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

the journey to develop and market a human drug can be long complex and filled with regulations but FDA Cedar small business and industry Assistance or sbia is here to help spia provides education and answers to help all regulated pharmaceutical Industries not just small business all over the world what do we offer we have resources for all your questions and training needs the popular regulatory education for

in-depth theater learn web-based learning tutorials stay current by signing up for our listserv or connect via LinkedIn and best of all everything is free I hope you all enjoyed that short animated video my name is Lieutenant Commander reynoldau and I work with Brenda and the rest of the sbia team in this presentation we're going to take a step away from those in-depth regulatory topics and discuss

our cedar sbia or small business and industry assistance program the program that brought you this amazing conference this week and how you can leverage sbia resources to educate yourself and to find answers to your questions in today's presentation I will focus on how sbia can assist you so after listening to this presentation you should be able to locate our sbia webpage and identify the resources it

provides identify at least three services that sbia offers to assist the pharmaceutical industry and finally understand how to register for our sbia events and also find recordings of the past events in the case that you miss them live So within Cedar uh we have the office of communications and under the office of communications there are three divisions one of which is our division of drug information

or DDI DDI handles thousands of inquiries that come into Cedar and we work very closely with other offices to anticipate and respond to Major initiatives and small business and industry Assistance or sbia Falls within the division of drug information sbia recently revised our mission to better reflect our current actions and also to Encompass our aspirations our mission is to provide industry stakeholders with immediate access to

resources Education and Training which allows for a more clearly informed and efficient developmental process and is aligned with Cedar's goal of approving safe and effective human drugs and biopharmaceuticals today's philosophy is that timely interactive communication with sponsors during drug development is a core activity to help achieve our mission and to facilitate the conduct of efficient and effective drug development programs and so ultimately the goal is

to enhance Public Health by making new safe and effective drugs available to the American public in a timely manner and we know that on the industry side it is not always easy to navigate these complex regulatory processes so then Cedar sbia often becomes the first stop for a pharmaceutical business trying to contact the agency our goal is to help these small pharmaceutical and large pharmaceutical businesses

all of Industry really navigate the wealth of information that FDA offers and to assist in understanding human drug product regulation we want to ensure that industry stakeholders have immediate access to resources Education and Training and so forth allowing for a more clearly informed and efficient development process with the goal of approving safe and effective human drugs and biopharmaceuticals and our vision is really to become this

Premier educational source to serve as the premier educational Source on human drug and biopharmaceutical development and regulation we want industry to come to us for the answers and for support and we we believe it with our real-time support for industry formed and in turn will have increased constructive interactions with FDA foreign so like I said though our focus is on small business our resources and Outreach

activities really extend to all of the regulated pharmaceutical industry and are not restricted to small business um are really for sbia purposes the term small business is defined as a business that has fewer than 500 employees including employees of Affiliates but like I said we are not restrictive and sbias open to everyone you don't have to qualify by the size of the business um we do

help all of industry but we do focus on helping small businesses since they may not have that expertise and the know-how of large companies as you can see on this pie chart here the majority of people that attend our events are from large Pharma with more than 500 employees but that means that about half of them are from small Pharma and this map here shows an

overview of where our audience is located so this map represents the reach of last year's regulatory best practices for Global accesses access to medicines conference so you can see that we have a very Global reach since companies can benefit from pretty much all of our services online and approximately 30 percent of our audience is outside the U.S so I'm now going to review the various resources

that we offer through sbia including direct communication services our web pages our training resources and our news and updates let's take a look at some of sbia's Outreach Services in detail so we have a staff of over 35 Healthcare professionals that answer direct inquiries from industry via phone and email you call us we will answer you email us we will respond we have dedicated phone numbers

and email addresses as you can see here on the slide last year alone we responded to over 6 000 inquiries so we receive a wide variety of questions and we respond pretty quickly whether it's providing you with an answer or letting you know that we need to consult a different group within FDA or provide you with information on whom you should be contacting but we always

get back to you in a timely manner so for instance if a question is specific to an existing IND the sponsor would really need to reach out to their FDA regulatory project manager um and if it's you know a general question about guidances and so on we can respond to that and the service is available to anyone like I mentioned so please take advantage and contact

us with your questions a huge part of sbia is our Outreach to stakeholders via our regulatory education for industry or ready conferences um and though we're currently at the ready annual conference we use ready to describe our topic specific conferences too so that's so to speak our trademark our audience for these events is small manufacturers of drug products who wish to learn oh well and large

who wish to learn about how FDA approaches drug regulation we typically have a hybrid format for all topic specific conferences where people can attend in person or online however since the public health emergency we have switched to 100 virtual in 2022 we hosted nine conferences and workshops and reached over 84 000 people in 130 countries via conferences webinars and recordings and we continue to innovate and

provide new and useful information for our stakeholders last year we introduced a workshop on regulatory best practices for Global accesses access to medicines including anti-tuberculosis medicines where we collaborated with usaid USP and the W health or the World Health Organization and reached low and middle income countries with top attendance from India Pakistan Nigeria Ghana and Kenya we also last year partnered with fda's national Center for

toxicological research in the Nano day Symposium we put on to address the development of products that contain Nano materials in their formulation and all of these conferences and workshops I will get to this in a couple slides but they're all if you missed it they're all posted online um on YouTube we also offer various types of continuing education credits depending on the conference sometimes providing CES

to support wraps okra sqa and acrp and sometimes providing CE for healthcare professionals and most if not all like I said of our conferences and workshops are recorded and they are absolutely free so in addition to our conferences and workshops we offer free webinars most of which also feature a question and answer or q a session with the FDA subject matter experts examples of recent webinars

include an update on field alert reports and biological product deviation reports we've had some on OTC monograph so OTC monograph drug user fee program or omufa fiscal year 2023 user fees and registrations we just recently held that we recently held a webinar on godufa 3 scientific meetings um we've had a webinar on electronic systems electronic records and electronic signatures to statistical approaches to establishing bioequivalence and

many many more um and like I said these recordings are all available on our web web page and on YouTube so we also have a newsletter which we call the sbia Chronicles we publish this every couple months um they're short two-page electronic newsletters and audio podcasts uh they're accompanied by Audio podcasts that we write um and we record we highlight different regulatory issues each time and

we usually interview a subject matter expert depending on the topic so some sample topics we published on recently include pharmacodynamic biomarkers and biosimilars cannabis and cannabis Drive compounds Adverse Events associated with compounded drugs from Outsourcing facilities and continuous Manufacturing so here's a snapshot of our sbia webpage our landing page if you've never visited I highly recommend that you bookmark it fda.gov forward slash Cedar sbia our

web pages are another means by which we reach out to Industry stakeholders this here is the sbia landing page and it really does contain very useful resources that you may have never even known existed up top here we have a calendar of upcoming events or sbia conferences workshops and webinars with links to the registration and this is just the first half of the page and this

is the middle of the page so as you can see here there are four Graphics each are hyperlinked to different web pages the first box is our regulatory references webpage which is essentially a database of regulatory information which you can search and I will show you that in detail we then have our sbia learn online training Repository and this repository contains links to all of our

