FAQ

What does CTD stand for?

CTD stands for Common Technical Document, a format or set of specifications for an application dossier for the registration of Medicines at major health authorities globally. Managed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The format is now largely replaced by the electronic version, eCTD.

What is eCTD?

eCTD is the electronic version of the Common Technical Document format, mainly consisting of PDF documents containing the information to be reviewed. The format follows a hierarchal folder structure, with a sequential 4-digit number being the highest level. The eCTD format introduces an XML backbone that provides electronic navigation between documents and in addition holds all the application metadata details. The electronic format also introduces the ability to add and remove documents with operators “new”, “replace” and “delete” allowing viewers to see a “current” view of the application’s lifecycle.

What is an eCTD TOC?

An eCTD TOC is an electronic Table of Contents, also known as the xml. It provides electronic navigation around the dossier via hyperlinks and replaces the need for manually creating and hyperlinking an index that would perform the same function.

What is the eCTD Hierarchy?

When discussing eCTD hierarchy, many will refer to the eCTD 3-tier triangle. In this, Module 1 would sit at the top tier; Module 2 summaries would be found below at 2nd tier and then below on the 3rd would sit Modules 3, 4 and 5.

In reality, once the eCTD sequence folder is opened, all 5 modules will sit on the same level and a hierarchal structure will follow within each of those. Due to this eCTD Structure may be a more relevant term used in industry.
tion.

What are the eCTD Modules?

There are 5 modules in total.

Module 1 is known as Regional Information, due to this it is not part of the overall CTD (Common Technical Document) because the content of that module will not be in common with another region. This module contains administrative documents like the cover letter, application form and labelling. Module document example: 1.2 Application From

Module 2 consists of the summaries and overviews of the quality, non-clinical and clinical information found in Modules 3, 4 and 5 respectively. Module document example: 2.5 Clinical Overview

Module 3 consists of the Quality (chemistry, manufacturing and controls reports) information. Module document example: 3.2.P.2 Pharmaceutical Development

Module 4 consists of the Non-clinical reports of the dossier. Module document example: 4.2.1.1 Primary Pharmacodynamics: Study 123

Module 5 consists of the Clinical reports of the dossier. Module document example: 5.3.3.5 Population PK Study Reports: Study 123

What is eCTD publishing?

eCTD publishing is the application of electronic navigation to regulatory PDF documents of which are to be placed into structured eCTD locations within a sequential submission. It is usually facilitated by a tool or software that can create outputs in the eCTD format.

Why use eCTD?

Quickly becoming mandated across regions and agencies.

Environmentally friendly, removing the need for printing of paper.

Facilitates electronic linking between documents or content previously submitted.

Dossier modifications are easier to make and more easily seen by reviewers.

Facilitates electronic upload, almost instantaneously compared to physical mail.

With multiple regions accepting, facilitates faster subsequent region resubmissions.

Provides faster more efficient clarity on what is current, proposed, approved or registered.

CTD vs eCTD: What are the main differences?

Essentially, an eCTD is just a CTD with an XML backbone applied.
With an XML, comes automated electronic navigation, created manually in a CTD.
Documents can be given “operators” of “new”, “replace” or “delete” in eCTD, allowing a traceable document lifecycle to be observed, not possible in CTD.
An eCTD provides checksums that identify correct document versions, not a feature of CTD.

How do we start an eCTD submission with ONIX?

1. Complete the Submission Request Form found on the Contact Page
2. We aim to acknowledge as soon as possible, at which point you can send us the files!

How can we transfer our content to ONIX securely?

We value client confidentiality and can set up a secure file transfer protocol (sFTP) between us and your company within minutes. However PDF’s or a ZIP package in an email are still also fully acceptable.

What is ONIX’ eCTD Submission Process?

• Send us the submission request
• We’ll acknowledge
• Send us the files
• We compile the package
• We provide to you for secure review
• Once approved we submit via gateway
• We then provide you with the delivery receipt and
• We’ll archive your submission

What submission types do you submit?

• Europe – Centralised, Decentralised, Mutual Recognition, National Procedures, CTA and IMPD, PIP, PRIME
• USA – IND, NDA, aNDA, BLA and DMF (incl. CRFs and Datasets)
• Swissmedic
• Health Canada
• Australia
• ASEAN, GCC and Rest of World
• Other : MS Word formatting of files and PDF publishing to make files eCTD submission ready.

