In detail
Authorisation procedure
The sponsor submits the application through the EU portal under Article 80, which is operated as the Clinical Trials Information System (CTIS). A reporting Member State coordinates the assessment of Part I, which covers among other things the anticipated benefits, the risks and the investigational medicinal products. Part II, including informed consent, compensation, recruitment, data protection and the suitability of investigators and trial sites, is assessed by each Member State concerned for its own territory. Under Article 47, trials must be conducted in accordance with the principles of good clinical practice. Since 31 January 2023 new applications have had to be submitted through CTIS, and since 31 January 2025 the CTR has also applied to ongoing trials authorised under the former Directive.
Investigational medicinal products: manufacture and QP
- Under Article 61, the manufacture and import of investigational medicinal products require an authorisation and at least one permanently available QP who meets the qualification requirements of Article 49 of Directive 2001/83/EC.
- Under Article 62, the QP ensures that each batch manufactured in or imported into the EU complies with the requirements of Article 63, and certifies this.
- Exempt from the authorisation requirement are, among others, re-labelling or re-packaging in hospitals and clinics by pharmacists or other authorised persons, where the products are used only at sites taking part in the same trial in the same Member State (Article 61(5)).
GMP for investigational medicinal products
Article 63 requires manufacturing practice that safeguards the safety of trial subjects and the reliability of the clinical data. This is specified in Delegated Regulation (EU) 2017/1569 and the Commission guidelines C(2017) 8179 of 8 December 2017. These cover, among other topics, the product specification file, blinding, randomisation codes and re-labelling when the expiry date changes.
Labelling
Under Article 66, unauthorised investigational and auxiliary medicinal products bear information on contact persons, the trial, the medicinal product and its use on both outer and immediate packaging. The details are set out in Annex VI. Under Article 67, authorised products may also be labelled in line with Title V of Directive 2001/83/EC, like commercial packs.
In practice at A&O Pharma
A&O Pharma carries out QP release of investigational medicinal products under the CTR, under its own manufacturing authorisation under Section 13 AMG. A&O Pharma also performs secondary packaging and labelling of trial medication and supplies the trial sites according to your specifications. The regulatory affairs team supports the submission of clinical trial applications.
Medicinal Product ReleaseFrequently asked questions
Since when has the CTR applied?
The Regulation has applied since 31 January 2022. Since 31 January 2023 new applications have had to be submitted through CTIS, and since 31 January 2025 it has also applied to trials originally authorised under Directive 2001/20/EC.
Does manufacturing investigational medicinal products require an authorisation?
Yes. Article 61 requires an authorisation for manufacture and import as well as at least one QP. Exemptions apply, for example, to certain re-labelling and re-packaging in hospitals and clinics.
Which GMP rules apply to investigational medicinal products?
Delegated Regulation (EU) 2017/1569 and the Commission guidelines C(2017) 8179. Where applicable, parts of the EU GMP Guide (EudraLex Volume 4) should also be taken into account.
