510k other de novo?
Either way, my advice would be the same: do NOT combine them! -why?
• add confusion  make things worse
• unless both devices and/or indications are in same clinical area, dealing with two different
groups at FDA
• assuming in-person pre-sub (my usual advice), schedule both meetings in same day i.e.,
morningafternoon or consecutive days i.e., TuesdayWednesday (my preference) to minimize
travel costs, etc.
• other reasons…
A customer asked an interesting question…

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What does “de novo” mean
Any guesses?
• Latin: meaning from the beginning, afresh, anew, or beginning again
• Law: trial de novo or a new trial
• Marketing and advertising: means “again but in a different way”
This used to be the case but not any more… how so?
What do we call a successful de novo?
clearance… approval… granted… predicate?
What ‘guidance’ is available
More and more as time goes on… but is that a good thing?
Remember,
Popularity ∝ Amount of Regulation/Guidance
Maybe it should be
Popularity ∝ 1 / Amount of Regulation/Guidance
Hint: could less regulation be an advantage?

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“Primary” De Novo Guidance
Guidance: De Novo Classification Process (Evaluation of Automatic Class III Designation) (October 30, 2017) here
CDRH Webinar: De Novo Classification Process (Evaluation of Automatic Class III Designation) (November 21, 2017) here
A progression in guidance… but has there been a progression in thinking?
What other guidance is available?
2011 “draft” guidance 2014 “draft” guidance 2017 “final” guidance
When
not
if!
Additional De Novo Guidance
Acceptance Review for De Novo Classification Requests (CDRH Draft Guidance, October, 2017) here
Also see: De Novo Classifications: FDA Drafts Guidance on Acceptance Reviews, Finalizes Guidance From 2014 (RAPS, 27 Oct 2017) here
Recommendation:
We have it so use it but…
do we really need it?
a.k.a. the de novo RTA guidance!
…15 pages long!

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De novo Database
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm
Need more help
You’re paying for this anyway… you might as well use it!

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A great place for help…
Division of Small Manufacturers, International and
Consumer Assistance (DSMICA)
www.fda.gov/cdrh/industry/support/
Manufacturers Assistance and International Staff Telephone Numbers:
800-638-2041 or 240-276-3150
Consumer Staff Telephone Numbers:
888-INFO-FDA (888-463-6332) - FDA's toll free number
As of April 1, 2014 now called
Division of Industry and Consumer Education (DICE)
Device Advice
Everything you want to know about medical devices and more!
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm

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513(g)
Request for
Information
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/ucm127147.htm
Most common uses of 513(g):
✓ is my device considered a "regulated" medical device?
✓ is my device (based on technology and indications for use) exempt from PMN (a.k.a. 510k)?
✓ if I “modify” my device, must I submit a new 510k?
✓ if my device is truly new (no direct predicate), what pathway to market do I use?
More commonly used prior to 2008 – why? Hint: think user fees!
Tell don’t ask… lead don’t follow!
How commonly used
is the de novo pathway
Not very but it could be…
and it’s use is increasing!

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How commonly used is the de novo?
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm
Remember,
From 1998-2009 only 54 devices brought
to market (<5/year)
Since Congress changed the law,
13 successful de novo’s in 2012
Can you see a trend?
De Novo Statistics
November 3, 2017 MDUFA III Performance Report here.
Also see: The De Novo Classification Process: A Work in Progress (Med Dev Online, Sept 8, 2015) here.
Will this trend continue?
Hint: Think user fees!
Number of De Novo Requests Granted 18 28 18 26 25
Listed in De Novo Database as of 11/21/17 here
Do these numbers tell the whole story? Nope!
Why aren’t these numbers reported? Is this bias?

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Medical Device User Fee Act 2018
FY2017 MDUFA User Fees (Sept, 2017) available here.
➢ In effect: October 1, 2017 through September 30, 2018
➢ Beyond the Money: What’s new? What’s Missing?
Ramifications of
MDUFA 2018
Podcast: Did Congress just kill medical device
innovation? (Medical Design and Outsourcing,
September 6, 2017) available here.
Podcast: Impact on Medtech Innovation
(Medical Product Outsourcing, September 7,
2017) here.

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Look beyond the averages…
EP Vantage (July, 2015) available here.
Lots of people ask for averages…
but remember there is huge variability!
Why?
How does the “old” de novo
compare to the “new” de novo
In other words…
Where we were  where we are  where we’re going

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De Novo Pathway of the Past
Goal:
• Created in FDA Modernization Act of 1997 (FDAMA)
•  efficiency of bringing “low-risk” devices to market
• Reclassification of devices previously classified Class III due to lack of suitable predicate
• Section 513(f)(2) became known as “De Novo process”
De Novo process was:
• Manufacturer submits 510(k) with standard review including risk analysis and SE rationale
• If device determined NSE  device automatically classified Class III
• Manufacturer submits request for evaluation of Automatic Class III designation
Form of Down-Classification: Class III  Class I or Class II
• If risk is appropriate for class I / class II  device can be cleared via 510(k)
• New classification/product code created adding device to predicate pool expanding market for
other manufactures considering similar devices
• If device not ‘De Novo-able’  PMA for Class III is required
Time and Statistics:
• Ideal Time: FDAMA required review <60 days
• Realistic Time: 62 days (2006)  241 days (2007-2010)
• Start-to-finish: average 482 days
• >3X longer than 150 day review goal for 510(k)s
• FDA not required to provide updates concerning status nor can manufacturer track submission
• 1998-2009 only 54 devices brought to market (<5/year)
• “New de novo” process allows manufacturer to simply submit a request to FDA for de
novo classification without having a previously rejected 510(k) application (if Class II
special controls should be included)
• FDA has 120 days to issue a classification decision
• Should  popularity and  review time… time will tell!
Recommendation:
Consider all possible pathways to market before deciding to pursue any one
De Novo Today

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How long does a de novo review take?
“The average review time for de novo
submissions is currently 166 days.”
Dr. Bill Maisel, Deputy Center Director at CDRH
MassMEDIC FDA conference (12/11/14)
Remember,
These are averages… actual results may vary!
Depends on complexity and risk
Suggestion:
File this quote away…
you can use it to provide a “push” if necessary… gently of course!
Some things
never change!
“The "de Novo" 510(k) Process and the Reclassification of
Class III Devices” (RAPS, March, 2006)
“FDA’s key task in approving or denying a de
novo petition under FDAMA is not to decide
whether a device is new technology, but to
examine the risks it presents and whether
those risks can be handled via Class II
special controls or Class I general controls.”
In other words…
A strong risk mitigation
strategy is key!
But remember…
There are many
connotations of risk!

19
True is theory…
Reality is far more complex!
One view of risk…
Question:
Where does the de novo pathway fit in the risk continuum?
Hint:
Risk mitigation strategy is key but…
remember, there are many connotations of risk!
Risk Continuum
HighLow

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Factors to Consider When Making Benefit-Risk Determinations in
Medical Device Premarket Approval and De Novo Classifications
(FDA, March, 2012)
Speaking of Risk…
Using Regulation as a
Competitive Advantage
“The "de Novo" 510(k) Process and the Reclassification of
Class III Devices” (RAPS, March, 2006)
“A key tactical decision faced in the de novo
process is whether to recommend the class
for the device (remember, this is optional).
It is recommended that a manufacturer
suggest the class that gives it most control
over its destiny. For a Class II device, this
includes trying to influence the type of
controls that might be required, especially
something that might be difficult for
competitors to match.”
Or put another way, think…
Competitive regulatory
strategy!

21
What’s the biggest
advantage of the ‘de novo’
compared to the 510k
You’re starting out with a
blank canvas and you can
paint on to it anything
you would like – assuming
you can support it that is!
Who can explain?
What does blank canvas mean?
With a 510k you start
with this and you must fit
in someone else's box…
With a de novo you start
with this and others must
fit in your box!
Which would you choose?

22
Can we Third Party Review
a De Novo 510k?
What’s third party review?
Can we Third Party Review a De Novo 510k?
Original Search: 3/7/13
Updated search: 1/13/15
Same result – ZERO!
So…
No De Novo Third Party Review – No Surprise!
But not that simple…
What about PMA  510k via de novo pathway
 subsequent (new?) 510k via third-party review?
 new form of predicate creep?
Using the 510k database…
We get…

23
Can we de novo an accessory?
CDRH Guidance (January, 2015) available here.
Short answer:
Yes.
What’s an accessory?
“Accessory: A device that is intended to
support, supplement, and/or augment the
performance of one or more parent devices.”
“Parent Device: A finished device whose
performance is supported, supplemented,
and/or augmented by one or more accessories.”
Does this answer your questions?
Accessory has never been clear… and now we have:
“FDA encourages manufacturers to utilize the de
novo classification process to request risk-based
classifications of new types of accessories.”
Nothing new – still comes down to risk!
Want to know more about accessories?
Webinar: Final Guidance on Medical Device Accessories: Describing Accessories and Classification Pathway for New Accessory
Types (Feb, 2017) available here.
Not sure if this will help but…

24
Rules and Exceptions
Average regulatory professionals know the rules…
the best regulatory professionals know the exceptions!
James Thurber (1894 – 1961) was an American cartoonist, author,
journalist and playwright known for his cartoons and short stories,
published in The New Yorker magazine.
Is there an international
version of the de novo
No 510k  No de novo
Regardless of pathways available,
Every region should have some mechanism to bring “new” low-risk devices to
market in a least burdensome fashion… what its called really doesn’t matter!
Shakespeare said a rose by any other name still smells as sweet.

25
How do we view the world?
“Discovery is seeing what everyone else has seen
and thinking what no one else has thought.”
– Albert Szent-Gyorgi , 1937 Nobel Prize in Physiology and Medicine
Case Studies

26
Is this a medical device or a sex toy?
FDA News (May 29, 2015) available here.
Device Classification available here.
“The £200 OTC device is
a vibrator (white object)
to desensitize the penis
as part of a 6-week
training programme - it
also comes with a
lubricant”
Ad available here.
Medical Device – Regulated by FDA… Sex Toy – Not regulated by FDA
Who has had a
colonoscopy
Was it a pleasant experience?

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Case Study: PillCam
Given Imaging’s PillCam COLON Approved Via De Novo Pathway
✓ Indication: incomplete colonoscopy for reasons other than inadequate preparation
✓ Cleared via de novo pathway for low-risk devices with no [direct] predecessor on the market
✓ Clinical trial of 884 patients, PillCam identified 69% of patients with ≥ 1 polyp measuring
≥6mm and 65% with ≥ 1 polyp ≥ 10mm [Why a clinical trial?]
✓ Device has video camera at either end and transmits 4-35 frames per second over a 10-hour
period to a recording device worn by patient  computer compiles video footage [video (10 sec)]
FDANews, Feb. 3, 2014
Why (how) was this de novo-able? Hint: risk mitigation is key!
Many connotations of risk:
• Probability of direct harm to the patient / Risk to user/operator
• Probability of not using the device/drug (other options?)
• Probability of providing the “wrong” information (all diagnostics!)
• Many other types of risk
Bottom line: must acknowledge and mitigate all to maximize probability of success!
How was this brought to market? More importantly… why?
Hint: Think “regulatory logic”
Colon Capsule Imaging System Risks and Mitigation Measures
Identified risk Mitigation measure
Adverse tissue reaction Biocompatibility.
Equipment, malfunction leading to injury
Electrical safety, thermal and mechanical safety.
Software validation, verification, and hazard
analysis. Non-clinical testing. Labeling.
Interference with other devices and with this
device (e.g., interference with image
acquisition, patient information compromised)
Electromagnetic compatibility testing. Software
validation, verification, and hazard analysis.
Non-clinical testing.
Poor image acquisitions
Optical imaging performance testing Non-
clinical testing. Labeling.
Failure to excrete Labeling.
Misinterpretation of the captured images
Clinical performance data. Non-clinical testing.
Labeling.
Possibility of missing a polyp, or falsely
identifying a polyp
Clinical performance data. Software validation,
verification, and hazard analysis. Labeling.
Abdominal pain, nausea, vomiting, choking Clinical performance data. Labeling.
Federal Register (May 16, 2014)

