In detail
Legal basis
Under Article 25 of Regulation (EU) No 536/2014, an application for authorisation of a clinical trial must contain information on the investigational medicinal products, in particular their properties, labelling, manufacture and control. The detailed content of the IMPD is set out in Section G of Annex I to the Regulation. The sponsor submits the application through the EU portal (Article 5). Manufacture, import and labelling of investigational medicinal products are assessed in Part I of the assessment report (Article 6).
Structure and content
- Quality data on the active substance and the investigational medicinal product in a logical structure, such as Module 3 of the ICH Common Technical Document (CTD).
- Summaries of non-clinical pharmacology and toxicology data, such as Module 4, including a statement on GLP status.
- Data from previous clinical trials and human experience, such as Module 5.
- An integrated risk and benefit assessment, unless it is already provided in the protocol.
Annex I requires the IMPD to be concise, to present data in tables where possible and to analyse the data critically rather than merely listing them.
Simplified IMPD
If the investigational medicinal product is already authorised or has been used in an authorised trial before, a simplified IMPD may be sufficient. Non-clinical and clinical summaries can refer to the Investigator's Brochure and, for authorised products, to the Summary of Product Characteristics (SmPC). Table 1 in Annex I specifies which parts must still be submitted. If an authorised product is modified, for example for blinding, quality data on the modified product are required.
Quality section and changes
For investigational medicinal products containing chemically defined active substances, synthetic peptides, herbal substances and radiolabelled substances, EMA guideline EMA/CHMP/QWP/545525/2017 Rev. 2 describes the information expected in the drug substance and drug product sections (S and P) and how changes during the trial should be handled. The sponsor applies for substantial modifications of the investigational medicinal product under Chapter III of the Regulation, using the documents listed in Annex II.
In practice at A&O Pharma
Through its regulatory affairs service, A&O Pharma supports sponsors with regulatory strategy and the submission of clinical trial applications. As holder of a manufacturing authorisation under Section 13 AMG, we release investigational medicinal products under Regulation (EU) No 536/2014 and package and label trial medication for clinical studies.
Regulatory AffairsFrequently asked questions
What is the difference between the IMPD and the Investigator's Brochure?
Under Article 2 of Regulation (EU) No 536/2014, the Investigator's Brochure is a compilation of the clinical and non-clinical data on the investigational medicinal product that are relevant to its study in humans. The IMPD also contains quality and manufacturing data and may refer to the Investigator's Brochure for its summaries.
When is a simplified IMPD sufficient?
When the investigational medicinal product is already authorised, its active substance is contained in an authorised medicinal product, or it has already been used in an authorised trial. Table 1 in Annex I to Regulation (EU) No 536/2014 specifies which parts must then be submitted.
How is the quality section of the IMPD structured?
According to Annex I to the Regulation, in a logical structure such as Module 3 of the CTD, with a drug substance section (S) and a drug product section (P).
