Regulatory Education for Industry (REdI) Annual Conference 2023 FDA Welcome and Keynote

thanks Captain Stoddard I'm delighted to be with you once again for this year of small business and industry assistance regulatory education for industry conference this meeting represents an integral aspect of the FDA mission that doesn't get enough attention the critical support and guidance we provide to businesses especially smaller businesses who are involved in the development of new medical products in this in the areas we regulate

how we communicate with you can make a big difference in your work whether you succeed and the speed of reaching a conclusion in product development depend increasingly on communication throughout the life cycle of product development we support you by providing information and resources that can reduce development time save money prevent waste or duplication and ultimately speed the development of essential and potentially groundbreaking medical products developers

such as yourselves share a focus with us on advancing and supporting scientific innovation of course we have the challenge of oversight and Regulatory responsibilities over a vast range of medical products involving three different centers our Center for devices our Center for drugs and our Center for biologics as well as many other offices across the agency I'm pleased that once again this year all three centers are

represented at this conference offering you the chance to hear from and Converse with our expert staff I should add from a personal perspective having been involved with product development in a number of different capacities including a variety of relationships with startup companies portfolio selection and Venture funding from larger companies and a good portion of my career focused on clinical research and efforts to strengthen the process

by which evidence is generated to evaluate risks and benefits of products then I especially appreciate the vital role that appropriate interactions with FDA Regulators can play during the medical product development process I'd further suggest that this role has grown in importance in recent years as we that is developers like yourselves and we at the FDA have worked to embrace the truly revolutionary scientific and technological advances

before us we're lucky to be living and working in a time of unprecedented scientific medical and technological breakthroughs we have a deepening understanding of the underlying mechanisms of disease and human biology genetics and genomics and the enormous opportunities afforded through the development and application of new technologies including the expanded ability to digitally collect review and share data these technological advances allow us to Envision explore and

realize unprecedented new approaches for preventing and treating a wider range of previously untreatable diseases I know that like the scientists and Regulators at the FDA each of you face challenges in keeping up with these advances the U.S continues to be the number one innovator in medical products producing drugs biologics tests and devices that fuel Health Care around the world and I'm proud that the FDA plays

a key role in supporting and spurring these developments but it's important and in fact necessary that we don't rest on past successes to retain our leadership we need to continue to strengthen our structures methods data collection and science to allow us to be even more efficient adaptive and effective in the exercise of our regulatory responsibilities and importantly we need to work with developers though not simply

in support of innovation for innovation's sake there must be an end goal that's focused on patients and consumers indeed it's the essence of the fda's regulatory role to help ensure that scientific breakthroughs are translated into viable safe and effective products that make a meaningful difference for patients and their families this meeting is designed to provide you opportunities to focus on your specific needs and furtherance of

this goal and over the next several days your participation will help ensure that we can meet our responsibility to support you in your scientific research Innovation this morning I want to give you a brief summary of some of the extraordinary work and achievements of our human medical product centers but being brief is challenging when it comes to speaking about what the FDA does there's much going

on in so many different areas it's no coincidence that this meeting is stretched over several days I'll start by mentioning the important role that user fees play in all our priorities and all our medical product centers helping us keep up with the many scientific developments that drive innovation let me begin with the center for drug evaluation and research the latest iteration of the prescription drug user

P law or Purdue fund has had a significant impact on a number of Cedar programs including efforts to expand the use of digital Health Technologies real world evidence a rare disease endpoint program several new programs for enhancing regulatory review and new meeting types that should add more flexibility in the type of meetings we hold with industry we're focused on putting these programs in place so we

can ensure their continued success over the next several years as well as strengthening our efficiency to meet our review and procedural goals for example the new drugs regulatory program or ndrp modernization effort is a cross-seater program focused on improving the efficiency and effectiveness of our regulatory review process the agency's real world evidence program provides an optional pathway for sponsors submitting rwe proposals designed to improve the

quality and acceptability of rwe-based approaches that can meet regulatory requirements in support of labeling for Effectiveness or for meeting post-approval study requirements other priority initiatives include the accelerating rare disease cures or Arc program designed to advance the development of drug products to address unmet medical needs for patients with rare diseases and a focus on digital Health Technologies which offer a vast array of potential benefits in

the development of medical products as the world enters the fourth Industrial Revolution in which rich and diverse sources of Digital Data are available at scale in real time with potentially unlimited storage capacity these data are becoming widely available as part of the clinical care system digital Health Technologies or dhts provide opportunities to Foster more efficient conduct of clinical investigations for instance dhts can facilitate the conduct

of decentralized clinical trials where data can be remotely recorded and analyzed directly from participants as part of everyday tasks wherever the participants may be such as homeschool work or Outdoors and the use of dhts in a clinical investigation can help improve patient access to and participation in clinical investigations by potentially reducing the burden of required visits to a research site let me also briefly mention important

work being done in biosimilars the FDA has been conducting applied research on pharmacodynamic biomarkers to help facilitate biosimilar product development This research includes clinical pharmacology studies in which participants receive varying doses of a biological product and investigators determine the biomarker's response the FDA and outside researchers have worked to identify and evaluate biomarkers and placebo-controlled studies using Advanced Technologies and simulations we also release of a super

3 regulatory science pilot program a research roadmap to provide additional information about the biosomal regulatory science research pilot program I'll turn next to our Center for biologics as you know sieber was at the center of the fda's efforts to respond to many of the demands we faced during the pandemic and they've continued to meet the emergency demands involved with reviewing investigational new drug submissions emergency use

authorization requests and biological license applications for vaccines to prevent cobit 19. just as April for example sieber amended the emergency use authorizations of the modern and Pfizer bio and Tech covid-19 bivalent mRNA vaccines to simplify the vaccination schedule for most individuals sieber also continues to work to improve health outcomes for people affected by other infectious pathogens by facilitating development of other biological products this includes other

vaccines blood products allergenic therapies bacteriophage therapies and cellular Gene and tissue-based therapies and xenotransplantation products the range of work is impressive it runs from the approval of a respiratory Sensational virus vaccine for active immunization for the prevention of a highly contagious lower respiratory tract disease that leads to approximately 60 to 120 000 hospitalizations and six thousand to ten thousand deaths among adults 65 years of age

and older to the approval of the first fecal microbiota product approved by the FDA for the prevention of recurrence of claustralia infection and sieber is also heavily involved in the advancement of gene therapy five of its novel approvals over the past year have been for gene therapy products this activity underscores the enormous promise in this area with profound implications for the development of new treatments and

cures for human disease as well as across the entire spectrum of humans animals and plants our work in this area as with much of what we do on medical products does not simply involve looking at products for review but also following up to make sure the public understands what's involved with these new therapies and that they are protected from unproven potentially unsafe or low quality treatments

for instance to reduce misinformation and promote patient engagement and understanding of the cellular and Gene Therapies sieber's office of therapeutic products has been strengthening its Outreach and engagement activities and building new mechanisms to reach its diverse stakeholders this includes workshops for patients and Advocates and public listening meetings and at the other end of the spectrum saber's office of compliance and biologics quality has issued a number

of compliance actions involving stem cell and related products as well as letters to clinics Healthcare Providers and manufacturers identified as involved in offering unapproved regenerative medicine products it's a One-Stop shop finally let me turn to the work of our Center for devices and radiologic Health which oversees more than 238 000 different types of devices that are made in over 27 000 manufacturing facilities worldwide that's an

enormous responsibility and as I mentioned at the outset user fees have played a key role in the evolution of the fda's devices program the most recent version of the medical device usop law or Medusa 5 is a Monumental reauthorization package that includes not only a continuation of device user fees but also a substantial investment in the future of the agency's medical device program over the course

of the evolution of the usury law the FDA and Industry have worked successfully to improve patient access to medical devices and to stream on regulatory processes while assuring the safety and effectiveness of devices at patients and Healthcare Providers depend upon and modified provides opportunities for the FDA to explore ways to improve patient science tools to Advance Health Equity helping to ensure all patients in the U.S

have access to safe and effective medical devices appropriate for our diverse population I'll mention just one specific component of madupa the total product life cycle advisory program or tap pilot Jeff Sherman will be speaking to you about tap in more detail but I wanted to underscore the importance of this program which provides industry with earlier and more frequent interactions with cdrh more strategic input for stakeholders

and proactive strategic advice from cdrh to spar more rapid development of high quality safe effective and Innovative medical devices first in the world that are critical to Public Health and that will lower the risk of medical devices tap will help assure that device developers have a clear predictable path to Market so that patients have timely access to new devices we believe it will help innovators avoid

pitfalls in early product development better ensure a clear predictable path to Market from development to bedside so that devices actually reach patients and will continue to Foster The Innovation pipeline let me also briefly mention two other groundbreaking developments cdrh was involved with this year the first is the final rule establishing a new category of over-the-counter hearing aids which allows certain hearing aids to be sold directly

to consumers in stores or online without a medical exam or a fitting by an audiologist the rule creates greatest access and Innovation for hearing aids allowing patients more affordable and Equitable access to these high impact devices the second involves the updates we published to the mammography regulations that include strengthening the fda's oversight and enforcement of facilities and help interpreting Physicians better categorized and assess mammograms this

action is the latest iteration of the agency's launch standing commitment to support Innovation to prevent detect and treat cancer under the authority of the mammography quality standards Act and truly reflects the fda's mission to protect and promote Public Health I'll close by mentioning another crh strategic priority to incorporate the voice of patients through its patient science and engagement program I mentioned it because the focus of

this important initiative is not reserved to cdrh incorporating the perspectives and experiences of patients to make sure the evidence reflects what matters most to and is most effective for these patients and their caregivers is something that we are involved with across the agency it seems obvious that if we want essential insights about what it's like to live with a disease the outcomes that matter in the

adequacy of treatment options we should ask people who are living with a problem or at risk of experiencing the problem both patients and caregivers our goal is to be able to design a more accurate more complete benefit rest framework that helps us to better evaluate the safety and effectiveness of a medical product across the vast expanse of patients and consumers with different values different education levels

and living in different Healthcare environments we need to assure that the experience of living with the disease is factored explicitly into development programs for all medical products including measures of benefit and harms within clinical trials as I think you can see this is no shortage of exciting and valuable FDA initiatives and programs that are making a difference time has allowed me just to touch on a

few recent developments luckily all of you have five days to immerse yourself in these and other topics I hope you'll have an enjoyable and rewarding meeting and speaking for the outstanding FDA staff I know they look forward to working with you both during this conference and in the future to apply the strongest science to achieve the best possible outcomes for the patients I care about thank

you thank you very much thank you very informative overview of the important initiatives being undertaken by the three centers and how they relate to our audience now it is my pleasure to introduce my cdrh colleague Elias malice who has co-hostes this ready event with us since 2012. as customary Elias will conduct this year's plenary session in his role as the moderator Mr malice began his 29-year

FDA career in 1994 and deported the next 17 years to the office of device evaluation where he conducted regulatory review and developed a policy for a diverse range of medical device programs such as 510ks Ides pmas and hdes he has held many varied leadership positions throughout the years and currently serves as the Director of the division of industry and consumer education in the office of communication

and education in the center for devices and radiological Health a position he has held since 2011. Mr malice leads the division whose mission is to educate industry and consumer stakeholders with understandable and accessible science-based regulatory information about medical devices and radiation emitting electronic products please let us welcome Elias malice [Music] thank you Brenda and a hearty thanks to everyone for joining us for ready 2023 it's

great to be with you once again for our 12th year now for our Global audience whether you're following us on YouTube live or are joining us through the FDA website it's truly my distinct pleasure to give you a warm welcome to the ready annual conference and I'm honored to serve as your moderator for this year's plenary sessions it's a time honored ready tradition to kick off

the technical portion of the five-day conference with the plenary session this is where all attendees from all the program tracks come together for the one time during the conference for a specific topic that connects us all it's always a creative Challenge and opportunity to select the right topic for the plenary each year a theme that connects drug device and biologics Regulatory policy now for those of

you who've been with us over the years you might recall some of the topics we've covered in the past combination products rare disease treatments and real world evidence and for the past two years we've focused on fda's public health response to the covid-19 pandemic featuring the three esteemed Center directors from cdrh Cedar and sieber madhufa padufa gadufa and basufa now these aren't phrases you'll find in

a child's nursery rhyme instead these words are featured in this year's plenary session birds are actually acronyms for the family of FDA user fee programs also endearingly known as ufas user fees have served as a vital pipeline of resources for the agency the earliest of which go back to the 1990s and these programs renew every five years as good timing would have it the FDA renewed

our most recent round of user fee programs in October 2022 so we thought this would be great timing to give you an update and we're especially fortunate that we'll once again be joined by the three Center directors who will provide updates on the user fee programs for their respective centers we'll hear from Dr Jeff Sherin director of the center for devices and radiological health or cdrh

Dr Patricia cavazoni director of the center for drug evaluation and research or Cedar and finally Dr Peter marks director of the center for biologics evaluation and research or sieber it's my pleasure to now introduce you to Dr Jeff shurin who will get things started for us today Dr Sharon has been the director for cdrh since 2009. over this extensive time he has provided executive leadership to

advance device Innovation and Advance the safety and effectiveness of medical devices and radiation emitting projects again thank you all for joining us at ready2023 and this year's plenary session titled user fee impact on FDA programs let's now hear from Jeff well thank you Elias and let me add my welcome to all of you to fda's small business ready annual conference one of the fda's user-free programs

is for medical devices the medical device use of fee amendments or medufa program medufa just celebrated its 20th anniversary you know when it started 20 years ago the main focus was providing additional resources to the FDA so we could perform pre-market review in a more timely manner and over the next two iterations of medufa we continue to refine the goals and the program and then what

madufa 4 we started to focus in on other areas important in pre-market review and then madufa 5 truly takes it to the next level under medufa five we still have performance goals and they're a little tougher this go-round and additional resources so we can conduct more pre-submission meetings we know how important it is to developers to have the opportunity to talk with our reviewers and get

their feedback and under the pre-submission program you can send in your questions and we'll provide a written response in the opportunity meet within 70 days of receiving that request and the medufa Phi program covers so much more so I'm going to take a few minutes and unpack it for you in medufa 4 we receive funding to start a pilot that's called the accreditation scheme for Conformity

assessment or aska now under that pilot we would identify accreditation bodies who would accredit Laboratories to conduct Conformity assessment testing against International and National consensus-based standards that are recognized by the FDA for purposes of this pilot and the value of such an undertaking is that if we have high confidence in the laboratory who's doing the assessment then we don't need to look at the raw data

we can just focus on a summary which reduces a lot of time that we have to spend in our review and for the company they have higher confidence of the data they submit will be accepted by the FDA well it turns out the pilot was wildly successful and as a result in the doofa five now expands and it's going to turn it into a permanent program

so I would check it out and if you have a device coming to us for review and you might be able to take advantage of one of those applicable standards then I would certainly consider participating in the ask a program medufa 5 also for the very first time provides funding support to expand our capabilities to advance International harmonization we know that in the global Marketplace it

becomes ever more important that we converge and optimally harmonize requirements across at least major countries so that developers have easier access into the marketplaces as part of our commitments later this year we're going to put out a draft strategic plan highlighting some of the important areas we're going to focus on over the next five years medufa 5 also provides funding and support to continue to expand

our patient science and engagement program we've been on an over 10-year journey to better incorporate and understand the voice of patients in the work that we do early on we started to focus on methods to better understand and to quantify patient perspectives such as the benefit risk trade-offs of patients are willing to make around particular medical devices what we call Patient preference studies as well as

the development of patient reported outcomes so that we're measuring things that are most important to patients and what medufa 4 we were able to expand that program and under medufa 5 we're going to further invest in our capabilities under medufa 5 we're going to update some of our policies like patient preference information guidance and we're going to expand our activities around patient generated Health Data to

advance the use of remote clinical trials and thereby also Advance Health Equity by providing easier and greater opportunities for diverse populations to engage in evidence generation particularly for clinical trials medufa 5 also continues to support our efforts on real world evidence starting over a decade ago we began to focus on creating more infrastructure and assuring that real world data would be fit for purpose to be

leveraged for regulatory purposes and includes issuing guidance that laid out the factors for consideration to determine whether or not real world data and the real world and the evidence generated as a result could be used to inform FDA decision making part of those efforts was to establish What's called the national evaluation system for health technology or Nest Nest is an attempt to build better infrastructure and

greater efficiencies so that real world evidence can be generated and used more often within our ecosystem and Nest now is transitioning it already has a series of data Partners who then provide data consistent with a common data model but now Nest is moving over to more of a general contractor approach where they are leveraging third parties as needed to provide additional capabilities such as around data

extraction and data curation platform for analysis and then conducting those analyzes to answer important questions for their customers including those that may be important for the FDA but also Nest is intended to answering questions that important for providers and patients to assure safe use of devices as well as to help inform payers around coverage and reimbursement decisions under medufa 5 will continue to support those activities

will update our real world evidence guidance and we'll expand and develop real world evidence methods and policies for pre-market submissions so we continue to increase the opportunities to leverage real world evidence in our pre-market decisions as well as our post-market determinations medufa 5 also supports our digital health program it's too has been on a journey for over a decade the current statutory framework for medical devices

is 47 years old and it's not fit for purpose for many of today's modern Technologies particularly those that are software based like digital Health Technologies recognizing this over a decade ago we began to revisit our policies in sort of right-size them under our current authorities to be better suited for digital Health Technologies under medufa 4 we received funding to help build a digital health center of

excellence and that Center has focused on looking at more Innovative approaches to the oversight of digital Health Technologies for example we ran a pilot on what's called pre-certification where we were looking at Key capabilities and manufacturers and opportunities to leverage our understanding of those capabilities in lieu of Performing the full deep dive into Technologies on a technology by technology basis the center has also put out

several important policies more recently final guidance on clinical decision support software and also a growing focus on artificial intelligence machine learning under medufa 5 we committed to issue a draft guidance for what's called predetermined Change Control plans in fact we issued this graph guidance at the end of March and here's the idea that for certain kinds of modifications a developer can identify those for the FDA

and how they would go ahead and verify and validate those modifications and if we agree that that's a good plan then the developer can go ahead make those modifications in the future as long as they follow the plan and not have to come back to the FDA for another pre-market review we've also committed to issue final guidance on submissions for device software and finally madufas supports

a very exciting pilot of What's called the total product life cycle advisory program or tap if you're a developer trying to get to the market is really fulfilled with pitfalls and traps it's a game of Shoots and Ladders where you not only have to get through the FDA from working authorization but coverage and reimbursement by payers and ultimately adoption in the marketplace by providers and patients

as I mentioned medufa early on was very much focused on streamlining pre-market review and yet we know that if you get everything right before you come in the door with your pre-market submission the review of that submission should go very smoothly so what tap is about is addressing those kinds of challenges essentially the Valley of Death going from concept to commercialization tap is intended to reduce

the time and cost and increase the predictability of that Valley of Death to help spur more rapid development and more rapid and widespread patient access to Safe effective high quality medical devices of Public Health importance the way we go about it is three ways first off creating a new position what we call the tap advisor now I mentioned that there's the opportunity today to seek advice

from the FDA through pre-submission meetings but those are kind of stage gated you send in your questions and then within 70 days we'll provide you with a response and we'll meet with you if you have more questions you throw them back over the transom and that process starts all over again the tap advisor rather than just simply reacting to what companies are asking about will engage

proactively and strategically we'll even independently reach out to the developer to start to identify what are going to be the key challenges and and questions that need to be addressed and then strategize on how best to do that to be successful secondly we're expanding our review capacity so that we have the opportunity to engage in much faster than that 70-day sort of stage gate approach ultimately

we'd like to make this more real or near real time to be able to answer questions and then third we know how important it is that developers understand the perspectives of providers and patients when they're designing their technology so that it best meets the value proposition for them as well as thinking about the design on clinical studies so they're best suited for patient participation also it's

important to get the perspective of payers therefore under the tap Pilot We essentially offer a menu of services and that includes if interested the opportunity to be connected with the key patient groups provider groups and payers so that you can develop the best strategy for how to get from concept to commercialization and do that as efficiently as possible that tap pilot was just launched in January

and as we committed to do was starting with just one office of Health technology so we're beginning with cardiovascular devices and in the first year we'll enroll up to 15. already we've enrolled four companies and four Technologies so essentially We're Off to the Races and you can see on the slide how this will progress over the course of medufa five as we expand to other technology

types and have more participants in the program to be eligible you need to receive a designation as a breakthrough device and not have engaged with the program in a formal manner so you've not had a pre-submission meeting and if you're eligible to be a part of tap I highly encourage you to do so because you'll have that opportunity for back and forth interactions to engage proactively

and strategically to be connected with other key groups if you're interested and in fact to help mold that program because we're Innovative and approach as well we're going to keep iterating our prototype for tap over the next few years and then of course we'll assess its performance that will help inform where we go in medufa 6. I know I throw a lot of acronyms at you

and you'll see those in the slides as well so I gave you a handy dandy cheat sheet that you can use when you go back over them so finally in summary we have been incorporating the lessons learned from previous Cycles into how the medufa program has evolved and the user fees that we collect are going to allow us to meet the needs of our customers and

drive Innovation into the future so with that I'll say a thank you and really appreciate your attendance at today's conference thank you Jeff for your remarks on how cdrh has implemented user fees to support our various medical device programs let's now continue this discussion and learn about the impact of user fees on fda's drug programs Dr Patricia cavazoni is the director of the center for drug

evaluation and research or Cedar since 2019 in her role Dr cavazoni provides executive leadership to advance Cedar's mission to ensure that safe effective and high quality drugs are available to the public thank you Patricia thank you Elias for that kind introduction I'm very pleased to be here today to talk about the impact of the user fee programs from a cedar standpoint so the user fee Amendments

have really made a very big difference when it comes to our review programs before the enactment of padufai 1992 the agency lacked sufficient staff to perform timely reviews or develop procedures and standards to ensure a consistent and predictable pre-market review process as a result of that America's access to Innovative new medicine often lagged behind other countries the user fee programs have enabled the agency to speed

the application review process without compromising fda's high standards for new drug review for safety efficacy and quality The Five-Year reauthorization cycle support continuous program Innovation evaluation and Improvement the enhancements improve potentials for first cycle approvals as well as getting safe and effective drugs to patients sooner with these enhancements the United States continues to be a global leader in drug Innovation and the Americans are now typically

the first to benefit from new safe and effective medicines so what you see on this graph is the share of new active substances that were launched on the World Market by region as you see the US is way ahead of other regions and as I said earlier this is largely the impact of the user fee programs now let me get into perufa 7. as you I'm

sure you have heard from Dr marks when it comes to sieber one of the major highlights for padufa 7 is enhancement of resources when it comes to the review of the Innovative products in Gene and in cell Therapies on the pre-market review front we're also going to see as part of padufa salmon the introduction of new approaches to improve the efficiency and expand the communications in

the human drug review program we're also seeing continuing enhancement when it comes to the application of innovative methods and tools to enhance regulatory decision making such as for instance a digital Health Technologies and last but not least there will be there are enhancements in Padu for sevens that will facilitate the review of manufacturing supplements particularly for areas of unmet medical need additional highlights on the post-market

review front includes some changes when it comes to the review of rents as well as other areas in post-market review as I mentioned earlier there are some enhancements that are really focused on the adoptions of digital Health technology and informatics the program continues on its path to enhance financial management and the sort of the transparency on the financial management and resource management and last but not

least a big focus of producer 7 as in previous padufa Cycles is the focus on strategic hiring and retention of world-class Technical and scientific stuff now let me focus on one particular program under padufa 7 this is a new pilot program that will focus on the advancement of endpoints in in rare diseases and as part of this commitment under producer 7 this new pilot seeks to

advance a rare disease drug development program by providing a mechanism for sponsors to collaborate with FDA throughout the efficacy endpoint and development process and as early as possible in development and this new program will promote Innovation and evolve in science by beginning early conversations very early in the development process as ideally in the pre-ind space between FDA and sponsors on potential new endpoints for rare diseases

