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Cloud Security: Secure Enough for the U.S. Department of Defense
posted by Jason Rock @ 9:32 AM
Tuesday, May 8, 2012
We have all heard of the high profile security breaches at the U.S. Department of Defense in the last few years — from state sponsored hackers stealing nearly 25,000 files related to new weapon systems to an army soldier providing secret documents to WikiLeaks, among others.
The fact that those breaches occurred on supposedly secure systems that DOD and its industry partners have operated for years shows just how challenging cyber security can be, even under the best of circumstances.
Speaking before the House of Representatives, Army General Keith Alexander, commander of U.S. Cyber Command and Director of the National Security Agency, said cloud computing provides the best way to secure DOD networks. Interestingly, he did not stress cloud computing’s ability to cut costs; rather, he emphasized its security benefits.
His statements may be surprising, but they echo an ongoing transition in public-sector thinking about cloud computing. In the past year, the federal government has become increasingly supportive of the cloud, and has adopted cloud models for key agencies.
As Jesse Lipson pointed out in a recent Forbes article: “Most cloud computing companies are like experienced airline pilots. They are well trained, have backup systems and contingency plans in case they encounter an issue, and they have a full staff of professionals regularly checking and maintaining their service. Cloud software companies, knowing the implications of a crash on their business’ bottom line, invest significant resources into insuring that such a disaster never occurs. Cloud computing companies can invest far more resources in data backup and security than your business can.”
Compare this, for a moment, to the levels of protection that your company provides.
The cloud is also provided by new systems that were out of reach for most organizations in the past. A couple of months ago, Amazon released new security measures that can encrypt data when writing the file. Decryption happens automatically when data is retrieved. This adds yet another level of security to your data that did not exist before.
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GlobalSubmit kicked off its second quarter Lunchtime Webinar Series with a presentation for IND & Pre-IND Companies.
During this presentation, GlobalSubmit demonstrated how IND & Pre-IND companies use our tools to see the same views as the FDA; build their application as the FDA sees it;
cut days off the time it takes to quality check bookmarks and hyperlinks; improve communications both internally and with the Agency; improve efficiency and meet important deadlines; reduce risk of technical rejections; and more!
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: Is it possible to set user permissions to restrict some users from adding content?
A: Yes, you may set user permissions to restrict some users from adding content. In fact, GlobalSubmit provides two levels of access for publishing. One level, also referred to as the Publishing Administrator, has certain rights, such as being able to create and set titles for documents. The standard publishing level does not have the right to do that.
Q: Are different views available in REVIEW, e.g. cumulative and/or current views?
A: There are 5 different views in REVIEW. 1. LifeCycle View lets the user see any lifecycle operations that were done on the submission. 2. Current View shows users current files. 3. Regulatory Activity View groups submissions, also known as sequences, that are part of the same regulatory activity. 4. Sequence View shows all the sequences in your application. 5. Finally, Origin View is what you can use to modify the application when you need to delete or add content.
Q:Is the Validator included in this application, or is it separate?
A: In the small business package, all the four modules are bundled; VALIDATE, REVIEW, PUBLISH, and CROSSCHECK.
Q: Is the system built only for drug INDs, or can it also be used for IVD and medical device application?
A: Although the system is built for other types of applications, such as the NDA, IND, ANDA, BLA, etc., currently we do not support medical devices.
Q: Do you link to outside documents prior to building your submissions, or do you link after it has been built?
A: When using our software, you should link your documents once the submission has been built.
Q: How do you add a child node e.g. 3.2.P.5.4?
A: To add nodes, where it is allowed, all you would have to do is right-click on the section where you want to add the node. Once the context menu is displayed, you can select ‘New’ which will then give you the option to create a child node.
Thank you again to all of those who participated in the webinar. We hold these events regularly, so if you were unable to attend, please visit our Events Calendar to join a future demo.
We look forward to seeing you online!
In September, the FDA issued its Proposed PDUFA V Reauthorization Performance Goals and Procedures for Fiscal Years 2013 through 2017.
There are many proposed improvements related to the FDA review procedures, including a mandate of the eCTD. This mandate will start 24-months after publication of the corresponding final guidance for marketing applications and 36-months after publication of the final guidance for commercial INDs and amendments.
