de novo clearance is increasingly important as a pathway to … · 2019-06-04 · de novo clearance...
TRANSCRIPT
De Novo Clearance is Increasingly
Important as a Pathway to Market for
New Technologies: How Is the
Program Working Now, and What
Does the Future Look Like?
Sergio de del Castillo, De Novo Program Lead, CDRH, FDAPaul Gadiock, Counsel, Wilson Sonsini Goodrich & Rosati
Ankur Kaushal, Senior Manager, Regulatory Affairs, Roche Sequencing SolutionsModerated by Kristin Davenport, Of Counsel, Covington & Burling LLP
The De Novo Program
Sergio M. de del Castillo
De Novo Program Lead
Office of Regulatory Programs (ORP)
Office of Product Evaluation and Quality (OPEQ)
CDRH/FDA
3
Outline
• De Novo Program Overview
• De Novo Review Process
– Classification summary (eligibility)
– Special controls
• Program Updates
– Refuse-to-accept (RTA) Guidance
– Proposed rule
De Novo Program Overview
5
What Is a De Novo Request?
1. Intended for devices that are automatically classified into Class III (new device type)
2. Request to classify a new device type into Class I or Class II (not substantial equivalence!)
3. If granted:
▪ creates a new classification regulation
▪ new device type is now regulated through 510(k)
6
De Novo and Innovation
Precision Flow (DEN170001)Deliver high flow oxygen and humidification to patients with respiratory distress and/or hypoxemia
NSS-2 Bridge (DEN170018)Aid to reduce the symptoms of opioid withdrawal
7
De Novo and Innovation
IlluminOss (DEN160062)Treatment of fractures from metastatic bone disease
IDx-DR (DEN170018)AI-based software to detect more than mild diabetic retinopathy
8
De Novo User Fees
• Standard fee = 30% of PMA user fee
• Small business fee = 25% of standard fee
User Fee FY 2019
Standard Fee $96,644
Small Business Fee $24,161
9
De Novo Performance Goals
• Based on 150 FDA days– Different than statutory deadline of 120 FDA days
• Based on % of De Novo requests reaching final decision (grant or decline)
Percentage of De Novos with Final Decision by Day 150
FY 2018 FY 2019 FY 2020 FY 2021 FY 2022
50% 55% 60% 65% 70%
10
De Novo Requests Received in CDRH(as of 5/24/2019)
* Open cohort
19 22
46 42
59 54
99
5643
0
20
40
60
80
100
120
FY 2011 FY 2012 FY 2013 FY 2014 FY 2015 FY 2016 FY 2017 FY 2018 FY 2019*
11
Average Time to MDUFA Decision: De Novos*(Receipt Cohorts as of 12/31/2018)
1000
900
800
700
600
500
400
300
200
100
0
238
162
77
43
43
7051
74
62
13
666
557
109
765
445399
367 256
189
866
471
394
781
467
314
466
254
212
327
209
118
163
96
258 273
184
89
278
194
84
280
176
243
140
183
114
69
190 2018**
104 103
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017**
Fiscal Year (Receipt Cohort)
Total FDA Submitter
* MDUFA (Grant/Decline/Withdrawal/Deletion) decisions only; times may not add to total due torounding
** Cohort still open; percentage of cohort closed: FY2017: 95%; FY2018: 50%
De Novo Review Process
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De Novo Classification Goals
1. Identify probable risks to health for the device
2. Determine level of control needed to mitigate risks:
▪ general controls only = Class I
▪ general controls + special controls = Class II
3. Determine if probable benefits outweigh probable risks
These provide reasonable assurance of safety and effectiveness.
14
De Novo Review Process
• Goal → Review in 150 FDA days
• Two review cycles (~75 days each)
• Can request Additional Information
• Final decision: grant or decline
15
De Novo Review Process
Initial review (e.g., eligibility)
Substantive review
Internal briefing for De Novo Staff
Issue letter
16
Eligibility
• Must be a medical device
– (Section 201(h) of FD&C Act)
• Must not fit into any existing classification regulation
– No predicate device (NSE)
– Doesn’t fit into existing Class I/II regulation
– Doesn’t fit into existing Class III regulation
• No approved PMA(s) for the same device type
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Eligibility
Conduct a reasonably thorough search of similar devices and regulations:
• Classification regulations/product codes
– 21 CFR Parts 860 through 892
• 510(k)s
• PMAs
• De Novos
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Eligibility
For each search result, explain why your device is different, for example:
• New intended use
• Different technology that raises different questions of safety/effectiveness
• Different risks to health
If NOT eligible, then we decline the De Novo immediately (no substantive review).
