Regulatory Education for Industry (REdI) Annual Conference 2023 Day 1 Session 2

foreign welcome back from the break my name is Ray Ford working with sbia and I'll be your host moderator for today's sessions we hope you're able to refresh your coffee or tea as we move into our presentations our first presentation in this session will be on the bio similar program updates and what's new under basufa 3 . our presenters are Dr Stacy Ricky who's the director

of scientific review staff and the office of therapeutic biologics and biosimilars within the office of New Drug Cedar and Dr Kimberly Maxfield she's the asufa regulatory Science Program Coordinator and the office of therapeutic biologics and biosimmers and O and D our final presentation before the Q a panel is on FDA formal meetings what's new Under Brit our presenter Elizabeth Thompson is the chief of project management

staff and the division of regulatory operations for non-prescription drugs office of regulatory operations and ond for a complete biography on each presenter today please refer to our speaker biographies located in the same area on our website as the conference agenda now please join me to welcome our first presenter in this session Dr Ricky hello I'm Kimberly Maxfield and I both work with our talented colleagues in

the office of therapeutic biologics and biosimilars thank you for joining us today for a presentation on several exciting updates about fda's biosimilar program today's presentation will provide a status update on our review of biosimilar and interchangeable products explain several enhancements to fda's biosimilar program introduced under the third authorization of the biosimilar user fee amendments including a new regulatory Science Program we'll also describe recent legislative updates

affecting biosimilars and highlight progress we've made to increase our educational Outreach to patients and providers this line shows a timeline of all U.S biosimilar and interchangeable bias similar approvals since the passage of the biologics price competition and Innovation act in 2010 created an abbreviated approval pathway for biosimilar and interchangeable biosimilar products their development has undergone steady growth from the first biosimilar approved in 2015. to a

total of 40 biosimlers approved today four of which are interchangeable these products can be used across many different therapeutic areas to treat a wide range of diseases and conditions including the side effects of chemotherapy brass lung and colon cancer hematologic malignancies autoimmune diseases such as rheumatoid arthritis psoriasis Crohn's disease and ulcerative colitis plus diabetes macular degeneration and many others and the list continues to grow one

of the 20 21 of these products are currently marketed in the U.S we expect many of the adult men biosimilarities to be marketed this year which should increase biosimilar uptake and availability Nationwide other metrics to note are the 102 proposed biosimilars under review and active biosimilar development programs and that FDA has met with companies to discuss proposed biosimilars to 53 different reference products and now for

some updates introduced under basufa 3. we are in the third iteration of the biosimilar user fee program and this included 10 areas of focused enhancement today we will discuss three of those enhancement areas highlighted here the new bla supplement categories specific to biosimilar programs addition of timelines for human factor analysis and protocol review and the new regulatory science pilot program there are now six new supplementary

bla categories a through f include expedited review timelines for safety labeling updates and labeling updates to add or remove an indication where FDA does not need to review new efficacy data if review of efficacy data is necessary the timeline is 10 months from receipt date these new categories allow for a more structured review process which helps FDA meet review timeline goals otbb is responsible for the

review and management of all category a b and c supplements currently and we'll be taking on more of this workload in the future details about the basufa 3 supplement categories are summarized in the next two slides with the a b and c on this slide and the d e and f on the next the First Column describes the contents of the different supplements the second column

summarizes review timelines and the last column captures the target dates for issuing acknowledgment letters for category a through C and filing letters for categories D through f a category a supplement will update the labeling with safety information that has been updated in a reference product labeling category B supplements are to add an indication when the conditions listed here apply category C supplements are seeking to remove

an approved indication category D and E supplements are also to add an additional indication when the conditions here listed apply and category F supplements are those seeking an initial determination of interchangeability consistent with padufa 7 60-day timelines were formalized for the review of use related risk analyzes and human factor study protocols related to biologic device accommodation products the basufa three commitments also include publishing guidance on

specific topics during year one FDA has committed to revise the guidance about formal meetings between FDA sponsors issue new guidance about category a through f Lea supplement categories and on labeling for interchangeable biosimilar products FDA will also issue traffic guidance on the use of alternative tools to assess manufacturing facilities named in pending applications and update relevant guidances maps and Sops is appropriate regarding best practices in

communication during application review by year two FDA will publish guidance on the topic of use related risk analyzes and human factor validation studies for biosimilar device combination products One On promotional labeling and advertising considerations for interchangeable biosimilar products and on the different reporting categories for post-approval manufacturing changes by year three FDA will publish guidance describing considerations for developing presentations container closure systems and device constituent parts

for proposed interchangeable biosimilar products I'll hand the presentation over to Kimberly who will discuss the new regulatory Science Program created under basufa 3. Stacy for the next few slides I will provide a high level overview of the regulatory science pilot program commitment under pursufa 3. outline in the commitment letter the FDA agreed to Pilot a regulatory research program that focused on improving the efficiency of biosimilar