including endpoints that might support accelerated approval and in addition to this FDA will issue guidance documents we'll run public workshops and will develop a public-facing website and all of this is really aimed at facilitating and accelerating the development for endpoints in rare diseases as we know that there is still a huge unmet medical need in hundreds and hundreds of thesis now I'm going to do a

little detour Beyond producer 7 to talk about the new program at theater that is really very complementary and if anything well actually it's turbo boost our commitment under rare diseases in producer 7 and this is the arc program or the accelerating rare disease cures program this program was set up at theater with division to a speed and Excel and increase the development of effective and treatment

options for rare diseases in this area of future medical need and so we set up this program to really create the connective tissue across all the disciplines within free theater that are involved in the development and regulation of drugs for rare diseases to really turbo boost our efforts in the space and obviously this includes our apparu for seven commitments now let me switch gears to the

biosimilar program as you will see in this chart the biosimilar program since its Inception has really led to significant savings when it comes to drug costs in 2021 reaching 7 billion dollars in the US so now let me walk you through some of the enhancements under the super 3. first a super 3 introduces some new supplement types and also some expedited review timelines for certain types

of supplements and this is all pointed at reviewing applications for biosimilars faster and more efficiently so that we bring these very important drugs to Market and really facilitate the access to biosimilars and biologics for patients the sofa 3 also includes some enhancements when it comes to meeting management and Communications and really adopts some of the best practices from hadoopa 7 keeping in mind that Basu for

3 is a much younger program and so we are seeing the sofa three really following in the steps of the padufa program as in the padufa program we're also seeing some enhancements when it comes to pre-licensure inspections some enhancement when it comes to the review of human factor studies and also some very focused efforts to improve the efficiency and the effectiveness of how we make decisions

about interchangeability which is a very important aspect of the biosimilar program and also the introduction of a new pilot program to enhance a regulatory decision making and facilitate science-based recommendations and I will tell you more about this program in the next slides as with padufa the basufa 3 commitment letter includes also elements related to financial management and transparency hiring and retention of Staff as well as

information technology now let me tell you more about this new basufa regulatory Science Program we're very excited about this pilot which really is similar to the very successful regulatory science program that we have had under the generic user fee program and I will touch on that a little bit later so this basufa 3 regulatory science pilot program is broadly applicable to biosimilar and interchangeable biological product

development however within this program there are two areas of particular Focus which will be the subject of demonstration projects the first one is the advancement of development of interchangeable products this is extremely important when it comes to the adoption of biosimilar programs why because we want to get to the point where biosimilars are interchangeable at the pharmacy as currently is the case for generics and in

order to do that we really have to study some scientific approaches to making determinations of interchangeability more efficient and effective and and take less time and effort and second we will also have a demonstration projects around improving the efficiency of biosimilar product development including seeing whether we require sort of less owners clinical trials and be able to make decisions and biosimilarity with relatively less clinical information

as part of this regulatory science programs FDA has committed to hold public meetings before October 2025 to review the progress of this pilot program into solicit input on future priorities FDA will also issue an interim reports on the progress of this pilot and will publish a final summary report on the outcome of this pilot by 2027. as one of the deliverables FDA has also committed to

publish a comprehensive strategy document within 12 months of completing these demonstration projects now let me switch over to gadoofit 3. now the generic drug program has had a huge impact on the access of drugs for the American people and has generated a huge savings when it comes to drugs in our country in 2021 as an example generic drugs generated 365 billion in savings and the top

three conditions that have generated saving for patients payers and the entire Health Care system by using generics instead of branded medicines are really three major areas heart disease mental health illness and diabetes these are all therapeutic areas that include diseases that are very highly prevalent in our country and in the world and it's not surprising that these are the areas where we have seen the most

savings and to give you another important figure so generics represent only about three percent of Total Health Care spending for a huge impact on sort of the wellness of the American people the generic drug program has increased access by introducing more treatment choices at a more affordable price borrowing competition which also has a beneficial impact on pricing the more competition the lower the prices and also

as I mentioned earlier in lowering a cost for the healthcare system now let's cover some of the garofa three highlights one area that I want to really flag is the goal of increasing the proportion of generic drugs that are approved after only one cycle of a review and historically for most of the generic drug applications it has taken more than one review cycle and of course

after each review cycle entails more and more additional months before the drug is approved and so one of the major goals is to minimize the issuance of complete response letters and get into a point when we approve drugs with the first cycle including some sort of additional tools under the garofa three program there will also be some enhancements to refine the pre-facility correspondence process and to

sort of expand control correspondence other highlights undergradufa 3 include expanded opportunities for early assessment of drug Master files before a certain priority iindiles are submitted in between review Cycles again this is pointed to trying to do work sort of upfront so that we minimize the delays in application review there's also some continued enhancements to the well-established regulatory Science Program which I mentioned earlier on when I

was speaking about basufa regulatory science program and this program as I will tell you a little bit later really continues to be particularly pointed on Expediting the development of complex generic drugs there's also some new goals for suitability petitions as well as enhancements of the management of user fee resources now let me talk a little bit about the communication and review enhancements around the review of

generic drug applications as I mentioned earlier we really want to see the number of review Cycles reduced through the use of imminent approval and gold date extensions which are new elements of the gadufa 3 commitment letter so that we're able to resolve major or minor issues that may arise during an application without necessarily having to issue a complete response letter and then having to start a

new review cycle there are also some revisions to the pre-submission facility correspondence pathway that we think will really further streamline the review of facilities as part of the application and we are also going to see an expansion of options for advice after a sponsor receives a complete response letter by adding to the scope of control correspondent and the post a complete response letter scientific conferences in

certain situations and this is again to improve the communication between FDA and sponsors in those situations where we have no option but to issue a complete response letter but we also want to make sure that the application is resubmitted quickly and that the sponsor has everything in hand to be able to address the deficiencies in the complete response letter other enhancements under garage include new goals

around the responses to suitability petitions to facilitate the development of new and as and this will make it easier for instance for applicants to request different routes of administrations of strength and dosage form with more Tighter and shorter timelines for FDA to respond and there will also be some opportunities for teleconferences correspondence and scientific meetings when there are changes in product specific guidances that impact ongoing

bioequivalent studies which has been a sort of a pain point for industry and understandably because these changes in product specific guidances which in the generic program represent you know how to recipe to achieve sort of bioequivalence for a specific product may happen while there is a development program underway and so this could cause some disruption and confusion for sponsors and so we really want to make

sure that we there is an opportunity to have these meetings to achieve sort of Greater clarity as to what the new requirements might be now let me speak a little bit more about product specific guidances they're extremely important for the generic program and they are really a roadmap on a product by product basis to tell sponsors what the expectations are when it comes to achieving bio

equivalence which is really the Cornerstone for generic development in 2022 Cedar issued 257 product specific guidances and very important 154 of those are for complex products including 54 product specific guidances for complex products in total theater has issued over 2 000 product specific guidances and I will really cannot emphasize enough the importance of these guidances for complex generics why because these are products that are more

difficult to develop it is more difficult to achieve bioequivalent and so it is critically important that we continue to issue product specific guidances for complex generics and gadufa 3 has some specific goals around that now as I said earlier the complex generic space is extremely important and if you look at the sort of pipeline of products we can expect that conflict generics will represent a greater

and greater proportion of products for underdevelopment by the generic industry and so garufa 3 really recognizes the increasing importance of complex products and introduces some enhancements that really point at making the development of these products easier so for instance there is a new goal under godofa three that establishes a new teleconferences of meetings when a product specific guidance impacts ongoing bioequivalent studies there is going to

be a greater focus on pre-submission meetings on key issues under review for a complex generic there is going to be more enhanced a scientific mid-cycle meetings with the goal of resolving more substantial issues within a single review cycle without having to start all over again and have more review cycles and then very importantly the roofer 3 establishes these new post-complete response letter meetings to immediately sort

of discuss with the sponsor how to resolve for the deficiencies and be able then to submit a new application as quickly as possible now let me talk more about the science and research program under cadufa this is a very successful program that has been in place now from previous Cycles so what gadufa 3 does is it adds some areas of focus and these areas of focus

