Regulatory Education for Industry (REdI) Annual Conference 2023 Day 1 Session 3

foreign moving into our presentations our first presentation is on the electronic submissions Gateway the road modernization our presenter Jessica Bernhardt is the admin apps program manager and ESG program manager in the office of information management and Technology within the office of digital transformation Office of the commissioner our next presentation is on the ectd version 4.0 and the latest on ectd our presenter Jonathan Resnick is a

project management officer in the division of data management services and solutions within the office of business informatics in the office of strategic programs in Cedar our final presentation in the session before the Q a panel is on the electronic submission practicalities and application tips our presenter Heather Crandall is an operations research analyst in the division of data management services and solution within the office of business

informatics in the office of strategic programs in Cedar please join me to welcome our first presenter Jessica Bernhardt greetings my name is Jessica Bernhardt I am the ESG program manager here at the FDA uh today we are going to cover the electronic submission Gateway also known as ESG and the road to modernization today on the agenda we will cover what is ESG how does ESG work

who receives ESG submissions ESG and Industry collaboration ESG growth recent ESG enhancements going green modernization ESG next gen and then we'll have a session for key takeaways and questions what is ESG PSG is the fda's electronic submission Gateway it is an agency-wide solution which accepts electronic regulatory submissions this enables industry to communicate with the FDA by sending a secure submission for pre-market and post-market regulatory information

for the fda's review how does ESG work in the next section we'll learn how submissions are sent and received through ESG how ESG works industry sends a single file or folder submission to the FDI via https ESG then receives the submission and assigns a unique ID fgisg then sends a receipt to the submitter acknowledging the transmission the submission is automatically transferred to the center's inbox then

a center acknowledgment is automatically generated and sent to the submitter via the FDA ESG the center will then validate and process the submission via accessing the center's inbox additional information about the process can be found on the ESG website here is the submission process as you can see the industry submitter will submit to the FDA ESG ESG will then forward the submission to the FDA Center

inbox this is similar to the mail process where you mail a letter the post office then receives the letter and then delivers the letter to your mailbox it's important to note that ESG does not open or review any of the submissions that does not occur until the center receives it how do users send submissions users can submit through ESG by using the web Trader or as2

the web Trader is a web-based interface compatible with Windows operating system which requires a client to send documents and receive receipts and acknowledgments from the FDA the web Trader application makes communication with the FDA simple cost-effective and time independent all submissions are signed using a pki certificate PKS certificates are used for authentication and adds an extra layer of security the web Trader is an excellent option

for small to medium-sized businesses or businesses without their own I.T Department as2 is a system to system connection this allows industry partners to access the Gateway via system to system communication system to system communication often referred to as an as2 account provides an automated connection to the FDA for submissions for seats and acknowledgments the system to system communication requires software from industry partners all submissions are

also signed with the the pki certificates which again is for authentication and adds an additional layer of security is2 is a great option for larger industry Partners or industry partners with their own I.T Department we have come to a challenge question challenge question number one which of the following statements is not true a ESG opens the submission file and reviews content for accuracy B ESG delivers

the submission file to the FDA Center without opening or reviewing content C ESD sends a receipt to the submitter to acknowledge the submission has been received which of the following statements is not true if you guessed a you are correct congratulations who receives ESG submissions in this section we will learn which centers offices and external Partners receive ESG submissions the FDA centers offices and Community Partners

receiving ESG submissions are as follows the center of veterinary medicine also known as CVM the center for biologics evaluation and research also known as sieber the center for drug evaluation and research also known as Cedar the center for food safety and Applied Nutrition also known as sifsan the center for devices and radiological Health also known as cdrh the center for tobacco products also known as CTP

Health Canada also known as HC office of Regulatory Affairs also known as Ora Office of the commissioner also known as OC for additional information on the centers offices and Community Partners receiving ESG submissions you can visit the ESG website ESG industry collaboration in this section we will learn how ESG and Industry communicate esg's collaboration with industry per prescription drug user fee act also known as padufa

FDA and Industry will collaborate to plan and conduct meetings review initiatives and engage industry to provide feedback and or participate in Pilot testing prior to implementing significant changes that impact Industries interaction with the ESG annually FTA leadership and padufa I.T leadership review initiatives and provide opportunity for industry input many of you may have experienced firsthand this collaboration between industry and the FDA prior to releasing major

software enhancements or upgrades fda's ESG team will send out communication to Industry requesting assistance with testing many of you may have participated in testing in the past industry testing is vital to ensuring software enhancements and upgrades the ESG releases are free of bogs and defects the testing also ensures industry does not experience any issues after the software release ESG team thanks industry for their participation in

this testing and their vital feedback they provide industry and collaboration continued in order to continue with the vital partnership between industry and the FDI it is recommended that we continue to participate in patufa quarterly industry meetings continue to participate in FDA and padufo Leadership meetings and continue collaborative activities with industry for impactful system and software changes ESG growth learn how ESG has grown from 2015 until