development and advancing development of interchangeable products yeah given that the goals or demonstration projects outlined in the commitment letter are very broad we formed a basufa regulatory science subcommittee to come up with how the research program should improve the efficiency of biosimilar development and Advance the development of interchangeable products our subcommittee identified two areas for regulatory impact that will help achieve the demonstration projects outlined in

the commitment letter these are pictorially shown here as a shift in Paradigm of the 351k data package on the left we have the current 351k data package Paradigm showing the components product quality comparative analytical assessment clinical pharmacology and comparative clinical studies through the regulatory research program as well as other components of the sofa 3 we envision that data package to rely more heavily on the comparative

analytical assessment and less so on clinical data as such there are two regular the two regulatory impact identified are one developing alternatives to and or reducing the size of studies involving human subjects and two enhancing the efficiency of the analytical ncmc characterization with these more clearly defined regulatory impacts or goals we were able to identify then 10 research topics are priorities or advancement is expected to

impact fda's evidence-based recommendations and or regulatory decision making I won't read all 10 research priorities here there's a link on the bottom of this slide where you can go to the research roadmap that was published publicly also note how each research priority is specific to one of the regulatory impacts that will help achieve the goals in the commitment letter the structure of these of these relationships

between the priorities the regulatory impact and the demonstration projects will serve as a framework for the pilot program to report outcomes and metrics of success Additionally the bottom gray box highlights an array of methodologies that can be employed to address any of the research priorities these include analytical methods biological assays efficient clinical trial design such as statistical methods in silico and in vitro modeling model informed

drug development real world data slash evidence in pharmacological studies goals for the research pilot program there are four main deliverables the interim report on progress of the pilot program which is coupled with an interim public meeting both on or before October 30th 2025. there was a final report due before the end of basufa 3 and a final strategy document due within 12 months of completion of

the demonstration projects in the pilot program in addition to these deliverables that are outlined in the commitment letter we are also doing additional stakeholder engagement through Contin through the continuous engagement meetings public comics on the current roadmap and other speaking events external funding opportunities as part of the program the first was in fiscal year 22 where we funded five grants that I will briefly briefly review

in the next slide our second cycle just closed on April 26 2023 the submitted applications are currently undergoing the objective review process our goal is to highlight the work from both of these funding Cycles at the interim public meeting here is a list of the five grants that were funded in fiscal year 22 from academic not-for-profit and for-profit and entities the breadth and research talk was

covered by these grants includes the alternatives to the comparative immunogenicity assessment currently conducted as part of the comparative clinical study and or switching study this these projects contribute to the goal of developing alternatives to and are reducing the size of studies involving human subjects additionally we have projects assessing the impact of differences of biosimilars and reference product presentations and container closure systems looking at standardizing approaches

for assessing and Reporting product quality attributes and improving on analytical Technologies all of these can contribute to the goal of enhancing the efficiency of analytical and CMC characterization thank you all for your attention and I will pass the presentation back to Stacy thanks Kimberly shifting gears I'll now address a few recent legislative changes affecting biosimilar by passing The Food and Drug Omnibus Reform Act or Fedora

Congress modified the general requirements for the data needed to demonstrate biosimilarity by replacing the language in the Public Health Service Act regarding animal studies with an assessment of toxicity which may rely on data derived from analytical or clinical studies Fedora also modified the first interchangeable exclusivity Provisions to clarify that one is several first interchangeable products are approved on the same day they each qualify for first

interchangeable exclusivity and two when a subsequent application for an interchangeable product is blocked by first interchangeable exclusivity FDA can improve that application as a bodysimilar Fedora also amended the fdnc ACT to include biological products these changes align certain reporting requirements for biologics with the reporting requirements for drugs by requiring holders of approved Blas to report to FDA when a biological product is discontinued from sale or

has never been available for sale boa holders are also required to submit a one-time marketing status report by June 27 2020 it's sorry June 27th of this year to confirm that there are products listed in the purple book are still available for sale next I'm going to provide a brief overview of the materials and information FDA has released or made available for health care providers about

biosimilar and interchangeable products and talk a little bit about our commitment to stakeholder Outreach education and Outreach is an important component of the work we do at FDA to increase understanding of biosellers we do this through several ways material development and testing and engaging with stakeholders such as patent patient advocacy organizations healthcare provider organizations and clinical societies and payers but FDA cannot do all this alone

stakeholders also have a responsibility to educate their members and we support that work by presenting to Their audience audiences reviewing materials and providing educational materials this slide has samples of the educational materials we have released for health care providers and shows the three most recent fact sheets we have released these are overview of biosimilars regulatory and approval and interchangeability but we also have for graphics and

videos that provide information about biosimilar and interchangeable products FDA recently released updated materials for patients including a new infographic a web page and two fact sheets one is geared toward patients with diabetes and the other fact sheet is a general overview these are also available in Spanish the patient materials use patient-friendly language to build a foundation of basic understanding and also to address topics concerns and