include the development of methods for generics to address nitrosamine impurities which is a very important area for us and we're seeing more and more generic applications that have to be where we have to issue a complete response letter because of the presence of nitrosamine or nitroso combine impurities so it's very important that we study and we develop methods to address these impurities so that they don't

hold up the approval of applications and then other areas of renewed Focus under the science and research program is complex generics and as you can see there are host of new areas of focus to improve the efficiency of Bio equivalence approaches for complex dosage forms and formulations or for complex drug device combination products so in summary from theater's perspective this new cycle of user fee is

going to really introduce some very excitement enhancements that will continue sort of to advance Innovation as well as support the rigor of our review program through new initiatives and processes the efforts will Cascade throughout various either programs including research efforts and collaboration with industry finally the user fee programs will continue to ensure that FDA remains a global leader when it comes to Innovation and bringing new

therapies to patients in areas of medical needs as well as making these therapies more affordable thank you for your attention today Patricia thank you for your insights on the impact of user fees on the various programs at Cedar let's now conclude our presentation segment with an update on vaccines and biologics with Dr Peter marks Dr Marx has been the director of the center for biologics evaluation

and research since 2019. over this time he has overseen sieber's efforts in assuring the safety and effectiveness of biological products including vaccines allergenic products blood and blood products and cellular tissue and Gene Therapies let's now hear from Peter and his perspective on the user fee impact on various saber programs so now that you've heard from Dr shurin and cavazone about the various user fees it allows

me to tell you how the user fees impact on our work at sieber and particularly to give you an example of how one of the areas that we work in relate to the user fees sieber products include a variety of biologic products including blood products vaccines allergenic products and cell tissue and Gene therapies so a pretty wide span of different biologic products some of which have

relatively complex manufacturing requirements for their production the user fee programs at sieber include four of the user fees that you've heard about most of our work is under the prescription drug user fee act but we do have some devices that are under medufa a little bit of work that's under basufa and a small amount of work under godufa so primarily our work is under the Prescription

Drug user-free Act but we do have some devices many of those in the area of blood or tissue either testing or production one of the areas at sieber that has undergone tremendous growth over the past years have been cell and gene therapy and you can see here on the slide that the growth in this area has been year over year until relatively recently and recently obviously

we had the pandemic which may have been responsible for a little bit of the Slowdown but on the right side of this illustration you can see that we continue to receive a tremendous number of amendments that go with our investigational new drug applications so continued growth here with approximately 2500 active investigational new drug applications in the cell and gene therapy space and that does indeed keep

us busy what we've seen now is those investigational new drug applications are turning into real products over the past year and in 2022 we have had five gene therapy approvals adding on to the seven before that so we now have an even dozen products that are approved at FDA in the gene therapy space these include cell-based Gene therapies including the chimeric antigen receptor T cells and

the modified stem cell therapies and the directly administered Gene therapies either locally is administered for hereditary eye disorder for one of them or systemically administered for hemophilia or for rare genetic diseases such as spinal muscular atrophy now in the padufa commitments there are various areas that apply to our Center particularly those in advanced manufacturing patient-focused development reviewer training and Staffing and there were actually also additional

directives that are part of the FDA Reform Act of 2022 our Center because of the focus on biologics manufacturing has a variety of initiatives in this area to try to improve manufacturing which is a key aspect of the production of our our products now our padufa commitments also include targeted hiring in the area of cell and gene therapy this is critical because in order to provide

the advice necessary for these Cutting Edge Products we have to have a sufficient number of staff and we're lucky enough through the recent user fee reauthorization to have about 125 new full-time equivalents that we'll be able to hire in the areas of cell and gene therapy these include about a hundred individuals that will work directly in the office that handles cell and gene therapy and then

25 full-time equivalents that will be in offices that support the development of these products such as those who go out to inspect facilities and our biostatisticians and obviously for these individuals it will be really critical that we are able to appropriately train them and have the appropriate systems in place to accomplish this training now the growth in the area of gene therapy has been remarkable over

the past years and I hope that you can see over the course of time with that growth we've been unable to keep up until more recently with the Staffing now that we have been Staffing up we have a different kind of problem which is that we have an office that has grown almost too large to handle the number of individuals in that office to have reasonable

spans of management supervision so recently we have reorganized what was our office of tissues and advanced therapies into a super office structure which has now six offices under a larger super office in order to have good control of the number of individuals in each office and so we now have separate offices for gene therapy Manufacturing Cell Therapy Manufacturing manufacturing of other biologics that are regulated in

the office of therapeutic products which is the new super office name we have a large clinical review branch which allows us to deploy clinical reviewers across any of the product areas and office of pharmacology and toxicology that provides those services for review of any of the products and then a project management office that helps make sure that everything is coordinated by having these different offices now

we're able to have reasonable spans of control with about 80 to 125 individuals in each office and that allows us to deploy our resources more effectively and make sure that there's appropriate management supervision as we move forward I want to highlight now some of the gene therapy initiatives that will be taking place as part of our padufo work during the coming years gene therapy is an

incredibly promising area that has the potential to make a huge difference on medical care because although it may not be absolutely Curative it potentially can provide long-term benefit for many diseases that currently have no effective therapy and to try to accomplish our goal we're going to be continuing to work on advancing Manufacturing Technologies for cell and gene therapy through additional research in this area we'll be

using and better defining the use of accelerated approval for gene therapy we'll be exploring concurrent submission and product review with other regulatory authorities around the globe and I'll tell you a bit more about that and we will also be introducing a pilot program looking to apply the learnings from operation warp speed which was originally for vaccines and other products for covid-19 to rare disease gene therapy

so to say a little bit more about how we're trying to get there Gene therapies can leverage certain aspects of the different Gene therapies that are similar in order to hopefully help move these products forward more rapidly through development now what's similar about different Gene therapies is that for a given group of Gene therapies they may all rely on the same Vector backbone that is the

part of the gene therapy that carries the unique part of the gene therapy the gene that part of the gene therapy that makes the pro protein of Interest into the body because we believe that we can leverage information from one vector to another potentially if the vectors are the same between the different Gene therapies and if they're manufactured using the same methodology we're hoping that we

can start to develop platforms and make use of the platform therapy provision that is part of Fedora 2022 we're also trying to then on top of that be able to leverage the use of accelerated approval for rare disease Gene therapies many of these diseases affect only a small number of individuals and many rare diseases have very long natural courses during which patients deteriorate continually over time

and it can be challenging to conduct studies over many years and the ability to use biomarkers to get an early readout about whether a gene therapy is having an effect or not may be crucial to getting some of these Gene therapies to patients ultimately the gene therapies May interrupt the deterioration that would otherwise occur that would be just an example for instance in some of the

neurologic conditions that are caused by lysosomal storage disorders or some of the other genetic defects so if we can use biomarkers or intermediate endpoints to get there faster we'd like to do that and we'd like to lean into doing that and so we anticipate working with sponsors in this regard over the coming years we also think that getting towards Global cooperation in this area is going

to be crucial in the United States we might only have 20 or 30 people with a given rare disease but if we can pool patients with people for instance in the European Union and in countries like Japan we might have a hundred patients to treat and by doing so we can take diseases or conditions that are otherwise commercially not viable and make them into commercially viable

entities for which sponsors will develop products that will require some collaboration cooperation perhaps even having some of us compromise on exactly what our requirements will be but at the end of the day we believe that if we can make those compromises and ensure that collaboration all of our populations will be better off through being able to have access to therapies that may be the only therapy

they can potentially address a given disease and finally we've come to realize from the operation warp speed that was done as part of the medical product development for covid-19 that communication is one of the most critical things that we do with sponsors at FDA it's probably among the most important things we can offer to help product develop move forward particularly in this space of rare disease

gene therapy where things are so new and Cutting Edge that the ability to have an ongoing dialogue may make the difference between years in having a therapy make it to Market the idea here is that currently meetings are held in a way that means that sponsors often wait a few months between sending in a meeting request and getting feedback what we'd like to be able to