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Granting a De Novo Request
✓ Identify probable risks to health
✓ Determine level of control needed to mitigate risks to health
– General controls only = Class I
– General controls + special controls = Class II
✓ Determine that probable benefits outweigh probable risks
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Special Controls and Performance DataIdentified Risk Recommended Mitigation
Measures
Supporting Data Contained in
De Novo
EXAMPLE: Adverse tissue
reaction
Biocompatibility Evaluation
(special control)
Testing in compliance with
recognized standard (Section
XX, page XXX)
EXAMPLE: Tissue
damage/trauma (due to
mechanical failure, software
anomaly, use error, etc.)
• Non-clinical Performance
Testing (special control)
• Device Specific Labeling
Requirements (special control)
Test protocols and results
(Section XX, pages XXX)
Draft device labeling (Section
XX, pages XXX)
EXAMPLE: Incorrect
interpretation of test results
Device Specific Labeling
Requirements (special control)
Draft device labeling (Section
XX, pages XXX)
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Risk/Mitigation (R/M) TableIdentified Risk Mitigation Measure
Infection • Cleaning Validation• Labeling
Adverse Tissue Reaction • Biocompatibility Testing
Skin Overheating / Burn • Clinical Performance Testing• Non-clinical Performance Testing• Software Verification, Validation & Hazards
Analysis• Labeling
Electromagnetic Interference / Electrical Shock
• Electromagnetic Compatibility Testing• Electrical Safety Testing• Labeling
Worsening Aesthetic Outcomes • Clinical Performance Testing
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Special Controls (for Class II devices)
• Legally required
• Written into the new classification regulation
• Each special control maps back to R/M table
• Least burdensome
Device MUST comply with identified special controls before the De Novo is granted.
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Special Controls (examples)1. Non-clinical performance data must demonstrate that the device meets all design
specifications and performance requirements. The following performance characteristics must be tested: over-heating, power accuracy radiofrequency, pulse cycle, waveform, pulse duration, and device characterization parameters.
2. The patient-contacting components of the device must be demonstrated to be biocompatible.
3. Labeling must include:a. Information on how the device operates and the typical course of treatment;b. A shelf life; andc. Validated methods and instructions for reprocessing any reusable components.
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New Classification Regulation
• Name of regulation (name of device type)
• Identification (description of device type)
– Intended use(s)
– Fundamental technological characteristics
• Regulation number (e.g., 21 CFR 878.XXXX)
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New Regulation (Example)Number: 21 CFR 878.4420
Name: Electrosurgical device for over-the-counter (OTC) aesthetic use
Identification: An electrosurgical device for over-the-counter (OTC) aesthetic use is a device using radiofrequency energy to produce localized heating within tissues for OTC non-invasive aesthetic use.
Program Updates
27
Draft De Novo RTA Guidance
• Purpose: Ensure De Novo request is acceptable for substantive review
• Facilitates efficient and timely review
• Similar to RTA policies for 510(k) and PMA
• MDUFA IV commitment (“submission checklist”)
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Draft De Novo RTA Guidance
• Determine if De Novo is administratively complete
• Not intended to be a substantive review
• Intend to complete RTA review within 15 calendar days of receiving De Novo
• De Novo is considered accepted if RTA review is not completed within 15 calendar days
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Draft De Novo RTA GuidanceAppendix A Appendix B
Acceptance Checklist Recommended Content Checklist
Required Not Required
Examples:Intended use
Device descriptionProposed special controls (if
recommending class II)
Examples:Prior submissions
Classification summary (eligibility)
Device labeling
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Draft De Novo RTA Guidance
• Not in effect at this time
• 60-day transition period after final guidance published
• Anticipated to be in effect late 2019
31
De Novo Proposed Rule
• Clarify statutory authorities
• Codify procedures for De Novo classification
• Provide greater transparency and predictability
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Major Provisions in Proposed Rule• Purpose and Applicability: Includes criteria for determining whether a device is
eligible for De Novo classification.• Format and Content: Identifies the basic structure and information/data required for
inclusion in a De Novo request.• Acceptance: Identifies the criteria for accepting a De Novo request for substantive
review, including required content.• Procedures for Review: Outlines the general procedures for review of a De Novo
request and other actions that may take place during the review and prior to a final decision.
• Actions on a De Novo Request: Outlines criteria for granting/declining and the circumstances under which a De Novo may be withdrawn from FDA review.
• Confidentiality: Describes our practices for the conditions under which the confidentiality of a De Novo request is maintained.
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Comments to Proposed Rule
1. Premarket facility inspections
2. Separating “S&E assessment” from “classification”
3. Disclosure
De Novo Clearance is Increasingly
Important as a Pathway to Market for
New Technologies: How Is the
Program Working Now, and What
Does the Future Look Like?
Sergio de del Castillo, De Novo Program Lead, CDRH, FDAPaul Gadiock, Counsel, Wilson Sonsini Goodrich & Rosati
Ankur Kaushal, Senior Manager, Regulatory Affairs, Roche Sequencing SolutionsModerated by Kristin Davenport, Of Counsel, Covington & Burling LLP