now ESG growth by year for ESG growth by year we look at the total submissions as well as the total transactions the total transactions include the submissions acknowledgments as well as receipts for ESG Earth by Year we're looking at 2015 to 2022. as you can see here the submissions from 2015 to 2022 has over doubled with 3 million submissions in 2015 and over 8 million submissions

in 2022 here you can see a huge increase from submissions in 2020 to submissions in 2021. this large increase from 5.7 million to 7.2 million is due to the covid-19 submissions we also look at the total transactions from 2015 to 2022 and the total transactions has increased from 9.2 million to 27.5 million from 2015 to 2022 which is a substantial increase the average annual growth from

2015 to 2022 for submissions is 15 percent acknowledgments is 18 data is 24 and accounts is 14 as you can see the submissions and transactions steadily increase for additional information on the submissions and transaction statistics please visit the FDA ESG website and look under submission statistics recent ESG enhancements this section will cover ESG enhancements for 2022 and 2023 2022 ESG enhancements the 2022 ESG enhancements included

account portal 1.0 and submission virus scanning account portal 1.0 was implemented in August of 2022. this delivered a new front-end portal which enhanced web Trader user experience and automated the onboarding account management process enables webtrader account holder to use self-service features the benefit for this enhancement provides self-service features which allows users to easily navigate the account creation process update passwords and digital certificates and upload mandatory

non-repudiation letters the account portal also adds role-based functions such as power users to manage specific account items for their company and conduct company submission searches the account portal system will also Auto promote accounts from the ESG pre-prod environment to production upon Center approval which will help to reduce onboarding time the second enhancement for 2022 was the submission virus scanning which was implemented July of 2022. this

enhancement implemented virus scanning software at the agency level prior to Downstream Center submission processing the benefit for this enhancement was that it enhances the ESG Security by adding another layer of protection prior to reaching the FDA internet esg's 2023 enhancements the 2023 ESG enhancement included a core technology refresh this tour technology refresh was completed in March of 2023. it included migrating ESG databases services and software

to a gov Cloud fed ramp High infrastructure it included implementing center user functionality within the account portal the benefits for this enhancement or to support the FDA technology modernization action plan also known as tmap and the data monetization action plan also known as demo strategies enhancement allowed for the reduction of the data center footprint providing a cost Savings of operating maintenance for all senders and aligned

with the fda's mission of going green the upload time between the industry user environment to ESG server in the cloud versus the on-premise server improved by 34 percent this enhancement enabled the use of modern Cloud technology which enables scalability when the need arises also allowed for a more reliable environment for a 24 hours a day seven days a week 365 days a year implementation ESG going

green this next section will cover how the ESG is making changes which supports fda's going green initiative ESG going green initiative effective February 2023 FDA will now accept non-repudiation letters electronically industry is no longer required to send a hard copy of non-repudiation letters and doing so is optional this will help to reduce the FDI and National Archive also known as Nars carbon footprint and aligns with

their going green initiative by reducing the amount of paper ESG modernization through padufa 7 and basuva 3 commitments in this section we'll learn how ESG is modernizing ESG modernization fiscal year 23 through fiscal year 25. continue modernization through prescription drug user fee act also known as padufa 7 and biosimilar user fee act also known as possufa 3 commitments and other FDA strategic initiatives through the development

of the ESG Max gen us of seven commitments in relation to ESG are to Monitor and modernize under this there are two Peru for southern commitments the first one FDA will continue to ensure the usability and Improvement of the ESG annually FDI will provide on the ESG website historic and current metrics on ESG performance in relation to public targets characterizations and volume of submissions and standards

adoption and conformance the second FDA will advance the ESG cloud-based modernization with an improved architecture that supports greatly expanding data submission bandwidth and storage while continuing to ensure its stable operation by the end of FY 2025 FDI will complete ESG transition to the cloud including setup and integration of an Enterprise identity and access management solution that will streamline applicant access to FDA resources annually FDA will

share progress against the implementation plan FDA will engage industry to provide feedback and or participate in Pilot testing in advance of implementing significant changes which impact Industries interaction with the enterprise-wide systems similar to padufa basufa also has commitments which include modernizing fda's Information Technology infrastructure and supporting of cloud-based Technologies in relation to the ESG vision for the next generation of ESG the vision for the next

generation of ESG is to provide the FDA with a trusted secured cloud-based and unified submission Gateway that is highly available scalable and accept a variety of electronic submissions for processing by line or subjects specific business processes as you can see this is the industry Partners this is the ESG next gen which will include an identify identity access management user provisioning and submission provisioning in a fisma

