4. Regulatory Authority (RA)/ Competent Authority (CA)

4.1 Provide a list of documents needed to be submitted for RA/CA review and approval including the number of copies and/or translations as relevant. 

See Annex 4 of the Clinical Trials Ordinance (ClinO) – here are the main categories for submission:

1. Application documents for Category B clinical trials of medicinal products [i.e. products licensed for use in Switzerland, but where proposed clinical trial is for a use outside of the scope of its licensed indication, including dosage] and transplant products:

1.1. Basic form

1.2. Protocol

1.3. Prescribing information for the medicinal product or transplant product

1.4. Documents on the quality of the medicinal product, only concerning any changes in the composition and manufacturing thereof

1.5. Investigator’s Brochure (IB), only concerning changes in the administration of the medicinal product

1.6. Proof of compliance with Good Manufacturing Practice (GMP)

1.7. Proof of compliance with correct labeling

1.8. Any decisions of foreign drug regulatory authorities concerning the clinical trial, including any conditions imposed and the reasons given

1.9. Information on any applications currently being reviewed by an ethics committee in Switzerland, and on any decisions of ethics committees in Switzerland

2. Application documents for Category C clinical trials of medicinal products [i.e. where the product is not licensed for use in Switzerland] and transplant products:

2.1. Basic form

2.2. Protocol

2.3. Documents on the quality of the medicinal product or transplant product

2.4. Investigator’s Brochure (IB), including information on risk assessment; if the medicinal product under investigation is authorized for the proposed use in a country with a comparable drug regulation system, the relevant prescribing information may be submitted; for clinical trials in which the medicinal product or transplant product under investigation is being used in persons for the first time: in addition, the study reports cited in the IB

2.5. For trials of transplant products or gene therapy: documents on preclinical and toxicology studies

2.6. Proof of compliance with Good Manufacturing Practice (GMP)

2.7. Proof of compliance with correct labeling

2.8. Any decisions of foreign drug regulatory authorities concerning the clinical trial, including any conditions imposed and the reasons given

2.9. Information on any applications currently being reviewed by an ethics committee in Switzerland, and on any decisions of ethics committees in Switzerland

3. Application documents for Category C clinical trials of products under Article 2a paragraph 2 of the [Therapeutic Products Act (TPA)]:

3.1. Basic form

3.2. Protocol

3.3. Case report form (CRF)

3.4. For clinical trials of a product under Article 2a paragraph 2 TPA that has not been reported pursuant to Article 6 paragraph 3 [Medical Devices Ordinance (MedDO) – in its version of 1 January 2002 in application of Article 108 paragraph 1 letter b Medical Devices Ordinance (MedDO)], the relevant documentation, comprising:

1. Investigator’s Brochure (IB), with a compilation of current clinical and non-clinical information on the product under investigation and its components,
2. list of the applicable standards for products under Article 2a paragraph 2 TPA and description of all deviations,
3. documentation of and reasons for any deviations from the standard ISO 14155, 
4. manufacturer’s statement or release in accordance with Annex VIII to Directive 93/42/EEC or Annex 6 to Directive 90/385/EEC,
5. confirmation that documentation is being kept available as specified in Annex VIII to Directive 93/42/EEC or Annex 6 to Directive 90/385/EEC,
6. if the sponsor of the clinical trial and the manufacturer of the product are not identical: agreement on risk management between the sponsor and manufacturer.

3.5. For clinical trials of a product under Article 2a paragraph 2 TPA [see above] that has been reported pursuant to Article 6 paragraph 3 MedDO in its version of 1 January 2002 in application of Article 108 paragraph 1 letter b MedDO [see above] which is not used in accordance with the intended purpose or the instructions: the relevant documentation, comprising:

1. Information on the conformity of the product under Article 2a paragraph 2 TPA
2. Product information on the product under Article 2a paragraph 2 TPA
3. Risk analysis for the new use and safety measures derived therefrom
4. Other elements of the IB concerning the new use
5. List of the applicable standards for products under Article 2a paragraph 2 TPA, description of deviations from these standards associated with the new use
6. Documentation of and reasons for any deviations from the standard ISO 14155

4. Additional application documents for Category B and C clinical trials of gene therapy and of genetically modified or pathogenic organisms:

4.1. Information on the risks of the investigational product containing genetically modified or pathogenic organisms.

4.2. Risk assessment of the conduct of the clinical trial with regard to the protection of human health and the environment.

4.3. A description of the safety measures required for the protection of human and animal health and the environment, and in particular to prevent the release of microorganisms into the environment during and after transplantation, and during transport, storage, and disposal.

5. Additional application documents for clinical trials of medicinal products or products under Article 2a paragraph 2 TPA capable of emitting ionizing radiation:

5.1. Details of all relevant radiological protection aspects, and in particular a calculation or estimate of the effective dose, organ doses, and any tumor doses.

