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Webinar Recap: Intro to eCTD

posted by jwatto @ 8:15 PM
Thursday, March 1, 2012

GlobalSubmit recently held an educational webinar entitled Intro to eCTD.

Under the draft PDFUA V bill, electronic submissions will be mandated in Q2 2015. Given this recent news, GlobalSubmit offered this free webinar to provide a comprehensive overview of the eCTD, including everything from basics and terminology to rules and regional standards to submission output and solutions, and more. If you were able to join us, we hope that you now feel better prepared to make the switch from paper to eCTD.

We received several great questions during the webinar, but unfortunately did not have time to address all of them. Please find these questions and answers below.

Q: If a company is submitting its first eCTD, is it necessary that they first get some dummy file validated or checked by the USFDA and then submit the real dossier?
A: No. That said, if you are creating the submission by hand, then it would be a good idea to submit some dummy files first.

Q: What would you consider to be the best publishing and validation software?
A: We certainly feel that we have the best offering for publishing, validation, and review. Our VALIDATE and REVIEW products are the very tools used by the FDA, and so the need for quality is quite clear. PUBLISH has been built to be simple, intuitive, and easy to use, and is built on our solid foundation of VALIDATE and REVIEW

Q: Where can I get a copy of the ICH guidelines?
A: The current ICH eCTD specification, V3.2.2, can be found on the ICH website.

Q: How should SAE safety reports be submitted in eCTD and to which module are they submitted?A: You should submit all serious adverse events through the FDA electronic submission gateway within the requisite time, preferably in ICSR format.

Q: What is the eCTD format for submitting Annual Report? Is there any guidance?A: The FDA provides a submission type for submitting Annual Reports and an annual report is formatted in eCTD like all other submission types.

Q: When will the FDA no longer accept any submission in paper?A: The FDA currently plans to mandate eCTD submissions in 2015.

Q: In MODULE, 5 it is shown as ISS ISE, what exactly does it mean?A: ISS and ISE stand for Integrated Summary of Safety and Integrated Summary of Efficacy, respectively. They would generally follow the same format as a clinical study and would be submitted in.

Q: What is the file type we use for checksum?
A: Checksums are generally stored as an attribute in the backbone and regional XML files, with the exception of the checksum for the backbone itself, which will be a text file in the root directory of the submission at the same level as the backbone XML file.MD5 is the checksum attribute that is used.

Q: Do we have any standard template for NDA and IND submissions to FDA?A: The FDA has Application Types for NDAs and INDs, with guidelines for each type.

Q: Can we submit both non clinical (module 4) and clinical trials (module 5) at once? If so, in which application type can we submit?
A: Yes, both clinical and non-clinical data can be submitted in the same sequence. The application type would be unrelated to this, and instead would be based on what type of application you intend to submit (e.g. NDA, ANDA, IND, etc.). The Submission Type would also depend on what stage of the application you are in, and what you’re submitting for (i.e. Original Application if you are on your initial sequence, Amendment if you are adding data to an existing sequence, or a Supplement if you are adding additional parameters to your application.

Q: In the study tagging file specification we go through new/append/replace/delete. In what circumstances is it shown and how it is used? It is mentioned as same name as the study, I just want to know whether it is study id or study title?
A: The study Id is the key identifier of the study tagging file. The operation (i.e. new, append, replace,and delete) will be located in the index.xml not the study tagging file.

Q: What is the difference between the publisher and author of application?
A: An author is a person who is actually writing the documents themselves, compiling the document in Word or a similar tool. A publisher is a person who takes these finished documents and places them correctly in the structure of the eCTD and generates the XML and associated required files.

Q: When lifecycling Annual Reports section 1.13, should these be done as NEW every reporting period or should a new reporting period REPLACE the previous year’s reporting period?
A: No. Annual Reports would be something you would want to persist. The best way to think of this is that when you are replacing a file, you are saying that the information and content of that document are no longer relevant and you are submitting a replacement for that data. Annual Reports represent cyclically collected data and would be something you would want to retain throughout the progression of your application.