The final guidance will be released no later than 12 months from the close of a public consultation period on the draft guidance. The corresponding draft guidance will be issued by December 31, 2012 at the very latest. The initial guidance will reference eCTD version 3.2.2; however, the final guidance might refer to a different standard, namely RPS, if the FDA determines the new standard is more efficient and effective. The FDA also mentions that they “shall also accept submissions using the previous version for no less than twenty-four (24) months.”
Although many of the goals for priority and standard NDA and BLA review (including Class 1 and Class 2 resubmissions, efficacy supplements, and manufacturing supplements) remain the same as under PDUFA IV, the proposed PDUFA V agreement establishes a new review model that will apply to all New Molecular Entity (“NME”) NDAs and original BLAs received from October 1, 2012 through September 30, 2017, including applications that are resubmitted following a refuse-to-file action.
The new program includes a pre-submission meeting, a mid-cycle communication, and a late-cycle meeting at which the FDA review team and the applicant will discuss the status of the review of the application. At the pre-submission meeting, the FDA and the applicant will agree on the content of a complete application for the proposed indication(s), and the applicant may also reach agreement on submission of a limited number of application components.
Another important change is the treatment of “major amendments” to pending applications.
Under PDUFA IV (and FDA’s regulations at 21 C.F.R. § 314.60), “[a] major amendment to an original application, efficacy supplement, or resubmission of any of these applications, submitted within three months of a goal date, may extend the goal date by three months. A major amendment to a manufacturing supplement submitted within two months of the goal date extends the goal date by two months” (emphasis added). Under the proposed PDUFA V agreement, however, “[a] major amendment to an original application, efficacy supplement, or resubmission of any of these applications, submitted at any time during the review cycle, may extend the goal date by three months”, and “[a] major amendment to a manufacturing supplement submitted at any time during the review cycle may extend the goal date by two months.”
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? 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? 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? Q: What is the difference between the publisher and author of application? 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? 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? 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.
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.
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.
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.
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.
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.
A: We believe you should select publish software that eases your process, allows for greater productivity, and produces quality output.
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
Regulatory Submissions Made Easy, Part III
posted by GuestPost @ 12:41 PM
Wednesday, February 15, 2012
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.
Hey Everyone. It has been a few months since my last entry. I trust your holidays were enjoyable. Hopefully you didn’t think about work too much. That’s what this final chapter is going to focus on, actually – not thinking about work.
In the previous installments, I talked to you about the tools and teams to help you make regulatory submissions easy. But since I’m going to assume that since I left you alone there for a few months that you’ve already got that finished and we can move on to the most important part – becoming the laziest team in your organization. As you may recall, in Part One, I said “Efficiency born out of laziness is one of the most powerful drivers of innovation and automation.” The only way to get to the point where you are not thinking about work is when you know your team is a well-oiled machine that will not break down. You know you have the right tools, people, and process.
The biggest stress and source of difficulty, of course, is waiting for final documents. While this is a concern for every Regulatory Operations team, in the grand scheme, you have no real control over this common phenomenon. So, the best you can do is be ready to react and have confidence in your team to work quickly and efficiently when the documents finally come through. The good news is, while you’re waiting – you can relax (more not working) knowing how well your Operations machine works.
I would like to close this series with a story that will give you hope (I hope). When I first joined the wacky world of Regulatory Operations a long, long, time ago, a Marketing Application event was monumental and scary. The sounds coming from the assembly area were loud and striking. Hole punchers, printers, and page number stampers echoed through the building for weeks leading up to the submission date. Multi-colored binders flew up in the air, paper cuts were rampant, and the little rubber fingers for checking pages stayed on in all situations. As the day really approached, the sound of boxes being assembled and tape guns furiously sealing up a mountain of cardboard replaced the earlier mayhem. Tape guns was a great sound to hear, until someone came running in with a late breaking change…then the ripping sound made everyone sad. Soon, a U-Haul was loaded with boxes and team photos were taken and the waiting began.
Several years later, as the lead publisher and I walked the fake DVD’s over to the Lead Regulatory Rep for a photo op (the submission was sent through the Electronic Regulatory Submissions Gateway, so there was nothing to photograph or hold) and there was calm. There was no noise. There was no mayhem. There was no U-Haul. There was no paper. We reminisced about the past and how much drama used to happen before electronic submissions. All that drama was now the press of a button. A 100% electronically QC’d, integrated package sent through the digital realm (almost) instantly. No trucks, no binders, no paper, no tape, no page stamper, no boxes. We didn’t miss it and you will not miss it either. I believe the remark was, “Oh, that’s it, huh?”. Yep, that’s it. The publishers were able to be lazy, relaxed, finished – and going home at 5:00. While we can’t always achieve the 5:00 thing – we should always aim for it. Life’s too short. Thanks for reading.
