Big Legislative Changes: What You Need to Know to Meet the New - - PowerPoint PPT Presentation

Big Legislative Changes: What You Need to Know to Meet the New Challenges

May 29, 2018

PRESENTED BY:

Steven Niedelman Lead Quality System and Compliance Consultant FDA & Life Sciences Practice Group King & Spalding LLP (202) 626-2942 sniedelman@kslaw.com

Today’s Agenda

• Impact of FDA Reauthorization Act (FDARA) on

medical device industry

• aka MDUFA IV
• Current status of 21st Century Cures Act (21CC)

implementation of medical device requirements

FDA Reauthorization Act of 2017 FDARA

• Effective August 18, 2017
• Contains user fee reauthorizations
• PDUFA
• MDUFA
• GDUFA
• BsUFA
• Also contains provisions regarding drug development and

access, generic drug access

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MDUFA IV

MDUFA IV (FDARA §§ 201-210)

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• Significant fee increases, to meet increasing statutory revenue

amounts:

• FY 2017 actual to FY 2018 actual

– Establishment registration: 37% increase – PMAs and PMA supplements: 33% increase – 510(k): 125% increase

• New user fee for de novo submissions
• 30% of the PMA base fee
• Small businesses get a break on 510(k) fee increases
• Increase of 12.6% from FY 2017 to FY 2018
• But increase of 33% on PMA-related user fees
• No reduction of establishment registration fees
• New statutory requirement to apply an inflation adjustment to the

user fee every year, including FY 2018

User Fees, FY2018-2022

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Fee Type MDUFA III FY 2017 FY 2018 MDUFA IV (FDARA) FY 2019 FY 2020 FY 2021 FY 2022 Establishment registration $3,382 $4,624† $4,548* $4,760* $4,975* $4,978* PMA/BLA $234,495 $310,764† $300,000* $310,000* $328,000* $329,000* 510(k) $4,690 $10,566† 3.4% 3.4% 3.4% 3.4% De Novo classification n/a $310,764† 30% 30% 30% 30% Panel-track supplement $175,871 $233,073† 75% 75% 75% 75% 180-day supplement $35,174 $46,615† 15% 15% 15% 15% Real-time supplement $16,415 $21,753† 7% 7% 7% 7% BLA efficacy supplement $234,495 $310,764† 100% 100% 100% 100% PMA annualreport $8,207 $10,877† 3.5% 3.5% 3.5% 3.5% 30-day notice $3,752 $4,972† 1.6% 1.6% 1.6% 1.6%

† Adjusted for inflation

* Subject to adjustments for inflation and to meet statutory revenue goals Note: Small business fees are 25% of the listed amounts, except for the 30-day notice (50%) and establishment registration (no reduction) fees

Device Provisions in FDARA

Inspections: Risk-Based Schedule (FDARA § 701)

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• Requires FDA to conduct establishment inspections on a risk-based

schedule, using the following factors:

• Compliance history
• History of recalls
• Inherent risk of the device
• Inspection frequency and history

– Whether there were any FDA inspections in theprevious 4 years – Foreign government inspections – Participation in international device audit programs (e.g., MDSAP)

• Replaces statutory requirement to inspect Class II and III device

establishments every 2 years

Inspections: Uniform Processes and Standards (FDARA § 702)

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• Requires FDA to establish “uniform processes and standards” for

routine (not for cause) device inspections, to include:

• Exceptions to processes and standards
• Pre-announcement of routine inspections

– Within a “reasonable time” in advance – Notification regarding the type and nature of the inspection

• Estimate of the inspection timeframe
• Opportunity for advance communication regarding working

hours and records to be requested

• Regular communication during the inspection regarding the

inspection status

• Draft guidance required by February 18, 2019

Inspections: Feedback (FDARA § 702)

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• New statutory requirement for FDA to provide feedback on afirm’s

483 corrective actions, upon request

• Feedback required if:
• Request is “timely”
• Corrective actions relate to:

– Public health priority – Systemic or major actions, or – Emerging safety issue

• Response within 45 days after receipt of a request
• Feedback is nonbinding

Inspections: Draft Guidance (FDARA § 702)

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• Draft guidance required by February 18, 2019

– Device inspection processes and standards for routine inspections – Feedback on corrective actions – Standard methods for communication regarding inspections and feedback – Standard timeframes for foreign and domestic device inspections

• Occurring over consecutive days
• Extensions upon investigator’s identification of a reason to

the establishment – Practices “to facilitate the continuity of inspections”

