Presentation to the Drug Information Association (DIA) Annual Meeting, June 26, 2013, focusing on: * Development of de novo concept * FDAMA changes * FDA guidances

1. An Overview of The “De Novo” Process
– Reclassifying Devices Automatically
Placed Into Class III
Michael A. Swit, Esq.
Special Counsel, FDA Law Practice
Duane Morris LLP

2. Disclaimers
• The views and opinions expressed in the following PowerPoint
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• These PowerPoint slides are the intellectual property of the
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3. Disclaimers
• These slides support an oral briefing and should not
be relied upon, solely on their own, to support any
conclusion of law or fact.
• This presentation is for general educational purposes
and does not constitute legal advice.
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4. Whence “De Novo”??
• Device Amendments of 1976 -- if not pre-
amendment or substantially equivalent (SE), a newly-
introduced device automatically placed in Class III
• Problems of Automatic Class III Status –
– PMA route mandated -- but many devices did not warrant
expense or time
– PMA for these devices may not reflect risk
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5. Whence “De Novo”?
• Problems of Automatic Class III Status ….
– PMA route is procedurally unwieldy --
• FDA -- first must issue rule officially classifying product
• Then -- separate rule requiring submission of PMA
– PMAs are substantively daunting -- clinical studies
raise expense
– Automatic Class III Status May Indirectly Cause SE
Drift -- firms trying to plug a new peg into an old hole to
avoid PMA route
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6. An “Answer” to Automatic Class III
Status – FDAMA?
• Devices Center -- began to address issue in “re-
engineering” -- which re-focused the agency on using
risk as linchpin of regulatory decisions
• Congressional Solution -- § 207 of the 1997 Food &
Drug Administration Modernization Act (FDAMA) --
“Evaluation of Automatic Class III Designation”
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7. Eligible Devices
• Legislative History -- “instructs the agency to limit
consideration to lower risk devices” found to be NSE.
[source: FDA 2/98 Guidance on 513(f)(2)]
– statute – is silent on what devices can be reclassified under de novo
• October 3, 2011 – New FDA Draft Guidance (DG)
– “this process provides a route to market for medical devices
that are low to moderate risk ...” -- that are automatically placed
in Class III (see DG at 3)
BUT CONTRAST --
– criteria to be applied – those under 513(a)(1) – thus, theoretically,
FDA should decide anew – “from an independent, risk-based
standpoint” -- if the device can be effectively regulated by Class II
or Class I controls (see DG at 4, Fn. 1)
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8. Risk Criteria – What Applies for
a De Novo Petition?
• March 2012 -- Final Guidance on Factors to Consider in Benefit-
Risk Determinations in Medical Device Premarket Approvals and
De Novo Classifications
– http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/Gu
idanceDocuments/UCM296379.pdf
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9. How A Device Becomes Eligible
for de novo Consideration
• To Be Eligible --
– 510(k) – old rule -- must have been submitted –and denied as NSE --
before could file de novo petition
– FDASIA – July 2012 -- eliminated need to submit a 510(k) first and
have it declared non-substantially equivalent (NSE)
• can directly request
• can include draft of special controls that would apply
• but, still can go via 510(k) – NSE – petition route
– FDA has 120 days to decide
– FDA can decline if:
• concludes device belongs in Class III;
• that appropriate special controls are not possible; or
• identifies an appropriate predicate
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10. The DG -- Additional Eligibility Criteria
• “New device should be low to moderate risk and
likely to meet the statutory standards for
classification into class I or class II under section
513(a)(1) … e.g., general and/or special controls
would provide reasonable assurance of safety and
effectiveness of the device; and …”
• You should sufficiently understand and be able to
explain all of the risks of the new device such that all
risks can be effectively mitigated through the
application of general and/or special controls.”
– DG at 5.
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11. DG: Two Approaches to De Novo
• PDS – “Pre” de novo Submission – newly created by
DG – not clear how FDA will deal with this in wake of
FDASIA.
– FDA – now says, in a new note at the start of 2011 DG, that you
should confer with FDA before filing a de novo petition
– would still appear to be a possible approach, but FDA does not
seem to have commented on the PDS post-FDASIA
• Traditional de novo petition – still technically available
after FDASIA
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12. The PDS
• Aim – early interaction with agency for a device for
which you feel there is no predicate and it is low or
moderate risk. Let’s FDA --
– see if device is suitable for de novo; and
– advise you on documentation needed in subsequent 510(k) and
de novo petition
– view on likely classification (II v. I)
– feedback on evidence, including performance or clinical data,
that may be needed to support the de novo petition
• Aim – make de novo process more predictable and
transparent
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13. The PDS …
• Format and Content (DG – Attachment 3)
• Timing – may be early, but should know intended use and key
aspects of device design
• Should contain “sufficient information to enable us to
provide guidance on the test methods and protocols to be
used for the collection of performance data.”