SBI events um and also future events and going back three years it's not only the events but it also has links to other training opportunities and our Chronicles newsletters online courses things like that the Third the third is a link to sbia on the LinkedIn platform an invitation to connect and then the fourth box it links to the sbia learning library on YouTube so let's go

through these sub pages one by one when you click on this first regulatory references web page it brings you to this webpage right here like I said it's a database of information for industry stakeholders essentially a systematic compilation of FDA web pages and very easy to search so here you can find information on different topics related to drug development from inds to new drugs to generics

otcs information on submissions labeling manufacturing quality safety and so on just so much more and you can either use the topic drop down bar to search for topics or you can simply use the search bar or a combination of the two so here I've just taken a screenshot showing you what the topic drop down looks like so if you find yourself lost looking for something on

the FDA website rather than turning to Google come here first that next graphic the second graphic on the main sbia landing page was to the sbia learn online training repository which is basically a database of training information for industry so this is where you can find links to all the trainings I mentioned both past and upcoming not only does it contain links to the web pages

for the sbia conferences workshops and webinars which in turn contain links to their recordings and slides but it also contains additional training and learning resources as I mentioned such as our sbia newsletters and courses and again this database is searchable by keyword or you can filter by topic as well if you search if you click on the topic carrot you'll find a drop down menu where

you can choose topics such as biosimilars clinical trials or and research drug development drug Master files drug quality and so on and again I forgot to mention you can see here I've included the QR codes for each of these pages so make sure you bookmark them um going back to the graphics on the sbia landing page that last graphic was for the svia YouTube learning library

which contains our most viewed recordings and contains links to the YouTube playlists you can also browse our recordings directly from YouTube by visiting the Food and Drug Administration Channel on YouTube clicking on playlists and then clicking on the cedar small business and industry assistance playlist you'll notice there's multiple organized by years there's 2023 2022 I think going back to 2017 or 2018. um and the sbia

playlists are all easily identifiable with our trademark orange fiery stripe and they contain the recordings of our sbia conferences workshops and webinars and which we try to make available within two weeks after each event we post a lot of recordings and we get viewership from all over the globe in 2021 alone we posted 225 recordings of presentations with over 477 000 views so these are very

useful the individual YouTube recordings are also found within the event pages in The sbia learn database but this is another mechanism to browse the events and click directly on the recording links to view them so we have multiple ways to get to this information um and although we have these recordings available we still highly encourage you to attend real time in person and take advantage of

the live q a sessions to interact with FDA experts and get answers to your questions right on the spot real-time attendance to many of our webinars and conferences will also enable you to receive continuing education credits for um for sometimes for Physicians Pharmacists and nurses when offered and a certificate of appreciation which supports CES for rap sofra sqa and acrp just depending on the event and

finally the landing page also promotes our sbia on LinkedIn and it leads to our LinkedIn page for sbia we currently have over 27 000 followers and we use LinkedIn to push information out to Industry stakeholders this could include information about Cedar and FDA meetings conferences workshops and webinars Federal Register notices new announcements new initiatives we also have these fun polling questions that we recently started for

many of our events and which I hope many of you have taken in anticipation of this conference so we encourage you to participate it's a great way to test your knowledge and kind of anticipate and figure out what's what's in store for you during the conference and to get your questions answered there in addition to LinkedIn we also disseminate information to Industry via our email listserv

or distribution list we have over 143 000 subscribers and we issue information daily regarding new regulations FDA announcements and initiatives webinars conferences and more so you can find a link to sign up for the emails right from our landing page which was fda.gov forward slash Cedar sbia if you scroll all the way to the bottom of the page there's a bar where you can type in

your email address and just click subscribe so this brings us to challenge question number one in which of the SBI resources can you find a database of searchable FDA web pages relating to drug development a regulatory references B sbia learn online training Repository C in the calendar of upcoming events or D on the sbia learning library on YouTube I'll give you a minute to answer that

so if you chose answer a this is correct by clicking on the box titled regulatory references on fda.gov forward slash Cedar sbia you will find a searchable database of regulatory information which includes a great deal of information on drug development note that the sbia learn online training repository contains links to recordings of webinars conferences and workshops rather than to web pages about specific information about the

topic and challenge question number two which of the following statements is not true a you can say connected with the latest regulatory information and offerings by subscribing to the sbia listserv and following sbia on LinkedIn B industry stakeholders may call or email sbia directly see sbia services are only available to companies with less than 500 employees including affiliates or D sbia offers many free conferences webinars

and workshops on various regulatory topics so which of these statements is not true and the correct answer the incorrect answer excuse me is C so sbia services are available to all industry stakeholders regardless of company size so I hope that I have enlightened you today with information about the sbia program and how to leverage sbia as a regulatory resource all of our programs are geared towards

training and educating industry across the entire spectrum of drug development so here I leave you with some action items email or call sbia with your regulatory questions we respond Monday through Friday 8 A.M to 4 30 PM Eastern Time here's our contact information bookmark these web pages fda.gov forward slash Cedar sbia and fda.gov forward slash Cedar sbia learn and you'll get access to all of this

great information that we provide browse our sbia playlists on fda's YouTube channel and finally follow us on LinkedIn And subscribe to our listserv to stay in the know and to stay connected we're really doing all that we can to help industry to help you and to achieve our vision to serve as the premier educational Source on human drug and biopharmaceutical development and regulation so I thank

you for your attention today and I'm available to answer any questions that you may have okay so we will now launch into our q a session so please enter your questions into the Q a chat pod uh if you have not already and we'll answer as many questions as time allows uh it looks like we have a few questions that have been submitted um our first

question should sbia be the point the first point of contact for questions uh that we can't find the answers for online for example would you refer us to the appropriate resource for a person to contact so great question uh yes if you cannot find the answer to your question please feel free to contact us contact sbia via email or phone and we will either answer your

question or consult the appropriate group within FDA or we will point you in the right direction so if you don't know where to go contact us and we will help you hopefully we can answer your question but if not we'll get it from the correct subject matter expert within FDA um or we'll we'll let you know where to go for answers okay uh we have a

couple more questions um question two have you considered providing your conferences and webinars in different time zones to make it easier for to attend for people in different areas of the world so we do recognize that a lot of you are not in the US are not in Eastern time um and we appreciate that you are dialing in from wherever in the world you are and

we have considered uh we have considered you know timing our conferences at different times to accommodate everybody but as you can imagine there's so many different time zones so it's very difficult to accommodate everyone um we have people attending from India China Europe Africa different time zones in the US and from all over the world so we need to consider all that we also need to

consider the availability of our FDA faculty so it's easier easiest to stick to Eastern Time um there are some exceptions though for example there was uh one pharmaceutical quality extended webinar that we did a few years ago we called it midnight madness um and that was specifically for industry in India and China where it was the middle of the night here in the U.S um and

we were able to provide that extended webinar in their time zone but I don't think we'll be able to repeat such a time zone accommodation it's very difficult coordinating all the speakers here in a different time zone but we do record the events we post them to YouTube so you can always watch them later you won't be able to receive the continuing education credits or submit

the survey to obtain the certificate of attendance but you will be able to get the information via those recordings okay I have a question can we ask an IND NDA specific question so if you you can contact sbia with your questions and we'll direct you if it's something that's specific to an existing application you would need to contact your project manager for that because there's just

so many nuances we can provide you with general information and guidances but it's if it's specific to an existing application your review team is the one you should be um communicating with let me see where um okay another question when and where would the recordings for the ready conference be posted um so for the ready conference or for any other conferences that we offer we usually

have their recordings up within two weeks on the and in this case it would be the 2023 playlist of fda's YouTube channel so if you visit fda.gov forward slash Cedar sbia learn and click on the right key conference it will lead you to the YouTube recordings once posted and we will also send out an email message for those who register we'll send out an email message

through our distribution list to let people know that the recordings are available um but it's two weeks uh for them about two weeks sometimes sooner um for the recordings to be posted on YouTube you can also just also go to YouTube go to the FDA Channel and then click on playlists and you'll see all the SBI playlists there okay do you work with NIH to help

companies in very early stages of drug development looking for Grants so in the past we have worked closely with NIH they used to have this annual conference and offered live consultation at these conferences from many different government entities so we were one of them so we used to go and participate in this live consultation and we still work with NIH to help them in a variety

of different capacities um but not via that conference and we're of course available via phone or email to answer questions okay um um let me see does sbia work with the office of new drugs to review applications we do not work with the office of new drugs to review applications but we often consult them when we receive questions from industry uh so they you know we

can contact them um we can contact the reviewers or whoever it is in the division if there's certain questions that we need to consult out and we also as you can tell from all of our speakers and panelists we work very closely with the office of new drug staff to put on conferences and webinars um and all of our events and to put out our different

courses and newsletters we are always working with them and to determine what it is that we can provide to Industry for training and education so they may tell us what is it what it is that their division needs to what messages they need to put out to Industry and we help provide that Outreach um when will the slides be posted to our website for this conference

so probably within a month so the recording should be up within two weeks but the slides probably a month give or take okay we do have a couple more questions can we find the clinical trial results of a certain drug in regulatory references so we get this question um quite a bit people looking for the results of clinical trials um so FDA does not publish the