high environment and will interact with FDA clouds and portals as well as other FDI systems and portals that are on-prem the vision for ESG nection in relation to FDA strategic initiatives division for ESG next gen use the three FDA strategic initiatives which are technology modernization action plan also known as tmap the data modernization action plan also known as dmapp and the Enterprise modernization plan also known

as emap to develop the vision for the ESG next gen the technology modernization action plan also known as tmap includes the modernization of fda's Technology infrastructure enhancing fda's capabilities to develop technology products to support its regulatory Mission and communication and collaboration with stakeholders to drive technological progress that is interoperable across the system and delivers value to Consumers and patients the FDA modernization plan also known as

dmapp includes identify and execute high value driver projects for individual centers and for the agency develop consistent and repeatable data practices across the agency and create and sustain a strong Talent Network combining internal strengths with key external Partnerships the Enterprise modernization action plan also known as emap includes creating the infrastructure to support change develop a common operational approach and ensure strategic alignment these three FDA strategic

initiatives were taken into account When developing the vision for the ESG next-gen solution the ESG next-gen approach the ESG next-gen approach has used the product approach which uses personas there are several personas which were considered When developing the vision for the ESG next gen those are the industry power use of persona the industry submitter Persona the ESG admin Persona of Center admin Persona and the FDA

center user Persona these personas are used to develop a story that story is used to document requirements for each of these personas the approach for the ESG connection is a complete technology refresh with the latest cloud-based and best of breed software it also looks to examine the current business process pain points that currently exist in the existing ESG in order to deliver a better user experience

for external and internal users the ESG NextGen team will collaborate with internal FDA stakeholders and Industry in order to solicit feedback and validate functionality ESG NextGen business process improvements the ESG Max gen team looked at the current ESG and the pain points that currently exist in order to come up with the process improvements for the ESG next gen these profits improvements include the following streamline industry

account or boarding process this will include streamlining manual user onboarding process by using modern intelligent business Process Management platform and icam solutions the next is to improve customer experience the Improvement of customer experience will reduce the help desk calls and improve customer experience by using CRM tools to provide updates on submission status and enable two-way communication between centers and users then access to improve the file

transfer process by increasing file submission processing speed support filed resume transfer function handle large file sizes and reduce the complexity in generating the proper submission packages the next business process Improvement will be to improve user management processes by consolidating user accounts and manual access management functions into a unified Enterprise identity credential and access management icam solution for end users the last business process Improvement will be

to support new use cases this one share future capabilities of ESG Ng will be able to incorporate new technologies that can support future use cases as they arise ESG next gen targeted milestones for FY 22 the FDA worked on the planning phase for the ESG Max gen this included developing the vision and planning as well as market research in FY 23 we kicked off the proof

of concept this included the development and execution of the proof of concept the proof of concept started in January of 2023 and is slated to end the end of the summer of 2023 the fy24 roadmap will include release one this will include the unified submission portal identity account management user interface application programming interface and data migration release 2 and 3 on the roadmap will take place

in fy25 release 2 will include enhanced unified submission portal and dashboard as well as self-service capabilities release three will include large file size submissions chat Bots and additional portal features which are to be determined as part of the road map we will provide industry Outreach and planning on a quarterly basis we will develop testing strategy with industry and solicit testers we will update the ESG next-gen

website with information specification user guides frequently asked questions and progress we will conduct testing with industry on each release before going live incorporating Lessons Learned Ford FY 23 proof of concept we will be reaching out to Industry to assist with testing of the proof of concept in addition we are in the process of developing an ESG next gen website which will provide pertinent information to Industry

and we have arrived at another challenge question challenge question number two the ESG next gen modernization will incorporate all of the following business process Improvement except a improve customer experience B improve file transfer process C check submissions for spelling errors or D improve user management process which of the following ESG modernization will incorporate all of the following business processes improvements except if you selected option C

check submission for spelling errors you are correct congratulations if you got the question right key takeaways and questions in this section we will cover the key takeaways from the presentation and allow for a question and answer session the key takeaways from the presentation are as follows the current ESG has been the fga central intake portal since 2005. since 2015 there has been an annual average increase

of 17 percent in submission volume and data size ESG will modernize to accommodate a continued rate of growth well into the future the current ESG has met all padufa requirements to date the current ESG has served us well however as Technologies and user requirements change the FDA is assertively taking actions to ensure ESG will meet future industry technology security and public requirements the ESG NextGen will

address pain points in the Legacy ESG as well as leverage technological advances to provide a modern and secure electronic submission Gateway for industry to provide critical information to the FDA if you have additional questions after today's question and answer session my name is Jessica Bernhardt and my email is jessica.bernhardt fda.hhs.gov please feel free to reach out for more information after the presentation and today's question answer