do with this pilot is see if in several cases we can show that having ongoing communication allows us to move development faster and so in the coming months we will put out a notice to get applications to see if sponsors would like to be part of this pilot we'll be putting forth criteria by which to select promising rare disease therapies and then we'll run this pilot

and afterwards see if it actually does make the difference that we think it will make in helping to get these products towards Market and ultimately the evaluation that we make of these products will help us decide whether or not we try to justify a larger application of this potentially with future user fee Act so just to summarize from sieber the user fees are providing us with

critically needed resources for the review of innovative cell and Gene therapies as well as other products that we regulate including vaccines and really we have quite a wide variety of initiatives ranging from manufacturing On Through To The Clinical development of these products so thank you very much [Music] thank you Peter and thank you to all of our panelists for your remarks on the USB impact on

various FDA programs you shared a lot of great information with us today once again I'm Elias malis let's now continue the plenary session with our Roundtable discussion the user fee programs generate a lot of questions to the FDA and we got into some very interesting specifics in the presentations just now based on all of this we've come up with a few questions as we have a

conversation about user fees now for the first set of questions I'll read out the question and ask each panelist to share their thoughts about the topic so let's get started with our very first question Jeff I'd like to start with you with our first question and this is an update to what we asked last year when we talked about covid to what extent would you say

our experiences with covet had an impact on the user fee programs we've put into place with these recent user fee programs I do think there's been an impact of the experiences we had with covet and it's both indirect and direct indirect in the sense that we learn from covid how important is that we have an agile organization you know during the pandemic we had a Justice

quickly as circumstances on the ground changed and in today's world you know science technology societal values and needs are evolving faster and faster and so we've got to be a Nimble organization so we've learned from covet and we've already been starting to make changes in the program to be more agile it's also had a direct impact you know during cobit we gave the opportunity for developers

to work with us in near real time for us to answer their questions what we call the pre-emergency use authorization and it was incredibly impactful for helping us authorize over 2 800 medical devices for covet and we were able to do that really well early in the pandemic we're going to have so many submissions well that experience helped inform our development of the tap pilot really

baked in those Lessons Learned into the pilot excellent thank you very much so Patricia will ask you the same question what was the impact of covet on the user fee programs that you started to implement at the end of last year I'm going to take a slightly different angle uh than Jeff but it's complementary angle and the what we learned during covid is that the user

fee programs were actually foundational in our ability to be able to do the work that we needed to do to develop new new Therapeutics at Cedar for instance so the structure that has been sort of established through the use and programs user fee programs the processes and so on we're really you know essential and foundational as with the you know cdrh we had to learn to

uh to respond to the pandemic thank you very much um let's wrap up this introductory question with you Peter with your thoughts yeah so I I think I would have to agree with Jeff that for us we did a lot of work on emergency use authorizations a lot of that work was not user fee work but it has rubbed off into US understanding for our user-free

work that need to be ever more agile and how we adapt to the challenges we're seeing very Innovative products that are being submitted as part of the user fee program and understanding how to adapt to now having very complex combination products that require complex review and and the need for more real-time interaction with sponsors has been an important learning excellent thank you very much all right

for this next question we'll start with Patricia our user fee programs operate in five-year cycles and we launched this current set of programs in October 2022 now that we're approaching the completion of the first year can you share a status update on how the rollout is unfolding well we obviously have a long to-do list as part of our commitment letters particularly for theater where we have

you know three programs with a a very sort of long list of commitments what we have done with this cycle is something a little bit different compared to previous Cycles we have actually put in place a sort of steering committee on top of each of the three user fee programs and this group is not only there obviously to track the how we progress against our commitments

but also to maintain continuity between now and the next sort of round of negotiations so that as we uh as we sort of look at sort of as we implement the commitment letters we also start thinking about what we would like to see in in the next cycle and we okay what we have seen in previous years is that while we have been very good sort

of at tracking our commitments there as being a bit of an on and off and off switch when it comes to the sort of negotiations and things sort of uh uh get quieter for a few years and then all of a sudden sort of we have these data calls to see what you want to do with an excitement do we think that it should be really

a continuous process from one cycle to the other so that we keep on thinking about how we can enhance these programs over time all right thank you very much Peter we'll go to you with the same question how are things going so far in this first year for user fee cycle yeah I think we're excited to be able to take advantage of the additional head count

and I think for us it's almost like the real estate joke location location it's hiring hiring hiring and so we are working to get people on board obviously we had the reorganization of the uh into the office of therapeutic products and getting bodies on board has been a major effort and I think we're doing reasonably well getting people into both leadership positions and into reviewer positions

in that office thank you very much we'll conclude this question with you Jeff your thoughts on how are things going so far with this current user fee cycle especially for medufo well I think to you know Echo Patricia and Peter um there's a lot on the to-do list uh and one of the big ones is hiring but you know so far uh pretty good you know

I think we're uh we've got a lot of important documents out changes to the program and we're on track at least at the moment you know to meet our performance and our hiring goals and that's really exciting sort of coming out of the pandemic and putting that in our rear view mirror that we're already on a good road moving forward thank you thank you very much

um let's conclude this first series of questions where we'll ask everyone the same Peter I'm going to start with you this time user view programs feature extended negotiations that occur between the FDA and stakeholder groups of interest and then from their proposals are submitted and ultimately determined by Congress how do you balance advancing the needs of the FDA while also factoring the perspectives of these other

important groups which may sometimes have different goals than what we may have at the FDA you know I think it's a matter of balancing exactly as you say and finding The Sweet Spot in what industry may want and what FDA may want we can't always get to exactly the same place but I think at the end of the day when we remember that our goal is

the same thing to develop you know medical products that benefit patients I think we generally find our way to the right place together I mean I think I've been impressed in the past user fee negotiations that that we actually did find our way pretty harmoniously to many of the things that we wanted to achieve thank you Jeff the same question to you about the spirit of

negotiation with the different stakeholder groups yeah well I agree with Peter you know we're always trying to understand and take into account the you know the needs of our customers um and at the end of the day I do think we have shared objectives and that helps us to get to a good place all right thank you and then Patricia concluding with your thoughts yeah I

will Echo what uh Jeff and Peter have said uh it's a balancing act um I would say that I would bring in also the patient groups and the patient advocacy groups they have a very strong voice in as we find our way through uh through the negotiation process but at the end of the day as we can see from this last round we really landed in

a good place excellent thank you so we'll switch gears now to the next set of questions for each of these I'm going to pick a theme that was revealed in each of your presentations but I'm going to ask you each of you has specifically tailored question so Jeff we'll start with you again for this first question so a connecting theme throughout each of the presentations is

the focus on the patient patients are indeed at the heart of what we do um for cdrrh cderh has seen a steady progression of strategic focus on the patient you outlined all of these initiatives in your presentation from patient preference to Patient science and engagement to real world evidence and to Nest to what extent would you offer that patients indeed have a voice and the regulatory

decisions that cdrh renders I think you know patients have a strong voice in the decisions we make in the work that we do and we've continued to expand their opportunities over the past several years you know let me give you three examples one we established the patient engagement advisory committee it's the it's the only advisory committee at the agency that's made up of patients so they

can weigh in on important issues pertaining to the FDA you know the second is I mentioned the tap pilot you know tap is a chance too for patients to engage with developers when they're designing the technology and make sure it really is designed to meet their needs and when we think about designing a clinical study that it's set up in a way that best meets the

needs of patients so they can optimally participate in that clinical study you know and lastly we've in the past few years had big focus on establishing and participating in what we call collaborative communities it's where the community comes together and the key stakeholders in that community in participate in an ongoing for Forum where they can deal with you know shared issues and come up with common