clinical trial results if an application has been approved you can find some of the information in the review documents posted in fda's drugs at FDA database which is right on our website you can look the drug up by the name or the application number click on review documents and you'll see fda's review of the clinical trials but if a clinical trial is unpublished you're you're not

going to find it on fda's website okay um although sbia is under Cedar do you give equal attention to sieber products and topics so we do sometimes include zebra topics or topics that apply to both Cedar and sieber but our main focus is Cedar on occasion an sbia webinar will address cross country cross-center guidances and topics um and we'll include faculty from all the relevant centers

including sieber and cdrh if applicable um and you know this conference as you know is is cross-center with all three centers but we do try to work with them uh I think that's all the questions we have for now uh let me just take one more look yeah I think I've covered it all um so thank you for your great questions I appreciate them um we

can now move on to our next two speakers Dr LaShawn schnupp and Dr Lolita sterret our first Speaker Dr LaShawn schnupp is a senior regulatory health project manager and star program manager in the program development implementation and management staff within the office of new drugs office of program operations she will be providing an overview of FDA split real-time application review or Star pilot program our second

speaker Dr Lolita Starrett will present on use related risk analysis and human factor protocol reviews what to submit for an efficient review Dr Starrett is associate director for human factors in the division of medication error prevention and Analysis 2. within the office of medication error prevention and risk management in Cedar's office of surveillance and epidemiology 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 speakers thank you for the introduction I appreciate it and it's great to be here hello everyone my name is Lashawn schnupp and I'm the cedar program manager in the office of program operations and part of the program development implementation and management staff today I'll be

discussing the split real-time application review or Star pilot program which started on October of 2022 so this slide provides the learning objectives for today's presentation for star and we'll discuss the background of star including podifis 7 and then I'll describe the star pilot program including why this program was created what it is and its goals I'll also describe the components of the overall star program I'll

outline Cedar's review of star applications and also share with you the Star website then we'll go over a quick review of what we learned as well as the program assessment for star and then lastly we'll review options for resources so now we'll go over some of the background for star and so under the prescription drug user fee act or pudufa 7 the star pilot program was

introduced and this program became available to applicants on October of 2022 so as you can see here this is just a snapshot of the letter that can be found online and on the FDA website and as you can see Star is listed under Section D of the letter so now I'll be going over the star program in more detail in these next slides so you may

be asking why we created the star program well during negotiations industry raised a common problem that they face which is that typically all of their data sets and other application materials for a supplement are ready a couple of months in advance of three components of their applications which are namely the clinical study report and then two of their integrated summaries for Effectiveness and safety and then

in instances where the product is intended to treat an unmet medical need that sometimes can represent a delight for patients getting access to these treatments and so in order to try and address that problem we created the star program so what is the star program well the Start program is a pilot program for qualified priority efficacy supplements to be submitted in two well-defined parts and I'll

talk to you in just a minute about what those two well-defined parts are but really the intent was to enable an earlier review in action in order to overcome the problem statement that I mentioned in the previous slide so the overall goal is to shorten the time from the date of complete supplement submission to the action date in order to allow earlier patient access to therapies

that address an unmet medical need so that can be kind of confusing and so I want to show you this graphic hopefully it'll help tell the story of the process I was describing earlier so this slide Compares star to a traditional application and I'm going to go into more detail with subsequent slides and so on this graphic though you'll notice that the blue bar which is

over here this is the priority review Bar for a typical efficacy supplement and above that blue bar you can see the Red Bar indicating the SAR review so that's right over here but you'll notice that it's shifted to the left and you may have also noticed the other key components within the start overview timeline they're different from a normal supplement review so for instance you may

have noticed on this graphic that a star entry request meeting will need to be submitted in order for FDA to determine whether it's accepted into the program so here is the start entry request you can also see here that we receive the supplement as a split submission in two parts so this is part one submission and part two submission so once you receive part one and

part two then we have a Target action date at least one month in advance of the padufa gold date so over here we have the start Target action date and this is the padufa gold date and we'll go into more detail with subsequent slides but as you can see here FD will begin application review upon receipt of part one of that submission and part one really

contains the entire application everything we need to start the review and the only things that are missing are those three components which are the clinical study report and the two integrated summaries for safety and Effectiveness which I mentioned a moment ago and those are often delayed on industry side as they go through levels of clearance so part two then is those additional three components again specifically

the clinical study report and the two integrated summaries when we get the part two submission that will complete the supplement and that's when the Padova clock starts which is shown here and as noted in this graphic you can see that FDA Begins the application review of part one which again is right over here by the time we receive those last three components it should hopefully enable

FDA to take an earlier action when timing it by the pedophile clock so it's kind of a women's situation where FDA still gets the full time to review but then at the end of the day we're hoping that we can get these treatments for unmet medical needs out to patients earlier so the first component is the start entry request that gets submitted to the FDA and

is reviewed and held either as a standalone t-con where we simply just speak with the applicant about whether their supplement meets the criteria to get into the Start program or if they wanted to discuss content and format of their anticipated supplement then the applicant would submit a type B pre-submission meeting just like they would now and we would talk about star within the context of that

type B meeting along with their other questions such as what would be submitted to the application and please also note that if the start entry request is submitted as a standalone t-con then there are no meeting minutes but a formal letter is sent to document the decision so we encourage an applicant to use option two only with questions related to what would be submitted in the

application such as part one versus part two will be asked and in terms of the content of the request itself for the start entry request the sponsors will submit the Top Line results from their pivotal trials and they'll also submit their proposed labeling and then also an explanation of how the supplemental application meets the star criteria and so please note that the acceptance into start does

not guarantee an application approval the application must still meet the applicable standard for an approval so I mentioned that there is criteria for getting into the star program and we'll be going over the four criteria and as you look at this slide you'll probably notice that the first two criteria looks somewhat familiar and and that was intentional so the first criteria states that clinical evidence from

adequate and well-controlled investigations indicate that the drug May demonstrate substantial Improvement on a clinically relevant endpoint over available Therapies and the second criteria states that the application is for a drug intended to treat a serious condition with an unmet medical need so these are the same two criteria that we use in the Breakthrough therapy designation program so the caveat though for star is that the application

does not have to actually receive a formal breakthrough therapy designation and for other products and other centers they won't actually have to have received other designations such as the regenerative medicine advanced therapy or arm at designation but they do have to meet the same standards that's outlined here within criterias one and criteria is two and so the last two criterias criterias three and four they're really

about timing and in some aspects of the complexity of the supplements so number three just states that the supplement can't have any component to it that would require a longer review time and an example here would be a risk evaluation and mitigation strategy or a rims because it adds a complexity to an application and then the last component on here Criterion number four it just points

out that if there is a need to inspect a foreign manufacturing site a supplement would also not qualify just due to the logistics of scheduling those inspections and getting them back however please note here that domestic site inspections may be allowed if it doesn't affect the expedited time frame also please note here that star is limited to Priority efficacy supplements so a supplement must really qualify

uh to be a priority review in order to get into the star program okay so assuming an application gets into the star program the applicant would submit their submission in two parts as I mentioned earlier and part one here is the entire application everything needed to review with the exception of those three components that take a little bit longer on the sponsor side which are namely

the clinical study report the integrated summary of Effectiveness and the integrated summary of safety and again the review data begins at the receipt of part one however the pedophile clock doesn't start until part two so please also note that you may also contact the RPM for any questions including questions regarding ectd submissions and in addition to the items mentioned in the earlier slide we have some

items here that we wanted to call to your attention that we've also asked to be included in part one as well because these items are often submitted as part of the clinical study report however they are items that are ready earlier and that can be submitted with part one so part one should also include the tables figures and listings as well as protocols and amendments for

pivotal trials the statistical analysis for for pivotal trials and the sponsors high-level assessment summary of safety and efficacy results as well as the deaf summaries so if FDA identifies substantive uh Missing information reviews will stop and a revocation of star status letter may be issued and please note that applicants who submit an incomplete part 1 they can still resubmit a complete supplement at a later time

but it just will no longer be reviewed under the star program two should be received no more than three months later and should include the remaining components of the supplement as listed here the CSR or clinical study report the ISC and the ISS and as mentioned earlier the Paducah clock starts upon receipt of the part 2 submission and again it should be received no later than