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Case Study: XTag GI Pathogen Panel (GPP)
FDA Clears Gastroenteritis Diagnostic Device Through De Novo Pathway
✓ FDA cleared new diagnostic test capable of simultaneously testing to identify any of 11 causes
of infectious gastroenteritis caused by many possible pathogens (viruses, bacteria or parasites)
✓ XTag GPP (Luminex) cleared through De Novo process which allows “novel” devices to be
cleared without requiring the submission of a premarket approval (PMA) application
✓ Previously unapproved devices or ones without an approved predicate are generally presumed
to be high-risk class III devices and the de Novo pathway is meant to bring low-risk innovative
products to market more quickly
✓ Tests of the device showed it to be “comparable” to individual tests and that all positive
results need to be confirmed by additional testing to rule out the possibility of a
false positive result. [Why?]
RAPS Focus, Jan, 2013
Comparison to cancer diagnostic?
How was this brought to market?
More importantly… why?
Hint: Think “regulatory logic”
Next: NxTag Respiratory Pathogen Panel
How was this brought to market?
510k – why?
Why is this EASY to do?
Hint:
Textbook Label Expansion
(De novo Xtag  510k NxTag  ??)
+
Validate ‘platform’  ‘application’
Question:
What does substantial equivalence
mean in molecular biology?
For a platform technology,
How would you choose the first
indication? Second? Third?
Hint: Go for biggest market?
Not Necessarily!
GenomeWed, August 26, 2015 available here.

29
Clinical laboratory News (April, 2017) available here.
Why?
Why?
How?
LDT  De novo Label Expansion
There are many choices!
Life in the medical device world is never simple…
Learn to use them to your advantage!

30
Have you had enough
Just on last question…
Polling Question
As we approach the end of this workshop,
Do you now feel comfortable enough to at least be able to
seriously consider the de novo as a potential pathway to market
for the appropriate medical device?

31
Deep thoughts…
with Jack Handy (Saturday Night Live)
and now
Don’t just follow the
rules… think!
Rules are mostly made to be broken
and are too often for the lazy to hide behind.
General Douglas MacArthur (1880 –1964) was an American general in the US Army during the
1930s and played a prominent role in the Pacific theater during World War II. He was one of only
five men ever to rise to the rank of General of the Army in the U.S.

32
Where are you aiming?
The greatest danger for most of us is not
that our aim is too high and we miss it…
but that it is too low and we reach it.
Michelangelo Buonarroti (1475–1564) was an Italian architect, painter, poet and sculptor.
Taking inspiration from one of best…
“Here's to the crazy ones. The misfits. The rebels. The
troublemakers. The round pegs in the square holes. The ones
who see things differently. They're not fond of rules. And they
have no respect for the status quo. You can quote them, disagree
with them, glorify or vilify them. About the only thing you can't do
is ignore them. Because they change things. They push the
human race forward. And while some may see them as the crazy
ones, we see genius. Because the people who are crazy enough
to think they can change the world, are the ones who do.”
Steve Jobs (1955 – 2011), entrepreneur, marketer and inventor, the co-founder of Apple Inc. and widely recognized as a pioneer
of the personal computer revolution.
More importantly…
“Imagine where we could be if discontent for the
status quo was the norm rather than the exception.”
Can you guess who said this?

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Questions?
Comments?
Suggestions?
Criticisms?
Complaints?