Solutions and FDA is just a participant in the community one of the other participants or patients you know they have equal voice at the table and if the community has a solution and it's in the best interest of Public Health and it's not contrary to our statutory mandate then we'll adopt that Community solution again it's a great way for patients to have a stronger voice in

what FDA does all right thank you thank you for your thoughts and your remarks Patricia will continue with you something that many of us can relate to and probably very dear to our hearts as patients and consumers ourselves is the price of medicine and the benefits that generic drugs may have for patients while the FDA does not control costs directly how would you say that gdufa

three program efforts might have an impact on drug pricing itself uh three and which is our generic program and I would add to that the biosimilar program already the Cornerstone of what sort of FDA and theater can do when it comes to a accessible making drugs more accessible obviously we cannot control the prices at the price of drugs as you have said we're not payers we

don't we learned the the price of a drug with everybody else after it's approved and the company announces what what it's going to cost what we do know however is that through our generic program in our biosimilar program we are the more drugs we approve the greater impact positive impact on pricing and this has been shown over and over again the more competition the the greater

the benefit on on pricing and we see it with other Commodities I mean you are when you have monopolies you generally do not have favorable favorable consumer environment when it comes to pricing and so these programs are are really essential to promote competition by approving sort of more and more drugs even more drugs that are sort of exactly the same class and and so on and

you know the numbers that I showed in my presentation speaks for themselves when it comes to cost savings for the Health Care system excellent thank you very much for your thoughts Peter let's conclude with you with this question you made reference in your talk about patient-focused drug development can you elaborate a little bit more about what you mean by that so for many of the the

rare diseases that we're dealing with and not so rare diseases there are specific aspects of a disease that are more bothersome to patients than others and in the past drug development was based on what a drug developer thought was important or perhaps what Physicians thought was important which is not always the same as what is really important to patients so a drug developer might think that

preventing an abnormal heart rhythm in a rare disease was what was really important but it turns out that for instance for the patients it was the fact that they just felt really tired all the time and a therapy that addressed that fatigue that came from the underlying genetic disorder was more important than just addressing the at some cardiac abnormality I mean they're both important obviously but

making sure that we focus at least part of what we're doing on what really matters to patients is important excellent thank you very much um so for our next question we'll talk a little bit about how FDA engages and engages early with our stakeholder community early engagement with our stakeholders is another recurring theme that came up in your presentation so Patricia I'll start with you for

this follow-up you mentioned improving the efficiency and expanding Communications in human drug reviews can you share a little bit about what this looks like and perhaps comment on the regulatory submission meetings between FDA and sponsors to take place for sure so I'll give the example of one of the enhancements in producer 7 which is the rare disease sort of endpoint pilot program so what we find

unfortunately more often that we would like to see are situations where drugs for for rare diseases sometimes even the first drug for a rare disease are submitted to us through an application and there is still lack of clarity about the endpoint and and some very basic aspects of drug development and so particularly when it comes to identifying new endpoints for clinical trials in for drugs for

rare diseases that might allow us to actually make those trials more efficient and to make the development program shorter it's very important that we have discussions very early in development and it's very difficult to have those discussions one week before we have to make the decision on an application the ideal place to have those discussions is actually even before the first studies in humans what we

call the pre-ind space and so we really encourage sponsors to come to us early to discuss these potential new endpoints including endpoints that might be able to support the use of accelerated approval and I know that this is a very big topic of interest for the rare disease Community but we cannot discover or start discussing these issues at the tail end of an application review we

really have to do it very early on and so this pilot is going to be very important but this you can you you can really expect that this will go broader than than this pilot this is something that we really have to to uh to facilitate this very early engagement excellent thank you for your thoughts there Peter will continue with you on this question theme of

early engagement um you mentioned a Communications pilot for specific rare disease products operation warp speed will the program be focused on the tissue product space or across other programs all throughout the center so thanks for the question the initially we're going to be focusing it on the rare disease gene therapy space because that's the area where we think there can be most impact that's an area

where for many of these diseases there isn't a small molecule or protein therapy that can help those diseases the gene therapy is the only thing out there potentially to address some of these conditions and so seeing those Gene therapies particularly for diseases where the disease takes someone's life early or leads to severe disability early in life we'd like to try to see if we could address

those more rapidly that would mean have making a big difference in how people survive or function and so we want to see if this communication can accelerate that because even a 25 percent reduction in the time for getting something through our process would mean a lot to patients and their families excellent thank you Jeff we'll conclude this question with you a new initiative rolled out in

madifa 5. you've already talked about it already here is the total product life cycle advisory program or tap it's a very fascinating concept and can you share a little bit about how this was developed how did it come to be well in part it's uh it's informed by our experiences from cobit you know that early engagement with developers but also our experiences with developers uh across

the life cycle of the product um and understanding what the challenges are they face them in fact the person we brought in who really uh has led this effort uh Doug Kelly one of my uh one of my deputies was a venture capitalist for 30 years so he he saw firsthand what it took you know to to create companies to create products and also has seen

the failures too and the things that go wrong and have really brought that mindset into informing the program excellent I have a part two for you to ask in your presentation you mentioned some quantitative metrics for the assessment of the pilot do you have specific goals for these metrics that you've identified well we do one of them is around that those interactions so prior to tap

you can engage with us and get our feedback anytime you know on the pathway you can do that early in development but you can go up to four topic areas in the pre-submission you send in your questions you throw them over the transom we send back written responses and we'll meet with you in 70 days right and if you have more questions you get to throw

them over the transom get to do it all over again tap is saying well let's let's first of all shrink that time frame and let's try to get to much more fluid back and forth so we did put in at least goals and if you're going with what would otherwise be a traditional pre-submission we're going to say we're in the seven days we're going to do

it within 40. in fact we want to do it sooner unless it's biocompatibility sterility that's 21 days and a lot of things that don't rise that level will engage within 14 days we kicked off the pilot already our involvement with the companies literally we are having multiple conversations with them already just over the past few weeks to try to problem solve so we're going to evaluate

that performance what's going to look at you know customer satisfaction and that's all the customers the companies the patients the providers the payers and our own Folks at the FDA wonderful work it's a very exciting program for our Center so thank you for spearheading that effort so for our next round of questions I'm going to just pick on unique questions from each of your presentations that

that you shared so Peter will start with you with this first set of questions as you outlined in your presentation sieber leverages four different user fee programs two of which are impacted by our two other centers medufa for cdrh and padufa for Cedar how does sieber approach these multiple joint efforts do you collaborate with each other do you work independently can you share a little bit

about that since you have so much involvement with different programs yeah no I think we we are a I I think we are the cross-center center because it actually goes broader than the other medical product centers because some of our products even cross into the veterinary medicine space um and into the the food space because of the the the crossover between some of the nutritional products

and the probiotics used for medical purposes same thing goes with some of the animals that are then become Medical Products because of either the products made from their milk or tissues so we have a lot of cross crossover and I think it's it's a matter of just working seamlessly with other centers I think we we take a role in helping to develop guidance in these other

areas to a greater or lesser extent depending on how much we actually have interest in those areas obviously padufa we have a lot of a lot of interest in medufa a fair amount and then we are a small player in the basufa and gdufa area but still and we because at some point we're hoping to see more biosimilars we still take active interest in these areas

excellent thank you um Jeff we'll go to you with the next question in your remarks you spoke of the digital Health Journey for cdrh both with a number of remarkably you know remarkable prior accomplishments as well as a lot of ongoing efforts are happening even right now as we all know geology continues to evolve at such a rapid Pace in many domains and of course through

medical devices as well where do you see the future of digital Health Products and how FDF how cdrage in particular may approach their regulation in the future but it's a great question um you know in the U.S we spend more money on Health Care per person than other developed countries and yet our mortality um is much greater folks die younger here in the U.S um and

that's got to change and ultimately to get there and to be able to provide access to all people and deal with issues of Health Equity you got to move care from Health Care Facilities to where people are whether it's at home at work and at play and it's digital Health Technologies that are really the linchpin that bridge not only for people with their providers but that

connection to be able to be in there to help with prevention in the first place then diagnosis and disease management and intervention ultimately we're looking at you've got to transform Integrated Health Care delivery and where you provided and that's our big effort on digital health is to try to advance that future State for the U.S Health Care system thank you for your thoughts there and Patricia

will turn to you for the next question as we know FDA is a science based regulatory agency and you outline the importance of research to advance veritatory science for drugs can you elaborate elaborate on a selection of priority initiatives that cedar has selected and are there other areas of importance to come with respect to regulatory science sure this is a very important area so to a

