ectd!&!!established!standard–!new!approach! … · 2016-07-28 ·...

eCTD -‐ Established Standard – New Approach A Comprehensive Guide for Beginners

3 March 2015

Whitepaper: Established Standard, New Approach

© Copyright Cunesoft GmbH Page

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Introduction Everyone working within the pharmaceutical industry is well aware of the requirements regarding the eCTD format. The timing for implementation of this standard is varied depending on which submission type and to which authority the submission is being made. The uptake of eCTDs by industry and regulators is even accelerating. We must all agree that eCTD is here to stay. As regulatory professionals develop submission strategies, they must untangle the web of requirements and carefully consider their collective impact. They must also consider the complexity of today’s working environment in their plans. This whitepaper provides a good overview of the current regulatory landscape surrounding the eCTD format along with a look at the pros and cons associated with the various approaches available for implementation. Changing Requirements It is truly a complicated exercise to keep track of just which authority is implementing the eCTD format, with which parameters, for which submission types and the timing for each of these. Dedicated personnel must tease through the regulations to keep up with the latest developments.

EMA has taken a leadership role in implementing the eCTD format. The final adopted version of the ESubmission Roadmap (Attachment A) was published in November 2014. While eCTD was already required for the Centralized Procedure, this roadmap gave definitive timing for most other application types. In summary, all EMA procedures (including DCP and MRP) will also require submission using the eCTD format by 2018. Veterinary applications are the one notable exception as they will continue to use vNeeS.

FDA will also require the use of the eCTD format for all application types (NDA, ANDA, BLA and INDs) with few exceptions. However, the exact timing is much more difficult to pin down. The two latest, final FDA guidances issued in December 2014 covered the overall implementation of eCTD and the submission of standardized study data. FDA will issue more guidances moving forward as they phase in the mandatory requirement for full electronic submissions. It is expected that implementation of the eCTD format for most application types will be during 2016. When one looks outside of Europe and the US, the eCTD picture is even less straightforward. The countries where the latest information is available can be divided into 3 distinct groups: Group 1 now requires eCTD submissions, Group 2 accepts eCTD and Group 3 is in the early stages of accepting eCTD.



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Group 1 – eCTD as a requirement.

• Switzerland just issued their final guidance in November 2014 and now accepts only eCTD as the format for electronic submission.

• Saudi Arabia FDA requires all submissions in the eCTD format as of January 2015.

Group 2 – eCTD accepted.

• Health Canada has partnered with FDA on the gateway for electronic. Timing for use of DTD format was extended to 09/2013, but eCTD has since replaced. Waiting for final guidance entitled Draft Guidance Document: Preparation of Drug Regulatory Activities in Electronic Common Technical Document (eCTD).

• Japan has accepted eCTD submissions since 2008 and requires the submission of the full eCTD even when only parts are modified/updated following the initial approval.

• Thai FDA accepts submissions in eCTD format.

Group 3 – Almost ready to accept eCTD.

• Australian TGA is currently in piloting the use of eCTD and their findings should be released in Q1 2015.

• South Africa encourages eCTD submissions as of May 2015.

Latest News -‐ ICH eCTD v4.0 Draft Implementation Guide v2.0 As expected, ICH eCTD version 4.0 of the Draft Implementation Guide v2.0 has been released along with related regulatory files that include: Draft ICH Code List v2.0, Specification for Submission Formats v2.0 and M8 Genericode Schema and Files. The most detail in this update is given to the following:



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• Fonts – allows for embedding of a subset of Japanese fonts (only those used within the document) rather than the full set.

• Methods for Creating PDF Document and Images – specifies using 300 dpi for scanning documents to balance “legibility and file size” and using 600 dpi for photographs. Also gives information for lossless compression of PDFs containing images.

• SVG – identifies this language for describing two-‐dimensional graphics in XML and states that its use in a submission should be discussed with the respective regulatory authority.

The deadline for regulatory consultation on these documents is May 22, 2015. Comments will then be reviewed and discussed at the ICH meeting scheduled in June 2015 in Fukuoka. The conclusion of Step 4 is expected in November 2015 when the implementation package is finalized and published. The timing for the regional implementation is still undetermined, but many countries have already issued specific guidance for how electronic submissions should be handled.