(http://prodimages.vertmarkets.com/image/9e1fd361/9e1fd361-33b8-4587-a35e-
c7ff4d3c04fc/original/hto_fda.jpg)
Secrets Of The De Novo Pathway, Part 1: Why Aren't More
Device Makers Using It?
By Michael Drues, Ph.D., President, Vascular Sciences
The de novo classification option, introduced as part of the U.S. Food and Drug Administration Modernization Act of 1997 (FDAMA), was developed as a new regulatory
pathway for novel low-risk medical devices. Interestingly, this alternative to the lengthy premarket approval process (PMA) has never quite caught on among device
makers. In fact, it remains one of the least-traveled routes to market for new devices.
Why is this the case? In the first installment of this two-part series, we will seek to answer that question by exploring the history and evolution of the de novo pathway. We’ll
also examine some recent changes to the de novo process that should make it more desirable to manufacturers.
The Need For De Novo
If you want to bring a new medical device to the market but no similar device exists — in other words, there is no precedent or predicate device — the FDA will designate
that device as Class III, the highest the three classes, by default. Class III devices are subject to the rigorous and lengthy PMA pathway.
Let’s say, for the sake of discussion, you want to bring a band-aid to market. Hypothetically, there are no other band-aids on the market yet, so the default classification for
your regulatory submission is Class III, which would put it in the same category as an implantable artificial heart. You don’t need a lot of degrees after your name to figure
out that putting a band-aid in the same class as an artificial heart doesn’t make any sense.
So the de novo pathway was created by the FDA to essentially allow a manufacturer to down-classify a low-risk product, even if it is the very first of its kind. The term “de
novo” is Latin in origin, and while there are a number of different interpretations of the phrase, my favorite for this particular application is “again, but in a different way.”
The basic premise was to bring novel, low-risk medical devices to the market in a new, more efficient way.
Why Nobody Used The De Novo Path
Unfortunately, when the de novo pathway was initially made available, it required manufacturers to jump through a lot of hoops to use it, and thus wasn’t a very attractive
option. Here are the steps a manufacturer would need to take to access the pathway:
1. Submit a full 510(k) application for a new low-risk device to the FDA, with all of the necessary components, including risk analysis and substantial equivalence
rationale (more on this in a moment).
2. Wait for the FDA to review the 510(k) submission and eventually determine that the device has no substantial equivalent, automatically categorizing it as Class III.
3. Submit a new application for de novo down-classification.
4. Wait for the FDA to determine whether the device is low-risk.
5. If the FDA classifies it as low risk, the device finally enters the de novo premarket evaluation process. If not, the device ultimately must seek PMA.
The statistics support device makers’ reluctance to go the de novo route. The ideal review time stipulated by the de novo regulation is less than 60 days. However, in 2010
the average turnaround time for a de novo device was 241 days.
And when you look at start to finish — from the initial 510(k) submission to de novo market approval — the average overall time was about 480 days. That’s about three
times the traditional 150 days it takes the FDA to review a Class I (low-risk) device.
Once again, there was really no incentive for a manufacturer to do make use of the de novo option. In fact, I would argue that there was a disincentive. Compounding
matters, the FDA wasn’t required to provide updates to a manufacturer concerning the status of its application in this convoluted submission process.
Guest Column | February 5, 2014
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A Brief Word On Risk Mitigation
Before we discuss recent changes to the de novo process and the way the program looks today, I’d like to touch quickly on the matter of risk mitigation, since it’s a key part
of the de novo submission process. In fact, I think it’s one of the two most important components of any regulatory submission, along with the substantial equivalence
argument. No matter what else you have in your application, if you don’t have a very strong risk mitigation strategy and a very strong substantial equivalence argument, you
probably won’t to be successful.
Again, we should think of the de novo as a form of down-classification. In other words, you’re telling the FDA, “This device is classified as Class III for no other reason than
we’re the first ones to do it, but we don’t think that makes sense based on how the device works or its intended use. We think it should be Class II, perhaps even Class I.”
Obviously, to convince the FDA, you have to do everything you can to mitigate that risk. Otherwise you simply are not going to be successful.
(While a thorough discussion of this topic is beyond the scope of this article, you can learn more at my upcoming webinar De Novo Path to Device Approvals: Tips for
Speedy, Successful Outcomes (http://www.lifesciencetraininginstitute.com/doc/de-novo-path-to-medical-device-approvals-0001).)