sort of frame the what I'm going to say we have two programs that are formally funded two research programs that are formerly funded under the user fee programs the one is the generic regulatory science program and then we have this new entrance the regulatory Science Program pilot for biosimilars we do not have a formally funded research program under padufa so let me speak to the first

two um these programs are really applied regulatory research meaning that they are meant to solve real regulatory problems that then are going to make us hopefully more efficient and effective in how we support the development of generics and biosimilars and so when it comes to generics the area of focus for the next or this current cycle is complex generics including a complex formulations including combination products

if you look at the what's coming down the pipeline for for uh in in generic uh sort of r d uh programs you see more and more complex generics why because that's what you see also in the sort of Innovator pipelines and and therefore you know the the you know the innovator or branded product pipelines become the r d pipeline for the generic industry so those

are big areas of focus when it comes to biosimilars this new program is really meant to a turbocharge our efforts to find faster and less cumbersome ways of uh to to develop biosimilar products hopefully by reducing the amount of or length or complexity of the clinical trials that we prior to make decisions about biosimilarity and within that a particularly important area is interchangeability we want to

get to a point where we can make decisions of interchangeabilities more efficiently and faster and in order to do that we really have to research this area we have to have a research program that answers a very important scientific and Technical questions that hopefully then will will chart the path for us to be able to to expedite these these decisions thank you Patricia Jeff we'll come

back to you with our next question and as I look at our panel I think you have the most experience with their use a few programs having been Center Director the longest of our three esteemed panelists here so as you reflect on the history of the medufa program over these years how would you say it's evolved over time and over these years and how you've approached

these user fee Cycles as now we're at to medufa five yeah I've got a few Battle Scars From over the years you know we we started small again the the focus was on pre-market review and I think with every cycle you know we continue to learn on the program we take those Lessons Learned and we make mid Court Corrections we make enhancements but over time too

we've become I think far more strategic and what we do we've built out the program to kind of Target key areas and now growing even further to truly try to address going from concept to commercialization you know when we look at it first of all we're always thinking about you know as as Patrizio said you're always thinking about what the next medufa maybe looks like we're

always planning for it and we kind of start with you know our vision on the center and where we think the ecosystem should be at the end of the next madufa cycle and thereafter and then we look at meduf and say how could medufa be appropriately modified to then help meet that future State and that really drives us what we do thank you Patrice will go

to you with the next question you talked about FDA staff hiring and retention I think that that came through also in some of the other presentations but as staff hiring and retention as core highlights for both but badufa and basufa efforts um can you share a few examples of some of the strategies that cedar has taken to advance these efforts well the as you heard from

uh from Jeff and and Peter uh we all have hiring goals uh as part of the user fees the strategies that we have taken is uh really has been fundamentally based on our use of the 21st century curious hiring Authority or title 21. so the our ability to meet the user-free commitment is intrinsically and very tightly connected and dependent on our ability to use title 21

in a way that is not overly bureaucratic and that does not create problems with the center and this is something that we have to you know keep in mind in particularly as FDA through our the new authorities that we we receive from Congress in January whereby you know FDA can expand the use of of title 21 or 21st Century Cure the Asian city is very important

to keep in mind how important this hiring and pay Authority is for the centers and for the center's ability to meet the user fee commitments excellent thank you so much for your remarks Peter will conclude with this question for you now in your presentation you talked about the efforts to establish a new super office structure model and this is a concept that's been previously used both

at Cedar and at cedarh in the past do you have any Lessons Learned From the prior experiences of these other centers that have informed perhaps have you how you're approaching it for sieber yeah I think we're trying to learn from the best practices by essentially deploying resources most efficiently trying to avoid duplication of functions while having optimal coordination so we'll continue to learn best practices I

think as we as as we watch our other centers go forward with this but I think the the concept of these a larger office that can have coordinated functions certain things you actually can get economies of scale on other things you can't and to deploy that correctly is what we'll aim to do all right thank you very much we're going to wrap up our segment with

a couple of questions I'll ask for each of you again Patricia will start with you for this again thank you for the time that you've taken and we really appreciate it um for this first question looking ahead and this again has come up during the remarks just now at what point do you start to look ahead and start to plan for the next user fee cycle

and can you share what goes into that planning yeah so as I mentioned earlier um when it comes to Theater which is a very large Center so it takes a lot of effort as the center director to just you know get all the parts to to to talk to each other um it used to be you know a bit of an on and off switch um

so uh about you know two or two months before you know a couple of years or a year and a half before uh the next sort of the renewal date activity would start up there would be a data call across all of the office to say what are the some of the ideas that you have and Etc that worked well and he really got us a

long way and as a way to continue to enhance that we think that it needs to be sort of more continuity more ongoing sort of thinking about potential enhancements like you've heard from from cdrh from from from from Jeff um right and and really think along the way uh as on about a sort of potential additional things that we want to see in the user fee

programs and then that longer term vision is really important to really set a vision that straddles more than you know two or three user fee programs so I'll give you an example of something that we're thinking about right now you know we have had very successful funded user fee funded research programs that we talked about for generics and value similar so is there a path forward

for instance to identify some applied regulatory research areas that could become sort of use cases for a padufa funded regulatory research programs in future in future Cycles that's one of the examples of the things that we're thinking about right now excellent thank you for your remarks there Peter will go to you for the same question about your thoughts on how when do you start to plan

ahead for the next user fee cycle yeah I I I agree with Patricia this is something that we we have to we it will happen it actually is going to start happening pretty soon as we try to in an organized manner work through proposals that may make sense in part because as we're implementing this set of user fees we're already starting to see what might be

good ideas for the next set so this will be an organized process and I think that the the organized nature I think is something that in a little over 10 years at the agency I've seen us get more and more organized in this process excellent is that the same question to you uh well it's sort of ditto I'll have what they're having it's really very much

the same and I I think just to build on too we also we do our homework you know we monitor our programs We Gather our data and a lot of things we do and what proposals we put on the table they're data driven at the end of the day and we've got a lot to back them up excellent thank you all right we've reached our last

question so Peter I'm going to start with you so if you had one wish what's the one new program area or initiative that you'd like to see supported through our user fee programs wow you know I I think we we already have some support in here but I think for for me for biologics it would be uh really continued uh support and uh even greater support

of manufacturing initiatives because I think in the in the world of biologics um we still are especially in vaccines Gene therapies we're still behind the eight ball on on manufacturing technology excellent Jeff I'll go to you what is on your wish list for next time uh for us uh post-market safety uh it's important to us was really important to patients we gave it a the college

try in medufa five we didn't get there but our hope is that we'll strike gold in medufa six excellent and then Patricia the last thoughts on this question well out of a very long list that I have in my head I would say clinical trial Innovation we are beginning to do some work internally to really think about how we could uh you know set up a

program that would bring together all of the pieces that will ultimately that are important when we think about how we can innovate clinical trials you know from how can we make them less complicated more pragmatic how can we really Embrace decentralized clinical trial uh sort of a tools how can we adopt digit you know a really embed digital Health Technologies in clinical trials how can we

use modeling for a greater extent there's all these pieces that may be sort of going on across the center but we really think that we want to create a really turbo turbocharge this work and so uh this uh we're thinking that this you know if we see some success in some sort of pilot that we're going to be doing within the center maybe this could become

something that we want to see Advance with the next user fee cycle for instance all right thank you and Patricia you have the last word for our segment here end with that this concludes the ready 2023 plenary session user fee impact on FDA programs I'd like to thank our esteemed panel of FDA leaders Dr Sharon of cdrh Dr kevazoni of Cedar and Dr marks of sieber

my thanks to you for spending this time to have a conversation with us about the important impact that user fees have on our Collective FDA work it was really fascinating to get a behind the scenes look at what it takes to roll out and implement the substantial effort my thanks to you our Global audience for joining us for this very special session I truly hope you

enjoyed learning from our fde leadership on this important topic this will now conclude the plenary session let's now take a break when we come back we'll start the drug tracks and the cedar sessions I'll pass the virtual baton to my dear colleagues at Cedar who'll serve as your host now for those of you joining us for the devices track and cdrh sessions I'll see you on

Wednesday morning at 8 30 a.m eastern time until then please take care