Clinical trial of medicinal products containing or consisting of genetically modified (micro-) organisms

The Swedish Medical Products Agency (Swedish MPA) and the Swedish Work Environment Authority cooperate regarding the regulation of clinical trials of medicinal products containing or consisting of genetically modified organisms (GMO’s)¹ or genetically modified microorganisms (GMM’s) ². This also includes clinical trials on animals covered by the Medical Products Agency's regulations³.

Deliberate release of GMO and contained use of GMM

The Swedish MPA is the supervisory authority for so‍-‍called deliberate release⁴ of medicinal products containing or consisting of GMOs, while the Swedish Work Environment Authority is the supervisory authority for so‍-‍called contained use⁵ of GMMs.

In Sweden, clinical trials with GMOs are assessed as deliberate release, but within the framework of the trial, there are parts that can be considered to constitute contained use of GMMs:

• Deliberate release of GMOs into the environment refers to the stage when the patient has been administered the investigational medicinal product. Thus, the Swedish MPA has supervisory responsibility from the time point at which the GMO‍-‍containing medicinal product has been administered to the patient.
• Other aspects of the clinical trial such as manufacturing, transport (indoors), storage (e.g. at the hospital pharmacy), administration and waste management regarding investigational medicinal product that contain or consist of GMM are counted as contained use and regulated by the Swedish Work Environment Authority’s statutes. The Swedish Work Environment Authority always also has the supervisory responsibility for work environment issues in these contexts.

¹A genetically modified organism according to Chapter 13 § 4 of the Environmental Code (1998:808) (in Swedish Miljöbalken) is an organism where the genetic material has changed in a way that does not occur naturally through mating or natural recombination. Examples of this are viral vectors, cells genetically modified with viral vectors (CAR-T cells and others), genetically modified bacteria and cells modified with the CRISPR technology. Plasmids that are not integrating or replicating or cells genetically modified with a non-integrating or non-replicating plasmid are not considered to be GMOs. Nucleic acid sequences (RNA and DNA) that are introduced into cells using lipid particles are not considered GMOs.

²According to the Ordinance (2000:271) on the contained use of genetically modified organisms, a genetically modified micro-organism means a micro-organism (any microbiological entity, cellular or non-cellular, which can reproduce or transmit genetic material, including viruses, viroids and cell cultures of animals and plants) whose genetic material has been altered in a way that does not occur naturally through mating or natural recombination.

³The Swedish MPA regulations (LVFS 2004:10) on deliberate release in investigational clinical trials and certain trials on animals of medicinal products containing or consisting of genetically modified organisms.

⁴Deliberate release refers according to Chapter 13 § 6 of the Environmental Code (1998:808) to an intentional introduction of genetically modified organisms into the environment without the use of such containment measures as referred to in § 5 of the same statute. Additional provisions are found in the Ordinance (2002:1086) on the release of genetically modified organisms into the environment

⁵Contained use according to Chapter 13 § 5 of the Environmental Code (1998:808) is an activity where someone 1) genetically modifies organisms or grows, stores, transports, destroys, gets rid of, or otherwise handles such genetically modified organisms and 2) uses specific containment measures to limit these organisms' contact with the public and the environment to achieve a high level of safety for the public and the environment. Additional provisions are found in the Ordinance (2000:271) on the contained use of genetically modified organisms.

More information (in Swedish):

Documents to the Swedish MPA

In order to start a clinical trial where the investigational medicinal product consist of or contain a GMO, a GMO-application and a permit from the Swedish MPA is required. The permit covers the medical approval of the trial and the environmental consequences of the trial.

A GMO application is made in accordance with Directive 2001/18/EC, Regulation 2002:1086 and LVFS 2004:10 and is submitted to the Swedish MPA.

The clinical trial application is made in accordance with Regulation (EU) 536/2014 which is applicable from January 31 2022. From January 31 2023 it is mandatory for all new applications to be submitted and carried out in accordance with the regulation.

After 30 January 2025, all clinical trials approved in accordance with the previous EU Directive 2001/20/EC must have been transferred to be regulated by Regulation (EU) 536/2014.

Content of the GMO application

• an Environmental Risk Assessment (ERA) in accordance with Annex II and IIIA to Directive 2001/18/EC. Shall be written in English.
• receipt that the Summary Notification Information Format (SNIF) in accordance with Council Decision 2002/813/EC has been submitted to the European Commission register ’Food Chain (ESFC) platform’, see further information via the link ’Field Trials’ below.
• a brief summary (½-1 A4 size) of the trial, in Swedish, focusing on the GMO part (this will be published on the Swedish MPA’s website).

Submission of the application

The GMO application should be sent by email to registrator@lakemedelsverket.se in parallel with the initial clinical trial application being submitted via the Clinical Trials Information System (CTIS). I tne GMO application, refer to the EU Trial Number for the clinical trial application concerned.

A GMO application is sent to the Swedish MPA also for a clinical trial of a GMO-containing medicinal product approved within the EU. In cases where the medicinal product has been approved and a GMO assessment has been carried out previously, the applicant shall state this and notify if any new risks have been identified.

Good practice and common application forms

The Swedish MPA approves the use of the EU Commission’s documents regarding good practice and common application forms for clinical trials of investigational medicinal products containing GMO.

Documents to the Swedish Work Environment Authority

Activities involving contained use of GMM may not be commenced until notification of so-called F or L activities has been made to the Swedish Work Environment Authority. Such a notification shall be made 45 days prior to the activity commences. The notification is not limited in time.

For R-activities, a permit from the Swedish Work Environment Authority is required. An application shall then be made 90 days before the start of operations. Permits are granted for a maximum of five years at a time.

Approved medicinal products containing GMM are exempt from notification to the Swedish Work Environment Authority, as they have already been approved for release on the EU market. Thus, there is no need to notify the Swedish Work Environment Authority if the clinical trial is conducted with an already approved GMM medicinal product.

Information on the Swedish Work Authority’s website

Related information

Information in Swedish: