FDA Outlook 2017Seth A. Mailhot, PartnerLead, FDA Regulatory Practice

January,25, 2017

Overview

• Gaming the Elections Influence on FDA in 2017• Potential Congressional Activity• PDUFA VI and MDUFA IV• Restructuring of FDA’s Field Operations (Program

Alignment)• CDRH 2017 Strategic Priorities

Election 2016• One of the most unusual elections in years due to

the “Trump Factor”• Public health debates surrounded two issues:

• Obamacare• Vaccine scheduling

• FDA was mostly a non-issue in the campaign

President-Elect Trump• Dr. Califf has resigned and been

replaced by Acting Commissioner Dr. Stephen Ostroff, M.D. (previously Deputy Commissioner for Foods and Veterinary Medicine)

• Currently waiting for announcement of nominee, and appointment may not be likely until well into 2017

• Potential for significant turnover among senior staff

• Several names have been floated as potential nominees

Trump Campaign Promises• Temporary moratorium on new agency regulations• Cancellation of all “illegal and over-reaching executive orders”• Review and elimination by agencies of all regulations

“imposed on Americans which are not necessary, do not improve public safety, and which needlessly kill many, many jobs”

• According to the Competitive Enterprise Institute, 3,378 final rules and regulations and 2,334 proposed rules were issued in 2015

• Make medical marijuana widely available to patients, and allow states to decide if they want to fully legalize pot or not

• Seeks to reform the Food and Drug Administration by putting a, “greater focus on the need of patients for new and innovative medical products.”

Initial Executive Orders

• On January 20, 2017, the White House issued a Memorandum to Heads of Executive Departments and Agencies halting or postponing all pending regulatory actions until review and approval by a Department or Agency Head or other individual appointed or designated by President Trump

• On January 23, 2017, the White House issued a Memorandum to Heads of Executive Departments and Agencies ordering a freeze on the hiring of Federal civilian employees to be applied across the board in the executive branch.

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Dr. Scott Gottlieb, M.D.

• Clinical assistant professor at New York University School of Medicine

• Resident fellow at the conservative American Enterprise Institute

• Internist at Tisch Hospital• Previously served as Deputy Commissioner for Medical

and Scientific Affairs at FDA from 2005 to 2007• Initiated early development of FDA's generic drug user fee program

and the Physician Labeling Rule

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Jim O’Neill• Managing director for Mithril Capital Management, a late-

stage venture firm owned by Peter Thiel• Does not have a medical background• Previously worked in the George W. Bush administration at

the Department of Education and Department of Health and Human Services in different capacities

• In a highly publicized speech at the 2014 Rejuvenation Biotechnology conference, stated that:• “We should reform FDA so that it’s approving drugs after their

sponsors have demonstrated safety and let people start using them at their own risk, but not much risk of safety. But, let’s prove efficacy after they’ve been legalized.”

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Balaji Srinivasan• Cofounder of genetics testing firm Counsyl• Venture capitalist at Andreessen Horowitz• Chief executive of a firm related to Bitcoin• Does not have a medical background• Possibly not in the running anymore following the discovery

of numerous tweets critical of the Agency

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Dr. Joseph V. Gulfo, M.D., MBA

• Professor of Health Sciences and Executive Director of the Lewis Center for Healthcare Innovation and Technology at Fairleigh Dickinson University (FDU)

• Visiting Scholar at the George Mason University’s MercatusCenter

• Author of Innovation Breakdown: How the FDA and Wall Street Cripple Medical Advances

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Congressional Priorities: 21st Century Cures Act• Bipartisan bill signed into law by President Obama

on December 13, 2016• Increases funding for National Institutes of Health

(NIH) in return for changing FDA regulatory standards

• NIH is scheduled to receive $4.8 over the coming decade:

• $1.5 billion for President Obama's Precision Medicine Initiative,

• $1.8 billion for Vice President Biden's cancer “moon shot” initiative

21st Century Cures Act – FDA Drug Provisions• Expedite the review process for certain drugs,• Facilitate the recognition of drug outcome measures,• Encourage the consideration of data beyond that produced

in randomized clinical trials to support approval,• Create a new priority review voucher (PRV) for material

threat medical countermeasures,• Extend the current rare pediatric disease PRV program,• Clarify the scope of permissible dissemination of health

care economic information (HCEI) by manufacturers, and• Require manufacturer publication of expanded access

policies

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21st Cent.: Real World Evidence• Permits use of “real world evidence” to:

