This article discusses the growing requirement by health agencies for electronic Common Technical Document (eCTD) submissions rather than paper applications and explores how this move can be beneficial for organizations.
Around the world, the electronic Common Technical Document (eCTD) is becoming the mandated submission format for drug applications. The US Food and Drug Administration (FDA), the European Medical Agency (EMA), Health Canada and Swissmedic as well as many other health agencies are accepting eCTD as a standard.1-4 The move away from paper is not only environmentally important (saving many trees in the process), but also facilitates the submission review for both health authorities and sponsors. Closer to home, the eCTD format negates the need for flipping pages in a binder and provides the ability to navigate XML elements and PDFs via bookmarks and hyperlinks, automatically focusing the agency reviewer right to the point of the submission. Transitioning to this move forward and leveraging the benefits of eCTD, sponsors need the correct tools, a strong process and a knowledgeable team.
The Correct Tools
The correct tools – including templates, validators and eCTD builders – are critical to ensuring success within regulatory operations. The technological advancements in eCTD are only just the beginning. One may expect additional improvements in the technology pushing medical advancements and data tracking forward while eCTD and the creation of submission filings will continue to catch up. Submission content will take precedent in terms of an acceptance or rejection from a health authority, so failing to adhere to validation specifications for eCTD and submission documents will impede the review process. Focusing on established technology, such as authoring templates, can avoid minor issues and provide standardization in formatting and styling. Templates also allow your subject matter experts to focus on their area of expertise without having to become word document experts. A submission that is put together well creates an easy review. If the content is easy to read and the navigational elements are applied correctly, questions and concerns from the agency will be minimized. A team member new to eCTD should leverage the technology of templates to speed up document formatting. To ensure authors include all the relevant information, good templates will include an outline or baseline with references to the appropriate guidance documents. The global migration to eCTD is coming.
As global health authorities migrate toward eCTD, sponsors able to establish robust processes and technology can harness the power of eCTD. Centralizing and harmonizing Standard Operating Policies (SOPs)/policies can ease filings for all sponsors, whether they are submitting too many regions with a high number of dossiers or are organizations with a smaller handful of submissions each month. Remember, health authorities are inching closer to eCTD 4, whose different regional specifications can make filing to multiple countries a daunting task.5 Tracking regulatory requirements and planning for the differences prior to submission "crunch time" can enable the sponsor to translate that effort into eCTD success. For example, understanding that Swissmedic has strict and specific file-naming conventions can help shape the file naming conventions of your MAA to other regions, making cloning files much smoother.6 Another example is planning an end-strategy for references. Often, removing files to accommodate global submissions can break links. For example, consider patient Case Report Forms (CRFs) – they are needed for an FDA New Drug Application (NDA), but these are files that should be removed before submitting to other regions, like Health Canada or the EMA.7-9
While many organizations may focus on the original application, it is just as important to have a plan and the correct tools to immediately transition to lifecycle maintenance of an application. Ensuring plans are in place to maintain the lifecycle of documents and studies, in addition to maintaining Structured Product Labeling (SPL), translations for global submissions, safety events and investigators, is fundamental to the success of maintaining regulatory applications with a variety of health authorities. Ensuring you have the proper tools and trained staff in place could help alleviate tracking issues, ensure smooth processing for eCTD and make for easier maintenance of applications. Managing the planned submissions, like Day 120 and 180 responses, against the 'surprises,' can be challenging. However, having a process in place to tackle the maintenance of the portfolio can lead to success.
