Overview of Common Technical Documents

What is a CTD?

The Common Technical Document (CTD) is a standardised format for preparing application dossiers for the registration of new medicines in participating regions including the EU, Japan, and the US. Since its finalisation in November 2000, the CTD has allowed for a simplified and harmonised submission process reinforced by good review practices [1].

The CTD is a large, multidisciplinary assembly of documents comprising five modules, into which all quality, safety, and efficacy information on the new medicine is compiled. Figure 1 shows the CTD triangle, illustrating which information about the investigational product goes into which CTD module.

Figure 1. Common Technical Document triangle

CTD = Common Technical Document.
The CTD is organised into 5 modules. Module 1 is region-specific and Modules 2‑5 are intended to be common for all regions [1]. Dashed red lines indicate the CTD modules that the Alchemy regulatory writing team specialise in.

Main CTD requirements and how Alchemy can help

The CTD modules consist of non-clinical and clinical elements. At Alchemy, we specialise in authoring a number of these modules, particularly:

Module 1 documents, including risk management plans (RMPs), paediatric investigation plans (PIPs) for EU/UK submissions, and paediatric study plans (PSP) for US submissions
Module 2 clinical and non-clinical overviews and summaries (Modules 2.4, 2.5, 2.6, and 2.7)
Module 4 non-clinical study reports
Module 5 documents, including clinical study reports (CSRs), integrated summaries of efficacy (ISE), integrated summaries of safety (ISS), and post‑marketing reports

The key requirements for developing comprehensive and effective CTD modules include:

Adherence to regulatory guidelines

We ensure your CTD modules adhere to regulatory guidelines outlined by the International Council for Harmonisation (ICH) and apply industry best practices to ensure consistency and compliance [1].

Relevant general ICH guidelines include the following:

ICH M4 (R4): CTD for the registration of pharmaceuticals for human use – organisation of CTD
ICH M4 (R3): CTD for the registration of pharmaceuticals for human use – questions and answers
ICH M4Q (R1): CTD for the registration of pharmaceuticals for human use – quality
ICH M4Q (R2): CTD for the registration of pharmaceuticals for human use – quality: questions and answers
ICH M4E (R2): CTD for the registration of pharmaceuticals for human use – efficacy
ICH M4E (R4): CTD for the registration of pharmaceuticals for human use – efficacy: questions and answers
ICH M4S (R2): CTD for the registration of pharmaceuticals for human use – safety
ICH M4S (R2): CTD for the registration of pharmaceuticals for human use – safety: questions and answers

CTD content coordination

Our writers use their regulatory experience to guide each CTD module through drafting and review cycles to incorporate recommendations from the sponsor, study team, subject matter experts, and internal governance.

Document publishing

We can perform submission-ready publishing of documents ahead of eCTD collation and publishing, which would be performed by a submission publisher.

Streamlining of entire CTD document

We offer streamlined writing support across all CTD modules to apply consistency, stylistic preferences, and regulatory adherence across the CTD.

How the CTD sits within the regulatory framework

The primary role of the CTD is to provide a standardised format for preparing marketing authorisation applications, new drug applications, and biologic license applications in participating countries. The European Medicines Agency, the UK’s Medicines and Healthcare products Regulatory Agency, and Japan’s Pharmaceuticals and Medical Devices Agency mandate the use of the CTD format for marketing authorisations. The US Food and Drug Administration also strongly recommend use of the CTD format. Since its inception, the CTD has been adopted in other countries including Canada, China, and Switzerland [1-3].

The standardised organisation of the CTD allows regulatory reviewers to quickly orient themselves with the contents of the application, facilitating timely and consistent review without the need to prepare separate dossiers for different regulatory agencies.

This standardisation does not, however, preclude the inclusion of essential region‑specific administrative information, which is captured in Module 1. Module 2 provides reviewers with an introduction to the investigational product and overviews and summaries of quality, non-clinical, and clinical information. Full quality, non‑clinical, and clinical information is then presented for review in Modules 3, 4, and 5, respectively. Since 2008, an increasing number of submissions have been prepared using the electronic version of the CTD, allowing for further streamlining of the review process [1].

Preparation of a clear, consistent CTD is therefore essential to support applications for marketing authorisation of a new medicine in the participating regions.

What is the general timeframe for writing a CTD?

Due to the multidisciplinary nature of CTDs, the timeframe for preparation of the entire package can be months to years, with each module typically requiring a few months to produce [4]. Timelines vary depending on the complexity of the submission, for example the number of indications being investigated and the volume of non-clinical and clinical data available [1]. Effective team alignment and communication from project kick-off will accelerate CTD development.

Overview of the development of a CTD module

CTD = Common Technical Document; QC = quality control; SME = subject matter expert.

Alchemy’s top tips for authoring CTD modules

Think of the CTD modules in terms of the audience for which they are being prepared, eg, regulatory authorities. Each part of the CTD should concisely address the topic at hand, be it quality, non-clinical, or clinical data. Think of questions the regulators might ask as they navigate the content and address them proactively within the text. The regulator should not need to dig for relevant information. Everything should be presented with the intention of making the regulator’s job of assessing all aspects of the drug as easy as possible.

As Tony Robbins once said, “Engaging people is about meeting their needs, not yours.”