misconceptions shown to be most important to patients such as the safety and effectiveness of biosimilars why biosemors cannot be exactly copied and the regulatory review process we have other materials available in Spanish including the biosimilar basics infographics the USP and FTC materials that will be highlighted in the coming slides in addition to the fdaa biosimilars consumer update we are also looking into translating our materials into

more languages one of our most comprehensive resources is our biosimilar curriculum toolkit that was designed to help educate students in healthcare professional degree programs such as medical schools nursing physician assistant schools Pharmacy schools this toolkit provides teaching faculty and other interested stakeholders with a variety of educational resources to help them understand apply and teach concepts related to biosimilar and interchangeable buy sellers along with information about

their corresponding regulatory approval pathway in the United States the modular toolkit is designed to meet a variety of teaching and educational needs and contains foundational as well as more in-depth information by levels level one materials provide a high level overview of foundational biosimilar topics and level 2 materials provide an in-depth look at scientific and regulatory information we also have four continuing education courses released with Medscape

to enhance understanding of biosellers series of accredited CE courses for health care providers including doctors Pharmacists and nurses and these cover a broad range of topics about biosimilar and interchangeable products and vary in length and time commitment some examples of recent work with stakeholders are that we partnered with the U.S pharmacopoeia USP to develop an infographic on biosimilars with a focus on quality we are also

working with the U.S Federal Trade Commission the FTC to developing more consumer-focused faction and as discussed before we continually present to various stakeholders and participate as panelists to reach multiple audiences I also want to highlight that this year we will release additional patient materials including video for health care providers in addition to working on additional Medscape CE courses and we also plan to add our curriculum

toolkit add to our curriculum toolkit in the next year I'll wrap things up by sharing direct links to these and other FDA resources that are available online where you can find out more information about biosimilar and interchangeable biosimilar products including the curriculum information at drugs at FDA and information in the purple book which includes um uh information on all FDA licensed biological products regulated by both

Cedar and sieber thank you for your attention good morning and thank you for attending today's session my name is Elizabeth Thompson and I am the chief project manager in the office of regulatory Operations Division of regulatory operations for non-prescription drugs too my presentation today is on FDA formal meetings what's new Under padufa basufa and omufa today I will discuss what's new with prescription drug and biosimilar

product meetings following the recent reauthorizations of those user fee programs in addition I'll cover the over-the-counter monograph meetings which are Midway through their first authorization I'll provide an update on FDA formal meeting formats to include where Cedar stands on face-to-face meetings at White Oak and last I'll provide several meeting tips and best practices please note that this presentation will not include meeting updates related to generic

drugs under godufa nor will it be an in-depth presentation on all FDA formal meeting types and formats the objective for today's session is to focus on what new meeting types have been added or how meetings have changed during the recent reauthorizations I'll begin with prescription drugs and will outline some of the new meeting types under the reauthorization of the prescription drug user fee act or pedopha

7 which began on October 1st 2022 and covers fiscal years 2023 through 2027. cadufas 7 reauthorization introduced several new meeting types that include type D meetings initial targeted engagement for regulatory advice on sieber Cedar Products are what we call interact meetings and follow-up opportunity on the next couple of slides I will provide more detail on these new beading types and why they were created I also

want to note that FDA will be issuing a revised draft guidance to include these new meeting types and expects to publish the draft guidance by September 30th of this year so let's take a deeper look at each of these three new meeting types a type D meeting is focused on a narrow set of issues to obtain timely FDA feedback at Key decision points Beyond Milestone meetings

type D meetings are appropriate for one but typically not more than two issues and Associated questions if the sponsor has several issues or a complex single issue with multiple questions a type c meeting should be requested rather than requesting several type D meetings in addition the issue should not require input from more than three disciplines or divisions it's the scope of the meeting is Broad or

includes complex questions or issues that require input from more than three disciplines or divisions then FDA will inform the sponsor that the agency will be converting the meeting to the appropriate meeting type whether that be a type B or type c meeting and the sponsor can either withdraw their request or accept the fda's meeting type conversion without submitting a new request some examples of appropriate requests

for type D meetings include a follow-up question that raises a new issue after a formal meeting and is more than just a clarifying question about an FDA response from a prior meeting a narrow issue on which the sponsor is seeking agency input with only a few Associated questions or a general question about an Innovative development approach that does not require extensive detailed advice meetings are intended

for novel questions and unique challenges in early development in other words prior to submission of an IND that we delay the progress of the product towards clinical development in the absence of this early FDA input and these tip these issues typically relate to IND requirements the sponsor needs to have selected a specific investigational product or a product derivation strategy to evaluate in a clinical study before

requesting an interact meeting questions and topics within the scope of an interact meeting include novel questions for products where there is no existing guidance or other information in writing the company could reference and FDA input on issues that a sponsor needs to address prior to a pre-ind meeting some examples of when to request an interact meeting might include discussion on the appropriate appropriate free clinical models