Challenges with eCTD in Today’s Environment The regulatory landscape has fundamentally changed with the uptake of the eCTD format over the last decade. In addition, the ways in which companies work has also changed dramatically. The co-‐location of development teams is no longer the norm and outsourcing of R&D activities is common. Industry has seen an escalation in the number of joint ventures and consolidation of entities that invariably impacts development and registration activities.

Many tasks previously completed in-‐house are now delegated to freelancers, consultants and/or CROs. Differences in language, culture and time zones are prevalent. While this delegation may be a more cost effective way to get the work done, it creates its own issues related to effective and efficient collaboration for regulatory submissions.

The graphic on the following page gives a quick glimpse at the various stakeholders in the regulatory submissions process. It should be noted that the submissions process also includes the various regulatory agencies. Software designed for the preparation of regulatory submissions in the eCTD format must also include the final submissions plus interactions with agencies as well.



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Stakeholders in the regulatory submissions process

Technology Conundrum When choosing which technology to utilize for the electronic compilation and submission of regulatory filings, there is a plethora of options available. Regulatory professionals can choose from a range of open source tools, on premise software or from the latest SaaS solutions to meet the needs for electronic submissions.

The use of open source materials is clearly the most attractive option from a pricing standpoint. While it may be tempting for a small company to choose to simply download eCTD backbones from web sources, these free of charge tools are inflexible by nature and offer a “one size fits all” approach. They cannot be updated quickly to meet diverse regulatory requirements and offer no customer support when things don’t go according to plan. As a company’s needs change over time, migrating information created from open source materials to a dedicated solution eventually becomes a necessity.

The old school vendors are offering on premise installation and validation, but this approach usually requires a significant initial expenditure and then maintenance fees over the life of the software. Because even the smallest changes to the regulatory requirements for eCTDs require software modifications on site, there is a revolving door of consultants who are needed to keep everything up to date and running smoothly.

The new, innovative vendors have decided to pursue Software as a Service (SaaS) as their business model. To address the ever changing regulatory landscape and the diffuse corporate environments, this approach is a viable, cost-‐effective option and should be considered.



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In an ideal world, regulatory affairs professionals would not need to worry about the continuous updates to technical eCTD requirements. They would instead be able to concentrate on the strategy and content of their regulatory submissions.

The “new approach” of Software as a Service manages the varying regulatory requirements and their updates and the corresponding validation required for the sponsor. When ICH eCTD version 4.0 of the Draft Implementation Guide v2.0 is published at the end of 2015, the hosted software can be efficiently updated without requiring work on the sponsor’s part. Validation activities are managed as a part of the SaaS offering.

Addtionally, SaaS solutions offer sponsors the capability to login from anywhere in the world and to work efficiently with access to all of the necessary data. With options available to limit or grant access to various stakeholders, work can be distributed across geographies and organizations as necessary. The sponsor can decide whether freelancers and/or consultants provide documents, have read only access or even actively participate in the review process.

SaaS differs from on-‐premise solutions also for its cost structure. Users typically pay a subscription fee for access to the software. Because system maintenance and upgrades are managed centrally, costs are further lessened.

On-‐Premises vs. Cloud Computing

eCTD done with SaaS solution (“Software as a Service”)



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Conclusions While the regulatory environment is complex, the bottom line is that eCTD is here to stay. It is a well established standard that is being implemented at a quick pace. It aims to streamline the preparation of regulatory filings on a global basis. The eCTD format increases collaboration not only within companies but also with regulatory authorities. eCTD being done with a Software as a Service solution provides an excellent technology alternative, especially for small and medium sized organizations to reduce the complexities involved with regulatory submissions matters. Contact us for more information and Product Demo: Cunesoft GmbH Marsstr. 4 80335 München Germany Phone: +49 (0)89-‐235 14741 Website: www.cunesoft.com Email: [email protected]



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Attachment A

ectd!&!!established!standard–!new!approach! … · 2016-07-28 ·...

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