three months after the part one submission for part two if the FDA identifies substantive and missing information then the reviews will stop and a revocation of star status letter may be issued and at that point the application is treated like any other complete application and receive a refuse to file or an RTF so to summarize for a star review the review begins with the receipt of

the part 1 submission the purduefa clock starts when FDA receives the part 2 submission and then FDA will Target an expedited review which means an action at least one month before the padufa gold date and so here we have a snapshot of the FDA Star website which launched again in in October of 2022 it's another resource that goes into the overview the eligibility criteria any process

considerations as well as any additional clarification so please feel free to visit this website if you're looking for information for start it is it is a great resource so going forward we'll be conducting an assessment of the Start program and the interim assessment will be conducted by the end of fiscal year 2025. in a public Workshop will be conducted by the end of quarter two and

fiscal year of 2026 and then please note here that the outputs from the assessment and workshop will be published in a publicly available report so we have a few Challenge questions to go over and here is my first challenge question for all of you when does FDA begin their review of a star application is it a once the star program acceptance letter is issued or B

upon receipt of the start entry request or is it C upon receipt of the star part 1 submission or D upon receipt of star part 2 submission take a moment to see which answer you think is correct and hopefully all of you selected answer C the FDA will begin the review of a start application upon receipt of the star part 1 submission and again part one

does contain the entire application except for the clinical study report the integrated summary of Effectiveness as well as the integrated summary of safety so for challenge question number two the question for all of you is when does the Padova clock start for a star application is it a once the star program acceptance letter is issued or B upon receipt of the start entry request or is

it C upon receipt of the star part 1 submission or D upon receipt of the star part 2 submission and again take a moment to see which answer you think is correct and hopefully all of you selected answer D the Padova clock starts for a start application upon receipt of the star part 2 submission so for challenge question number three the question is when is the

integrated summary of safety submitted is it a with the start entry request for B with the star part 1 submission or is it C with the part 2 submission or D 120 days after the complete supplement and again take a moment to see which answer you think is correct and the answer here is C the integrated summary of safety is submitted with the part 2 submission

so these are some additional resources which includes the link to the padufa commitment letter as well as the fda's Star website which I encourage you to visit for more information on the star program and so to summarize Stars goal is to shorten the time from the date of complete submission to the action date tool out earlier patient access to therapies that address an unmet medical need

the application is submitted in two parts to enable earlier review and action and also star is only limited to Priority efficacy supplements that meet a specific criteria so again this is just an overview of the star program we went over all of the different parts we now have gone through the process including the star entry request we discussed steps to get into the program we discussed

the application review and the submission part 1 and part two and the star Target action date so this is just a quick visual again of what we've discussed and if you have any questions please feel free to reach out again my name is Lashawn schnupp and I'm the cedar program manager for the star pilot program and as a closing thought please remember to include all components

required for each of the two part submissions to utilize the benefits of the star pilot program and that concludes my presentation I'll be back shortly to answer any questions thank you everyone hello my name is Dr Lolita surette and I'm from the division of medication error prevention and Analysis within osc as part of Cedar and FDA and today I'm going to talk to you about the

use related risk analysis and human factors protocol reviews and what to submit for an efficient review first let's talk about our learning exceptions Define the objective of a use related risk analysis Define the objective of a human factors validation study protocol describe the biosimilar user fee Amendment specific three prescription drug user-free amendments could do for seven commitments related to human factor submissions describe common agency initiated

information requests for HF submissions identify tips which may result in a more efficient agency review of Ura and human factors validation study protocol submissions and lastly discuss the importance of the early identification of human factor data needs for medical product development a little bit about the division I work for the method the method resides within the super office called the office of surveillance and epidemiology osc

monitors and evaluates the safety profiles of drugs available to American consumers using a variety of tools and disciplines throughout the life cycle of drugs osc has four core functions pharmacovigilance pharmacal epidemiology Medicaid error prevention and Analysis and risk management is further divided into two offices and five divisions under omekrum is where dimethylize and to map is highlighted here in green now let's talk a little bit

about dimetha's mission our mission is to increase the safe use of drug products by minimizing use error that is related to naming labeling packaging or design of drug products to achieve this Mission the mepa is involved in all of the following conducting a safety assessment of proprietary names for drug name confusion that may lead to wrong drug errors and we serve a signatory for these name

reviews we are included in the review of labels labeling and packaging and product design to promote safe use of medications we review post-marketing error reports to identify safety signals and take action if needed and we participate in the development of guidance for industry and FDA staff work groups and advisory committee meetings lastly we review human factor studies and data to optimize product design and minimize the

risk for use error that may lead to medication error at medication errors safety evaluators within the mepa which was created in 1999 we're composed of Healthcare professionals scientists and Engineers with very professional backgrounds we're further divided by therapeutic categories into the mecca 1 and demepa 2. relief Cedar's review pertaining to medication error prevention and Analysis and human factors for drug and therapeutic bylaws so we just

said that demepolis cedar in the review of medication error and the review of human factors evaluations for drugs and therapeutic biologics but how do we do that a key component of the evaluation of medication errors for combination products or complex drug products is to evaluate the submission for the need for human factors data keep in mind that do we do not limit our focus on combination

products there may be human factors considerations or certain instances where we have complex instructions or novel packaging of drug products that are not considered combination drug products but still their complexity may arise to the level of needing additional data to ensure safe use some of you may be familiar with our practices that we use to apply best practices to decrease vulnerability to medication error and labeling

and naming of products but how do we evaluate medication errors from human factors and perspective it's important to note that we do not work alone we consult with our experts within the agency to help us win those evaluations so let's walk through the process of how the mepa engages other offices within the agency to form perform human factors evaluations so after receiving a submission for review

the mecca will determine if that submission is such that we need to insult other offices at that time we may issue an inter-center consult to a team such as cdrh in their human factors team when input is needed for certain device heavy products for example we consult the crh human factors team for things like external infusion pumps or an on-body infuser or maybe a software-driven medication

dispenser or software-driven device in those instances we rely heavily on cdrh colleagues to provide their expertise in the device heavy component of the proposed product we use their conclusions about the device to help determine what and how those May weigh in on medication errors and the intended use of the proposed product depending on the attended user of the product the mecca may also consult the patient

labeling team for review of the ifu to ensure that the language is patient friendly let's say a particular combination products ifu contains Specific Instructions for the lay user to administer the product in a home setting in this instance we consult PLT and work with them in in the review of the ifu or quick reference guide to gather their input on how to best provide clear instruction

for the layperson as we get those consoles back we'll refer to them within our review and also use their input to help us determine what the data is needed for human factors considerations foreign types of human factors and let's Define the types of human factors submissions that we'll discuss today first use related risk analysis the use related risk analysis is a risk management tool that supports

the entire human factors Engineering Process and should be utilized as part of an overall risk management framework the URL informs the human factors validation study design testing and evaluation of a medical product a useful latest analysis is important to help identify use related hazards associated with the combination product as well as to characterize risks so they can be mitigated or eliminated through improved product user interface

design as a reminder conducting a use related risk analysis is an iterative process as part of the product development and testing of the product prior to agency review there may be times during the product development when additional use risks or mitigations are identified this could be identified as part as formative work or information gathered as part of clinical trials but as a result there may be

additional changes to the user interface required to address use risk or to test mitigations in these cases it is a good practice to document and continuously update the Ura to reflect that these iterations for comprehensive record of use risk and how those risks are mitigated essentially the Ura does help characterize youth related risks and it's the risk that we're trying to characterize and understand in order

to then consider if further risk mitigation strategies are needed now that we've identified the risks in our use related risk analysis how do we use that use related risk analysis to determine or even design human factor data needs for the proposed product first based on the findings of the Ura human factor data has been determined that it may be needed so the risk analysis may have

identified use risks that need further mitigations in this case if it is unclear if that risk mitigation proposed will address the risk you may need to provide data from a human factors validation study to support that your mitigations are sufficient the risk analysis can inform the design of your protocol as part of your human factors protocol design the risk analysis should be used to ensure that

you've addressed all of the steps in the use of your product and include any use scenarios to study and address any possible use risks the submission of a human factors validation study protocol for agency review is not required but it is encouraged to ensure you that your methodology is appropriate to achieve the study's objective by getting input from the FDA early on your protocol that may