• Support the approval of a new indication for a previously approved drug

• Support or satisfy postapproval study requirements• “Real world evidence” is data regarding the usage,

or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials, including from ongoing safety surveillance, observational studies, registries, claims, and patient-centered outcomes research activities

21st Cent.: Limited Population Antibacterials/Antifungals

• Exception for approval of antibacterial or antifungal drugs that are intended to treat serious or life-threatening infections in a limited population of patients

• Approval is based on the benefit-risk profile of such drug in the intended limited population, taking into account:

• the severity, rarity, or prevalence of the infection the drug is intended to treat and

• the availability or lack of alternative treatment in such limited population

• Drug approval may be issued notwithstanding a lack of evidence to fully establish a favorable benefit-risk profile in a broader population

21st Century Cures Act - FDA Device Provisions• “Breakthrough devices” program to expedite development

and provide priority review for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease that represent breakthrough technologies

• Increasing the population requirements for Humanitarian Device Exemptions (4,000 to 8,000)

• Changes to recognition process for device standards• Requirement on FDA to review list of devices subject to

premarket notifications [510(k)s]• Changes to CLIA Waiver process• Least Burdensome provisions• Revised definition of a medical device which exempts

certain types of medical software15

Prescription Drug User Fee History• The Prescription Drug User Fee Act (PDUFA) is a

law that authorizes FDA to collect fees from drug companies that submit marketing applications for certain human drug and biological products

• PDUFA was originally enacted in 1992 for a period of 5 years

• In 1997, Congress passed the FDA Modernization Act that reauthorized the program (PDUFA II) for an additional 5 years

• In 2002, Congress extended PDUFA again through FY 2007 (PDUFA III) in the Public Health Security and Bioterrorism Preparedness and Response Act

Prescription Drug User Fee History (cont.)• In 2007, the Food and Drug Administration

Amendments Act of 2007 reauthorized PDUFA through FY 2012 (PDUFA IV)

• Most recently, PDUFA was reauthorized through FY 2017 (PDUFA V) as part of the Food and Drug Administration Safety and Innovation Act

Summary of PDUFA• PDUFA's intent is to provide additional revenues so that

FDA can hire more staff, improve systems, and establish a better-managed human drug review process to make important therapies available to patients sooner without compromising review quality or FDA's high standards for safety, efficacy, and quality

• As part of FDA's agreement with industry during each reauthorization, FDA agrees to certain performance goals

• These goals apply to the process for the review of new human drug and biological product applications, resubmissions of original applications, and supplements to approved applications.

PDUFA VI Proposed Commitment Letter • Ensuring Effectiveness of Human Drug Review

Program• Review Performance Goals• Program For Enhanced Review Transparency And

Communication For NME NDAs And Original BLAs• First Cycle Review Management• Review Of Proprietary Names To Reduce Medication

Errors• Major Dispute Resolution• Clinical Holds• Special Protocol Question Assessment And Agreement• Meeting Management Goals

PDUFA VI Proposed Commitment Letter (cont.)• Ensuring Effectiveness of Human Drug Review

Program (cont.)• Enhancing Regulatory Science And Expediting Drug

Development• Enhancing Regulatory Decision Tools To Support Drug

Development And Review• Enhancement And Modernization Of The FDA Drug

Safety System• Enhancing Management of User Fee Resources

• Resource Capacity Planning And Modernized Time Reporting

• Financial Transparency And Efficiency

PDUFA VI Proposed Commitment Letter (cont.)• Improving FDA Hiring And Retention Of Review

Staff• Completion Of Modernization Of The Hiring System

Infrastructure And Augmentation Of System Capacity• Augmentation Of Hiring Staff Capacity And Capability• Complete Establishment Of A Dedicated Function To

Ensure Needed Scientific Staffing For Medical Product Review

• Set Clear Goals For Drug Review Program Hiring• Comprehensive And Continuous Assessment Of Hiring

And Retention

PDUFA VI Proposed Commitment Letter (cont.)• Information Technology Goals

• Improve The Predictability And Consistency Of PDUFA Electronic Submission Processes

• Enhance Transparency And Accountability Of FDA Electronic Submission And Data Standards Activities

• Improving FDA Performance Management• Progress Reporting For PDUFA VI And Continuing

PDUFA V Initiatives

Medical Device User Fee History• Prior to passage of the Medical Device User Fee and

Modernization Act of 2002 (MDUFMA), FDA’s medical device program suffered a long-term, significant loss of resources that undermined FDA’s ability to review medical device premarket submissions