Q: What are the eCTD requirement dates for: CDRH, CBER, EU?A: The FDA currently plans to mandate eCTD submissions in 2015, while the EMA and CDRH has not announced any plans to mandate electronic submissions.

Q: How do you select the right electronic publishing software for eCTD?
A: We believe you should select publish software that eases your process, allows for greater productivity, and produces quality output.

Q: Some word files are also used in the submission, how we will ensure its integrity after submission?A: The integrity of the data can be checked at any later time by recomputing the checksum and comparing it with the stored one checksum in the submission. If the checksums match, the data is not altered.

Thank you again to all of those who participated in the webinar. For your reference, the webinar slides are now available for download here.

We look forward to seeing you at future events.

Free Webinar: Intro to eCTD

posted by jwatto @ 8:37 PM
Thursday, February 16, 2012

As you may already know, under the draft PDFUA V bill, electronic submissions will be mandated in Q2 2015. Are you prepared?

Navigating eCTD regulations and guidelines is easier said than done. Same goes for assembling and reviewing applications. Your application must be technically sound and structured correctly. Most importantly, it has to be ready for review by the agency upon submission.

GlobalSubmit Inc., a leading developer of eCTD review and validation software for FDA use, wants you to be prepared for the trials and tribulations that occur while creating NDAs, INDs and related amendments.

That’s why GlobalSubmit is offering a free educational webinar Intro to eCTD on Wednesday, February 29th at 12:00pm EST.

During this discussion, we will provide a comprehensive overview of the eCTD, including everything from basics and terminology to rules and regional standards to submission output and solutions, and more. By the end of this session, you should feel better prepared to make the switch from paper to eCTD.

Top 3 Learning Objectives:
1. Understand eCTD terminology and rules
2. Realize the challenges of eCTD and solutions to address those challenges
3. Learn how to assemble a basic eCTD application

For more information and to register: GlobalSubmit Events

Webinar Recap: Understanding the New FDA Validation Criteria

posted by Jason Rock @ 4:43 PM
Thursday, October 20, 2011

GlobalSubmit recently held an educational webinar on the Understanding the New FDA Validation Criteria.
The purpose of the webinar was to provide an overview of the US FDA’s draft version of the new “Specification for eCTD Validation Criteria,” which outlines many of the new error conditions that the FDA will be checking for in the next version of its validation software. During the webinar, facilitated by Daniel Clark, Sr. Manager, Strategic Regulatory Innovation, Novo Nordisk Inc., GlobalSubmit’s CTO Jason Rock discussed the more important changes to the criteria, when the new validation criteria will go into effect, best practices for ensuring your application is free of technical errors, and more.