help decrease pain points later on in your development process especially after an application has been submitted so for example you did not have any prior agency feedback on your protocol or your product development plans before you submit your application for your NDA or bla you run the risk of the agency deeming that you need to submit human factors data as part of your Market application or

if you've already completed your study without agency feedback on the protocol we may then deem that your methodology is flawed and not accept the results as a result we may require a new study from the application from new study to support the application that has already been submitted so these things will definitely eat into your timeline so you've determined and we've agreed that data from a

human factors data validation study is needed to support your marketing application we reviewed your protocol which I like to repeat and reiterate a protocol review is optional but encourage and after these steps have been completed the next step is to actually run the study and what is the goal of a human factors validation study a study which is conducted to demonstrate that the final finished combination

product user interface can be used by the intended user without serious use errors or problems for the product's intended uses and under the inspected use conditions the study should demonstrate that use related hazards for the final finish product has been eliminated or that the mitigation for residual risks are acceptable these are the types of things we look for in the study of note we generally find

it feasible to conduct these studies under simulated use conditions but there are rare occasions where we would need to see that studying actual use when talking about study results making errors is not always a bad thing because it is likely that used errors will occur in every study our Focus though would be to learn from those errors to ensure that we are finding what mitigations are

required and if we find the residual risk is acceptable these are things that can be discussed in the human factors validation study report the study participants are representative of the intended users and study conditions in the expected use conditions is one key component that we would like to see in your study in the past lives we talked about human factors and we talked about drug products

and we mentioned combination of drug products but what is a combination drug product the formal definition can be found in 21cfr 3.2 which reads therapeutic and diagnostic products which combine more than one either drug device or biologic product combination product can combine drugs devices occur or biologics they can be physically combined for example drug inside of an auto injector or chemically combined such as a pill

which is embedded with a sensor combination products can be co-packaged into kicks for example a drug vial which is co-packaged with a syringe for administration or measurement or it can be a separate cross label products for example a drug label which indicates to use the drug with a specific device like a nebulized drug which is to be used with a fasting clear 510k clear nebulizer and

here are some examples of combination drug products IV Fusion bags which are pre-filled pre-filled syringes pin injectors or Auto injectors pharmaceutical aerosol delivery devices or inhalation products transdermal Delivery Systems or patches drug infusion devices kits contain drug and administration devices and because of the combination products may include drugs biologics devices then you can imagine there are different regulations that we must adhere to this is where

it becomes important that we reach out to our agency experts in different areas such as devices or biologics to ensure that we provide accurate information about human factors needs without causing conflict this is truly a group effort as we discuss combination products it's important to note that there are instances when we may ask a company to apply human factors considerations for products which are not combination

for example birth control pills and a blister with novel packaging design or a unique shape with blister labeling which is unique enough that there could be a medication error concern of confusion for the intended user to determine when to where in that packaging to start and where in that blister to stop if taking on sequence or just taking incorrectly this use error could result in pregnancy

so in this case we may ask the company to provide and evaluate the risk and the use of this product in this product design to be considered it may stop there or depending on what the risks are that have been identified it may go further further to the point where proposed mitigations are not enough and we need to see data from a simulated use human factors

validation study this is just an example but it definitely could happen with novel Packaging or unique design in addition we need to consider a new user group new user groups could be an instance where a standalone vial presentation and when I say Standalone I mean it is not co-packaged with syringes it's just a violet cell so that Standalone vial is proposed to a new patient or

caregiver User Group who traditionally has not had exposure to withdrawing preparing or administering a dose from a vile presentation perhaps this group is accustomed to using an auto injector or pre-filled syringe something where it's already measured up and they just need to administer it so in that case we're comfortable with the administration steps and we feel that those users will be aware of that but for

the task of preparing the bile measuring a dose from the vial those things will be new to this user group in this case we may not have enough data to assure us that the user will be able to perform these tasks as intended we would advise the company to provide additional data to justify that this user would be able to understand and perform these new use

tasks as intended additional data doesn't always mean study data it could mean literature search anything to justify your position that these intended users will be able to use this product as intended what about complex instructions this is another instance where it may not always be apparent that users will be able to prepare measure and Minister the product as intended this could be a unique product where

again a standalone vial could be stored at room temperature but once you combine that vial which is has lyophilized powder once you combine that file with the diluent the vial must then be placed on a chiller before Administration to activate the drug product and once chilled you have a limited amount of time to draw out the dose before it's no longer stable a youth error in

any one of those steps could potentially lead to Patient harm so you see these particular human factors considerations should be considered in other products not just combination products because they may have a use risk that causes a concern for vulnerability to use error based on the design of using the user interface or the design of the product characteristics in these cases it may not be so

clear to the sponsor what human factor needs are required this is why it's important to reach out to the agency early to help in that determination be thinking why is human factors David even a consideration let me walk you through the regulatory history for devices and briefly explain how we got here and where fda's regulatory authority to consider human factor studies stem from we can start

with a device regulation 21 CFR 820.30 which is a regulation which in general requires each company to use quality control methods to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met the goal here is really to ensure that safe and effective use by implementing quality controls for the proposed device for combination products we may

not always ask for data but we always remind companies that according to this particular CFR you have the obligation to ensure good manufacturing quality control methods have been used in the development of your product also a drug regulation comes from the Food Drug and cosmetic act specifically the key for Harris Amendment to the 1938 fujra and cosmetic Act which is requirement to show that a drug

is effective now if we put the device regulation together for good quality along with the amendment to the food drug and cosmetic act for efficacy we can further say that based on this information human factor studies may be needed to be submitted for agency review to demonstrate minimalization of elimination or elimination of use related hazards and medication errors the keywords are may be needed so we

don't always ask for human factor studies data to be submitted to some more application however we do ask that you use tools to evaluate use risks and to subsequently determine if any additional human factor data is needed to be submitted for agency review to justify safety efficacy of any proposed product and these tools help in making that determination you may also be you may also be

thinking when do I need to begin my considerations for human factors considerations at what phase in your development this slide shows drug development process and where human factors and demand for involvement fit in so dimetha usually begins um within the IND once the IND is filed but sometimes it can be as early as pre-ind phase human factors work including product design preliminary analysis formative work and

validation testing can begin during pre-ind and can continue through phase four which is post-marketing updates to the use related risk analysis are made continually throughout the drug development process as risk is continually assessed and reassessed for example if a company finds errors during the formative study and subsequently the design is modified for the product then the URL needs to be updated to reflect that modification that

revision needs to be assessed for risk the same can apply for human factors validation study if the sponsor identifies any failures or risks that could lead to Patient harm that particular failure needs to be assessed and mitigations need to be proposed and implemented those need to be updated as part of the Ura keeping in mind that after each revision the user into the user interface of

product design the sponsor also needs to determine whether or not after updating the risk analysis does that mitigation require an additional validation study or if the revisions are such that it doesn't impact usability there's no additional studies needed that justification will be added to the human factors validation study report for our alignment so continual updates to the risk analysis are key continually evaluating risk is important

so when we talk about user interface changes please understand that the user interface is not only limited to the device anything that the intended user interacts with is the user device its user interface so that includes all points of interaction between the product and the users including things like a display a control packaging product labels instructions for use Etc thus knowing this definition of user interface

helps us to understand why the term user interface is not limited to only combination drug products it could be relevant for own drug products now that I've gone over some background information on human factors and some key terms let's talk about the latest basufa and padufa commitments as it relates to human factors the first commitment I like to talk about pertains to performance goals for human

factors protocols submitted for biologics so beginning in fiscal year 2023 which is October 1st coming up on 2022. we agree to review and provide the sponsor with written comments for 90 of filed human factors validation protocol submissions within 60 days of receipts of that protocol submission for biologics what this means is that in addition to the already human factors validation study protocols that we currently review

for drugs we will now add the review of those biologic human factors protocols it is likely that the number of human factors protocol submissions to the agency may increase with this agreement to reach 90 performance goal for all those protocols submitted to the agency so as you can imagine we really have a work cut out for us here with these protocol submissions another commitment which is

related to human factors is is about urra submissions in summary we will have like we have agreed to a stage implementation of the review for use related risk analysis in producer 7 and Pacifica 3. we agreed to review and notify sponsors of agreement or non-agreement with comments within 60 days of receipt for 50 of filed submissions beginning in fiscal year 2024. after that we agree to