Today’s Slimmed-Down De Novo Process
The good news is that, within the last year and a half, Congress has enacted changes to the de novo regulation that, at least in my opinion, have made the pathway much
more attractive for medical device manufacturers — at least for certain kinds of applications. Basically, FDA has simplified that process, streamlining it into what some
people are calling “the new de novo process” (even though it’s substantially similar to the “old” de novo).
Now all manufacturers of low-risk devices have to do is simply submit a request to FDA for de novo classification, right out of the gate. No longer do they need to first
submit a 510(k) and have it rejected. They go straight to FDA and say they have a new device with no precedent, but that it shouldn’t be considered Class III and here’s why.
(Again, here’s where a good risk mitigation strategy comes in.) The FDA then has 120 days to issue a classification. This streamlining of the process should, in my opinion,
reduce review times and increase the popularity of the de novo pathway moving forward.
Of course, only time will tell, but up until about a year ago, there had been a grand total of 80 successful de novo petitions since the program was introduced in 1997. That
means the average number of devices brought to the market using the de novo pathway was less than five per year. Over the last year, however, there have been 16
successful petitions — an increase of almost 3x in the number of medical devices coming to market through this seldom-used pathway. I think we’re beginning to see a trend
here or at least a potential for a trend that this could in certain circumstances become a more commonly used tool to get our medical devices on to the market.
Looking Ahead: De Novo And Third-Party Reviews
One interesting question to consider is, “How will the third-party review process affect the future of de novo?” It’s a rhetorical question, because it hasn’t happened yet, but
looking to the future, it certainly raises the question.
For those unfamiliar with third-party review, it’s a path that allows manufacturers making very low-risk medical devices to essentially sidestep the FDA instead. It’s very
similar to the notified body system that’s been used in the European Union (EU).
In the future, will manufacturers be able to utilize third-party review to get new medical devices successfully down-classified to Class I via the de novo process? If so, it
could lead to a very interesting form of predicate, which is one of the things that has really gotten the 510(k) program into a lot of trouble in recent years.
This is purely hypothetical, of course, but it illustrates an important point. We must always consider the long-term ramifications of any new regulation or change to
regulation, whether it’s for de novo or anything else.
Is De Novo Right For Your Device?
The bottom line is this: You need to understand all of the different pathways to market that are available for your particular medical device, not just the common ones — not
just the 510(k) or the PMA. You need to understand the advantages and disadvantages of each pathway in order to decide which one is best, given your particular situation a
given point in time. If you don’t know what the possible options are, then quite frankly, how can you do your job?
We’ll explore this topic further in the second installment of this two-part series, examining the concept of competitive regulatory strategy and how it relates to the de novo
pathway.
For a more detailed discussion of these and other topics related to de novo, check out my upcoming webinar De Novo Path to Device Approvals: Tips for Speedy,
Successful Outcomes (http://www.lifesciencetraininginstitute.com/doc/de-novo-path-to-medical-device-approvals-0001), which will take place on February 24 at 1:00
pm (EST).
Sources:
• FDA De Novo Process 101 For Medical Devices (http://blog.fdazilla.com/2011/04/fda-de-novo-process-101-for-medical-devices/) (April 2011)
• De novo device reclassification: What have you done for me lately? (http://www.ask-cato.com/2012/09/de-novo-device-reclassification-what-have-you-done-for-me-
lately/) (Sept. 2012)
About The Author
Michael Drues, Ph.D., is president of Vascular Sciences, an education, training, and consulting company offering a broad range of services to
medical device, pharmaceutical, and biotechnology companies. He has worked for — and consulted with — leading medical device,
pharmaceutical, and biotechnology companies ranging in size from start-ups to Fortune 100s.
Drues works on a regular basis for the U.S. Food and Drug Administration (FDA), Health Canada, the U.S. and European Patent Offices, the
Centers for Medicare and Medicaid Services (CMS), and other regulatory and governmental agencies around the world. He is also an adjunct
professor of medicine, biomedical engineering, and biotechnology at several universities and medical schools, teaching graduate courses in
regulatory affairs and clinical trials, clinical trial design, medical device regulatory affairs and product development, combination products,
pathophysiology, medical technology, translational medicine, and biotechnology.
He received his B.S., M.S., and Ph.D. degrees in biomedical engineering from Iowa State University.