Q: FDA forms have PDF security. Is this a problem in validation, and if so, how should it be dealt with?
 A: Any file in the forms sections will not be validated again PDF checks; for example, PDF security. Forms have special validation; for example, ensuring that the application number is correct. 
 Q: Some ICH regions have provided free validation tools as a collaborative effort between agency and vendor. Does FDA/GlobalSubmit have any plans to provide a free validation tool to industry?
 A: Currently neither GlobalSubmit nor the FDA has plans to provide free validation tools to the industry.
 Q: When will the new FDA Validation criteria version 2.0 be implemented at the agency? The FDA website says November 2011. Is this still the timeframe?
 A: No, the tentative date is February 2012.
Q: How do we get a list of validation errors from the FDA from each of our submissions?
 A: You should request the validation errors from your Project Manager.
Q: We have numerous CBER multi-BLAs (both with multiple products in a single application number), and numerous applications where we submit a single submission impacting all the applications.  Can you provide more details on the multi-product aspects of CBER product submissions?  Is it for multiple products in one application, or submissions across multiple applications?
A: Trans BLAs, a CBER program, can target multiple products. CDER does not have such a program. The FDA has provided a draft specification that will allow CDER and CBER to accept one submission to multiple applications.
Q: If during the lifecycle we accumulate errors, is there any “baseline” submission possible?
A: Unfortunately, no. eCTD does not have any mechanism to fix mistakes in attributes or clean up misplaced documents.
Q: For the validation criteria “STF doc-content title and leaf title must match”, what elements is this criterion looking for? Is it looking for the Name of the Study Report folder to match the value of the Full Report Title, instead of the Report Number?
 A: This error looks for the Leaf’s Title and the Study Tagging File Title. These two titles must be the same.
Q: Is there any real benefit to the sponsor in using fillable forms and is there a timeline for fillable forms to be mandated by the FDA?
 A: The benefit to the sponsor is that the submission will be routed to the reviewer quicker.
 Q: We’ve never had any issues to date re: our forms.
A: The FDA has not been systematically rejected submission based on the application form. The FDA have announced that rejections can be expected based on the form not being fillable when the implement the new validation criteria.
Q:  About the fillable forms, if the chemical name is truncated in the form, does that affect the review process? Should we send a scanned copy with the full name?
A:  This does not have an effect on the review process.
Q:  Have complete response letters been issued for electronic submission errors, or just based on submission content?
A:  Complete response should be for scientific reasons. If there are technical issues in your submission, finding content might be difficult. This can lead to a complete response.
Q:  If fillable forms are not mandated, then how can it be a ‘high’ severity in the validation criteria? The concern is once FDA moves to an automated technical validation, the submission would be rejected.
A:  The validation errors are posted by the FDA. If any criteria is considered troublesome, it would be best to bring that to the FDA’s attention.
Q:  This question is in regards to the validation error triggered by the eCTD application number not matching the folder name.  It is my understanding that the FDA includes a three letter prefix in their eCTD folder names, for example ind777777. Will this prefix trigger a validation error?
A: The validation checks the last 6 characters in the application folder.
Q: Does submitting a fillable form without electronic signature and  a scanned form with signature still leverage advantages of using fillable forms?
A: Yes, The system looks for the fillable form.  
Q: Currently, the Annual Report form will not allow for a leading 0, but instead changes the application number to include a comma. Does FDA plan to update this form, or is the best practice now to use a 356h fillable form and select the “annual report” option?
A: We will provide this answer on this blog shortly.
Q: Are the new validation criteria linked to the new planned version of the FDA Module 1? Is there a draft specification for the new US M1 available?
A: The validation criteria is NOT linked to new M1. I will follow up with a blog post on where the new M1 draft specification is posted. 
Thank you again to all of those who participated in the webinar. For your reference, the webinar slides are now available for download here.
We look forward to seeing you at future events.

Regulatory Submissions Made Easy, Part II

posted by GuestPost @ 3:46 PM
Thursday, October 6, 2011

Today’s entry was provided by Matthew J. Neal, Director of Knowledge Management & Innovation in Global Regulatory Affairs & Safety at Amgen, Inc. in Thousand Oaks, CA.  He led the Regulatory Operations group there for seven years and managed submissions for GSK in Philadelphia, PA for 7 years before that.

So, last time, I told you about assembling a team of believers.  Those believers are the “customers” you serve on both sides of the fence in regulatory operations.  Not only are you getting documents from all the different members of the extended filing team (Regulatory, CMC, Pre-Clinical, etc.), but you’re then serving a different master in your health authority.  If you need to review, please read the previous post.

This time, I want to focus on getting the most out of the tools and process which drives your efficiency.  Getting to the heart of the matter, operations functions of all shapes and sizes exist – and so do solutions to meet those needs.  While it is true that you can create a valid eCTD with some very simple and inexpensive software tools, there is no way I would want to do it by those means.

You could certainly PDF all your documents one at a time from MS Word and then code the XML in notepad.  But, using the PDFMaker plug-in for word will automatically link your TOCs and cross-references for you and any of the software packages out there made for eCTD will do all of your XML for you.  Tools that help you do that work have many different price points, enterprise license options, hosted solutions, etc.  Just Google “eCTD software solutions” and you’ll see what I mean.