session you can access additional information on the fda's ESG website at this website address www.fda.gov backslash for industry backslash Electronics submission Gateway backslash default.htm also you can email the ESG helpdesk at ESG helpdesk at fda.hhs.gov we'd be more than happy to answer any questions you may have hi my name is Jonathan bresnick we're going to cover the fundamentals of the eccd 4.0 Concepts we'll be talking

a bit about the FDA implementation strategy and how you can prepare for 4.0 so let me begin by showing you some things that are directly from the ich ectd 4.0 implementation guide this is an excerpt it says the goal of upgrading to ectd 4.0 is to facilitate the processing of review of electronic regulatory submissions and it goes on to say that some of the key business

drivers include document reuse which is the ability to submit a document once to a regulatory Authority and then be able to refer to that document again in other sequences or in other applications without actually providing the physical file over and over document and metadata lifecycle this is about the ability to manage versions of documents and the metadata around them and then management of context groups this

is talking about ability to group documents together based on their nature of use so let's get into the actual 4.0 Concepts so let's take a look at the concept of harmonize submission unit and document reuse with harmonized submission unit what we have is all content for module one through module 5 is now contained in a single exchange message or a single ectd backbone file within the

sequence so you can see here how I've contrasted ectd 4.0 versus 322 and 4.0 you have a single submission unit.xml file it contains all the backbone information for the submission including the studies with 322 we had our regional backbone file our index backbone file and individual study tagging files for each study with the document reuse concept a document ID is established whenever your sending in a

new file and that document ID captures information such as the document title for the file and the path to that file so now if you wanted to reuse that particular file in a future sequence it's very easy to do all you have to do is reference that unique document identifier that you set up all right so let's take a look at another concept here with 4.0

it's called context of use it's about the placement of a document within a table of contents and it provides information regarding the usage of that document and its life cycle if you haven't already drawn the connection context of use is very similar to the current Concept in 322 of leaf element now there's also a controlled vocabulary that's used quite heavily in ectd 4.0 and we use

what's called keywords and they give additional information to that context of use in other words keywords really are replacing the ectd322 attributes and valid values so here on the last line we have an example of a context of use that has the predefined table of contents heading combined with the keyword so you see in purple 3.2.s.2 manufacturer that's the actual context of use or table of

contents heading combined with the information you see in green which are the keywords now taking this a little further we talk about a context group and a context group is just that combination of the context of use with the keyword so we have up here the combination of a context of use and a keyword defines the context of the submission contents if any one of them

is different the context is considered different and that's important because if you use different keywords under a context of use that can result in creating multiple headings in the ectd viewer tool so let's take a look here so I have context of use x and you can also think of this as context of use group X and context of use why in context both of them

if you look at the purple writing have the same heading 3 2s2 manufacturer but they differ in terms of the keyword that the submitter has applied to the context of uses so in the example of context of use x the keyword is substance one and manufacture one with context of use y if substance one but it uses manufacturer 2. so it changes the context group and

that is why when you look at this visual on the right hand side you see two three two S2 manufacturer headings displayed because the keywords were different between them another Concept in 4.0 is called group title this is leveraging keywords so there is a group title keyword and it's applied to the lowest level of a context of use context group to further organize content under a

ctd heading when multiple documents are allowed and the sender assigns the group title to specify how the content should appear together so of course you know a picture is worth a thousand words so let's take a look here on the right of this visual so I want to call your attention that we have the lowest level heading M3 2p7 container closure system blister and there's six

documents listed underneath that heading and what the submitter has done is they've used the group title keyword to separate out those six documents into two groups this is a new feature with 4.0 now we get to Priority number priority number is all about the ability for the submitter to set the order of the documents within a section or heading it defines the display order in the

ectd viewer tool of the documents underneath that context of user context group right so it doesn't matter which tool vendor you're using to view your ectd submission you should see the documents listed in the same order another feature of priority number is is allows the submitter to change the order of the documents without having to actually life cycle them so the sender can reorder submission content

or insert documents so this visual here is giving an example so in sequence one document 1 2 3 and 5 were submitted and they're in chronological order the submitter decides in sequence 2 they want to change that order and so you see now they have document 5 listed first along the subject of documents we have document identifier every document is assigned a unique identifier a unique

identifier approach means that documents can be referenced reused more effectively without resubmitting the physical file without having to provide the path to that physical file this can be used across a submission unit which is a sequence it can be used across regulatory activities with an application or even across applications these document identifiers are important they're used to reference the document under a context of use or

context group you have the ability to reuse the document metadata so remember when you set up a document ID that is including the title that you're associating with that physical file and the path to where that physical file is located you can also do some other things here with document information you can update the document title and you can do this again without actually lifecycling the

document so for example if you made a typo in sequence one like this visual is showing where you wrote manufact instead of manufacturing process and controls you can do an update by using the priority number feature similar to the way that you can update the document titles you can also update the display name values of a keyword so in this example the submitter has provided a