An innovative approach to fight viral pathogens has been discovered by researchers at the Massachusetts Institute of Technology (MIT). The new drug DRACO, an acronym for double-stranded RNA activated caspase oligomerizers, has the potential to fight many known viruses, including the common cold, flu, stomach viruses, polio, and many more. While the drug is still several years away from clinical trials, DRACO has seen early success in the laboratory. DRACO has demonstrated that it is nontoxic in 11 mammalian cell types, effective against 15 different viruses, and eradicates H1N1 in infected mice.
This groundbreaking treatment employs a novel approach to viral infection. While current therapies typically target a specific virus and often have undesirable side effects, DRACO covers a broad spectrum of viruses by targeting genetic material found only in infected cells. When a cell is infected, a virus reprograms the cell to make copies of the virus. While manufacturing new viruses, the cell creates double-stranded RNA (dsRNA) which is not normally found in healthy human and animal cells. DRACO is designed to enter cells that contain dsRNA and then deliver a message for the cell to self-destruct, a process called apoptosis. In doing so, cells that are infected are quickly destroyed and additional copies of the viruses cannot be made. Because DRACO is specifically designed to only enter cells with dsRNA, healthy cells are left alone.
Even though DRACO is still in the laboratory, the ingenuity of this novel approach to drug discovery is refreshing. As traditional drug discovery continues with its struggles, these types of groundbreaking ideas are critical to ensure new therapies are found in the future.
For more information, click here.
Mergers and Acquisitions, A Regulatory Operations Perspective – Part II
posted by GuestPost @ 7:49 AM
Wednesday, January 11, 2012
Today’s entry was provided by Rachel A. Wagner, LinkedIn Profile.
In Part 1 of this topic <hyperlink Part 1 blog>, I provided a framework for why companies out-license and in-license of products as well as the type of information that will be exchanged. In Part 2, I will discuss best practices, starategies, and the tools used during my experience.
MS Excel is a tool that I have found most reliable for developing the inventory listing. Excel can be used to inventory the documentation, export/import information to a database (in a tab delimited format), and then validate/verify the received inventory.
The spreadsheet will include such information as date of document/submission, submission number, document/submission type, description, and other data deemed valuable for the product history. Another suggestion is to keep an overall list of the products. This spreadsheet might include the product name and dosage, the type of submission (NDA, ANDA, IND, etc.), the status of the submission, the regulatory agency/division, etc.
Once the inventory is collected, inventoried, and ready for transfer, the next step is to find a good method for the interchange of the inventory. There are many good methods to choose from including eRooms, portable hard drives, CD/DVD, FTP/SFTP sites, and of course the legacy paper being shipped via courier.
Once the inventory of product documentation is received and verified electronic submissions must be quickly integrated into the corporation’s eCTD publishing tool. This can be challenging. I suggest utilizing the expertise of the vendor. Vendors know their software much better than most RegOps staff and can be quite useful in integrating the submissions quickly into the publishing system.
Hard copy documentation must be assessed for future use. A decision should be made to scan the documents or merely validate the inventory and store the documents. If the decision is made to scan the documents, do so in black and white to keep file size to a minimum (gray scale and color scanning usually results in a larger file size).
It is important, during the process of in/out-licensing, to include Information Technology staff in the process of collecting and receiving documents and data. Information Technology staff can be quite useful by ensuring the clean transfer and permanent storage of documents for out-licensing and smooth acceptance and storage of documents during in-licensing. Information Technology staff will ensure there is sufficient drive space and networks are not bogged down, important logistical requirements for the acceptance of a large inventory of documentation and data. Information Technology will also ensure that the security settings for folders are properly set.
Strategies for ensuring all of the above is done with little interference starts at the top. Executive management may consider creating a strategic plan for in/out-licensing and mergers and acquisitions. This strategic plan should include the technical aspects of such an undertaking. Such topics as systems to be used, network and security, and staff involvement (including when to involve staff) are important strategies to ensure success.