– FDA may ask for clarification or more info to address protocol
deficiencies or other types of data FDA wants
• will do so within 60 days of initial PDS submission
• Can request a meeting to discuss the PDS – no earlier than
30 days after PDS submission
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14. Format & Content of PDS
• Administrative Info
• Regulatory History
• Device Information &
Summary
• Classification
Recommendation
• Supporting Protocols
& Data
• Summary of Benefits
• Summary of Known &
Potential Risks to
Health
• Risk and Mitigation
Information
• Device Labeling
• Classification
Summary
Note – actual de novo petition is same
format, plus add section on how changed
since PDS (see Slide 20)
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15. FDA Review – The PDS
• Preliminary review – to see if PDS contains adequate info
to allow FDA to review for de novo suitability
– more info requests – within 60 days of PDS receipt
• fail to reply within 180 days – FDA will regard PDS as withdrawn
• Suitability Review – once FDA deems you have sent in
adequate info.
• Threshold questions FDA will ask:
– Is there a likely predicate device for the device?
– Is device a type that FDA has classified into Class III on risk?
– Is device a type that has been approved under a PMA?
If yes to any of these, FDA will send a letter immediately saying (i) you
are not eligible for de novo and (ii) why
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16. FDA Review – The PDS …
• If survive threshold questions, will continue PDS
review to see if general and/or special controls are
likely to be able to provide reasonable assurance of
safety and effectiveness
– if agree with de novo, then will send you a Suitability Letter
– if do not agree de novo is possible, will say why not
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17. The PDS – FDA Response
• “Suitability Letter”
– 60 days after receipt of all information needed to complete the
review (see Slides 15 & 16 for PDS review process)
– Will specify:
• whether the device appears suitable for de novo
– if not, why not
• the likely class
• likely special controls – if any
• necessary performance data [note – the data you gather may end up
raising issues that will take you out of de novo process and keep you
in Class III]
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18. Impact of a Positive PDS Suitability Letter
• Next step – concurrently submit both 510(k) and de
novo petition containing the info and data detailed in
the suitability letter
– Can x-reference between the 510(k) and the de novo petition
– Post-FDASIA – should not need to submit the 510(k); but
FDASIA also does not bar you from pursuing the “old”
approach to a de novo – i.e., 510(k) – NSE - Petition
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19. The Post-PDS Concurrent
510(k)/de novo Petition
• Screening review – within 20 days of receiving
concurrent submission to see if both are adequate
– if not, review clock reset to 60 days once you submit rest
• if don’t submit rest in 180 days, deemed withdrawn
• Substantive review
– does a likely predicate device now exist?
• If so, petition will not be filed and 510(k) will be reviewed per
Substantial Equivalence (SE) standard
• If not, will issue NSE within 60 days of the submission and then
file the de novo petition and review it (see Slide 23 for petition
review process)
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20. The “Traditional” de novo Petition
• Request for Evaluation of Automatic Class III
Designation
– Format & Content
• See Attachment 3 of DG for more detail
• Same as for PDS (see Slide 14) – but also describe all changes since
the PDS submission
– Describe the device
– Recommendation (if any) as to classification – supported in detail
– Reasons for Class recommended
– Identify risks and benefits of device – “all information and
evidence supporting the safety and effectiveness”
– The controls (general and/or special) to apply to the device
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21. The “Traditional” de novo Petition …
• The Request ...
– If recommending Class I, include info whether device
should be exempt from:
• 510(k)
• Design Controls
– If recommending Class II, include info on the special
controls to govern
– Any available data on human experience
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22. The “Traditional” de novo Petition …
• Due within 30 days of the date-stamp on the NSE
letter
– if miss that deadline, you can either submit a new 510(k) –
leading to a new NSE (and a new user fee) or pursue the PDS
route
• Addresses for filing – in DG at p. 8
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23. FDA Review –
“Traditional” de novo Petition ...