display name for their manufacturer keyword of Ace manufacture in sequence one and then for whatever reason they realized they needed to change the manufacturer name to Acme manufacturer they were able to do this by just updating the display name value for that manufacturer keyword they used they don't have to you know delete or suspend the contents underneath the heading and then submit it as new like

one would have to do with the current ectd life cycle is another enhancement with documents with 4.0 so today with 322 of course life cycle is very powerful and you can replace documents and ectd tracks the linkage between the different versions but you can only do a one-to-one replacement today with 4.0 this functionality is expanded so not only do you still have the ability to do

one to one but you can also do many to one Replacements or one-to-many so I have a few visuals here so the first visual is replace many to one and you'll see in sequence one under context group one three documents were submitted then in sequence 2 the submitter has replaced those three documents with a single document called document 4. that's that many to one further to

the right that visual is showing the replacement operation of one to many so we take this a little further so now this submitter says you know what I want to change from the one document over to three documents again replace one to many and you can see how that happens from document four they replace it into what would be documents five six and seven and the

ectd viewer tools will be able to track that linkage and Association so this is a good spot here to ask a couple of Challenge questions so the first one is in ectd 4.0 sequence contains a harmonized submission unit message called submissionunit.xml is that true or false I'll give you a few seconds to think about it okay and the reveal true this is one of the nice

advantages of 4.0 over what we have today it consolidates all those backbone files that we get in every sequence in 322 to just a single backbone file with ectd 4.0 and it's called submission unit.xml let's take a look at challenge question number two the ectd 4.0 document lifecycle functionality allows one-to-one replacement one to many replacement many to one replacement or is it D all of the

above we'll give you a few seconds to think about the answer okay and now the reveal D all of the above so let's switch gears here and let's focus in on fda's 4.0 implementation strategy of course FDA can't Implement anything until ich has the ectd 4.0 specifications ready to go and they do so ich put out the 4.0 implementation package um out there it's on the

ich website it's currently on version 1.5 that was posted in May of last year there's also a question and answer change request document available on the site as well the latest version 1.7 available as of June of last year also on this ich page our regional implementation information such as Regional Technical Pilots implementation dates and links back to Regional Pages where you can find their Regional

implementation guides and other Associated documents later on in this slide deck I will have the link directly to this site so you will have it all in one place now the FDA activities if D.A has put out a 4.0 technical conformance guide as well as the regional 4.0 module 1 implementation package this was originally posted in February of 2020 for public comment it's undergone a few

revisions the latest one is actually version 151 of the regional implementation package it was posted September of 2022. there's also a specifications for the validation criteria specific to 4.0 as well as comprehensive table of of contents headings in hierarchy those are all up there on our ectd website we've created a 4.0 section of our website to help organize all of the content for you other activities

that we've been doing here at FDA is testing out our software we are busy testing out the latest versions of the ectd software and validation tools that we use to make sure that uh we're getting into position to be able to fully support 4.0 and it's working as intended we've also recently concluded a small technical pilot so that we get tests and Sample submissions not just

that we create but that we get from industry looking at our FDA implementation strategy or planning to have an initial release in 2024 and the scope of that will be to accept new applications in ectd 4.0 in order to get there we just recently completed a technical pilot that was to ensure that our FDA systems and tools were working properly with 4.0 we also plan to

open the door to allow industry to submit sample ectd4 submissions into FDA in the later part of this year to give you an opportunity to get feedback and then as far as future phases we're looking at about a year after we start accepting new applications in 4.0 to be able to accept the transition of current applications so if you had already sent something in 322 you

could follow it up with an amendment or a supplement in 4.0 and then once we have that all rolled out and working then we would look uh at putting into place the two-way communication now this slide is a really great resource for everybody it has the hyperlink to the ich webpage and the hyperlink to the FDA ectd Ford auto webpage so you have access to all

the implementation guides and packages and specifications everything you need to prepare for ectd 4.0 so the ich webpage has the implementation package supplement documents for 4.0 implementation Regional implementation information and links and change control information on our FDA page that's where you get the regional stuff the FDA implementation package the FDA technical conformance guide c talk validations so a little bit how can you prepare for

4.0 we have some recommendations we recommend you discuss the Ford auto development plans with your vendor your it organization understand the specs is there a plan for transitioning to 4.0 and you can always send questions into ich or FDA but come familiar with the Ford Auto Concepts and enhancements ich has put together a couple of PowerPoint presentations that are available on the ich 4.0 website look

at the FDA tactical conformance guide it's written in in a more plain English uh you know type of writing to make it easier for even a non-technical person to understand and then nowhere to find the 4.0 information and I'm hoping that this presentation will go a long way in helping you there and then finally think about submitting up an ectd 4.0 sample submission for technical feedback