70 of file submissions within 60 days will be reviewed and then lastly in fiscal year 2627 we agreed to notify sponsors within 60 days of receipt for 90 percent of filed human factors use related risk analysis submissions so in the past although we have provided a review and written recommendations for useful later risk analysis submissions we've not had a commitment for the review timelines of urr

submission by a certain time frame with this implementation of producer 7 and Pacifica 3 along with the goals I just talked about the number of urra submissions to the agency we expect to increase as of October 1st so the last commitment to discuss here today relates to a new guidance with the increase in urra submissions we would like to ensure that the submissions are comprehensive and

complete so by the end of fiscal year 2024 FDA will publish a new draft guidance for review staff and Industry describing considerations related to drug device and Drug products on the topics such as guidance that will convey fda's current thinking regarding how a Ura along with other information can be used to inform when the results from an HF validation study may need to be submitted to

a marketing application this guidance will also provide a comprehensive systematic and stepwise approach with examples when applicable to illustrate how to make the determination this is important because if you recall in my last slide I said that we have never had any commitment as far as an enforceable review clock as far as Ura submissions are concerned so we were in the past able to provide a

thorough and detailed review of uras that were submitted to the agency in a reasonable time frame is possible however with the new implementation of urra goal dates we are required to meet the review of you are a 60 days as of October 1st so we have had some time and experience with these reviews over the past few years so um we we are familiar with the

review process however to ensure that we are providing a good and comprehensive yet timely service in the review of these Ura submissions we need to be able to provide the tools and guidance to Industry enable for you guys to be able to follow um for a complete submission and this guidance will eliminate a lot of back and forth on what we need to perform our review

and just to note this guidance is currently under um under penmanship but it's not quite yet published okay so now we've gone over some background materials and also discussed some new commitments in light of these new commitments how can we cut back on the amount of time we spend Gathering necessary information or lacking information to perform an efficient agency review I'll go over a few times

when we could not complete our review or the review of human factors data was delayed due to a lack of clarity or missing information in the human factor submission I'll also give you some tips on how to avoid these issues and lead to more efficient and Tiny review oftentimes when we're in a position where we cannot perform a comprehensive review at the agency level it's because

of confusion or uncertainty regarding human factors data needs the company who submitted to submission may not be aware of or may be unsure of what the human factors requirements are so how does one find out what human factor data needs are required we have guidances which are available and references are included at the end of this presentation to refer you to those guidances but the first

step would be to refer to the guidance which the agency has developed to help outline the process although we aim to write our guidance as basic as possible sometimes there may be situations which are unique or novel and those basic guidances may not provide exactly what a company needs to formulate their submission this may lead to more questions not specifically addressed in the guidance because they're

more custom questions remember a guidance is a suggested guide which should cover the most routine routine situations it may not always meet your needs as it as the only resource if you have any unique or novel circumstances in that situation early interaction with the agency to ensure that you've prepared for and consider if any human factor data's needs exists for your proposed product this will help

and lead to an early determination that your product is a combination product or has been identified as a product which requires additional studies based on novel or unique design in this case it's determined that data from a human factors validation study is needed to support your application we have performed the review of the protocol for the company we provided written comments and now the company is

back and they submitted a response to previous human factors advice but there are not enough details provided or maybe no question submitted to help us determine what exactly is needed in the submission that's we're left to figure out what is needed what are we reviewing to avoid this delay we we have to ask questions we have to send an IR do you need Clarity on recommendations

previously made did you implement all of our recommendations did you disagree with any of our recommendations and because of this we need to wait for your response and it's important to provide Clarity on the intent if your submission is the the key takeaway for this line if we don't know what actions you want us to perform we may spend time combing through the submission trying to

figure out exactly what is our task in hand we'll then need to send an IR asking these um clarifying questions that I just read below in the slide and after we have these answers then and only then are we able to proceed with our review however the back and forth with the IRS will eat away as your timeline so what can you do to preserve this

timeline we think that the use of the cover letter is a good idea use the cover letter to give us a quick summary of what you need from the agency communicate your intent that way for example you may say we have a line with most of the agency's recommendations and seek clarification or recommendations four and seven as part of the cover letter and then this is

just a suggestion but it helps us keep everything in one one spot but to help clarify we'd like you to format your submission of those questions using the same table presentation that the agency initially sent just adding an additional column with your concerns over to the right again this is not a requirement but using this particular format helps us understand what was the identified concern what

was the agency recommendation and what does the sponsor have a concern with in response to that recommendation a third example of um an issue we've encountered here in the human factor submission is we have received a revised human factors protocol but we don't know why that revised protocol was submitted what is the intent again there may be instances when you want the agency to provide another

review of your revised of your revised human factors protocol this could be when we previously reviewed the recommendation the protocol and providing recommendations but the revisions that were implemented were significant enough that it rewards a new and complete review of the protocol once again this could be a case where the user groups have changed or the device design has changed significantly enough that it required additional

tasks or even the company who initially proposed the product has changed hands and they want to go in a different direction these things could warrant a totally new review ultimately alternatively there are many instances where the intent is just to submit your revised protocol for documentation sake so do you align with all my recommendations that were given but you're just submitting a revised protocol for the

record we've seen this in certain instances where we've already performed the review of your protocol we provided recommendations and we got that second submission without detail we're not sure if you want another review or if you want just to document for record um so both of these situations would result in an IR being sent out to clarify the intent of the submission again those IRS will

take time to be once cleared from the agency then sent from the agency then we have to wait a response it could take a week or more to get this particular issue rectified so what can we done what can be done again we suggest Clarity in the cover letter it's a very quick quick way to let us know that you are simply submitting the revised protocol

for the record or you truly do request an additional review of the revised protocol so here's a few um two example languages that we've come up that we've seen um in the cover letter it may say we have aligned with the agency's recommendations and are submitting the final human factors protocol for the record or we may have had something similar to we've determined that our user

groups are no longer representative this revised human factors protocol provides a new methodology as well as new user groups and this is just one point of clarification I like to make um I want to make sure it's clear that adding a summary sentence or two to the cover letter does not mean we do not need the details in the submission we still need that detailed information

about the revision that you made to your protocol in order to make our determination on the acceptability of the new components of your submission so providing those comprehensive details within the submissions are still warranted along the same lines as the previous line This is in Situation Number Four when we may get a revised protocol submitted for agency review and there's a quick summary in the cover

letter that tells us exactly what's changed and that the changes were significant enough to Warrant another review our first thought is well what are those changes that we need to look at so for example what revisions were made to the methodology what are the revisions to the moderator script if any are there any changes to the ifu and do any of these changes requiring updates to

the Uria these are four questions that may impact our previous review and also may impact our forthcoming recommendations so these questions do not have to be answered in the cover letter but they need to be considered and included within your submission it would be beneficial if we knew what those changes are before and before and after so that we can provide a more comprehensive review one

health or approach to provide with your submission in this case is when you have submitted a review a revised protocol for review provide us with a side-by-side or Red Line version to identify those changes this way we can easily pinpoint three visions and then make a quicker determination on what has changed and how that change may impact our previous determinations this is in addition to a

clean version of your human practice protocol within your submission so this approach may be helpful to ensure that none of the new or revised information impacts our previous recommendations The annotation in your submission of what has changed will lead to more efficient review combined with a high level summary in your cover letter that yes we do need a review for this particular reason so in example

number five there are times when we have human factors protocol submissions and we find that the Ura is incomplete or missing if there is no Ura then that's problematic because as we spoke earlier as I spoke earlier I stated that the Uria is the backbone for the human factors protocol submission sometimes we get a high level Ura or maybe only a few select critical tasks have

been evaluated but without a comprehensive Ura of all steps and use of the product we'll not know the task for lethality or even if the use scenarios that are selected are needed to be included in the protocol in these instances we'll be forced to send an IR asking for a detailed list of exactly what's needed we cannot move forward without this particular missing information because like