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Secrets Of The De Novo Pathway, Part 2: Is De Novo Right For
Your Device?
By Michael Drues, Ph.D., President, Vascular Sciences
In Part 1 (http://www.meddeviceonline.com/doc/secrets-of-the-de-novo-pathway-part-why-aren-t-more-device-makers-using-it-0001) of this two-part series, we explored
the history of the FDA’s de novo classification — what it is, why it was established, why it has been underutilized by medical device makers, and what the agency has done in
recent years to make it a more attractive option.
But is de novo the appropriate pathway to market for your novel low-risk device? This second installment seeks to help you answer that question by contemplating several
key regulatory and business considerations related to the de novo process.
Risk Mitigation — The #1 Regulatory Consideration
From the regulatory perspective, the critical question to ask is: Do you feel confident that you can do a good job of mitigating the risk associated with your device in an FDA
submission? Risk mitigation strategy is important for any regulatory submission, but it is especially important for de novo submissions.
It is important to point out that there are many different connotations of risk. Most people think of risk in terms of the direct harm a medical device can cause to a patient.
However, that’s only one type of risk; there are others. For example, what harm can be caused to a patient if we don’t use a particular medical device?
Or consider the field of molecular diagnostics, which carries the risk of providing the wrong information. Let’s say you’re working on cancer diagnostics, and your device
says that the patient does have cancer when, in fact, they really don’t. Or even worse, what if your device says that the patient doesn’t have cancer when, in fact, they really
do? These are just a few types of risk, but there are others as well.
How does a manufacturer know when to use the de novo pathway? Most importantly, they need to determine whether they can mitigate the risk sufficiently to get the
device down to a Class II or even a Class I designation. If so, de novo is a viable option for your device.
Do You Really Have A Competitive Regulatory Strategy?
Viewing the de novo question from a strictly regulatory standpoint is shortsighted. You also have to be aware of the competitive landscape for your product — what the
military call situational awareness. Do you really want to lower the regulatory bar, which could accelerate your product’s time to market but also make it easier for the
competitors that will inevitably follow? The de novo question is as much a strategic business decision as a regulatory one.
This is where the development of a competitive regulatory strategy becomes critical. When most people hear that phrase, they think it means, “What did my competitor
do? What strategy did they use to get their product to market?” To me, that’s not competitive regulatory strategy. That’s playing follow the leader, because all you’re doing is
trailing what somebody else has done.
Competitive regulatory strategy means something very different to me. Anyone can design a regulatory strategy to get a particular medical device through the FDA to
market. The real challenge is designing a regulatory strategy that will not only get your product to market, but also act as a barrier to entry to your competition. Ideally, you
want your regulatory submission to make it more difficult for your present and future competition to get their products onto the market.
This is an aspect of regulatory strategy that, in my opinion, most regulatory folks never even consider, which is unfortunate. Many organizations view the regulatory process
as nothing more than overhead — a set of hoops they have to jump through whether they like it or not. Just a cost of doing business…
Guest Column | February 18, 2014
Design & Development (/resource/medical-device-design-development) Regulatory (/resource/medical-device-regulations)
Manufacturing (/resource/medical-device-manufacturing) Logistics (/resource/medical-device-logistics) Search
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I don’t look at it that way. If you have to jump through these hoops, how can you use those hoops to your advantage? Can you set those hoops up in a certain way so that you
can get through them while simultaneously making it a little more difficult for your competitors to do the same? If so, you can gain a pretty significant advantage in the
market.