Additionally, it is recommended that RegOps and Information Technology collaborate to create a strategic plan for the necessary tasks they will have to perform during these activities. A full understanding of the corporate systems and processes is vital to the success of the integration and divesting of products. This information is important to ensuring the newly acquired information is quickly integrated into the corporate system and that information being sent during a divestiture is quickly gathered.
To ensure success a few high level recommendations are suggested:
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Ensure the current practices work whether they be methods for storage or publishing practices.
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Involve RegOps and IT early in the process to ensure quick and accurate collection of inventory.
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Be flexible and scalable not just in the technology but also in the utilization of staff and outside assistance.
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Use contractors, temps, and vendors when necessary.
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Integrate new staff quickly (6 months or less is a good practice).
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Understand and leverage the expertise and knowledge of staff, including newly acquired staff.
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Processes, tools, and management may change, be prepared to manage the transitions.
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Understand that there will be stressful times during the process. Recognize the signs of stress and handle them quickly.
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Remember that people are a corporation’s most valuable resource, keep them informed and let them know they are important to the success of the current undertaking.
Mergers and Acquisitions, A Regulatory Operations Perspective – Part I
posted by GuestPost @ 3:30 PM
Monday, December 19, 2011
Today’s entry was provided by Rachel A. Wagner – LinkedIn Profile
I had the great privilege of speaking at the DIA eCTD conference this past November. The subject of my talk was on the out-licensing and in-licensing of products. Many of you may have had to undertake these tasks in the recent past as this has become a frequent occurrence in our industry. This is the first entry of a two part post where I will share my experiences during the past year including the issues and lessons learned.
The purpose of out-licensing is to raise money for the corporation, or to divest a developed technology. During the out-licensing process it is necessary for the RegOps group to organize and transfer the information and documentation to the new company. This may include the submissions, labeling, correspondence, and other documentation for the product. Additionally a chronology of the product documents, whether that be hard copy, electronic, or both should be included as an “inventory” check.
In-licensing is accomplished to add new products to the corporate pipeline, and procure resources needed for final-stage development, clinical trials, manufacturing, and distribution of products. It should be noted that with any in-licensing there will be a large amount of incoming inventory (documentation) and there is normally an urgency to integrate and streamline the information being received. The documents must be added to the corporate network folders, the EDMS, the publishing system, or other storage methodologies. This must be done quickly and accurately.
The merger/acquisition of companies brings the same type of product on-boarding to a corporation along with the integration of staff and possibly the integration of divergent systems.
There are many tools and methods to make these challenges and opportunities less difficult. These tools will be used to transfer information, inventory documents, and validate the received inventory.
Transfer of Documents:
Transfer of documentation should be done in a logical structure. To this end it is important to create a folder structure that is logical to follow. One suggestion is to create a folder structure that includes such a format as:
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Product
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Country
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Submission Type
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Submissions
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Correspondence
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Labeling
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Data
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If the corporation does not already have a logical folder structure for storing the inventory of documents that are vital to a product portfolio, I suggest starting that procedure prior to in/out-licensing. Waiting until the critical moment to do this is time consuming and will delay the timeline for completion of the project.
In part two of this topic I will discuss best practices, strategies, and the tools used during my experience.
During the opening session of the recent DIA Electronic Submissions Conference in San Diego, Gary Gensinger, Deputy Director, Office of Business Informatics at CDER spoke about the not-too-distant future at the FDA when electronic submissions will become mandatory. Under the draft PDFUA V bill, electronic submissions will be mandated and Gary provided us a timeline for the implementation under the proposed mandate.
In December 2012, the FDA will release draft guidance for this new era, which, among other things, will require electronic submission. The draft guidance will be open to comment for a period of 6 months followed by the release of the final version. It will then be implemented 2 years after the final version, bringing us to mandated electronic submissions in Q2 2015.
There is another important take-away from this presentation. In the future, the FDA will use this same pattern for implementation of new requirements and guidance. We can expect when the FDA alters its requirements the following timeline will be used:
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Draft guidance will release for public comment
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Six-month comment period
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Revision and release of the final version
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Implementation of the changes 2 years later
With this pattern in place, the process of iterative improvement of FDA standards should be much more consistent going forward. For sponsors, this means greatly improved predictability which allows for greatly improved preparedness