• Congress enacted MDUFMA to provide FDA with resources necessary to better review medical devices, to enact needed regulatory reforms to allow medical device manufacturers to bring new devices to the market at an earlier point in time, and to ensure safety and efficacy of reprocessed medical devices

Medical Device User Fee History (cont.)• MDUFMA had a 5-year life and contained two particularly

important features which relate to reauthorization:• User fees for review of medical device premarket

applications, notifications, reports and supplements to provide additional resources to make FDA reviews more timely, predictable, and transparent to applicants

• Negotiated performance goals for many types of premarket reviews to provide Congress, FDA and industry with benchmarks for measuring improvements

• Since MDUFMA was first passed in 2002, it has been reauthorized twice: the 2007 Medical Device User Fee Amendments (MDUFA II) and the 2012 Medical Device User Fee Amendments (MDUFA III), which will expire in 2017

Medical Device User Fee Amendments 2017• Without new legislation, referred to as

reauthorization, FDA will not be able to collect user fees after fiscal year (FY) 2017 to fund the medical device review process

• Prior to reauthorization, FDA must consult with regulated industry and make recommendations to Congress regarding agreed upon goals

• On August 15, FDA, Advanced Medical Technology Association (AdvaMed), Medical Device Manufacturers Association (MDMA), Medical Imaging & Technology Alliance (MITA), and American Clinical Laboratory Association (ACLA) agreed to draft a Commitment Letter

MDUFA IV Commitments• FDA will improve consistency and predictability

through enhanced supervisory oversight and routine quality audits

• FDA will establish a dedicated premarket Quality Management team, which will be responsible for establishing a quality management framework

• FDA will improve the quality and consistency of Additional Information and Major Deficiency letters by providing the basis for deficiencies and appropriate supervisory review

• FDA will improve tracking and reporting of performance commitments

MDUFA IV Commitments (cont.)• FDA and Industry will reduce average decision time

in FY2022 to 108 days for 510(k)s and 290 days for PMAs

• FDA will improve the CLIA waiver by application process by establishing a centralized program management group within the Office of In Vitro Diagnostics and Radiological Health, among other things

• FDA will implement IT improvements that correspond to new performance goals and reporting, including an industry dashboard that displays near real-time submission status

MDUFA IV Commitments (cont.)• FDA and Industry will participate in an independent

assessment of the CDRH review process• FDA will implement a more effective recruiting and

hiring strategy, and improve employee retention through incentive pay for managers

• FDA will improve the Pre-Submission process and ramp up to a performance goal for written feedback on at least 1,950 Pre-Submissions within 70 days or 5 calendar days prior to the scheduled meeting, whichever comes sooner, in FY2022

• Industry affirmed its responsibility to provide draft meeting minutes within 15 days of the meeting

MDUFA IV Commitments (cont.)• FDA will ramp up to a performance goal for completion

of 70% of De Novo submissions within 150 days in FY2022

• For PMA submissions that require Advisory Committee input, FDA will issue a MDUFA decision within 60 days of Advisory Committee recommendation

• For PMA submissions that receive a MDUFA decision of Approvable, FDA will issue a decision within 60 days of sponsor’s response to the Approvable letter

• FDA and Industry will establish a conformity assessment program for accredited testing laboratories that evaluate medical devices according to certain FDA-recognized standards

MDUFA IV Commitments (cont.)• FDA will strengthen the Third Party Premarket

Review program by offering training to Third Party review entities, conducting audits, publishing performance reports of individual Third Party entities and seeking authority to expand the scope of the program

• FDA will improve consistency in review of software as a medical device and software in a medical device through establishment of a centralized digital health unit, streamline and align FDA review processes with software lifecycles, continue engagement in international harmonization efforts related to software review

MDUFA IV Commitments (cont.)• FDA will develop internal expertise on patient engagement,

support the increased use of patient preference information (PPI) and patient reported outcomes (PROs) in premarket submissions, publish a PRO validation guidance, hold one or more public meetings, and clarify that PROs are voluntary and can be one mechanism for demonstrating safety and effectiveness or substantial equivalence

• FDA will enhance IT infrastructure to collect and report on structured data; to develop and maintain a secure web-based application that allows sponsors to view individual submission status in near real-time; and to develop structured electronic submission templates as a tool to guide Industry’s preparation of premarket submissions

MDUFA IV Commitments (cont.)