The point is, you do not need a million dollar, validated system to build your eCTD’s.  But, eCTD lifecycle is a serious commitment, so you have to be prepared to have an ongoing relationship with those tools.  The maintenance submissions far outnumber the original filing, so getting to know and trust the software companies that make those tools will be crucial to your success.  There are point solutions, desktop solutions, web-based systems, hosted systems – the choices are many and varied.

Certainly, outsourcing is trending these days.  There are some extremely capable partners with extensive eCTD experience out there.  Do your homework, ask colleagues at industry meetings, go to message boards online.  No software is perfect, and no vendors are perfect…but, some are better than others.  This is a long term relationship you’re entering into, so do not take it lightly.

Be sure that the tools you select maximize your talent pool at your disposal.  There are very few MS Word experts out there – so if you have one, maximize that potential and give the authors a break.  Medical Writers in Pharma and Biotech do not need to be MS Word experts, but many operations groups do try to force them to be just that.  They should be experts on science and data.  Keep that in mind as you start to pull your submissions together.

In summary, much like building the best team, choosing the right tools that fit your needs is a very strategic and important decision.  Look at all your options and choose wisely.  Consider budget, long-term implications, and what makes the most sense for your situation before jumping into anything this big and in order to maximize the efficiency of electronic submissions.

Regulatory Submissions Made Easy, Part I

posted by GuestPost @ 8:45 AM
Wednesday, August 17, 2011

Today’s entry was provided by Matthew J. Neal, Director of Knowledge Management & Innovation in Global Regulatory Affairs & Safety at Amgen, Inc. in Thousand Oaks, CA.  He led the Regulatory Operations group there for seven years and managed submissions for GSK in Philadelphia, PA for 7 years before that.

Did that title catch you?  Did you think I was going to reveal the secrets of pulling together millions of pages of data, reports, and information into a cohesive, user-friendly, searchable, and (one could argue) beautiful unit commonly called the eCTD?  Well, sorry.  There is no way to do it easily.  In the upcoming several part series, I hope to take you through some of the things that I think will lead to a better experience navigating the unbelievable complexity that surrounds regulatory submissions.  There’s a lot of science in there – good thing the publishers don’t have to actually read it.

Hopefully some of these tips and comments will help you not only make your submissions better, but also give you some idea of how to explain your job at parties. 

First order of business, make sure that the extended team (by this, I mean everyone – the Regulatory liaison, the CMC rep, the pre-clinical teams, the regulatory writers, the senior leaders that chose the submission date randomly 2-3 years ago) understands that you will be the last one to touch their stuff and without you, the submission does not go to the agency.  Also, make sure they understand that rushing it out the door may lead to it not getting filed at all.  Do not be afraid to stand your ground, but choose your battles wisely.  You may only get away with one threat per filing – so make sure it’s real.  You are the gatekeeper.  With great power comes great responsibility.

For example, cast your mind to the mid-1990’s when companies were still submitting paper in quintuplicate with different colored binders and hand-stamping page numbers.  One company, in a rush to get a CD-Rom full of datasets out to meet a deadline on a submission, sent instead a CD-Rom of classical music to the agency instead of data.  Needless to say, the agency, while they may have enjoyed the relaxing symphony selections, was unable to review the data.  I digress…

Second order of business (and probably the most important), surround yourself with people who know what they’re doing, know the software tools at an expert level, and are extremely lazy.  Yes, I said lazy.  Do you know why?  Efficiency born out of laziness is one of the most powerful drivers of innovation and automation.  Why would I want to draw thousands of links in a Clinical Study Report by hand if I could write a linking script with an Acrobat plug-in that will do ninety percent of the linking in the background for me while I finish up the formatting on other documents?  Or better yet, allow the linking script to run overnight so I can go home and be with my family instead of burning the midnight oil.  The bottom line – whenever possible, work smart not hard (maybe lazy was too strong).

There’s a saying in carpentry – measure twice, cut once.  The same applies to regulatory submissions.  QC and make sure everything works before you send it out.  Spend the time and care to be sure that what you’ve spent so much time preparing is right.  Believe me, the one link you forgot to check is the only one the document control room will click on before they accept your submission. 

More to come in part two


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