right before you actually send a live submission again later this year probably near the end of this year we are planning to open the door so you could send in those samples and get feedback all right so I've got a I've got a poll question here for you my company plans to submit an ectd 4.0 test submission in a 2023 B 2024 C we've already submitted

or D we have no plans at this time all right so in summary ectd 4.0 it builds upon the success of our current ectd how does it do that it enhances document replacement it harmonizes the submission unit backbone file provides better utilization and more of the control vocabularies gives the ability to rename documents and context groups 4.0 is ready to implement it's ready now Regulators are

actively working on their Regional implementations FDA has published the specifications pleaded its Pilot's testing and is now working toward buttoning up all the other things behind the scenes so that we can start accepting these 4.0 submissions next year in 2024. and finally FDA has put together a web page that has all of the ectd 4.0 content and you can easily get to it by going to

our our normal fda.gov ectd webpage where it has all of our current ectd specifications you'll see there's a link there for the 4.0 page so that's the end of The Talk today and I look forward to answering your questions thank you very much Crandall and I am here from the cedar electronic submissions team in the office of business informatics to talk to you today about ectd

it's more than just the documents within it so the learning objectives today by the end of this presentation you should be able to understand where to find new information that is put out about ectd submissions you should be able to list the most common errors that are made by sponsors when submitting an ectd format and you should know where to find resources available that will help

answer common questions that are received by the electronic submissions team about ectd submissions in December of 2022 the actd submission standards was put on a new web page in the FDA ectd site so previously the submission standards were located in a PDF file and an Excel document that housed all of the specifications and attribute files for ectd version 3.2.2 as of December 2022 they are now

located on a web page where you can search for the documents and you can find that web page in the quick links on the main FDA ectd site also in November of 2022 the ectd technical conformance guide was updated to include information about submitting structured data files in module 3 as part of the substance information three a handful of validation errors were updated a new error

1738 became effective and 1738 is looking for a match between the study ID as listed in the study tagging file XML and the study ID or spref ID listed in the trial summary xpt file and this is a medium level error which as I previously said went into place in mid-march of 2023. also with that update I wanted to highlight the change of scope for validation

error 1737. previously 1737 looked at a subset of modules 4 and modules 5 to check and with the update in mid-march 1737 now looks at everywhere a study tying file is expected to be and as a refresher set validation code 1737 is checking that um files submitted to a study that are of the same name and leaf title are not both submitted as new so if

there is an update to a file in your study you should be submitting the newer version as replacing the previously submitted version some metrics around ectd submissions looking at the overall metrics and then digging down into the top errors that we are seeing in uh ectd submissions so I'm going to be looking at Cedar ectd formatted submissions between October 1st 2022 and April 30th 2023. So

within that time period more than 198 000 submissions were received by Cedar and that includes ectd formatted submissions uh paper applications and electronic uh non-e-ctd applications but 94 the vast majority of those were received in ectd format within that 94 percent only roughly one percent of those ectd submissions are rejected and of that one percent we um I wanted to focus on four errors that we

see for the majority reasons why these submissions are being rejected more than 50 are because of a duplicate sequence number 1765 of them uh were submitted or rejected in that time frame for duplicate sequence so that means that we already have a sequence number for that application in our database that was already submitted to us and then it is being submitted again so we cannot accept

that each sequence number must be unique and so it will get rejected we also see rejections for single file submissions so the file can't be coming through the Gateway zipped and more than one file needs to be present in an ectd submission for it to be a proper ectd formatted submission um also we see submissions with no backbone files so that means they're either missing the

index.xml file or their us regional.xml file but the area I'm going to focus on in the next couple slides is the second most common error bucket which is high validation errors I broke out the high validation errors into the top 10 error codes that we see there are more than just these uh that are bucketed within other high errors but these are the top 10 error

codes that result in high validation errors and rejections roughly 50 of the high validation errors come from two validation codes around Leaf elements so it's 46 percent of the high errors and the first code is validation 1306. which means that there is No Leaf element found for a file submitted so a file has been included in your ectd submission and there is no Leaf referencing that

file within the backbone file submitted the second code is validation 1323. which is the opposite situation where there is a leaf element in one of your backbone files but there is no file uh that it is referencing the file cannot be found that it is supposed to be referencing the next set of Errors have to do with submission types and this is 18 of the high

validation codes so validation 2034 is saying that the submission type is invalid for the application type so this would be a situation where in your ectd metadata you have indicated your application is an NDA but your submission type is an IND safety report that submission type is invalid for submitting to an NDA and similarly validation 2022 is saying that um the submission subtype in that backbone

file is invalid for the submission type so the chart of valid application types with their corresponding submission types and submission subtypes can all be found in the module 1 specification on our ectd website and the final set of high validation errors I'm going to focus on have to do with study data so these are 10 of our high validation error codes and the first one is