What electronic portals do you have access to?

EMA Gateway, FDA Gateway, CESP, Swissmedic, Health Canada, Portugal Infarmed SMUH-ALTER Portal.

How do we manage a Drug Substance Manufacturer Name Change?

Once a drug substance manufacturer name is in place it cannot be modified going forward or retrospectively, the history of the eCTD must remain as is. Going forward, the new name can be applied in a new sequence at which point another drug substance folder will appear. Subsequent sequences can be submitted under this new folder.

What is the folder structure for eCTD Module 5?

The structure for Module 5, including presentation of clinical study reports and the clinical overview and summaries in Module 2, can be found in the ICH guideline M4E(R2).

What CRF’s do we need to submit?

Submitted Case Report Forms should include deaths, other serious adverse events, and withdrawals for adverse events.

What is the folder structure for eCTD Module 3?

The structure for Module 3, including the quality overview and summaries in Module 2, can be found in the ICH guideline M4Q.

What is an eCTD baseline submission?

This phrase refers to the scenario in which a CTD (Paper or Nees) dossier that has already been approved is submitted to an agency in eCTD, facilitating a conversion in format. This submission will likely be the initial in the eCTD application but there are cases where the baseline may be submitted later. It is recommended to submit modules 1 to 3 and possibly follow up with all modules in future.

What are the eCTD PDF Specifications?

The PDF specifications are a set of rules and pre-requisites that the PDF document must adhere to regarding aspects like margins, page numbering, version and file size. These specifications change slightly from region to region and are subject to updating, thus the best approach is to source each region’s PDF specification guidance.

What is eCTD Metadata?

Metadata in eCTD submissions can be found in two places. Firstly, the application metadata, typically displays the submission number, applicant name, product name, indication and a few other product details that generally tend not to change from submission to submission. It is also know as the structural metadata. Secondly, is the sequence metadata, which displays the information specific to that sequence, like the sequence number and submission type and description. This is also known as the descriptive metadata.

How can I make an MA transfer?

Transfer dossiers should consist of a cover letter signed by the transferor, the relevant signed (by transferor and transferee) attachments, all the revised product information and revised mock-ups. Guidance on this procedure and what attachments to submit can be found here on the EMA website: https://www.ema.europa.eu/en/human-regulatory/post-authorisation/post-authorisation-procedural-qa/transfer-marketing-authorisation-questions-answers

When filing an MA Transfer, at which point should we change our name in the application metadata?

We recommend leaving the name as is during submission of the transfer, as the transfer submission is still requesting the change. Once the transfer has been filed the name can be changed going forward. However, please be informed that we have had clients request that the applicant name be changed in the metadata at the time of the transfer submission and no agency or validation issues have been received.

Have ONIX ever submitted safety reporting in eCTD?

Yes, ONIX has experience of submitting safety reports in eCTD format for a number of clients. We submit the CIOMS in the safety report section of the relevant study.

As a CRO can ONIX submit the PSUR on behalf of our client?

Yes ONIX can, we would require the previously submitted sequences and once we have submitted the PSUR we would provide the submitted PSUR sequence for your client to import into their eCTD software.

Can you upload PRIME submissions on our behalf via Eudralink?

Yes, ONIX can submit on your behalf.

Who will receive the Regulatory Health Questions when we submit an eCTD: ONIX or us?

In the cover letter you state the contact details of the person who is responsible for eCTD / Regulatory queries, that contact will receive the questions.

What do I need to do for you to upload to FDA ESG gateway?

Send an original signed letter to the FDA ESG team via courier post and also the scanned letter can be sent via email giving ONIX authorisation to upload on your behalf.

When does Health Canada’s REP pilot start?

Their pilot had already started and concluded in July 2019; from 1 November 2019 they commenced a REP pilot for clinical trials.

Can ONIX submit to FAERS on our behalf?

The creation of the AERS, which has now transitioned from PDF to XML files, will be the responsibility of the sponsor. ONIX can make the submission of the AERS (XML) and AERS Attachments (PDF files) via ESG. This will only be the case for NDA applications as this process is not yet available for INDs.