dissecting newly released ode guidance documents€¦ · deciding when to submit a 510(k) for a...
TRANSCRIPT
What’s New, What’s Not, and How Will They Impact Your Submission Strategy
Sheila Hemeon-Heyer, JD, RACMassMEDIC FDA Update
December 12, 2017
Dissecting Newly Released ODE Guidance Documents
47 guidance documents applicable to CDRH issued• 32 final
• 15 draft
31 applicable across device types: 25 final, 6 draft
9 device specific: 3 final, 6 draft
4 IVD specific: 2 final, 2 draft
2 specific to clinical study design
1 specific to combination products
Complete list at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm
2
1. Deciding When to Submit a 510(k) for a Change to an
Existing Device: Oct. 25, 2017
2. Deciding When to Submit a 510(k) for a Software Change to
an Existing Device: Oc. 25, 2017
3. De Novo Classification Process, Oct. 30, 2017
4. Requests for Feedback on Medical Device Submissions: The
Pre-Submission Program and Meetings with FDA Staff, Sept.
29, 2017
5. Developing and Responding to Deficiencies in Accordance
with the Least Burdensome Provisions, Sept. 29, 2017
6. Unique Device Identification: Direct Marking of Devices,
Nov. 17, 2017
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CDRH presents webinars approximately 1 month after final guidance is issued
• Provide detailed review of guidance
• Answer stakeholder questions
Webinars are announced in advance. Sign up for email notices at http://go.fda.gov/subscriptionmanagement
Presentation slides and transcripts for past webinars are available online at https://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm411063.htm
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Replaces the withdrawn 1997 guidance
Does NOT change FDA policy or process for deciding when a new 510(k) is required to implement changes
Is intended to “enhance the predictability, consistency, and transparency of the “when to submit” decision-making process.”
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What’s the same?
• A new 510(k) is required if any one change:
Could significantly affect safety or effectiveness (+ or -) or
Result in a major change in the intended use
• Changes must be considered individually and cumulatively with all prior changes since the last 510(k) clearance
• Key is the risk-based assessment: does the change introduce a new risk or modify an existing risk?
• Assessment is pre-mitigation: new 510(k) may be needed even if V&V results show no actual change in risk level
• If decision is no, document per 21 CFR 820.30
• If decision is yes, document and file new 510(k)
• New 510(k) must describe the change(s) that triggered the 510(k) plus all other changes implemented since the last 510(k)
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What’s new?
• More details on risk-based assessment approach
• Consideration of the unintended consequences of changes
• More details on the role of V&V in the decision-making process
• Clarification that changes intended to significantly improvesafety and/or effectiveness will likely require a new 510(k)
• Clarification that expansion of the indications for use will likely require a new 510(k)
• More clarity on evaluating individual and cumulative changes
• More details on the information required in a new 510(k)
• Clarification that changes not requiring new 510(k) can be immediately implemented even if simultaneous with changes requiring 510(k)
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What’s new?• Flowcharts now accompanied by detailed explanations of
decision points
Labeling Changes
Technology, Engineering & Performance Changes
Material Changes
Technology, Engineering, Performance & Materials Changes for IVDs
• Appendix A provides hypothetical examples of changes with decisions in each of these categories
• Appendix B provides a discussion of the expected documentation with two examples
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New guidance for:• Software that is embedded within, a component of, or an
accessory to a medical device or IVD
• Stand-alone medical software
• Pre-amendments, 510(k) cleared, or De Novo classified
Out of Scope• Any changes other than software: use the “Deciding When .
. . Devices” guidance
If making both SW and non-SW changes, apply both guidance documents
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What’s the same?• Guiding Principles for decision-making are the same as in
the Device guidance
What’s new?• Principles specific to software
Recognizes that the impact of software changes on safety and effectiveness may not always be clear, especially for code maintenance or infrastructure changes
Potential for unintended consequences is greater for code developed without a clear architectural structure
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What’s new?
• Identifies and defines six common software change types
1. Infrastructure changes (software support systems)
2. Architecture changes (operating systems, hardware platforms)
3. Core algorithm changes (impact to intended use / performance)
4. Clarification of requirements (no change to functionality)
5. Cosmetic changes (no change to functionality)
6. SW maintenance (re-engineering or refactoring)
• Appendix A provides flowcharts and examples covering common types of software changes. Four questions:
1. Change made solely to strengthen cybersecurity? – document
2. Change made solely to return SW to specs of previous 510(k) (e.g., bug fix)? – likely document
3. Otherwise, apply risk-based assessment: new or modified risk?
4. Significant change to clinical functionality or performance?
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Four documents issued:
• De Novo Classification Process (Evaluation of Automatic Class III Designation), Oct. 30, 2017, final
• FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals, Oct. 2, 2017, final
• User Fees and Refunds for De Novo Classification Requests, Oct. 2, 2017, final
• Acceptance Review for De Novo Classification Requests, Oct. 30, 2017, draft
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What’s the same?