• FDA Review of Request
– initial review – for content sufficiency
– had 60 days to review and reply; post-FDASIA, FDA
may claim it is 120 days
– may go to an Advisory Panel (in 60-day period)
– may request additional info -- if you don’t reply in 30 days,
“FDA will maintain the device in Class III” (see 2/98
Guidance, p. 4)
– will also consider info in the original 510(k)
– Final action -- by written order (may be in form of letter)
classifying the device
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24. How the “Old” (not de novo)
Reclassification Petition Differs
• Is a public process – goes to FDA Dockets – in
contrast, the de novo “petition” has been to the
510(k) file and was not initially public
– but, will that change after FDASIA? Not clear, because
the technical language is not “petition,” but “request”;
not clear will go through public dockets
• “Old” petition -- see 21 CFR 860.134
• FDA must publish proposed order on
reclassification in Federal Register for public
comment
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25. De Novo Classifications -- Examples
• Diagnostic Assays
– Antigen Invasive Fungal Pathogens
– Sirolimus Assay
– Test Factor V Leiden Mutaions, Genomic Dna Pcr Kit
– Ninhydrin and L- Leucyl-L-Alanine (Fluorimetric), Phenylalanine
Assay
– Immunomagnetic, Circulating Cancer Cell Emuneration System
– Elisa Antibody, West Nile Virus
– Nitric Acid Breath Test
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26. De Novo Classifications – Examples …
• Heimlich Maneuver Assist Device (Sept. 30, 1999):
Class II
– Cardiovascular
• Intended Use: to remove a foreign body airway obstruction
through generation of expulsion pressure
• Risks: incorrect use resulting in damage to internal organs; faulty
design generating too much pressure resulting in patient injury
• Special Controls: labeling with instructions for reporting
complications; adequate instructions for lay users; design controls
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27. De Novo Classifications – Examples …
• Breast Lesion Documentation System (Jan. 31, 2003):
Class II
– Obstetrics Gynecology
– Intended Use: producing surface map of the breast as an aid to
document palpable breast lesions during clinical breast exam
– Risks: failure to produce appropriate map; misinterpretation;
improper use; skin irritation or toxicity; electric shock;
electromagnetic interference; tissue trauma
– Special Controls: labeling; materials safety information;
performance characteristics; bench testing; software information
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28. De Novo Classifications – Examples …
• Infrared Hematoma Detector (Dec. 20, 2011)
– Ophthalmic
– Intended Use: detection of traumatic supratentorial hematomas
of greater than 3.5 ml in volume that are less than 2.5 cm from
brain surface … to assess patients for need for CT scans but
should not serve as a substitute for CT scans
– Risks: excessive laser power, interference with other devices,
unit malfunction, software malfunction, operator errors, false
positives or negatives, adverse tissue reaction, battery failure
– Special Controls: Rx use, ES and EMC, Performance testing,
software requirements, biocompatibility, labeling, training
– Guidance document – not clear will be issued
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29. Examples of Special Controls
Imposed Via De Novo
* Many detailed device descriptions appear in the Guidance
Documents for inclusion in the 510(k), but are not listed specifically as
a special control.
* Clinicals -- many instances where the guidance created as the
“Special Control” says clinicals may be required if other data is
insufficient to show safety or effectiveness of the device, citing “Least
Burdensome” principle applicable to the device process.
* Animal testing -- was possibly required depending on other factors.
* Devices with software often required verification and validation as a
special control.
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30. Questions Not Yet Answered
(or clearly):
• Must the device be “low risk” – or is “lower” risk
enough?
• Is the agency applying consistent with law and
legislation?
• Do you want to recommend the class for your device
(you don’t have to)?
– If you do and recommend Class II, must include special controls
recommendation
• Is this the route for your device -- pros and cons?
• Is this route being used too little...too much?
• Ever see a Class I reclassification (has not yet
happened under formal de novo process)?
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31. For more information ...
• 21 U.S.C. §360c(f)(2) – Section 513(f)(2) of the Federal
Food, Drug, and Cosmetic Act
– See next slide
• 1998 FDA Guidance Document:
– http://www.fda.gov/downloads/MedicalDevices/DeviceReg
ulationandGuidance/GuidanceDocuments/ucm080197.pdf
• October 2011 Draft Guidance –
– http://www.fda.gov/downloads/MedicalDevices/DeviceReg
ulationandGuidance/GuidanceDocuments/UCM273903.pdf
• Matrix of De Novo Petitions Approved – 1998 to 2011 –
with Special Controls Detailed by Type
– (available from the speaker)
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32. 32
Section 513(f)(2) of Federal Food, Drug, and Cosmetic Act
(as amended by the Food and Drug Administration
Safety & Innovation Act of 2012; PL 112-144)
(2)(A)(i) Any person who submits a report under section 360(k) of this title for a type of device that has not
been previously classified under this chapter, and that is classified into class III under paragraph (1), may
request, within 30 days after receiving written notice of such a classification, the Secretary to classify the
device.