Inspections: Refusals (FDARA § 702)

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• Devices are now deemed adulterated if an establishment delays,

denies, limits, or refuses an inspection

• FDA Guidance, “Circumstances that Constitute Delaying,

Denying, Limiting, or Refusing a Drug Inspection” (Oct. 2014)

• Delay

– Postpones the start of an inspection without reasonable explanation – Leaves the investigator without access to requested documents or personnel for unreasonable time

• Limiting

– Discontinues manufacturing during inspection or limits direct observation without reasonable explanation – Prohibits photography without reasonable explanation – Unreasonably redacts requested documents

Inspections: Pathway to CFG Issuance (FDARA § 704)

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• FDA must provide a written explanation of the basis for a CFG denial
• Identify the finding upon which the denial is based
• For denials based on QSR non-compliance, include a substantive

summary of the specific grounds for noncompliance – Unless basis is injunction, seizure, Class I or II recall

• Prohibits CFG denials based solely on 483 observations if the firm “has

agreed to a plan of correction”

• Requires process for a review of CFG denials
• Firms can request a review and submit new information, including

evidence of corrective actions to address the identified non- compliance

• Requires draft guidance by August 18, 2018

Inspections: International Recognition (FDARA § 705)

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• Adds statutory permission for FDA to “recognize” auditors usedby
• rganizations established by foreign governments
• Improve international harmonization of inspection standards
• Increase FDA access to audit data
• FDA retains ability to classify inspections
• Related: FDARA § 703 reauthorizes FDA’s ability to conduct

inspections via accredited organizations through 2022

Pediatric Devices (FDARA § 502)

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• Extends for five years the ability to sell pediatric Humanitarian Use

Devices for more than the development and production cost of the device

• Until October 1, 2022 (unless extended again before then)
• Requires FDA to hold a public meeting to discuss thedevelopment,

approval, or clearance and labeling of pediatric medical devices

• Scheduled for August 13-14, 2018

– Registration open until August 6 – Meeting will be webcast – More details here: https://www.fda.gov/MedicalDevices/NewsEvents/Workshops Conferences/ucm596777.htm

Medical Device Accessories: Alternative Pathway to Market (FDARA § 707)

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• Pathway for classification and reclassification of accessories based on the

accessory’s risk, not the parent device

• Initial classification: may request separate classification of parent device

and accessories in 510(k) or PMA submission

• Reclassification: may request reclassification of accessories already

approved or cleared under a parent device’s PMA or 510(k) – FDA must provide opportunity to meet before submission of written request – FDA must respond to the request within 85 calendar days

• If FDA denies the request, must include a detailed justification
• Must publish granted reclassifications in the Federal Register

within 30 calendar days

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm5 89858.htm

• Every 5 years, FDA must publish a proposed list of Class I accessory types

Report on Quality, Safety and Effectiveness

• f Servicing Medical Devices
• FDARA Section 710 charged the Secretary to issue a report on the

continued quality, safety and effectiveness of medical devices with respect to servicing that was published May 15, 2018, on its due date

• Report as an outcome of March 4, 2016 FR Announcement requesting

comment on “Refurbishing, Rebuilding, Remarketing and Servicing of Medical Devices mostly by third party providers

• FDA held open public workshop on October 27-28, 2016 on the same

topic.

• Based upon information presented as well as other objective evidence

available to FDA, they concluded:

• The currently available objective evidence is not sufficient to conclude whether

there is widespread public health concern related to servicing including by third party providers that would justify imposing additional/different regulatory requirements

• Objective evidence reviewed indicated to FDA that both OEMs and third party

providers provide high quality, safe and effective servicing

• FDA did not find objective evidence to conclude there is a widespread public

health concern related to servicing provided by third party providers.

Report on Quality, Safety and Effectiveness

• f Servicing Medical Devices (cont.)
• FDA is proposing the following:
• Promote adoption of Quality Management Principles by

third party providers

• Clarify the difference between servicing and

remanufacturing

• Strengthen cybersecurity practices associated with servicing
• f medical devices
• Foster evidence development to assess the quality, safety

and effectiveness of medical devices

Over the Counter Hearing Aids

• FDARA creates a category of over-the-counter (OTC) hearing aids

intended for adults eighteen (18) years or older to compensate for mild to moderate hearing impairment

• Proposed regulations establishing the new category of OTC hearing

aids must be published before August 2020 that provide for:

• Reasonable assurance of the safety and effectiveness of these

devices

• Provide the requirements for labeling
• Provide a determination about whether OTC hearing aids require a

510(k) premarket notification

• FDA must update and finalize its guidance distinguishing hearing aid

devices and personal sound amplification products.