I said before the Ura is very critical to us evaluating the methodology of the protocol so in the letter that you received from us we'll include language something similar to um until we have this Ura information submitted to us we'll be unable to proceed with our review so what do you do to prevent this from happening well guidances are available uh we do have one Guidance

the content of a complete submission for threshold analysis and human factor submissions to drug and biologic applications which is still in draft but it does offer some guidance for what to expect to be included in a human factors protocol submission um and because the risk analysis is the background of the protocol submission is very important that that risk analysis is very um is very detailed and

has evaluated all steps in the use of the product um providing things like task criticality proposed mitigations things that you see here at the table as table headers if we do not have all this information in the use related risk analysis we'll send that detailed IR out again the guidance is there to help you to avoid us with the IR and the back and forth so

human factors protocol submissions um issue number six and the user interface there these are examples where when we will send a letter to you asking for missing information about things like description of attended product users uses use environments intended dosing training these are things we need in order to us make sure that all steps and use of the product have been considered um we need graphical

depictions of labels and labeling things that help us to see what the intended user will see and how they will interact and how we we need to have user and scenarios built around them if there's no ifu we need that ifu in order to go through the steps and use of the product we don't have an ifu then we don't know if all the risks have

been involved because we don't know how to product is intended to be used so we need all of these user interface pieces in order for us to go forward with our review so what can we do in this case again refer to that same guidance contents of a complete submission for threshold analysis and human factor submission for drug and biologic applications and without this detailed information

I think I think I made it clear that we cannot move forward and it limits our ability to opine on the acceptability of your protocol methodology or if all the risks have been considered so additional information of what we consider complete submission is included in that draft guidance and I encourage you to use it as a resource challenge question number one when determining if your proposed

product may need human factors data you should include a narrative of your independent determination once you submit your NDA on vla reach out to discuss with the agency as early as possible before you submit your MDA bla leave the Box on the 356h form unchecked and someone will reach out to you to follow up or the FDA does not allow the approval of combination products in

the correct answer would be B reach out to us as early as possible before you submit your NDA I think I've um noted several times here that early interaction is key challenge question number two which of the following statement is true only combination products requiring submission of human factors validation data to support safe use if you are approved for an accelerated approval like Fast Track um

your proposed product is exempt from the submission of human factors data it is safe to say that a product proposed in a vile presentation for self-administration will never require human practice data or indeed a use related risk analysis is is important to help identify use related hazards associated with combination products as well as to characterize risks so they can be mitigated or eliminated through improved product

interface design so the answer is d we need to know you know the usulated risk analysis is the backbone so we need to make sure we have that in order to determine any type of risks in the use of the product and how that would impact your product interface design so in summary I'd like to thank you all for your attention um but in summary here

we have learned about or heard about the implementation of padufa 7 and bazoofa three and the number of protocol submissions to agency which we think may increase and to ensure the timing and efficient review is imperative that each human Factor's submission is a complete submission and we recommend you come to us early to seek advice on your human factors development plan and to determine if we

see any indication to encourage you submit we encourage you to submit your human factors validation study protocol for agency review So based on this information and the concerns we want to ensure that your submissions that you send us in are in good shape and for providing efficient review in closing my hope is that you're able to use these tips in such a manner that they will

contribute to the efficient review of your proposed product so we'd like you to consider your call to action is to re review the information presented today and your future submissions to options to help to ensure a complete and Tiny review this is a slide of resources and now I'd like to open up for questions thank you both for those excellent presentations we will now begin our

q a panel session for these two presentations and we'll also be joined by J Paul Phillips director of The Office of program operations in Cedars office of new drugs and if you have not yet had a chance to enter your questions into the Q a chat pod please do so now we will answer as many questions as time allows well we do have some questions that

have come in our first question is for Dr schnupp Dr schnapp what is the difference between Star and RTO good question so star is a Paducah program Open to development programs from any therapeutic area whereas our tour uh or the real-time oncology review is not a pujifa program and it's only available for oncology development programs and if you have more questions about our tour uh oncology

product sponsors should contact the RPM in the office of oncologic diseases or Ood they're division seeing the their application thank you thank you Dr schnapp next question if an ISE ISS is not needed for a supplemental NDA per agreement with the review division is the star program then not appropriate this is another good question so in that case benefits of the timeline for the program would

not be realized since there couldn't be a part two submission so it would not be a good fit for the star program if you do not plan to have an ISS or an ISE thank you thank you Dr schnupp let's do one more question for you uh what if you fail to submit part two within three months of the part one submission with the star submission

then be canceled good question thank you uh yes the application would be removed from the Star program thank you thank you Dr schnapp let's move on to Dr Stewart uh so your first question is how would sponsors know when to submit a use related risk analysis for a product not all products would require a urra correct uh yes thank you for that question um it is

a great question and it is um one day we get quite often it is correct that a risk analysis will measure risks of the use for your proposed product but not all products require a use related risk analysis um one of the clear-cut ways is to know when you need to submit a risk analysis is considering when you have a a combination drug product for those

a use related risk analysis should always be developed to examine what the risks are in the use of that product to make sure that you've addressed all the potential errors in the use of that combination drug product um if your risk analysis doesn't uh identify any new or unique risks in the use of that product then we would we would not um we would still need

to see your risk analysis along with the justification that you have determined that no new data is needed because there's no new or unique risk um that have been identified in the use of your product um so that is kind of a clear-cut way everyone um is pretty clear on combination drug products but when it gets tricky is when you don't have a combination drug product

this could be yes or no you may or may not need to submit a usulated risk analysis and when you don't have a combination of drug product you still may have risk and you see your product so we still need to see a risk analysis in cases of something like novel packaging or um if there's a a new identified user group for an already established product

um or if there are complex instructions that are needed in order to safely and minister or measure or prepare your proposed product so this gets to be tricky because um these are subjective opinions of what is novel packaging what is complex instructions so in that case we like for you to reach out to us early to you know just to get a peek at what you're

proposing and and the times when we have um determined that your particular product could be prone to use error or could be confused and lead to medication error leading to Patient harm this is when we would we would advise you at that time that it would be a good idea to provide or complete a comprehensive use related risk analysis to determine that no risk has you

know would be presented to the intended users of your product um so that was a long way to say I guess it depends but you do not need to always submit a usulated risk analysis there are times when it's clear-cut and there are times when it's not but in any event reaching out early to the agency for to have a discussion on your product development would

be beneficial thank you thank you Dr sturette for that very informative response we do have another question on use related risk analysis so when a sponsor submits a um a human factors validation protocol for FDA review do they also need to submit the um the use related risk analysis do you review that as well and when should this protocol be submitted for FDA review thank you

for your question that's a great question um so we have a guidance a draft guide is actually that is titled contest of a complete submission and within that guidance it provides uh details of what you should include with each type of submission now we don't go into details on how to evaluate the human factors submissions there in this guidance but we do give you kind of

like a checklist of what to include with each particular type of human factor submission so for a human factors protocol yes we do need a isolated risk analysis to be submitted as part of a human factors protocol submission as mentioned earlier we know that a use related risk analysis is considered to be the backbone of of your human factors development process because it examines the risks

and help us to identify what particular use scenarios need to be evaluated in your protocol if there are any use steps that are identified as problematic then those u-steps could be focused on as critical in your evaluation and your human factors validation study so yes we do need the use related risk analysis we will review it as part of our protocol review one of the key

steps is to re review their use related risk analysis in combination with the instructions for use to make sure that every step that is in your ifu is also included in your use related risk analysis and once those steps have been determined that all steps have been evaluated and considered then and only then do we can we give the comprehensive review that your human factors protocol

methodology as far as the steps and is complete um and I think the last question is when do you need to submit your human factors protocol so just to reiterate the submission of a human factors protocol is not required but it is recommended and we do recommend that you send us your protocol before you do your study so before you run your study and we ask

that the human factors protocol be submitted as part of the IND phase um just keeping in mind that we need a minimum of 60 days to provide a written response for the review of your protocol so you need to factor that into your product development plan but like I mentioned it's not a requirement but if you don't submit your human factors protocol for review prior to

running your study that is a business decision that you can make for your company but just know that once you've completed your study and you've submitted your formal marketing application we will look at your results and we'll evaluate your results to see if they are indicative of ensuring safe use for the intended users in the use environments Etc but if the methodology that you use as