or necessary toxicology studies for novel drug platforms or drug candidates CMC issues or testing strategies aim to demonstrate product safety or adequacy to support a first in human study development of innovative devices used with the product or use of cutting-edge testing methodologies advice related to the design of proof of concept or other pilot studies necessary to support administration of an investigational product and a first inhuman

clinical trial General recommendations regarding a future first and human trial and a Target clinical population where the population is novel and there is no prior precedent or guidance and recommendations on approach for further development of an early stage product with limited CMC non-clinical and or clinical data that were collected outside of a US IND of FDA feedback from previous meeting discussions or a written response only

questions of a clarifying nature will be permitted in other words to confirm something in meeting minutes or a written response issued by FDA rather than raising new issues or new proposals FDA will develop criteria and parameters for permissible requests and FDA May exercise discretion about whether these requests are in scope the clarifying question should be submitted officially to the application as a request for clarification within

20 calendar days following receipt of meeting minutes or a written response for questions that meet the criteria FDA will issue a response in writing within 20 calendar days of receipt of these clarifying questions fda's response will reference the original meeting minutes or written response please note that fda's response does not need to be included in a formal letter to finish my discussion on formal meetings under

padufa I've included a slide that shows meeting types and the pertinent goal dates associated with them I have listed all padupa meeting types here but will focus on only the new meeting types I outlined earlier which are listed here in bold for type D meetings FDA will respond within 14 days of receipt of the meeting request the meeting will be scheduled within where a written response

will be issued within 50 days of receipt background packages are due at the time of the meeting request and preliminary comments if applicable will be issued five days before the meeting please note that if FDA has granted the meeting as written responses only preliminary comments will not be issued for interact meetings FDA will respond within 21 days of receipt of the meeting request and the meeting

will be scheduled within or a written response will be issued within 75 days of receipt background packages like type D meetings are due at the time of the request and if applicable preliminary comments will be issued five days before the meeting for follow-up opportunities a request for clarification should be submitted within 20 calendar days following the receipt of fda's meeting minutes or written response FDA will

respond within 20 days if the request is in within scope next I'll just discuss file similars and we'll outline some of the new meeting types or meeting changes under the reauthorization of the biosimilar user fee act or basufa 3 which began on October 1st 2022 and covers fiscal years 2023 through 2027. authorization introduced two new meeting types biological product development or what we call BPD type

2A and follow-up opportunity I'll note here that the previous BPD type 2 meetings are now type 2B type 2A meetings will be focused on a narrow set of issues often one but not more than two issues than Associated questions and requiring input from no more than three disciplines or review divisions Buffet meetings have a shorter review cycle which is 60 days than the previous type 2

meetings which were 90 days consistent with Purdue for meetings there is a follow-up opportunity where sponsors May submit clarifying questions within 20 days after a meeting or a written response to ensure understanding of FDA feedback the super 3 reauthorization also introduced a few changes to existing meetings notably there is a change with the biosimilar initial advisory or Bia meetings where preliminary comparative analytical data comparing the

proposed biosimilar to the U.S reference product will no longer be required however sufficient information should be provided with the meeting request to enable FDA to make a preliminary determination related to potential licensure under Section 351 K and to provide meaningful advice additionally there are timing changes with respect to when needing packages can be submitted for a Type 4 meeting which can now be submitted 14 days

after the meeting request previously the meeting package had to be submitted with the meeting request I also want to know one other change related to biosimilar meetings which deals with user fees there is a new change under basufa 3 related to the initial BPD fee the timeline for paying this fee to join the program was increased from five days to seven days after receipt of the

meeting granted letter from FDA in addition FDA will be issuing a revised draft guidance to include these new meeting types and meeting changes and expects to publish the draft guidance by September 30th of this year this slide shows all the super meeting types important and cold days again I've listed all the super meeting types but will focus on the new meeting types I outlined earlier and

again are shown here in bold for a BPD type 2A meeting FDA will respond to the meeting request within 21 days the meeting will be scheduled within or a written response will be issued within 60 days of receipt background packages are due at the time of the meeting request and preliminary comments if applicable will be issued two days before the meeting again please note that if

FDA has granted the meeting as written response only preliminary comments will not be issued for a BPD Type 4 meeting background packages may now be submitted up to 14 days after FDA receipt of meeting request instead of previously being due at the time of the meeting request and consistent with padufa follow-up opportunity sponsors May submit clarifying questions within 20 days following receipt of meeting minutes or

a written response FDA will respond within 20 days if the request is within scope last I'll discuss monograph meetings which are currently under the first authorization of the new user fee program referred to as the over-the-counter monograph user fee act or a mufa which began October 1st 2020 and covers fiscal years 2021 through 2025. FDA issued a draft guidance titled formal meetings between FDA and sponsors

or requesters of over-the-counter monograph drugs this Guidance specifies the principles and procedures for formal meetings between FDA and meeting requesters it establishes procedures under which meeting requesters can meet with FDA to obtain advice on the studies and other information necessary to support submissions under Section 505g to obtain advice on other matters relevant to the regulation of non-prescription drugs and to obtain advice on the development of

