15/16 September 2020
As previously reported the final "Detailed Commission guidelines on GMP for IMPs for human use" have been published in December 2017 in Annex 13 of the EU GMP-Guidelines.
The previous Annex 13 contained detailed requirements and guidance for IMP (investigational medicinal product) labelling together with a summary of labelling details provided in Table 1 of Annex 13. This table is not provided in the Detailed Commission Guidieline and requirements and guidance for labelling have been moved from GMP to GCP as they are now part of Regulation (EU) No 536/2014 (Clinical Trials Regulation, CTR) including its Annex VI. For unauthorized IMPs it has been amended, for example, that "in the case of blind clinical trials the name of the substance is to appear with the name of the comparator or placebo on the packaging of both the unauthorized IMP and the comparator or placebo".
Furthermore, some of the particular requirements have been amended in the CTR in regard to limited labelling of immediate packaging (i.e. in cases where primary and secondary packaging are provided together or small primary packaging systems like blister packs or small units such as ampoules are used) in comparison with the previous Annex 13. According to the CTR the period of use (expiry date or re-test date as applicable), in month and year format and in a manner that avoids any ambiguity has to be provided on the primary packaging.
Additionally, replacing of information and providing this information by other means, e.g. by using a centralized electronic randomization system / centralized information system, is only allowed in specific cases for specific parts of information (for example particulars on the main contact like sponsor, contract research organization or investigator).
In Detail, Section 6.6. Labelling of the Detailed Commission Guideline states:
Chapter X Labelling of the CTR contains the following information on what shall appear on the outer packaging (secondary packaging) and on the immediate packaging (primary packaging):
(a) information to identify contact persons or persons involved in the clinical trial;
(b) information to identify the clinical trial;
(c) information to identify the medicinal product;
(d) information related to the use of the medicinal product.
The information which is to appear on the primary and secondary packaging shall ensure subject safety and reliability and robustness of the data generated in the clinical trial, while taking account of the design of the clinical trial, whether the products are investigational or auxiliary medicinal product, and whether they are products with particular characteristics. The information which is to appear on the primary and secondary packaging shall be clearly legible.
(a) in accordance with Article 66 of the CTR (a-d, see above); or
(b) in accordance with Title V of Directive 2001/83/EC.
Where the specific circumstances, provided for in the protocol, of a clinical trial so require in order to ensure the safety of the subject or the reliability and robustness of data generated in a clinical trial, additional particulars relating to the identification of the clinical trial and of the contact person shall appear on the primary and secondary packaging of authorized IMPs.
The products shall be labelled appropriately in order to ensure the safety of the subject and the reliability and robustness of data generated in the clinical trial (Article 68).
The CTR and the Detailed Commission Guideline are expected to become applicable in the second half of 2019. More information on Annex 13 and the Detailed Commission Guideline can be found in EudraLex, Volume 4.