The introduction of CTD in 2019 in Brazil signified an essential shift for Brazilian pharmaceutical entities, and because of ANVISA's eCTD implementation, an even more significant change is expected. As the trusted solution provider for more than 35 regulatory authorities worldwide, including the European Medicines Agency (EMA), we know what this means for the national regulatory processes and life science organizations' challenges.
That is why we dedicated a special webinar to this vital topic. With Milena Barrozo (Vita Pharma Consulting) and Juliana Rocha (N.G. Reis Consultoria), our valuable partners in Brazil, we conducted two webinars to accompany the Brazilian pharmaceutical industry's journey towards eCTD.
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Milena Barrozo
Co-Founder and Director at Vita Pharma Consulting
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Juliana Rocha
Partner at N.G. Reis Consultoria |
We are excited to share the answers to all the open questions from our recent webinar, as this topic is of great importance to everyone submitting to Brazil. Please find all the questions and their answers in this Blog Post.
1. What are the main differences between eCTD v3.2.2 and v4.0?
The main differences between eCTD v3.2.2 and eCTD v4.0 are centered on improvements in flexibility, metadata management, and interoperability. eCTD v3.2.2 uses 2 XML backbone files that set the structuring of the dossier but has limitations and is not very flexible. eCTD v4.0 has only one XML file and uses the Regulated Product Submissions (RPS) standard developed by HL7 (Health Level Seven International). RPS offers a more flexible and comprehensive framework for regulatory submissions, increasing the ability to manage complex data and metadata structures. The main differences, as presented in the workshop, are listed in the table below.
2. How will eCTD be implemented at Anvisa? Will there be some "synchronization" for companies with this software when uploading documents to an agency portal? For those who don't, uploading should be done manually.
Anvisa published in its 2023 Management Report for GGMED (available here) a proposal for a provisional flow for implementing eCTD. However, information about what the Anvisa portal will be like has not yet been available. Other agencies, such as the FDA and EMA, have a gateway where the submission of the finalized eCTD is transmitted as a zipped folder through a secure portal. There is no synchronization between the company's software and the agency's; instead, an output of the company's software is generated and transferred to the agency. In the case of version 4.0, generating the eCTD without appropriate software is impossible.
3. What does "publishing" mean when we talk about eCTD?
An eCTD is a CTD with metadata and an electronic backbone file to allow lifecycle operations. This backbone (XML files) is typically done by a publishing software. First, users' compile' their submission dossier, meaning that submission documents must be placed in their defined submission structure. In the second step, the submission needs to be 'published,` which means it is exported from the software (during this export, the electronic backbone is created, and folders and files are exported with their compliant name in accordance with the ICH and national legislation. This export is then submitted to an Agency. 'Publishing' can, therefore, be considered as compiling and exporting an electronic submission.
4. Is submitting the Cover Page and Table of Contents for the DMF (= DIFA) compulsory?
A DMF is represented by section 3.2.S of the dossier in CTD format and, if applicable, some information in section 3.2.A. The Table of Contents (ToC) is recommended and expected in CTD format but not in Nees and eCTD formats.
In the case of the CTD, the module number, volume, and partitions (if applicable) are expected to be presented in the ToC. A Cover Page is usually presented in a CTD (paper) to show the document being made available.
5. Will all these files with all this granularity differ for each country? If not, how do I know which countries they are submitted to?
The granularity allowed for modules 2 to 5 is defined in the ICH guideline and applies to countries that accept the CTD format. Module 1 and section 3.2.R differ for each country, and the rules are published in specific regional guidelines.
6. Apart from the administrative protocol issues, which are very specific to Anvisa, what are the other main differences between Guide 24 and Guide M4?
In addition to the administrative protocol issues and adoption of the CTD format for already registered products, Guide 24 provides information about Modules 1 and 3.2.R, which are specific to Brazil. This information is described in Annex I and Annex II of Guide 24. Additionally, Guide 24 includes specific details about certain categories of products, such as herbal medicines and particular products, and information about post-approval changes not included in Guide M4.
On the other hand, Guide M4(R2) has an appendix that explains the granularity and the use of keywords in eCTD version 4.0, elements that were not included in Guide 24.
7. Can more than one person change the product dossier simultaneously?
If more than one person can work on a document or dossier simultaneously, it depends on the software you are using. For EXTEDO software, we can say that both are possible:
- If the question refers to the editing stage of a regulatory document (in this case, eDOCSmanager powered by CARA, part of EXTEDO's Document Management Hub, which was briefly demonstrated during the webinar), this is possible using collaboration options. Collaboration allows multiple users to work on the same document at the same time as long as the document is in draft.
- If the question refers to the submission dossier itself, it is also possible that multiple users work on the same submission in EXTEDO's eCTDmanager, part of EXTEDO's Submission Management Hub. One user could work in Module 2, and another could already work in Module 3.
8. Is it recommended to draft, edit, and review documents within the system? In this way, does the experience in other countries involve not having the documents/dossiers/submissions in folders on the corporate network/computer?
Yes, indeed. Documents can be created and maintained on a file share, but we have exactly the problems you mentioned there. Document version control or the sharing of documents between divisions is not always done correctly. In this case, document management systems can help reduce the maintenance and search effort.
If you have any questions regarding the transition to eCTD and how to approach it, please contact us any time: info@extedo.com. We are happy to support you!