new OTC monograph drugs the guidance also establishes procedures to facilitate efficient participation in joint meetings by multiple meeting requesters and or organizations nominated by them to represent their interests in addition a webinar hosted by FDA on March 27 2022 can be referenced and will provide a more in-depth overview of the draft guidance on monograph meetings today I want to provide a brief overview of monograph meeting

types and Associated timelines currently there are three monograph formal meeting types Type X Type Y and type c we will take a deeper look into these meeting types on the next slide a Type X meeting is the meeting that is necessary for an otherwise stalled over-the-counter monograph order development program to proceed for example this could be a meeting that is requested within three months of FDA

issuing a refuse to file letter for an over-the-counter monograph order request or Omar or after FDA has declined to issue an administrative order a Type X meeting is also a meeting that is necessary to address an important safety issue that needs immediate action when the meeting requester learns about a safety issue related to an OTC monograph drug that is marketed or being developed a type y

meeting is the meeting intended for Milestone discussions during the course of the over-the-counter monograph order development program for monograph ingredients and monograph conditions of use examples of appropriate circumstances for type line meetings include a meeting to discuss the overall data requirements to support a grade's determination or overall data requirements to support an omor or a pre or more or pre-submission meeting may also be requested when

nearing completion of the development program for an Omar these priest and Mission meetings are intended to present a summary of the data supporting the Omar discuss the proposed format for the omr obtain FDA feedback on the adequacy of The Proposal of the omor submission and discuss the appropriate categorization of an Omar for example Tier 1 or tier 2. type y pre-omor meetings should be held sufficiently

in advance of the planned submission of the omor to allow for Meaningful response to FDA feedback it should generally occur not less than three months before the planned Omar and last type Z meetings are any meetings that are not type X or type y this slide shows the performance goals associated with monograph meetings once a meeting is received FDA will respond to the request within 14

days for a Type X or type y meeting in 21 days for a type c meeting FDA will schedule the meeting or issue a written response either 30 days from receipt for a tie backs 70 days for a type Y and 75 days for a type c meeting packages are due at the time of a meeting request for Type X meetings and either 50 days before

the meeting or written response goal date for type y or 47 days for a type c meeting FDA will generally not send preliminary responses for Type X meetings and will issue preliminary responses five days before the meeting for type Y and type c meetings the types of formal meeting formats that are available and also provide some updates on these formats in particular for face-to-face meetings please

note that my discussion on the next several slides regarding face-to-face meetings include meetings under padufa basufa and omufa Cedar formal meeting formats are available as face-to-face teleconference or written response only the padufa 7 in basufa 3 commitment letters provided an update to the definition of face-to-face formal meetings with industry this update this update clarifies that a face-to-face -to-face includes both in-person meetings meeting virtual meetings on

it platforms that allow for both audio and visual communication in other words meeting between FDA and Industry is find as either in person or virtual with cameras on what we are calling video conferences while a mufa does not have this formal definition monograph meetings may also be conducted in person or using the virtual meeting format allowing for both audio and visual communication FDA is in the

process of updating our formal meeting guidance documents to reflect this revised definition in the interim we are highlighting this change on our public website to help reduce uncertainties on this point note that in person face-to-face meetings can have a hybrid component with some participants joining remotely in order to accommodate participants that can't be fully in person I will go into more detail on the next slide

and provide updates on where Cedar stands on in-person meetings as conference rooms at White Oak are being updated with the latest audio visual visual equipment to support these hybrid meetings in early 2012 to a hybrid workplace with staff returning to work on site at the White Oak campus for a portion of the work time this transition has enabled some face-to-face hybrid in-person formal meetings between FDA

and Industry to support hybrid meetings White Oak conference rooms are being upgraded in phases over the course of 2023 with new technology for example noise canceling microphones and face conversation tracking video cameras to avoid overcrowding in the conference rooms FDA will focus on having only core participants but the primary speaking role in person While others join virtually FDA encourages industry to follow this same pattern therefore

all face-to-face in-person formal meetings will have a hybrid component virtual attendees in addition to in-person attendees the availability of hybrid conference rooms will initially limit the number of in-person meeting requests that can be granted the number of meetings that can be granted and held in person with a hybrid component will increase as conference rooms are upgraded over the course of 2023 updates on fda's transition to

face-to-face in-person formal meetings will be communicated in advance on the fda.gov website on February 13 2023 due to the initially limited availability of upgraded conference rooms Cedar began scheduling face-to-face in-person industry meetings with a hybrid component starting with type A BPD type 1 and type X meetings face-to-face meeting requests for other meeting types if granted will be held as virtual or what we call video conference

meetings and the in-person format will not be considered as FDA is gaining experience with the hybrid meetings and Technology we've learned that the ideal number of in-person attendees or core participants is 12 people total this can be fixed from FDA and six from industry or a mix thereof this number ensures in-person attendees can be seated in the room in a way that maximizes the use of

