The following is a list of the most common considerations that occur in the validation phase. The BfArM recommends following the recommendations in order to avoid objections to the relevant points and thus enable a faster evaluation

Considerations in the area of validation

Formal

Incomplete cover letter

The cover letter is incomplete. Please note the requirements for cover letters in accordance with EU (Regulation) 536/2014 Annex I (B). A cover letter template has also been provided by the CTCG. Use of this template is encouraged.

Manufacturer's information on approved IMPs is missing

No manufacturer is named for study-specific labeling of approved IMPs. Please correct.

The Pharmacy Manual was not submitted.

The applicant is asked to provide the Pharmacy manual.

Investigational medicinal products are not defined by active substance

The investigational medicinal products have to be defined by active substance name since various commercially available products are being used. Please revise CTIS section „Products“ accordingly.

SmPC changes without tracked changes

Substantial modifications: Amendments in the updated SmPC are not comprehensible, track change version missing.

Application documents not compliant with formatting requirements under EU Regulation 536/2014

Submitting a copy-protected and/or non-searchable document makes it more difficult and delays the processing of an application for a clinical trial. Please only submit searchable documents in this context, cf. Regulation (EU) No 536/2014 Art. 81 para. 2 “...all data stored in the EU database must be in a readily searchable format...”.

Missing protocol code in CTIS

The protocol code of the clinical trial has to be entered in the corresponding CTIS field. Please add.

Active substances not recorded as separate IMPs in CTIS

In CTIS, the various active ingredients (xxx and xxx) are listed as one investigational product “Role: Test” in the “Products” section. Different active ingredients must be entered as separate investigational products. Please correct.

Submitted documents were not named according to CTCG guidelines

Please precede the name of all documents with CTR annex I corresponding letter. This will allow the member states to have a structured list of documents after download of each Part of the dossier from CTIS. We refer you to the best practice on naming of the documents in CTIS as published on the CTCG website: CTCG best practice guide naming of documents, version 2.01, 9 March 2023

Inconsistent study title between CTIS, protocol, and cover letter

The title in CITS does not correspond to the title of the cover letter and trial protocol. The sponsor is requested to correct the title in CTIS.

Update function in CTIS not used correctly

Update functionality in CTIS not used to upload new versions of updated documents.

Documents containing tracked changes not suitable for publication

Documents with track changes should not be subject to publication. Reference is made to Q&A on the protection of Commercially Confidential Information and Personal Data while using CTIS, question 1.8. Please delete all applicable files.

ASMF reference to national procedure not acceptable according to CTR

The documentation on the active substance x refers to a national ASMF procedure submitted to the BfArM. This is not possible for an application under CTR (EU) No 536/23014, since the submitted documentation must be available for all member states. This also applies to mononational studies, since mononational studies can be extended to other member states after approval. You have the following options for your application: All parts of the ASMF can be submitted separately by the ASMF holder via an IMPD-Q only application. Information on the IMPD-Q only procedure can be found in CTR (EU) No 536/23014 Questions & Answers, version 7.1, March 2025, point 125. Alternatively, you can also refer to an authorized finished medicinal product instead of an active substance part. If the active substance x in the investigational medicinal product is the same active substance as in the authorized finished medicinal product 'y' (same manufacturer, same manufacturing process), you can refer to its authorization with a simplified IMPD. The basis for this can be found in Annex I of CTR (EU) No 536/2014, section 1.2 (simplified IMPD).

Reference to EudraCT number missing on label

In footnote to primary and outer container label, reference to EuCT xxxxxxxx is missing.

The submitted IB is older than 12 months.

Last IB-update has been conducted more than 12 months ago. Please file an updated IB.