Competitive Regulatory Strategy And De Novo
When you consider de novo in light of competitive regulatory strategy, the downside to pursuing this pathway becomes apparent.
As discussed in Part 1, if there is no precedent (predicate) for new device, its default class is Class III. The goal of the de novo process is to down-classify new, low-risk
devices to Class II or Class I, because it’s going to be easier for you to get your product onto the market. You also have to keep in mind, though, that you are also making it
easier for your competition to get their products to market afterwards.
So some companies opt not to use de novo, even when their products are well-suited to the pathway, because they don’t want to clear the path for their competition. The
classic example a large medical device manufacturer — with a lot of money and resources — that chooses to forgo the de novo option, because its competition is a bunch of
small companies and startups that are not as well-funded.
Lack Of De Novo Guidance = Opportunity
Over the last few years, FDA has published several guidance documents (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm297411.htm) either
directly or indirectly related to the de novo classification. However, there isn’t a ton of information out there on de novo and other less commonly used pathways, like the
humanitarian device exemption (HDE) and the custom device exemption (CDE). Quite frankly, the FDA only has a finite amount of resources, and they need to put the
majority of those resources into pathways that are used the most often, like the 510(k) and the PMA. I hear from a lot of frustrated manufacturers who want to use the de
novo but can’t find enough information.
On the surface, this lack of guidance may look like a disadvantage. But to me, it’s a huge opportunity. Rather than simply doing what somebody (FDA) tells you to do, you
can use it to your advantage and — to some extent — create your own path. Again, the goal of competitive regulatory strategy is to set a course that is the least burdensome
to you and more burdensome to those coming after you.
If you decide to go this route, do so with caution. I’ve seen the approach backfire on occasion: A manufacturer tries to make the path a little bit more difficult for its
competitors but fails to consider the future regulatory impact on the next generation of its own product. You don’t want to set up future hurdles for yourself. So it’s a fine
line — to a certain extent it’s like walking on the edge of a knife. Tread carefully.
For a more detailed discussion of these and other topics related to de novo, check out the upcoming webinar De Novo Path to Device Approvals: Tips for Speedy,
Successful Outcomes (http://www.lifesciencetraininginstitute.com/doc/de-novo-path-to-medical-device-approvals-0001), which I will host on February 24 at 1:00 pm
(EST).
About The Author
Michael Drues, Ph.D., is president of Vascular Sciences, an education, training, and consulting company offering a broad range of services
to medical device, pharmaceutical, and biotechnology companies. He has worked for — and consulted with — leading medical device,
pharmaceutical, and biotechnology companies ranging in size from start-ups to Fortune 100s.
Drues works on a regular basis for the U.S. Food and Drug Administration (FDA), Health Canada, the U.S. and European Patent Offices, the
Centers for Medicare and Medicaid Services (CMS), and other regulatory and governmental agencies around the world. He is also an
adjunct professor of medicine, biomedical engineering, and biotechnology at several universities and medical schools, teaching graduate
courses in regulatory affairs and clinical trials, clinical trial design, medical device regulatory affairs and product development, combination
products, pathophysiology, medical technology, translational medicine, and biotechnology.
He received his B.S., M.S., and Ph.D. degrees in biomedical engineering from Iowa State University.
You can reach him at mdrues@vascularsci.com (http://www.meddeviceonline.com/Feedback?address=mdrues%40vascularsci.com&referrer=http%3A%2F%
2Fwww.meddeviceonline.com%2Fdoc%2Fsecrets-of-the-de-novo-pathway-part-is-de-novo-right-for-your-device-0001).
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For additional information, www.VascularSci.com/seminars,
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novo-path-to-medical-device-approvals-0001
Want to know more? Follow Michael Drues on LinkedIn!

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