the audio visual equipment Cedar will be monitoring conference room upgrades monthly and as upgrades are completed we will transition in phases such that all types of face-to-face formal meetings can be considered for in-person for example phase two of this transition would permit additional face-to-face formal meeting types other than type A BPD type 1 and type X to be considered for in-person scheduling the Final Phase of

this transition will enable any face-to-face formal meeting to be considered for in-person format before I close out my presentation I wanted to offer a few meeting tips and best practices for your consideration before meeting with FDA sponsors should refer to fda's guidances on padufa besupa and monograph meetings I've included links to these guidances in my resources slide communicate with your assigned regulatory project manager or RPM

and ask questions if you have them before you submit your meeting request notify the RPM of any changes to meeting attendees your meeting package should be clear concise and concise and focused on the meeting discussion topics or issues if you change your agenda after receiving fda's preliminary comments please alert the RPM assigned to your meeting also do not add new topics or issues to the agenda

if you have slides or handouts please provide those to the RPM before the meeting and last during the meeting sponsors should remember that this is your meeting take the lead and be cognizant of the time if you have materials to present make sure your questions are addressed and be sure to summarize any agreements discussion points and action items on the next couple of slides I've provided

some resources related to today's discussion on this slide you will find links to fda's draft guidances for formal meetings for padufa basupa and monograph meetings as well as the webinar on the draft guidance for monograph meetings that I mentioned earlier I've also included the commitment letters which outlines the performance goals and procedures for padufa basufa and amufa these goal letters or commitment letters represent the product

of fda's discussions with regulated industry and public stakeholders as mandated by Congress you will find the meeting information I discussed here today in these letters as well as many other aspects of the human drug review programs in addition I've provided the link to stay updated on fda's progress with in-person meetings that concludes my presentation today I want to thank everyone for attending and I will have

be happy to address any questions thank you thank you thank you all for the great presentations for our attendees if you haven't had a chance to enter your questions into the Q a chat pod please do so now we'll answer as many questions as time allows looks like we have a few questions coming in right now moving into our first panelist we have a few questions

that came in for Dr Stacy Richie and here is the first question for Dr Richie with the change to the PHS Act introduced by fedora can you explain why animal studies are no longer required for the demonstration of biosimilarity hi thank you for that question so this is an important question because there's a lot of confusion around whether animal studies are required to support a demonstration

of biosimilarity and this change in the statutory language codifies the practice that FDA has used for uh many years now where we do not require animal studies to support the demonstration of biosimilarity because it was identified soon after the biosimilar price competition and Innovation Act was passed in 2010 that animal studies were very unsensitive very insensitive for detecting differences between products so this change in the

statutory language just codifies our standard practice thanks thank you for responding to that question we do have a few more questions for Dr Richie and here is the next question are interchangeable biosimilars better than biosimilars thank you that's another great question and another point of confusion um fda's approval of an interchangeable product does not indicate a higher standard of biosimilarity there are different statutory criteria that

reflect scientific considerations related to the potential for substitution of an interchangeable product without the intervention of the of the healthcare provider who prescribed that product for their patient so an interchangeable biosimilar product can be substituted at the pharmacy without the prescriber knowing that it has been subject to state laws but patients and their providers do not need to wait for a biosimilar to become an interchangeable

product they're they're different considerations that the manufacturer may consider in deciding whether to seek a licensure for their product is biosimilar or is interchangeable and in fact there's misinformation that FDA is working hard to dispel that somehow the interchangeable product is better than about a similar when in fact the product themselves the the biologic that's manufactured would be the same whether it's biosimilar approved as biosimilar

or interchangeable and and this this misinformation can have a negative impact on the uptake of all biosemors by increasing this confusion thank you thank you for responding to that question moving on to our next panelists we've got a couple questions that came in for Dr Kimberly Maxfield and here is the first question for Dr Maxfield what metrics is FDA using to measure the success of the

pilot program thank you for that question in general we see regulatory impact as the effect of f the effect the effect on FDA recommendations that are usually science-based or are always science-based excuse me um and or regulatory decision making um as such we created the draft research priorities and the regulatory goals for the pilot program into in areas that were advancement is scientific and Regulatory advancement

is expected to inform the science-based recommendations and Regulatory decision making additionally we would consider a an effort that achieves a critical Milestone towards informing a science-based recommendation or regulatory decision also part of our regulatory impact definition thank you thank you thank you for responding to that question we have got another question for Dr Maxfield and here's the question can you share some of the challenges that

the FDA has seen in the development and approval of biosilmers that this pilot aims to address thanks for that question another really uh great question uh there are many different uh components to buy Solar Development and delivery in the healthcare setting uh typically fda's purview and particularly for biosimilar is is really focusing on the cost of develop and time to licensure of biosimilar as an interchangeable

