The De Novo 510(k) Process - Is There Hope at FDA for Lower Risk Innovative Devices?

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FDA Legal Services -- for the life of a Life Sciences Company

Law Offices of Michael A. Swit

The De Novo Petition:

Is There Hope at FDA for Lower Risk,

Innovative Devices?

Michael A. Swit, Esq.

Vice President, Life Sciences

FX Conferences

An Audio Conference

February 15, 2012

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Standard Disclaimers

• These slides support the oral briefing provided by

this audio conference. As such, the reader should

not rely solely on these slides to support any

conclusion of law or fact.

• The views expressed in this webinar are mine alone

and do not necessarily represent those of any of my

clients or any other third party.

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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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Whence “De Novo”?

– 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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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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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• October 3, 2011 – New FDA Draft Guidance (DG)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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How A Device Becomes Eligible

for de novo Consideration

• To Be Eligible --

– 510(k) – must have been submitted

– found to be NSE – but not due to a failure of performance data;

rather due to:

• lack of an identifiable predicate;

• new intended use; or

• different technological characteristics raise new questions of S & E

– not previously classified in any class, including III

– request under 513(f)(2) -- due within 30 days of receipt of NSE

determination (timeline is statutory)

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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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DG: Two Approaches to De Novo

• PDS – Pre de novo Submission – newly created by

DG

• Traditional Petition

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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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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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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 18)

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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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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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The PDS – FDA Response

• “Suitability Letter”

– 60 days after receipt of all information needed to complete the

review (see Slides 13 & 14 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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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

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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 21 for petition review process)

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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 12) – 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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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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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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FDA Review –

“Traditional” de novo Petition ...

• FDA Review of Request

– initial review – for content sufficiency

– has 60 days to review and reply

– 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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How the “Old” (not de novo)

Reclassification Petition Differs

• Don’t need to have filed a 510(k)

• - Also don’t need NSE determination

• No time limit from an NSE finding

• Is a public process – goes to FDA Dockets – the

de novo petition is to the 510(k) file and is not

initially public

• “Old” petition -- see 21 CFR 860.134

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Statistics – Petitions by Therapeutic Area Panel (alpha order) Petitions Approved

Anesthesiology 2

Cardiovascular 2

Clinical Chemistry 6

Dental 3

EN&T 3

Gastro/Urology 4

General & Plastic Surgery 8

General Hospital 3

Hematology 1

Immunology 9

Microbiology 10

Neurology 4

Ob/Gyn 5

Ophthalmic 1

Pathology 1

Toxicology 2

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Petitions by Therapeutic Area

Panel (by # of de novo petitions processed) Petitions Approved

Microbiology 10

Immunology 9

General & Plastic Surgery 8

Clinical Chemistry 6

Ob/Gyn 5

Gastro/Urology 4

Neurology 4

Dental 3

EN&T 3

General Hospital 3

Anesthesiology 2

Cardiovascular 2

Toxicology 2

Hematology 1

Ophthalmic 1

Pathology 1

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Petitions by Year Approved Year Number Approved

1998 2

1999 1

2000 8

2001 2

2002 1

2003 5

2004 10

2005 5

2006 4

2007 7

2008 3

2009 4

2010 4

2011 8

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Special Controls by Type

Type of Special Controls How Often Required

Rx Status 62

510(k) Required 62

Labeling 55

Bench Testing and other Data Collection Duties 50

Guidance Document 48

Software Requirements 23#

Clinical Studies 20/16**

Biocompatibility Testing 22

Other Testing 21

Voluntary Standards Conformity 11

Device Description 6*

Animal Testing 5/3***

Design Requirements 5

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Notes on Special Controls

* Many detailed device descriptions appear in the Guidance Documents for inclusion in the 510(k), but are not listed specifically as a special control.

** 16 instances where Guidance 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

*** Three instances when animal testing was possibly required depending on other factors

# Four devices were listed as requiring if the product contained software.

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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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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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• 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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• 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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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)?

• Is this the route for your device -- pro’s and con’s?

• Is this route being used too little...too much?

• Ever see a Class I reclassification (has not yet happened)?

• Will Congress eliminate need for filing the 510(k) prior to the de novo petition?

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For more information ...

• 21 U.S.C. §360c(f)(2) – Section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act – http://www.fda.gov/RegulatoryInformation/Legislation/FederalFood

DrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/ucm110188.htm

• 1998 FDA Guidance Document: – http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationan

dGuidance/GuidanceDocuments/ucm080197.pdf

• October 2011 Draft Guidance – – http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationan

dGuidance/GuidanceDocuments/UCM273903.pdf

• Matrix of De Novo Petitions Approved – 1998 to 2011 – with Special Controls Detailed by Type – http://www.fdacounsel.com/files/De_Novo_Decisions_--

_1998_to_2011.xlsx

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http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/ucm110188.htm



http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080197.pdf



http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM273903.pdf



http://www.fdacounsel.com/files/De_Novo_Decisions_--_1998_to_2011.xlsx




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Call, e-mail, fax or write:

Michael A. Swit, Esq.


1422 Caminito Septimo

Cardiff by the Sea, CA 92007

Phone 760.452.6568

Fax 760.454.2979

Cell 760.815.4762

[email protected]

fdacounsel.com

Questions?

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About your Speaker …

Michael A. Swit, Esq. develops and ensures the execution of an array of legal services to clients, with an emphasis

on FDA challenges. His expertise includes FDA legal issues relating to product development, compliance and

enforcement, recalls and crisis management, labeling and advertising, submissions and related traditional FDA

regulatory activities, as well as clinical research efforts for drug, biologic, device, IVD, and other life sciences

companies, plus those in the food and dietary supplement industries.

Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. After seven years as a Vice

President at The Weinberg Group, a premier FDA scientific and regulatory consultancy, he returned to private law

practice to focus on bringing his vast and multi-faceted experience to serve the FDA legal needs of life science firms.

His legal career includes serving for three and a half years as corporate vice president, general counsel and secretary

of Par Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and

commercial perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as

CEO of FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products

for the FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel

in the FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food &

Drug Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first

practiced FDA regulatory law with the D.C. office of Burditt & Radzius.

Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial

activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and

editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the

Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences

sponsored by such organizations as RAPS, FDLI, and DIA. He received his A.B., magna cum laude, with high

honors in History, from Bowdoin College and his law degree from Emory University School of Law. Mr. Swit is a

member of the California Bar.

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The De Novo 510(k) Process - Is There Hope at FDA for Lower Risk Innovative Devices?