An Overview of The “De Novo” Process – Reclassifying Devices Automatically Placed Into Class III
3 likes460 views
The document provides an overview of the 'de novo' process for reclassifying medical devices that are automatically assigned to Class III. It discusses the challenges of such classifications, the legislative solutions like the FDAMA, and the criteria for reclassification under the de novo route, emphasizing the importance of risk assessment. Additionally, it outlines the procedural steps for submitting de novo petitions and the interaction with the FDA, detailing the requirements and potential outcomes of the process.
![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• October 3, 2011 – New FDA Draft Guidance (DG)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)
7](https://image.slidesharecdn.com/switdia2013-denovopresentation-171212012531/85/An-Overview-of-The-De-Novo-Process-Reclassifying-Devices-Automatically-Placed-Into-Class-III-7-320.jpg)
![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]
17](https://image.slidesharecdn.com/switdia2013-denovopresentation-171212012531/85/An-Overview-of-The-De-Novo-Process-Reclassifying-Devices-Automatically-Placed-Into-Class-III-17-320.jpg)
An Overview of The “De Novo” Process – Reclassifying Devices Automatically Placed Into Class III
- 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 slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Communities (formerly known as SIACs) or affiliates, or the law firm with which the presenter is employed, or any of the law firm’s clients. • These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, Drug Information Association Inc., DIA and DIA logo are registered trademarks. All other trademarks are the property of their respective owners. 2
- 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. 3
- 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 4
- 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 5
- 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” 6
- 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) 7
- 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 8
- 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 9
- 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. 10
- 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 11
- 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 12
- 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 13
- 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) 14
- 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 15
- 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 16
- 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] 17
- 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 18
- 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) 19
- 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 20
- 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 21
- 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 22
- 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 23
- 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 24
- 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 25
- 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 26
- 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 27
- 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 28
- 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. 29
- 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)? 30
- 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) 31
- 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 33
- 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. 34