Agnes Cwienczek- Director of Product Management, ArisGlobal.
After a considerable time in development, the eCTD 4.0 standard has finally materialized. With the details of the standard now in hand and timelines taking shape, pharmaceutical enterprises have a chance to alleviate the load of dossier preparation and simplify their submission procedures. ArisGlobal’s Agnes Cwienczek offers suggestions for actions that can deliver the benefits of consistent data management while ensuring compliance with the new standard when it becomes mandatory.
By as soon as 2026, regulatory bodies around the world will start to require compliance with the more recently finalized and published eCTD 4.0 dossier submissions standard(s) (details can be found on the ICH website). Up to then, compliance is largely voluntary across international markets, but between 2026 and 2029, the new requirements will start to be enforced. Unless they are properly geared up for the new requirements before then, pharma companies risk not being able to get new drugs authorized, or changes to existing drugs approved, in some major markets internationally.
Despite this very real-time pressure, there is still such a great focus on IDMP and associated data as the be-all and end-all of current shifts in regulatory requirements that the urgency around changes to dossier preparation, publishing, and submission is often being missed. This is a huge oversight, which could leave companies seriously unstuck.
The electronic Common Technical Document (eCTD), which allows for the electronic submission of the Common Technical Document (CTD) from pharma applicant to regulator, devised by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), is today widely accepted by markets including EU member states, the UK, Switzerland, the US, Canada, several countries across the Middle East and Asia Pacific, as well as Australia, and South Africa.
Plan for Consistent Vocabulary, Key Words, and Content Tagging
Although the updated expectations for electronic document submissions under eCTD 4.0 are based on a vision and approach that appear very similar to those for IDMP, and follow the Health Level Seven (HL7) range of global standards for the transfer of clinical and administrative health data between applications, compliance preparation is a separate tranche of work with little actual overlap with IDMP. In fact, it is this shared purpose yet diverse application that emphasizes the importance of pharma companies having their own overarching plan for consistent vocabularies, keywords, and content tagging. A plan that transcends (yet is compatible with) adherence to individual sets of regulatory standards.
The strategic aims of eCTD 4.0, compared to previous electronic submission specifications, include speeding up the submissions process and making this more flexible; improving exchanges with regulatory agencies; and making regional requirements and process harmonization more of a reality.
So what are some of those benefits?
eCTD 4.0 – Prioritize a Single Source of Truth
Firstly, eCTD 4.0 supports more streamlined submissions. Instead of dossiers being created hierarchically and strictly in terms of their structure (e.g., different folder levels with dependencies), these will now be generated dynamically using metadata, keywords, and document types which will define the document location with the Table of Contents.
This, and the ability to assign a unique identity to every document within a dossier, such as a clinical trial file, means that companies will no longer have to resubmit pre-approved content as part of new processes – e.g., new marketing authorization applications/updates, or dossiers for additional applications as long as the content is available already to the agency. In the future, they will be able to simply reference pre-submitted files as part of their new submissions by referencing those documents’ ID - allowing that already-known content to be called up from a regulatory agency’s repository in the new context. This ability to call into play previously submitted and already accepted source materials will save a lot of time and work on both sides.
Enhanced content lifecycle and metadata management will also pave the way for greater flexibility and requirements/process harmonization across different markets – for instance in the way studies are grouped and tagged – to the benefit of all stakeholders as they strive to accelerate the delivery of drugs to market. The emphasis on a flat hierarchy of files and the use of keywords will also reduce the burden for companies as regulations are updated and tools have to be upgraded because far less will change in practical terms around the way content is managed.
In due course, regulatory bodies will also use eCTD 4.0 to improve the process for communications exchanges. Support for two-way communications will enable greater continuity so that queries and dossier submissions can be handled seamlessly via the same channel. This facility may not be in place from the start, as it is complex to achieve (the FDA has already changed its stance to state that two-way communications won’t be supported from day one), but it is part of the plan longer term.
Ultimately, the changes under eCTD 4.0 will make everyone’s lives easier and improve the gaps that have been observed over the past years. But it would be wrong to think that the transition is chiefly technical, affecting the dossier publishing software primarily. Although new capabilities will be needed here to cope with the new XML schema, the flat file hierarchy, the latest PDF compression standards, and the requirement to view dossiers (rather than a browser, as up to now), the greater preparatory work will be around the way that teams work, and where and how content is captured and managed internally.
To maximize the opportunities presented by eCTD 4.0, companies will need to prioritize the designation of a single source of truth for documents within their organizations. All of the various contributors and dossier authors will need to be trained in the new way of preparing documents. They will need to be taught to tag content correctly and consistently use the same agreed vocabulary and keywords. They must also become familiar with the new technical means that will now need to be used to view/review dossiers before submission.
Five-Point Plan for Action
The confirmation and detailed publication of the eCTD 4.0 standard may have been a long time coming (this latest, significant iteration has been many years in the making), but now that the specifics are known and timelines are being set, life sciences companies have a powerful opportunity to reduce the burden of dossier preparation and streamline their submissions process and associated dealings with the various authorities internationally.
That’s as long as they are taking steps now.
Our recommended next actions would be to:
- Look up from IDMP and see eCTD 4.0 preparations as at least as critical an undertaking, if anything one with greater urgency because of the direct link with marketing authorization/license maintenance submissions.
- Prioritize a review of existing eCTD metadata (e.g., product, substances, manufacturer references), and review this for accuracy, completeness, and keyword consistency.
- Ideally, align vocabularies and contain data internally so that references are consistent both for eCTD, IDMP plus other use cases in the future, even if the respective systems and processes don’t overlap yet.
- Establish a clear view and understanding of all documents and their use across different types of submissions (e.g., investigational/trial related versus marketing authorization applications versus dossier updates); which are the trusted source materials; and where these are located; making also sure that new requirements to PDF compression are incorporated
- Allocate a dedicated project and budget for eCTD 4.0 preparations, and develop a roadmap, all of which is distinct from any work towards IDMP and other Regulatory standards-based initiatives.
With at least two years’ breathing space until eCTD 4.0 compliance starts to become mandatory across key markets internationally, pharma companies do have time to approach this properly and maximize the benefits of the refreshed and streamlined standard. Embracing the standard while requirements are still voluntary offers regulatory teams a chance to test the internal process benefits and get this right.
Pharmaceutical firms might initially perceive eCTD 4.0 preparations as a technological endeavor. However, embracing the enhanced protocol's advantages from a business process angle necessitates a re-evaluation of internal content and document management practices, as well as a reconsideration of work methodologies. In order to allocate ample time and resources for these changes, it's imperative to begin formulating projects as soon as possible.
Agnes Cwienczek is Director of Product Management at ArisGlobal with a remit including the provision of business process and data management expertise in the areas of Regulatory Information Management, Document Management, Submission Management, and Labeling Management. Prior to joining ArisGlobal, Agnes worked at Merck in its Global Regulatory and Quality Assurance department, a milestone in a career spanning nearly two decades at the frontline of regulatory information management. She holds a Master’s degree in Information Management from the University of Koblenz-Landau in Germany. https://www.arisglobal.com [email protected].
Publication Details
This article appeared in Pharmaceutical Outsourcing:
Vol. 4, No. 24
Oct/Nov/Dec 2023
Pages: 22-23
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