Benefitting from eCTD
Companies often need to balance several submissions following the initial filing: agency questions, safety reports, new protocols, more investigators – the list of submissions goes on and on. Often, the planning and strategy going into the first submission does not "trickle down" into these maintenance submissions. As a result, companies may scramble to respond, pulling their medical writers into a room, rushing the word documents to their formatters, then calling upon their regulatory team to ensure timely delivery. Companies use Excel sheets, memory and other methods to track the lifecycles of their documents. Lifecycle maintenance can run seamlessly or it can cause significant burden for sponsors. Too often, it is a "roller coaster" with peaks of high and low activity. Ensuring planning and consideration into these submission types happen up-front and can help smooth out processing kinks down the line. As FDA and other health authorities move closer to consistent formats for submission and evolve submission practices for a more standardized approach, it is (as always) an exciting time to be in regulatory operations.
Records and Information Management (RIM) is another "hot-button" topic in industry, one that impacts many lines of business. Often, regulatory teams assume their IT teams are covering implementation and feel they do not need to worry about reviewing or learning technology until it is a reality. Moreover, some sponsors do not feel a need to make changes in their data collection practices until there is an agency requirement for the data. Involving all lines of business and creating standards in the early stages of development allows companies to quickly react to ever-changing industry recommendations and requirements. Technology should not be feared; its power should be harnessed to better strategize submissions and quickly respond to agency requests and changing data standards.
Having the right team in place will help organizations rise to the challenge presented by evolving submission standards. Even collecting internal metrics on quality and submission processing time can help speed up submissions allow regulatory teams to identify areas or improvement or areas that could be streamlined. A team that can define a process around agency specification updates, work through tool implementation and efficiently process eCTD submissions typically give the agency more time to review a high-quality dossier. Creating processes and defining roles within a team structure the submission process and create a smooth sequence.
The emergence of eCTD has created many efficiencies in submission filings. Among them are not having to worry about postage, deliveries, binders and paper cuts. It is true eCTD can make life a lot easier for many pharmaceutical companies and agencies when data standardization and tracking allows sponsors easier access to their own data, creating faster analysis and quicker timelines for agency responses. However, there is still room to grow and efficiencies to be gained. With eCTD4 around the corner, harmonization from the International Council for Harmonization (ICH) and non-ICH members would allow sponsors to file faster and with clearer understanding and expectations. The result would not only be significate cost savings, but patients could be receiving their critical medications faster.
- Electronic Common Technical Document (eCTD). FDA website. https://www.fda.gov/ectd. Accessed 20 March 2018.
- The eCTD (electronic Common Technical Document). EMA website. http://esubmission.ema.europa.eu/ectd/. Accessed 20 March 2018.
- Updated: Notice - Mandatory use of the electronic Common Technical Document (eCTD) Format. Health Canada website. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/activities/announcements/notice-mandatory-use-electronic-common-technical-document-ectd-format.html. Accessed 20 March 2018.
- eCTD. Swissmedic website. https://www.swissmedic.ch/swissmedic/en/home/services/submissions/ectd.html. Accessed 20 March 2018.
- Electronic Common Technical Document (eCTD) Version 4. FDA website. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm309911.htm. Accessed 20 March 2018.
- Op cit 4.
- Op cit 1.
- eCTD - Common Technical Document (CTD) - Guidance Documents - Applications and Submissions - Drugs Products. Health Canada website. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/ectd.html. Accessed 20 March 2018.
- Op cit 2.
About the Authors
Jillian Carinci is an associate director, regulatory operations for Accenture Accelerated R&D services. Carinci partners with sponsors to manage numerous regulatory submission projects. She ensures compliance with global regulatory requirements, delivering within scope, on time and with the highest quality. She holds an MS in regulatory affairs and quality assurance from Temple University. She can be contacted at firstname.lastname@example.org.
Sandra Krogulski is a submission manager in Accenture's global regulatory operations team. In this role, she supports clients through lifecycle maintenance through training, overseeing actual submissions and consulting. She oversees the management of numerous regulatory submissions ensuring projects follow global regulatory requirements and meeting submission timelines. She can be contacted at email@example.com.
Cite as: Carinci, J. and Krogulski, S. "Regulatory Operations: Leveraging eCTD Benefits." Regulatory Focus. March 2018. Regulatory Affairs Professionals Society.