Medicinal products for animals

Regulations

Clinical trials in animals are regulated by Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products, by the Medicinal Products Act 2015:315 (in Swedish läkemedelslagen) and by the Swedish Medical Products Agency (MPA) regulations HSLF‍-‍FS 2021:110.

The EU Regulation applies from 28 January 2022 and repeals Directive 2001/82/EC.

The Swedish MPA regulations HSLF‍-‍FS 2021:110 applies from 28 January 2022 and repeals HSLF‍-‍FS 2016:78.

Definition from the EU Regulation:

Clinical trial means “a study which aims to examine under field conditions the safety or efficacy of a veterinary medicinal product under normal conditions of animal husbandry or as part of normal veterinary practice for the purpose of obtaining a marketing authorisation or a change thereof ”.

Studies, which are not intended to be included in an application for marketing authorisations for veterinary medicinal products of change of an authorisation, fall outside of the requirement for authorisation of clinical trials in accordance with the EU Regulation.

GCP

Clinical trials shall be carried out taking due account of the international guidelines on good clinical practice of the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH).

Go to Guidelines/‌Pharmaceuticals/‌Efficacy/‌Good clinical practice.

GMP

The manufacture of medicinal products shall take place in appropriate premises, be carried out with the aid of appropriate equipment, and also otherwise take place in accordance with Good Manufacturing Practice (GMP). Regulations on GMP can be found in the Swedish MPA regulations (HSLF‍-‍FS‌ 2021:103) on good manufacturing practice for medicines.

Application

In an application for a clinical trial the following documentation is to be submitted:

• Completed and signed application form (so far only in Swedish).

• Trial protocol with the content set out in section 6.3 of the VICH guidelines. The trial protocol shall be signed by the sponsor and the investigato or, in the case of multicentre trials, the coordinating investigator.
• Declaration from the sponsor with the content specified in section 4.2.1 of the VICH guidelines.
• Documentation concerning the investigational medicinal product and any other medicinal products which are included in the trial, and which are indicated in Annex 1 of HSLF‍-‍FS 2021:110. The documentation shall be summarised and can be adapted to the current trial phase and be preliminary and less complete than when applying for a marketing authorisation. See also below section Requirements for investigational medicinal products.
• Information on the labelling of the investigational medicinal product in accordance with Annex 2 of HSLF‍-‍FS 2021:110.
• Information on planned long‍-‍term follow‍-‍ups, in particular with regard to adverse events.
• Summary of the scientific advice provided for the trial in question where applicable.
• Information on the trial to the animal owners before their consent to participate is obtained.
• Invoicing documentation.

Ethical approval 

The application for clinical trial shall also include a copy of the regional ethical committee approval for animal experiments in accordance with Chapter 7, Section 9 of the Swedish Animal Welfare Act (2018:1192) (in Swedish djurskyddslagen). If the decision of the regional ethical committee is not available at the time of the application, it should be submitted to the Swedish MPA as soon as possible.

Information on ethical approval and the e‍-‍service for application is found on the Swedish Board of Agriculture web site (so far only in Swedish ).

The Swedish MPA decision

The Swedish MPA shall issue a decision to approve or refuse a clinical trial within 60 days of the receipt of a valid application.

Changes in the trial

Authorisation needed

Some changes to a clinical trial for veterinary medicinal products or to the investigational medicinal product require authorisation from the Swedish MPA. An application has to be submitted if the change:

• could have an impact on the safety of animal patients,
• could have an impact on the scientific value of the study
• or is significant for some other reason.

The application shall be submitted in accordance with the requirements for the initial authorisation application for the clinical trial on animals in relevant parts, such as cover letter and updated documentation concerning the change.

No authorisation

Changes other than those specified above do not require authorisation from the Swedish MPA. Nor is authorisation required when the sponsor and the investigator have to make immediate changes which can be regarded as urgent safety measures or to resume a trial which has been interrupted as part of an urgent safety measure.

Reporting of adverse events

Pursuant to section 4.2.10 of the VICH guidelines, the sponsor must report all adverse events to the Swedish MPA in accordance with the applicable regulatory requirements. This means that the sponsor must report any serious adverse events during the clinical trial of medicinal products whose nature or seriousness do not correspond with existing data about the investigational medicinal product or any other medicinal products included in the trial.

The serious adverse events must be reported no later than 15 days after the sponsor became aware of the event. If the trial is being conducted at more than one trial site, the sponsor must also inform all investigators about the serious adverse events.

Reporting of urgent safety measures

The sponsor shall as soon as possible notify the Swedish MPA of the urgent safety measures that the investigator or sponsor has taken as a consequence of the observed adverse events.

The initial notification can be either oral or written and shall be followed as soon as possible by a written report on the circumstances, the measures taken and any further measures planned.

Requirements for investigational medicinal products

An Investigational Medicinal Product Dossier (IMPD) or, if applicable, a simplified IMPD, or a Summary of Product Characteristics (SmPC) shall be attached in the application for each investigational medicinal product (including placebos) and other possible medicinal products .

Guidance on IMPD content

In order to facilitate the Swedish MPA assessment, it is an advantage if, where applicable, it is clear (for example in a list) what changes have been made to the IMPD compared with the previous version submitted to the authority.

Reporting of completed trials

If a clinical trial of medicinal products on animals is terminated prematurely, the sponsor shall report this to the Swedish MPA no later than 15 days after the trial is ended. The sponsor shall state the reasons why the trial was terminated and, where applicable, the follow‍-‍up measures taken for safety reasons.

The sponsor shall report the results of the trial to the Swedish MPA no later than 12 months after the clinical trial has been completed.

The report shall have the content specified in Annex II of Regulation (EU) 2019/6 of the European Parliament and of the Council in accordance with Commission Delegated Regulation (EU) 2021/805.

The report shall consist of a summary of the trial results, adapted to the current trial phase, as stated in Appendix 1 to HSLF‍-‍FS 2021:110. It should therefore not consist of a presentation of all the results required for the application for marketing authorisation (according to Annex II to EU Regulation 2021/805).