• FDA will provide funding for the National Evaluation System for health Technology (NEST) to conduct a pilot to establish the value of real world evidence (RWE) and linkages among data sources to enable greater use of RWE to accelerate patient access in the premarket setting, to develop guidance and hold a public meeting on the use of RWE including in the context of medical device reporting for certain devices. FDA and Industry agreed that an independent assessment would occur during MDUFA IV to assess whether the premarket efficiencies highlighted by FDA are being realized

• FDA committed to treating LDTs no less favorably than other devices to which MDUFA performance goals apply and to report on corresponding key performance metrics

Office of Regulatory Affairs (ORA)

• Lead office for all FDA Field activities• Provides FDA leadership on imports, inspections,

and enforcement policy• Responsible for

• inspecting regulated products and manufacturers,• conducting sample analysis on regulated products, and• reviewing imported products offered for entry into the United

States• ORA’s staff works in 5 Regional Offices, 20 District

Offices, 13 Laboratories, and more than 150 Resident Posts and Border Stations

FDA Program Alignment

• In 2014, FDA developed action plans to modify its functions and processes to address challenges posed by:

• Scientific innovation,• Globalization,• Increasing breadth and complexity of products FDA

regulates, and• New legal authorities

• The plans represent what each Center and ORA have agreed are the critical actions to jointly fulfill FDA’s mission

FDA Program Alignment (cont.)

• The critical actions outlined in each action plan are focused on the key areas of:

• Specialization;• Training;• Work planning;• Compliance policy and enforcement strategy;• Imports;• Laboratory optimization; and• Information technology

FDA Program Alignment (cont.)• FDA has determined that in order to address these

challenges, FDA must transition to distinct commodity-based and vertically-integrated regulatory programs with:

• well-defined leads,• coherent policy and strategy development, and• well-designed and coordinated implementation

CDRH 2017 Strategic Priorities• Establish a National Evaluation System for Medical

Devices• Increase Access to Real-world Evidence to Support Regulatory

Decision Making• By December 31, 2017, gain access to 100 million electronic patient

records with device identification• Increase the Use of Real-world Evidence to Support Regulatory

Decision Making• By December 31, 2017, 100% increase in number of premarket and

postmarket regulatory decisions leveraging real-world evidence (compared to FY2015)

CDRH 2017 Strategic Priorities (cont.)• Partner with Patients

• Promote a Culture of Meaningful Patient Engagement by Facilitating CDRH Interaction with Patients

• By December 31, 2017, 90% of CDRH employees will interact with patients as part of their job duties

• By December 31, 2017, obtain patient input on key pre- and postmarket issues facing CDRH by fostering participation of 20 patient groups

• Increase Use and Transparency of Patient Input as Evidence in CDRH Decision Making

• By September 30, 2017, 100% of PMA, de novo and HDE decisions will include a public summary of available and relevant patient perspective data considered

CDRH 2017 Strategic Priorities (cont.)• Promote a Culture of Quality and Organizational

Excellence• Strengthen FDA’s Culture of Quality within CDRH

• By September 30, 2017, 25% increase in CDRH staff with quality and process improvement credentials

• By September 30, 2017, have systems and procedures in place to be eligible for ISO 9001 certification

• By December 31, 2017, submit to an Alliance for Performance Excellence member organization a formal application to assess our progress towards adopting the Baldrige Performance Excellence Criteria and achieving organizational excellence

CDRH 2017 Strategic Priorities (cont.)• Promote a Culture of Quality and Organizational

Excellence• Strengthen Product and Manufacturing Quality within the

Medical Device Ecosystem• By December 31, 2017, propose a voluntary program to recognize

independent evaluation of product and manufacturing quality

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Questions

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Seth Mailhot is a partner and lead of the FDA Regulatory Practice Group in Michael Best & Friedrich’s Washington D.C. office. His 14 years working in the U.S. Food and Drug Administration (FDA) has provided him a unique perspective when counseling clients on a broad range of matters involving the FDA.

Seth’s practice includes representation of the medical device, pharmaceutical, dietary supplement, tobacco and food industries, and covers both premarket and post-market issues. His practice is focused on development of premarket submission strategies, and FDA enforcement of good manufacturing practices, both domestically and abroad.

Admissions District of Columbia Massachusetts U.S. Patent and Trademark Office

Education New England School of Law, J.D.,

Valedictorian, summa cum laude University of Massachusetts, B.S.,

Chemical Engineering

Seth A. Mailhot601 Pennsylvania Avenue, N.W.Suite 700 SouthWashington, D.C. 20004-2601Phone: (202) 747-9566Cell: (617) 842-0484Fax: (202) 347-1819samailhot@michaelbest.com