part of your study is something that we cannot align with we may ask that you provide additional data and one good way to make sure that we're in alignment with your methodology is to have us do a review of your human factors protocol before you actually run your study so I think I answer all of those questions so thank you so much thank you Dr Strat

um so Dr schnupp we have a couple more questions for you the first question is does the star Pro does the star pilot apply to oncology products or should oncology applicants only pursue our tour good question so both star and our tour uh they are available to oncology products sponsors may discuss their preference with the RPM of the of the relevant division for their particular product

thank you okay your next question is star available only to supplemental applications yes so currently star is only available for certain efficacy supplements and as I noted during the presentation assessments will be conducted to consider the feasibility of expansion in the future thank you thank you Dr schnupp uh let's see another question for you asking how long will the pilot plan Run for the star program

that's another good question uh thank you it is premature to discuss uh since we will be conducting assessments and workshops in order to evaluate Stark and we have not yet received feedback and results from those efforts uh which will help uh inform us of any decisions about next steps thank you thank you and one more question for you how does star compare to BTD if the

criteria for clinical evidence are similar again that's also a very good question so brexit therapy designation or BTD it primarily provides benefits during the development or IND phase whereas star is is more intended to provide a benefit during the early review of the supplemental marketing application thank you thank you Dr schnapp let's move back to Dr saret for a few more questions Dr Strat can you

please provide a typical sample size and duration for a human factor study validation hi yes thank you for your question um so a typical sample size it will depend on your number of distinct users how many different types of distinct users you have um so we usually require or we we suggest and recommend 15 distinct users per user group so that final number of sample size

will change depending on if your product is intended to be used in healthcare providers only or if it's to be used in patients caregivers and then there may even be subsets of patients um who are injected in naive or ingestion experience we even sometimes have a distinct User Group who are distinct because of their age so um that's the final sample size number is something that's

going to be unique to your specific product but and I guess in the intended use of the product as well but what we do know is um based on references that we use here at FDA it's been published that a sample size of 15 is sufficient to find a minimum of 90 percent and an average of 97 percent of all use problems so that's going to

be your your starting number it's going to be 15 per distinct User Group um now the second question about the duration the duration of your study it's also going to depend on how many steps are required to use your product so if you have a a fairly small or short instructions for use with you know just a few steps then of course your study will be

shorter but if you have a complex product which may have an upwards of 10 20 steps in order to administer your product that's going to drive the duration as well um just want to reiterate that an agency review of your draft protocol before you complete your study will help us determine if you've identified the correct sample size and and the correct intended user number of distinct

users um so that we can say that your methods are acceptable thank you thank you um let's see one more question for you is submission of product samples required in order for FDA to evaluate the human factors validation protocol if yes how many samples will FDA allow the sponsor to set up the product for FDA reviewers in the same way that the sponsor sets it up

for users thank you for your question that's a great question um so samples are not required for the review of human factors protocol we do realize that by the time we receive a submission to review a human factors protocol it is fairly early on in the product development process we do expect that within the human factors validation study you are evaluating the product um that you

intend to Market as close as possible to the intent to Market product but we do also realize that sometimes you may not have a physical sample for um whatever reasons we have had issues um with people getting our samples due to mailing or Transportation types of concerns but if we don't have a physical sample we would like to have a graphical depiction at least um so

that we could look um at a real picture of what was used in the study and to see all sides of the labeling the cart and the container the device itself if it can contains a device so it's not a requirement that you submit samples it is ideal and we would love to have samples but if not we we will work with you to um to

get of alternate means of us evaluating your samples um well I think that was it I think that was it thank you so much thank you uh let's turn it back over to Dr schnupp Dr schnupp if uh the drug product and packaging are conducted I'm sorry if DP and packaging are conducted in the U.S but API is manufactured at xux X us excuse me with

this qualif disqualify from participating in the star pilot program with this disqualify from participating in the star pilot program another good question thank you um due to the timelines for scheduling a foreign inspection they do not align with the intent and timelines for the star program so supplemental applications that require an inspection of a foreign manufacturing site do not qualify for star and therefore whether a

supplement with inactive pharmaceutical ingredient or API manufactured at an ex-us site with qualified dispense depends on whether or not review of the supplement would require inspection of the um the xus site uh if FDA determined that an inspection is required um at the foreign site then the supplement would not qualify for Star so thank you for that question thanks and one more for you how long

will the pilot program or the pilot plan Run for the star program um again it's it's premature to discuss since we will be conducting assessments and workshops uh to evaluate star and we haven't yet received feedback from the results from those efforts which will help us uh in terms of informing us of any decisions about next steps so thank you okay Dr Strat we have a

few more questions for you the first one what is the agency's timeline for review of clarifying questions for a response to a previous human factors advice great question okay so the agency timeline for review of clarifying questions for previously provided advice um well because we've already provided a response and you know in writing in advance we should be very familiar with the protocol and we won't

need much time to get back to the sponsor on their clarifying question um usually we can get that back fairly quickly considering um the clarifying question is submitted very soon after our initial correspondence that would be you know helpful so it's kind of still fresh in our minds but if uh if there may be times when the clarifying question is very complex or if that question

may require us to reach out to our counterparts our colleagues and FDA for additional input for the experts in their fields and we don't uh we don't have a established timeline per se for getting back on those clarifying questions so I guess in this case the answer would be it depends on how much time you need to put into considering um the response however we are

aware that these questions aren't necessary to be answered to move forward with their the sponsored study so we keep that in mind and make sure that our goal is to get back to the sponsor as soon as possible so as not to um hold up their development process for their human factors timeline um thank you foreign for you if I am submitting a user related risk

analysis must I also submit comparative analyzes thank you for that question um okay so this is also going to be a question an answer that's going to be it depends um well let's start with as I stated in the presentation the risk analysis we know is going to be used as the backbone for submission of the human factors um to determine if any human factors is

data is needed because you know it's going to determine what risk is needed and the use of the product and also determine if any additional mitigations of are identified that are needed for risk controls um so when considering the submission of a comparative analysis it's going to be in conjunction with the use related risk analysis the risk analysis may be used the comparative analysis could be

used as a supportive documentation to the risk analysis and when I say that I mean that in your risk analysis if you determined any level of risks you can also provide a comparative analysis to identify a comparator that's similar or sane and go through an exercise where you will do a comparison with the labels the labeling labels and the tasks to determine if there are any

already or same similar products on the market that have already approved in that presentation and use that comparative analysis as kind of a tool or a a reference item to say that hey this product is already marketed it's very same or similar as the one that I have this risk is controls are already put in place so I should not have to provide any additional data

so we'll use we'll we'll ask the sponsor to use the comparative analysis just to justify that their product um is whatever is different about their product or whatever risk has been identified for their product in the risk analysis we'll use the comparative analysis as a tool to justify that there's no need for a submission of additional risk because of what's already been proven in the market

um so if the if the sponsor will determine that you know there's no need for additional data based on the risk analysis and they submit a comparative analysis to further validate that conclusion um then we will provide uh we'll ask that they submit that along with the justification so that we could look at both the risk analysis and the comparative analysis before we make a determination

that we agree no additional data is needed so it becomes a tool for um I guess supportive documentation that no additional study is needed thank you thank you I think we might be able to squeeze in one more question for you I am not sure that my human factors protocol methodology is correct is there an option to request a meeting and to ask for questions on

my protocol design oh sorry yes thank you for that question um if you're not sure that your your pro your protocol methodology is correct we would like for you to um first of all just submit your protocol a meeting to have us review your protocol is not always the most efficient way to look and see if we can help you with your methodology um just because

of the the time constraints and the amount of comprehensive study that we need comprehensive review that we need to provide so what we'd like you to do is submit that protocol to the agency for review and then what we'll do is ask that you also provide those same questions that you have for us that you wanted to submit as a meeting provide those questions with your

protocol submission and then we'll do a comprehensive review of your protocol and your questions and get back to you within 60 days in a written format so that you'll be able to move forward with your product development thank you thank you thank you to the presenters and to the audience for answering for asking the questions the presenters for answering and for the great presentations that's all

the time we have for questions right now uh and so let's take a short break and we will reconvene at 11 o'clock Eastern time thank you