• Hearing Aids were FDA’s first restricted device by regulation
• FDARA preempts any state law that restricts or interferes with the sale
• f OTC hearing aids.

Other FDARA Device Provisions

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• 510(k) clearance or PMA approval for medical imaging devices when

intended for use with a contrast agent in a manner different from that in the contrast agent’s labeling (FDARA § 706)

• Pilot projects to improve postmarket surveillance (FDARA §708)

FDA Actions Required by FDARA

Guidance Topic Deadline FDA Action? Report on FDA website re: servicing ofdevices May 15, 2018 Published

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Scheduled for

• Aug. 13-14, 2018

Meeting on pediatric device development

• Aug. 18, 2018

Draft guidance on CFGs, explanation of denials andreview process

• Aug. 18, 2018

On CDRH FY 2018 guidance development Alist Draft guidance on inspection process, timeframes,and feedback

• Feb. 18, 2019

Not on CDRH FY 2018 guidance development list Report to Congress on postmarket surveillancepilot projects

• Feb. 18, 2019

Not yet Final guidance on regulatory requirements for hearingaids and personal sound amplificationproducts Date that final OTC hearing aid regs are issued Not on CDRH FY 2018 guidance development list Report to Congress on OTC hearing aid adverseevents 2 years after final OTC hearing aid regs n/a Third party review of the postmarket surveillancepilot projects

• Jan. 31, 2021

n/a

21st Century Cures Act

21st Century Cures Act (21CC)

• Was President Obama’s final legislation, signed into law as he

left office in December 2016

• 21CC was a major set of compromises patched together and

was attached to unrelated legislation when it passed

• Affects drugs, devices and biologics
• Lobbyists and Senators blasted “Controlled Clinical Trial”

requirements as too restrictive and cumbersome

• Has prompted continuing dialogue in Congress to accept “real

world evidence” and “right to try” paradigms, minimizing dependence on clinical data to support effectiveness

• Eliminated some FDA controls on devices
• Sought to speed approvals
• Sought to press FDA to accept foreign data

Devices: Subtitle F

Subtitle F—Medical Device Innovations

• Sec. 3051. Breakthrough devices.
• Sec. 3052. Humanitarian device exemption.
• Sec. 3053. Recognition of standards.
• Sec. 3054. Certain class I and class II devices.
• Sec. 3055. Classification panels.
• Sec. 3056. Institutional review board flexibility.
• Sec. 3057. CLIA waiver improvements.
• Sec. 3058. Least burdensome device review.
• Sec. 3059. Cleaning instructions and validation data requirement.
• Sec. 3060. Clarifying medical software regulation.

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21st Century Cures Implementation

• Establish Breakthrough Device Pathway
• Change HDE Limit to 8000 Patients
• Streamline Process for 510(k) Exemptions
• Modifications to Classification Panels
• Allow for Central IRBs
• Update CLIA Waiver Guidance
• Recognition of Standards
• Train and Audit Least Burdensome
• Clarify Medical Software Regulation
• Cleaning and Validation Data

William H. Maisel, MD, MPH – MDMA 2018

Digital Health

• Clarified that certain digital health technologies – such as clinical administrative

support software and mobile apps intended for maintaining or encouraging a heathy lifestyle – generally fall outside the scope of FDA regulation

• They tend to be low risk but provide great benefits to patients and the

healthcare system by keeping them better informed about their health

• FDA issued 510(k) Software Modification Guidance in October 2017 that clarifies

policy on digital health

• FDA issued draft guidance in April, 2018 on devices with multiple software functions –

where some functionalities fall outside the scope of FDA regulation – but others do not

• FDA did not limit the scope to only cover 21CC mandates – therefore, any

manufacturer that includes both FDA regulated devices software functions and non-FDA regulated device software should become familiar with the draft

• 21CC provides that in the case of a product that contains at least one function that

meets the definition of a device and one that does not, FDA is prohibited from regulating the non-device software as a device, however, FDA can assess the impact

• f the non-device function on the device function
• FDA’s draft guidance, “Multiple Function Device Products: Policy and Considerations

follows the principles of 21CC

Breakthrough Devices Program

• FDA is committed to assuring that devices that fulfill an unmet medical need

will move through FDA as quickly as possible

• FDA issued a draft guidance regarding Breakthrough Devices Program that

builds upon the Expedited Access Pathway program established in 2015

• The Breakthrough Program is intended to help patients have more timely

access to certain devices that more effectively diagnose or treat life-threatening