1734. this is this validation is looking for a data set named ts.xpt so the trial summary data set to have information on the study start date um within your submitted studies in a subset of the module 4 and module 5. within the time period that we are looking at code 1734 at least for some of this time also included checking for the study ID match between

the study tagging file and the study ID in the trial summary file however as of mid-march of 2023 So within the time period that this data is pulling from that was shifted to its own medium level validation code of 1738 so 1734 is looking for that study start date within the trial summary file still and then code 1789 is also part of these top 10 high

errors that we see in 1789 is looking for um a file submitted within a module 4 module 5 section to be referenced within a study tagging file and the study tagging files tell the viewer what files are part of a study so it can group them all together underneath their appropriate study ID and study title foreign challenge question so most ectd submission failures are due to

a a duplicate sequence number B and ectd validation error see a missing backbone file or d a single file submission and the correct answer is a a duplicate sequence number question number two the majority of high validation errors are due to a a missing ts.xpt file B an invalid submission type or subtype C Leaf elements and files are missing and not referencing each other or D

data is not referenced in an stf and the correct answer is C there are Leaf elements not referencing files and files not being referenced by Leaf elements so the final part of my presentation I wanted to get into some of the common questions that the electronic submissions team receives about ectd submissions to give some resources and some references if you should have similar questions uh where

you might look for the answers or who you can reach out to about these questions so I'm going to cover where do I place content within the ectd how do I cross-reference to another application what are our recommended file formats do I need a digital signature and what file tags should be used so the first question where do I place content the main resource to help

you answer this question is the document of the comprehensive table of contents headings in hierarchy there's a screenshot of it here this is a document available on our FDA ectd webpage and it lists out the standardized headings that are available to place documents and files within your ectd submission if you have further questions on this we recommend looking at the ich organization document that the headings

and hierarchy document is based off of and of course you can reach out to your FDA regulatory project manager and the electronics submissions help team the second question how do I cross-reference another ectv application in our backbone specification for my module 1 document we have a section that talks about how to cross-reference a document submitted to another ectv formatted application so you can take a look

at this that document is linked here or if you have further questions you can email esub file formats are expected so the recommendations for file formats are in our file format type specification so all of the documents broken down by type of file that they would apply to and where they are recommended to be placed are in the specification but of course if you have questions

about a particular file format you can reach out to your RPM or email ESOP so do I need a digital signature on my 1571 or 356h form there's information available about digital or electronic signatures on the FDA webpage found here and that gives you information about submitting a flattened digital signature a scan signature and what is acceptable or of course if you have a specific question

uh you can reach out to esap and finally what file tag should I use so this is specific to study data files but you can find more information about study tagging files and the file tags in our specification there is also information about specific file tags and when they should be used in the study data technical conformance guide the full list of acceptable file tags is

found in the valid values.xml file and there's a snapshot of it here and then of course if you have questions about a specific file and file tag you can email ESOP so our final challenge question where can I find recommended file formats in the comprehensive table of contents of headings and hierarchies in these specifications for file format types using ectd specifications in the ectd technical conformance

guide or D the ectd backbone file specification for module 1. the correct answer is B the file format type specification so in summary if you have questions or want to look for announcements updates and the specifications please check out our FDA ectd webpage linked here and keep in mind when you're putting together your ectv submission next the most common mistake we see that results in a

rejection is the use of a duplicate sequence number so here are some resources that are available to you that you may find helpful and if you have any questions after this presentation please reach out to the electronic submissions team for Cedar at esub fda.hhs.gov and thank you thank you all for the great presentations for our attendees as a reminder if you haven't had a chance to

enter your questions into the Q a chat pod please do so now we'll answer as many questions as time allows looks like we have some questions already coming in in the first group of questions will be addressed to Jessica Bernhardt and here is the first question for Miss Bernard how does the ESG next gen change the way Partners use it that's a great question so right

now the ESG next gen is in the proof of concept phase so we're still working out all the technical details we will um as development continuous we will keep in touch with industry partners and advise of the changes that are coming and provide ample notice industry will be involved in all uat testing so they'll have an opportunity to test everything out make sure everything is working

prior to us releasing ESG next gen thank you for responding to that question we've got a few more questions for for Miss Bernhardt and here is the next question are there any plans of including the referrals payment and the FDA OAA database into the ESG database at this time no there are no plans to include those in the ESG database thank you for responding to that

question we've got just a couple more questions from us Bernhardt and here's the next question when will the ESG next-gen be available to Industry the SG next gen will be available to Industry in fy25 and we will be communicating uh as the date gets closer specific dates and times of when the release will take place but we are targeting fy25 at this point thank you for

responding to that question we have one more question for Miss Bernhardt and here is the question what will happen to the current ESG when ESG next gen is released uh we will sunset and retire in the Legacy ESG once all Industries transferred to ESG next gen that sun setting will take place thank you for responding to that group of questions moving on to our next panelists