(ii) In lieu of submitting a report under section 510(k) and submitting a request for classification under
clause (i) for a device, if a person determines there is no legally marketed device upon which to base a
determination of substantial equivalence (as defined in subsection (i)), a person may submit a request under
this clause for the Secretary to classify the device.
(iii) Upon receipt of a request under clause (i) or (ii), the Secretary shall classify the device subject to the
request under the criteria set forth in subparagraphs (A) through (C) of subsection (a)(1) within 120 days.
(iv) Notwithstanding clause (iii), the Secretary may decline to undertake a classification request submitted
under clause (ii) if the Secretary identifies a legally marketed device that could provide a reasonable basis for
review of substantial equivalence under paragraph (1), or when the Secretary determines that the device is
not of low-moderate risk or that general controls would be inadequate to control the risks and special
controls to mitigate the risks cannot be developed.
(v) The person submitting the request for classification under this subparagraph may recommend to the
Secretary a classification for the device and shall, if recommending classification in class II, include in the
request an initial draft proposal for applicable special controls, as described in subsection (a)(1)(B), that are
necessary, in conjunction with general controls, to provide reasonable assurance of safety and effectiveness
and a description of how the special controls provide such assurance. Any such request shall described the
device and provide detailed information and reasons for the recommended classification.
(B)(i) The Secretary shall by written order classify the device involved. Such classification shall be the initial
classification of the device for purposes of paragraph (1) and any device classified under this paragraph shall
be a predicate device for determining substantial equivalence under paragraph (1).
(ii) A device that remains in class III under this subparagraph shall be deemed to be adulterated within the
meaning of section 351(f)(1)(B) of this title until approved under section 360e of this title or exempted from
such approval under section 360j(g) of this title.
(C) Within 30 days after the issuance of an order classifying a device under this paragraph, the Secretary
shall publish a notice in the Federal Register announcing such classification.
(3)(A) The Secretary may initiate the reclassification of a device classified into class III under paragraph (1)
of this subsection or the manufacturer or importer of a device classified under paragraph (1) may petition
the Secretary (in such form and manner as he shall prescribe) for the issuance of an order classifying the
device in class I or class II. Within thirty days of the filing of such a petition, the Secretary shall notify the
petitioner of any deficiencies in the petition which prevent the Secretary from making a decision on the
petition.

33. Questions?
• Call, e-mail or fax:
Michael A. Swit, Esq.
Special Counsel, FDA Law Practice
Duane Morris LLP
San Diego, California
direct: 619-744-2215
fax: 619-923-6248
maswit@duanemorris.com
• Follow me on:
– LinkedIn: http://www.linkedin.com/in/michaelswit
– Twitter: https://twitter.com/FDACounsel
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34. About Your Speaker
Michael A. Swit, Esq., is a Special Counsel in the San Diego office of the international law firm,
Duane Morris, LLP, where he focuses his practice on solving FDA legal challenges faced by
highly-regulated pharmaceutical and medical device companies. Before joining Duane Morris in
March 2012, Swit served for seven years as a vice president at The Weinberg Group Inc., a
preeminent scientific and regulatory consulting firm in the Life Sciences. His expertise includes
product development, compliance and enforcement, recalls and crisis management, submissions
and related traditional FDA regulatory activities, labeling and advertising, and clinical research
efforts for all types of life sciences companies, with a particular emphasis on drugs, biologics and
therapeutic biotech products. Mr. Swit has been addressing vital FDA legal and regulatory issues
since 1984, both in private practice with McKenna & Cuneo and Heller Ehrman, and as vice
president, general counsel and secretary of Par Pharmaceutical, a top public generic and specialty
drug firm. He also was, from 1994 to 1998, CEO of FDANews.com, a premier publisher of
regulatory newsletters and other specialty information products for FDA-regulated firms. He has
taught and written on many topics relating to FDA regulation and associated commercial
activities and is a past member of the Food & Drug Law Journal Editorial Board. He earned his
A.B., magna cum laude, with high honors in history, at Bowdoin College, and his law degree at
Emory University.
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