there are as I mentioned many cooks in the kitchen related to patient access and from the FDA perspective we are trying to make biosimilar development as efficient and predictable as possible to ensure that the approved products meet the same high standards for Quality safety and efficacy as their reference products and we hope that some of the research that we engage in will address some of the

uncertainties um and result in Greater that will address the greater data expectations um so we can reduce those gaps thank you thank you for responding to that group of questions moving on to our next panelist we've got a few questions that did come in for Elizabeth Thompson and here is the first question from Miss Thompson is it acceptable for a sponsor to discuss with FDA with

an FDA project manager prior to submitting a type D meeting request or briefing package whether the topic is narrow enough thank you for that question so I would first encourage all sponsors to utilizes utilize all of fda's resources to include the draft guidances that are out there on formal meetings if you still have questions regarding whether or not it's an appropriate meeting type or what type

of meeting to request so in in this case if you're trying to determine whether or not the topic for a type D meeting is within the scope after you've reached out and and looked at the guidance is yes I would say it is acceptable to approach your assigned FDA regulatory project manager in order to ask those questions thank you thank you for responding to that question

moving on to our next question for Mr Thompson is the following are interact meetings only applicable to biological products or is molecules uh thank you for that question that's another good question uh interact meetings are applicable to all products so all of Cedar Products to include the biological products and also small molecules thank you thank you for responding to that question we've got a few more

longer questions from Ms Thompson that came in and here's the first one we can repeat it repeat it if needed what is the difference between a face-to-face meeting that is virtual with cameras on as defined in recent FDA updates on face-to-face meetings and a video conference as defined in the current FDA garnets on formal meetings with the agency also if a sponsor wants a virtual meeting

where they can present slides and just speakers or on camera not not necessarily everyone participating which type of format should be requested uh thank you again for that question so that there's no difference between what we are calling a video conference and a virtual meeting so FDA has defined three formal meeting types those being a face-to-face meeting a teleconference and a written response only for a

face-to-face Meeting those are separated out a little bit more into what we call an in-person meeting which can also be done hybrid and then the video or video conference or virtual and so if you are looking at requesting a virtual meeting with FDA where you present slides and the speakers are on camera that would be considered a video conference for video conferences uh they are not

limited to the amount of people that go on camera so if there's going to be any participant participant that goes on camera to include the speakers then we would call that a video conference thank you thank you for responding to that question we do have one more for Chris Thompson and here's the question can you clarify if a meeting specifically focused on delivery device development for

example risks specifications testing is in the scope of an interact meeting before a pre-ind for the combination product has been conducted thank you that's another great question so as I noted in my presentation interact meetings are intended for novel questions and unique challenges and if we are looking at this question is asking about a novice drug dealer a novice delivery device this would fit into what

we call an interact Meeting those do relate to the development of innovative devices used with a drug or biologic to include combination products so this would this type of meeting would would fall under in an interact meeting thank you thank you for responding that group of questions moving back up to the beginning of our panel we've got a few more questions that came in for Dr

Richie and here is the first question can you elaborate on the differences between a category b and a category D supplement since they are since they both are to add indications but have different review timelines hi sure the the category B supplement would seek to add an indication to an already approved biosimilar where either uh the the application is not including a new a product that

would um be administered through a a different route of administration than had previously been approved for the biosimilar and it wouldn't also be a different dosage form strength formulation or presentation such as device um it also would the the the application would include and agreed upon initial pediatric study plan that would address the requirements under the the Priya statute for the additional indication that's being proposed

to be added the those conditions wouldn't apply for a category D supplement so a category D supplement could include information to support say a new Strength dosage form rather Administration or presentation that would be used for the patients uh that that new indication is intended to treat it also wouldn't need to have an up-to-date agreed upon initial pediatric study plan and in that in that supplement

the applicant would include their plan for addressing Priya in the supplement um along you know along with any other information to support the approval of the biosimoid for that new indication thank you thank you for responding to that question we do have one more question for Dr Richie at this time and here's the question where can I find information about the analytical and clinical studies that

were done to support fda's decision to approve biosimilar and interchangeable products information included in the roosted at the drugs at FDA website that for all all new um drugs and and biologics approved by uh by Cedar some of you could go to just type in to your web browser drugs at FDA and it'll take you to that web page and then you can search on the

product that you're looking for and the reviews that FDA wrote to uh that would include the um the basis for the approval would all be contained in that website thank you for responding that question moving on to our next panelist we have a couple more questions that came in from our Dr Kimberly Maxfield and here's the first question for Dr Maxville foreign how is FDA engaging

their stakeholders to obtain input on the pilot program great question thank you the pilot program has several key deliverables and um stakeholder engagements that are part of the commitment that can be seen in the actual commitment letter which is the interim report and public meeting the final report and then the strategy document within 12 months of completion of the demonstration projects but additionally to those those

engagements we have been engaging through the continuous engagement meetings that are part of that are include the the super three negotiation individuals and groups that they're usually held by or try annually we've had we had one back in February um early February that talked about the right side program additionally with the regulatory roadmap that highlighted our 10 research priorities we had a public comment period on