we've got a few questions that came in for Jonathan Resnick he and here's the first question for Mr Resnick can ectd 4.0 be used for all submission types including cdrh submissions thank you Ray uh you know this is a good question um So currently Cedar and sieber are working together on the ectd 4.0 implementation so the submission types that one could use under eccd 4.0 is

or for the submissions to those two centers so we're talking about the ndas the andas the Las inds drug Master files you can even you know send it an eua for example as well but in general it's submissions that are going to Cedar and sieber only at this time thank you thank you for responding to that question we've got a couple more questions from Mr Resnick

and here's the next question how do you create group under Section 3.2.p.7 so you know another really good question I definitely recommend um that people take a look at the ich website at the ectd 4.0 orientation materials there's two uh PowerPoint slide decks there available that help describe some of these things but in general right for this for this question how do you create a group

underneath the lowest level other ectd heading and you do that with keywords so um there is a keyword that you can use for group title that you that you enter now exactly how this will work from a user perspective that depends on the ectd tool vendor and how they implement the user interface in their in their publishing program but they'll be following a set of harmonized

standards for ectd 4.0 so I guess long story short I really recommend you check with your ectd tool vendor that's providing the 4.0 functionality to ask them a specific question like this one thank you thank you for answering that question got a couple more questions for Mr Resnick and here's the next question in this new system when filing a bla will you be able to reference

documents previously submitted to an IND without resubmitting yeah another good another good question it's good to good to see that people are really focused in on what we're talking about with our presentations here so um you know with document reuse right what it enables you to do is when you submit a file you are establishing a document ID with that file and underneath that document ID

it has the path to the file it has the document title that would be used with that file whenever you reference the document ID so if you were to reuse that document ID and you can do that across applications what's going to be displayed to the reviewer is that document title that you set up that initial time when referencing the file the first time so if

you're just reusing a file if you had submitted a particular file under the IND and now you're coming along down the road and you're submitting the NDA and absolutely nothing about that file has changed including the document title that you want displayed under your submission to the NDA then you could use that document reference functionality so you don't have to actually you know include the file

the physical file again in the in the sequence folder thank you thank you for responding to that question we have one more question that just came in for Mr Resnick and it's the following has there been any discussion at the agency to require ectd format for research inds in the future so um as far as I know no I haven't heard about any discussion and a

little background for the rest of the audience in the ectd guidance as we call it the 745a electronic submission guidance for the drug applications to to Cedar and sieber currently there is an exemption for what's called non-commercial inds which covers the research IND so those don't have to be submitted in ectd format although we very much encourage you to do so it certainly helps us when

those research inds come in ectd format but as far as I think what this person is is getting at here is is there a change in the works with our guidance where we're no longer going to offer that exemption um no I'm not I'm not aware of any any changes coming down the road for that thank you it was a good question though thank you for

responding to that group of questions moving on to our next panelist we've got a few questions that came in for Heather Crandall and here is the first question from Miss Crandall is FDA form 3938 effective yeah that's a good question um so form 3938 is available to be filled out and used on the FDA forms web page um even though it is as you um as

the questioner pointed out it's not under uh the form section in the table of contents of headings and hierarchies there is a a code for it in the form attribute file within our FDA specifications so if you assign it the proper code then that would be submitted under Section 1.1 thank you for responding to that question I have a couple more questions from Miss Crandall and

here's the next question if a drug application is transferred to another entity how can it come how can we confirm with the agency the last sequence that was submitted so we recommend when an application is transferred that the full history of the application be transferred as well but if you have any questions about what the agency has received about an application that you own you can

reach out to the esub team for cedar or sieber has their help desk at esub prep and they can help you with that thank you for responding to that question we do have one more question for Miss Crandall and here is the question should a TS dot xpt be submitted with every submission which includes an stf or just the first time the stf is submitted yeah

thanks Ray this is a really good question um so a ts.xpt a trial summary file should be submitted with every study um and of course every study should be referenced within a study tagging um dot XML file so you only need to submit and um another TS trial summary file for that study if you need to make updates to the trial summary file so once you've

submitted it um then it is part of your study and you only need to submit a new one if there are updates to be made um you know in accordance with the cdisc standards thank you for responding to that question we've only got a couple minutes left we're going to try to get one more question in and we had a question just came in for Jessica

Bernhardt and here is the question how will industry receive communication about the transition to ESG next gen that's a great question um so the ESG next the ESG site will have a link to ESG NextGen for information as it becomes available we'll be posting it there we also be providing updates at the quarterly padufa meetings uh we will have meetings with industry Partners as well to

provide that information and we will communicate uat testing as well that industry is encouraged to participate in foreign thank you for responding to that question and that's all the time we have for questions in this panel another huge thank you to our presenters for answering numerous questions that came in we'll now enter our break until 2 30 p.m eastern time enjoy your break