• Definition and principles of De Novo process
De Novo is a process to request classification of a device into Class I or II
A De Novo request is:
Denied - if FDA finds there is a valid predicate device or General and/or Special Controls are not sufficient to provide reasonable assurance of safety and effectiveness; or
Granted – results in creation of a new device classification for that device type, after which device #1 becomes predicate for future 510(k)s
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What’s new?
• Defines three pathways for De Novo Request
Following 510(k) NSE decision (traditional pathway)
Pre-Sub followed by De Novo (encouraged but not required)
Direct De Novo request (established by FDASIA in 2012)
• 510(k) NSE followed by De Novo Request
FDA will indicate in the NSE letter if the device may be suitable for De Novo classification
De Novo request can be submitted any time after NSE – 30 day requirement removed by 21st Century Cures Act in 2016
De Novo request can reference 510(k) for information, but must include additional sections specific to De Novo
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Pre-Sub for De Novo
• FDA provides feedback on whether device MAY BE eligible for de novo, the likely regulatory controls, and required documentation to support de novo
• Must be far enough along in development process for FDA to provide useful feedback
Enough data to show Special Controls can be developed
Evidence of why no suitable predicate
• Guidance provides recommendations for the information to be included in the Pre-Sub and sample questions for FDA
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De Novo Request
• Attachment 2 provides recommended content
• Similarities to a 510(k) (but no SE section)
• Sections unique to De Novo
Regulatory History – summary of any prior submissions
Classification Summary – justification for no existing classification, no suitable predicate device
Classification Recommendation (I or II)
Proposed Special Controls (if Class II)
Summary of benefits, risks, risk mitigations, and why probable benefits outweigh risks
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FDA review process similar to 510(k)
• 15 day administrative review per De Novo Refuse to Accept
(RTA) checklist – issued in draft, comment period ends Dec. 29
• Interactive review questions/requests can be issued at
reviewer discretion
• Additional Information (AI) letter can be issued by email – puts
review on hold, applicant has 180 days to respond
MDUFA IV established FDA performance goals
• Final decision reached within 150 days on 50% of requests;
increases by 5% each year
• No cycle goal(s) established
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MDUFA IV granted FDA authority to collect user fees for
De Novo Requests starting in FY2018
• Standard: $93,229 (30% of PMA user fee)
• Small business: $23,307 (25% of standard)
User fee exemption for devices solely intended for use in pediatric population
No refunds once De Novo is filed
If another De Novo for the same device type is granted after your De Novo is filed, you will be required to withdraw, submit 510(k), and pay 510(k) User Fee.
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Revision of the 2014 Pre-Sub guidance document
Adds details, but no significant changes
Table 1 provides
• List of Q-Sub types
• Method of feedback (written and/or meeting depending on Q-
Sub type
• Specific timeframes for feedback (from receipt of submission)
More detailed information about Q-Sub types
More detailed information about meeting process
More examples for content and questions of Q-Sub
types (including e.g., Q-Sub for HDE, Q-Sub for IVD)
December 12, 2017 19
Revision of a guidance issued in 2000
Applies only to deficiency letters issued for marketing applications
Provides guiding principles for issuing deficiencies
• Consider interactive review before drafting letter
• Deficiencies must be relevant to regulatory process
• Deficiencies must be based on least burdensome principles and necessary to reach regulatory decision
• Major deficiencies are those that must be resolved in order to reach favorable decision
• Minor deficiencies are those that must be resolved to meet regulatory requirements but are relatively straightforward
• Major and minor deficiencies should be distinguished and presented in order of importance to review deciion
• If only minor deficiencies, attempt to resolve interactively
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Supervisory review
• All deficiency letters will undergo supervisory review before issue to assure deficiencies meet the guiding principles
• Supervisors should consider the totality of all deficiencies to determine whether each individual request is appropriate
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Applicant response
• Guidance provides suggested format for responses
Restate FDA deficiency
Provide requested information, or alternative information and why it is appropriate, or why deficiency is not relevant to marketing decision
• Appendix A provides examples of appropriate deficiencies
• Appendix B provides examples of appropriate responses
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A device required to bear a UDI on its device label must have UDI direct marking on the device if it is intended to be used more than once, on different patients, with reprocessing before each use.
Reprocessing = high level disinfection and/or sterilization
Device marking must be permanent and last the expected life of the device
Device marking must include both DI & PI
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Exemptions only given if• Direct marking would interfere with device safety or
effectiveness
• Direct marking is not technologically feasible
• Single use device subjected to reprocessing for an additional single use
Document justification for exemption under quality system
Compliance dates • Class III devices: 9/24/2016
• Class II devices: 9/24/2018
• All others: 9/24/2020
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