that that draft roadmap from January through the beginning of April and are now um looking at the comments that were submitted and revising that roadmap now um in from our actual reviewers for the actual Grant applications that are undergoing review right now we have elicited external FDA reviewers some external FDA reviewers to help with that um that review and our first uh round of funded projects

uh will be submitting their annual report shortly and we've requested from those grantees that we can make those reports public so um we're as transparent as possible with our progress additionally we're exploring other options of additional public meetings or public webinars um Beyond so in additional to that interim on or before October 25th 2025. we're looking at other forums that can gain additional input thank you

thank you for responding to that question we've got a couple more questions that came in from Dr Maxfield and here is the next question what is the process the timeline for the funding announcements as part of the regulatory Science Program thank you for that question uh we for external funding announcements we follow the office of acquisition and Grant Services timeline which is part of it which

the HHS external Grant policy um and then the grantees will receive those comments and those scores um before file fund um as final funding recommendations so the whole process can take anywhere from six to eight months um as we follow the HHS process that's defined for us thank you thank you for responding to that question we do have one more question for Dr Maxfield and it's

the following when is the next external funding cycle uh great question so uh we are in the process of negotiating that right now or thinking about what that would look like um we're gonna we have we are currently reviewing the Apple applicants from this last funding cycle I think once we get through that review hopefully have some type of public webinar this fall I think we'll

get enough stakeholder feedback to inform that decision so it really ultimately this is similar to the previous question we really want external input on um sort of what gaps people would like to see and how and sort of what at what timeline that would be helpful for so I think look out sometime this fall for um for an announcement about that thank you thank you for

responding to that group of questions moving on to our next panelists we've got a few more questions that came in for Elizabeth Thompson and here's the first question for Miss Thompson can you please remind me which type of meetings will be provided face-to-face and priority thank you for that question so in February we announced our phased approach on our public website and we started our in-person

face-to-face meetings with type A BPD type 1 and type X meetings recently we announced on our website that beginning on June 12th that we will expand in person face-to-face interest industry meetings with a hybrid component to include requests for type B and to phase two meetings and so those will be in addition to the ones that we have previously announced I do want to say that

um face-to-face meetings meeting requests for other meeting types if granted will be held virtually so the in-person format will not be considered and also just to note that existing meeting requests received before June 12th as this is our most recent announcement that we made or meetings that are already scheduled regardless of the scheduled meeting date won't be converted to an in-person format and this is just

in order for us to permit Fair implementation of this transition thank you thank you for responding to that question we've got a few more questions that just came in from Ms Thompson and here's the next question how many in person face-to-face meetings has the agency had thank you great great question so as of May 31st of this year FDA has received 10 qualified requests for in-person

face-to-face meetings uh per the phase one eligibility criteria so again this is type A BPD type 1 and type X for our for all of our padufo basufa and amufa programs all 10 of these requests were granted with an in-person component we've held six of these meetings so far successfully and the remaining four that are scheduled should be completed in the next couple of weeks thank

you thank you for responding to that question got another question on face-to-face meetings and it's the following when will all meeting types be eligible for in-person face-to-face meetings thank you for that question so once our full complement of conference rooms and so those are the conference rooms that we used prior to the pandemic for non-hybrid meetings once they've all been upgraded to accommodate successful in-person face-to-face

meetings with a hybrid component then the FDA will move to our final phase of transition which will expand eligibility of all of in-person face-to-face meetings to all formal meeting types thank you thank you for responding to that question we've got a couple more questions that just came in for Ms Thompson and here's the next question we requested a face-to-face but we were and received a written

response only can we negotiate uh yes great question so when FDA receives meeting requests upon review we determine whether or not that a written response to the sponsor's questions is the most appropriate means for providing feedback and advice to the sponsor so if you have requested a face-to-face meeting but received a written response only and you believe that a face-to-face meeting would be more valuable then

the sponsor should provide a rationale and a follow-up correspondence to your assigned regulatory project manager explaining why you feel a face-to-face meeting is more valuable and warranted FDA will review your rationale and determine if a face-to-face meeting is appropriate at that time thank you thank you for responding that question we have just under a minute left and we have to try to squeeze in one more

question for Ms Thompson we just received and here's the question how do sponsors share presentations at in-person hybrid or virtual only face-to-face meetings thank you for that question so first I want to say that presentations by sponsors are generally not needed because the information for a meeting discussion should be part of the meeting package however if a meeting requester plans to make a presentation they should

discuss it ahead of time with their assigned FDA project manager in order to determine if this presentation is warranted and then also to ensure that FDA has the presentation materials ahead of the meeting for our in-person hybrid or virtual only face-to-face meetings we are conducting those through Zoom therefore sponsors will be able to be able to present using that it platform thank you well that's all

a time we have for questions in this q a panel a huge thank you to our presenters for answering numerous questions that came in we'll now enter to our lunch break time until 12 45 PM eastern time enjoy your break