• r irreversibly debilitating diseases or conditions for which there are no

alternatives available or offer a significant advantage over existing FDA cleared

• r approved alternatives
• The draft guidance provides for a more agile pre-submission process for

breakthrough devices

• Novel, breakthrough technologies may be more complex to assess,

therefore earlier and more frequent interaction between FDA and manufacturers should make most efficient use of resources to bring novel technologies to the market sooner

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Breakthrough Device Pathw ay

(Formerly Expedited Access Pathw ay)

65 devices accepted into the program

since April 2015

1st breakthrough device approved

December 2017

• Interactive & Timely

Communication

• Pre-Postmarket Balance
• Flexible Clinical Study Design
• Senior Management

Engagement

• Priority Review

510(k) Modifications

• Many devices undergo subsequent modification based on feedback

from patients, medical professionals and others to improve device’s performance

• FDA finalized two guidance documents in October 2017 to help

innovators determine when they need to submit a new premarket notification (510(k)) prior to making a change to a legally marketed device

• The final guidance documents will help innovators introduce iterative

changes that can improve a product’ safety and performance by providing more predictable, consistent, and transparent criteria for when FDA will need to review such changes

• The new guidance documents do not change FDA’s review standard,

but will provide better predictability by better describing the regulatory framework, policies and practices underlying the decision

Least Burdensome Device Review

• 21CC expands least burdensome provisions for device review and

requires least burdensome training for review staff (both CDRH and CBER)

• Least burdensome concept is integrated into all device review and
• ther device related activities – not just select premarket activities
• As well FDA has revised its guidance with regard to properly

responding to deficiencies in accordance with least burdensome principles.

• FDA shall issue upcoming guidance on over-arching principles of he

least burdensome concept to make the review process more efficient and are collecting information only when necessary and at the right time during the review process without compromising safety and effectiveness.

510(k) Exemptions

• Under 21CC, FDA exempted more than 70 Class I device types and

more than 1,000 Class II device types from premarket notification (510(k)

• Device types that are exempt from 510(k) are NOT generally exempt

from other regulatory controls such as quality system requirements, MDR reporting, registration and listing) that provide consumers confidence in FDA’s oversight of these devices

• These action provide FDA increased capacity to focus on oversight of

higher risk products

Modernizing Review of Reusable Devices

• 21 CC provided FDA with authority to require instructions for use and

validation data regarding cleaning, disinfecting, and sterilization for certain reusable devices such as duodenoscopes.

• FDA published a list of such reusable devices in June 2017 for which

this requirements applies which will ensure premarket requirements for these deice types are clear and predictable.

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21ST Century Cures Act Implementation

Provision Implementation activities completed Date completed Least Burdensome Issued draft guidance (not mandated); trained staff 15 Dec 2017 CLIA Waiver Issued draft guidance 29 Nov 2017 Breakthrough Devices Issued draft guidance 25 Oct 2017 Classification Panels Published FR Notice soliciting public input for panel membership; finalized “Procedures for Meetings of the Medical Devices Advisory Committee” guidance including Cures- related changes 23 Jun 2017 (FR notice) 1 Sep 2017 (guidance) Cleaning & Validation Published FR Notice identifying reusable device types for which 510(k)s are required to include certain validation instructions for use and validation data regarding cleaning, disinfection, and sterilization 9 Jun 2017 Central IRB Published amendment to regulations removing the word “local” where needed to comply with new law 7 Jun 2017 Humanitarian Device Exemptions Amended regulations changing the HDE population limit from 4,000 to 8,000 7 Jun 2017 Exemptions Published lists of Class I and Class II devices exempt from requirement to submit a 510(k) Final Class I list: 13 Apr 2017 Final Class II list: 11 Jul 2017 Software Detailed on subsequent slides

In Summary

• Be prepared – stay on top of draft guidance documents and

submit comments where appropriate

• Be familiar with any changes in final guidance documents
• You will be held accountable to the final document
• Remember – guidance documents do not have the effect of law or

regulation – but do convey FDA’s thinking on a topic

• There may be alternative ways to reach the same end point - but

be prepared to justify them as being as robust and scientifically sound

• Many moving parts that are moving quickly with

congressionally mandated timeframes for issuance of documents

• Pin those dates on your calendar and watch for them!
• They are important for your continued success
• Conformance with them will keep you out of the crosshairs of FDA!

Questions?