Non Clinical and Clinical CTD Modules
08 Jul 2017
What is CTD?
The common technical document (CTD) is a set of specifications to prepare the application dossier for the registration of medicines across Europe, Japan and the United States. It is a format used for the submission of applications to the regional regulatory authorities for their approval to market new drugs within the participating countries. The format was developed and mutually agreed upon by the European Medicines Agency (EMA, Europe), the Food and Drug Administration (FDA, U.S.) and the Ministry of Health, Labour and Welfare (Japan). The time and resources required by the industry to compile applications for global registration is significantly minimized due to the common format adopted for the technical documentation.
Benefits of CTD
- More “reviewable” applications
- Complete, well-organized submissions
- More predictable format
- More consistent reviews
- Easier analysis across applications
- Easier exchange of information
- Facilitates electronic submissions
The CTD is organized into five modules. Module 1 is region specific and Modules 2, 3, 4 & 5 are intended to be common for all regions (Europe, US and Japan). Module 1 is not the part of CTD.
Module 2 includes 2.4-Nonclinical Overview, 2.6-Non clinical written and tabulated summaries for non-clinical data, 2.5-Clinical Overview and 2.7-Clinical summary for clinical data presentation. Module 3 is for quality purpose, Module 4 for non-clinical study reports and Module 5 for clinical study reports. Lambda has helped various clients in preparing CTD modules especially M 2.4, 2.5, 2.6 and 2.7 which are very important parts of CTD.
M 2.4 should be presented in the following sequence:
2.4. Nonclinical Overview
2.4.1 Overview of the Nonclinical Testing Strategy
2.4.5 Integrated Overview and Conclusions
2.4.6 List of Literature Citations
The Nonclinical Overview serves as a preface to the entire CTD with a structured and critical assessment of the pharmacological, pharmacokinetic and toxicological evaluation of the molecule. The maximum preferred length of the Nonclinical Overview is 30 pages.
The tabulated summaries should be appropriately cited as references in the Nonclinical Overview. Evaluation of the studies conducted to establish the pharmacodynamic effects, the mode of action, and potential side effects should be done, and the significance of any issue that arises should be assessed. The pharmacokinetic, toxico-kinetic, and metabolism data should be assessed with relevance to the analytical methods used, the pharmacokinetic models, and the derived parameters. The onset of the toxic effects should be discussed along with their intensity and duration. The dose-dependency and the degree of reversibility (or irreversibility), and species- or gender -related differences should also be evaluated.
The implications of the nonclinical findings, with respect to the safe human use, should be discussed from the products’ pharmacology, pharmacokinetics, and toxicology results. The document should logically conclude with arguments in support of the safety of the product for intended clinical use based on the non-clinical studies conducted.
M 2.5 should be presented in the following sequence:
2.5.1. Product Development Rationale
2.5.2. Overview of Biopharmaceutics
2.5.3. Overview of Clinical Pharmacology
2.5.4. Overview of Efficacy
2.5.5. Overview of Safety
2.5.6. Benefits and Risks Conclusions
2.5.7. Literature References
The Clinical Overview is generally expected to be a short document of not more than 30 pages, primarily referring to the application data in the Clinical Summary, Clinical Study Report and other related reports. The document should capture the results and interpretation of the data presented in those documents and should not just duplicate the information. It should provide a concise discussion regarding the implications of the clinical and the efficacy data along with any other relevant information (e.g., pertinent animal data or product quality issues that may have clinical implications).
2.6-Non clinical written and tabulated summaries
This section provides a summary of the nonclinical data and includes the pharmacology written summary, pharmacology tabulated summary, pharmacokinetics written summary, pharmacokinetics tabulated summary, toxicology written summary and toxicology tabulated summary related data.
Here, a detailed summary of the clinical data from the clinical study reports; any meta-analyses if done, or other cross-study analyses is provided. The full reports of these data must be included in Module 5. The post-marketing data for products that have been marketed in other regions is also included.