5.2. The licenses required under Article 28 of the Radiological Protection Act (mandatory licensing) of 22 March 1991.

5.3. For medicinal products or products under Article 2a paragraph 2 TPA containing radioactive sources:

1. Information on the properties of the radiopharmaceutical, and in particular on pharmacokinetics, quality, stability, radiochemical purity, and radionuclide purity;
2. For authorized radiopharmaceuticals: the prescribing information;
3. For non-authorized radiopharmaceuticals: information on the manufacturing and quality control processes for the radiopharmaceutical, the names of the persons responsible for these processes, and details of their professional qualifications,
4. The names of the persons responsible for the use of the radiopharmaceuticals in humans and details of their professional qualifications;
5. Information specified in the FOPH form for clinical trials of radiopharmaceuticals or radiolabelled compounds.

6. Application documents for Category C clinical trials of transplantation of human organs, tissues, and cells:

6.1 Basic form

6.2 Protocol

6.3 Proof of the origin of the organs, tissues, or cells used

6.4 Documents on the quality of the organs, tissues, or cells used, and in particular on the tests performed

6.5 Proof of compliance with duties of care, particularly with regard to the assessment of fitness to donate and mandatory testing, and the procedure in the event of reactive test results

6.6 Proof of compliance with correct labeling

6.7 Authorization, if the handling of the organs, tissues, or cells used is subject to authorization

6.8 Any decisions of foreign regulatory authorities concerning the clinical trial, including any conditions imposed and the reasons given

6.9 Information on any applications currently being reviewed by an ethics committee in Switzerland, and on any decisions of ethics committees in Switzerland

See also Swissmedic’s Clinical Trial Application dossier guideline. On page 1, Swissmedic notes that “[f]or confidentiality reasons, documents may be submitted by different providers. E.g. in investigator-initiated trials, the PQD is submitted by the Drug Master File holder and the rest of the dossier is submitted by the Sponsor.”

4.2 Time required for RA/CA review and approval process and turnaround time if any query is raised during the review process. 

See Art 33 of the Clinical Trials Ordinance (ClinO), Annex 3:

“Procedure and deadlines

1. [Swissmedic] shall acknowledge receipt of the application within 7 days and notify the sponsor of any formal deficiencies in the application documents.
2. It shall reach a decision within 30 days of acknowledgment of receipt of the formally correct application documents.
3. If a medicinal product or product under Article 2a paragraph 2 TPA [devitalised human tissues or cells, or their derivatives], is to be used in persons for the first time or manufactured in a new process, this deadline may be extended by a maximum of 30 days. [Swissmedic] shall inform the sponsor of the extended deadline.
4. If [Swissmedic] requests additional information…. the clock shall be stopped until this information has been received.
5. [Swissmedic] shall inform the responsible ethics committee and other competent cantonal authorities of its decision.”

Where a ‘significant change’ (see below) is sought to be made by the sponsor, then, according to Art 34 of the Clinical Trials Ordinance (ClinO), Swissmedic shall reach a decision within 30 days after receipt of the complete application documents affected by the change. The provisions of Article 33 also apply. The following are considered to be significant changes: 

1. changes to the medicinal product or product under Article 2a paragraph 2 TPA [devitalized human tissues or cells, or their derivatives ], or to its administration or use; 
2. changes based on new preclinical or clinical data which may affect product safety; or 
3. changes concerning the production of the medicinal product or product under Article 2a paragraph 2 TPA which may affect product safety.

Other changes that affect the documents submitted to Swissmedic must be notified to Swissmedic as quickly as possible.

There are additional provisions governing clinical trials of gene therapy, clinical trials of genetically modified or pathogenic organisms, and clinical trials involving ionizing radiation – see Art 35 ClinO.

4.3 Does the regulation support electronic submission?

Yes – From 19 June 2023, applications for clinical trials with medicinal products and ATMPs can be submitted via the eGOV service portal.

Swissmedic provides detailed information and guidance under the “Applications for clinical trials for medicinal products” webpage.

4.4 Does the regulation require the applicant to be a Principal Investigator (PI)/Chief Investigator (CI)?

No, the applicant doesn’t have to be the PI or CI - see Swissmedic’s information sheet “Clinical Trial Application (CTA) Questions and Answers”, dated 11 May 2023, accessible from the Swissmedic Q&A and important links: 

“Who is allowed to sign the submission forms (i.e. CTA form and the forms for submission of changes and for reporting)? 

The applicant can be any authorized person (sponsor, sponsor representative, CRO, etc.). Swissmedic does not need to receive the delegation log for signatures.” 

And:     

“Is the trial protocol (or protocol amendment) to be signed, and by whom? 

For submission to Swissmedic, only the sponsor’s signature is necessary on the trial protocol and the amendment(s). It goes without saying that the trial protocol must be signed by the sponsor and the investigator prior to the start of the clinical trial. With their signatures, both parties confirm their agreement to the protocol or protocol amendment(s) (ICH E6 8.2.2).” 

4.5 Please describe the process of RA/CA submission for clinical trial approval. 

Art. 32 of the Clinical Trial Ordinance (ClinO) provides that:

“For clinical trials of medicinal products, [Swissmedic] shall review: 

1. the completeness of the application; 
2. the safety of the medicinal product, and in particular the preclinical and clinical pharmacology, toxicology, formulation and pharmacokinetics, and the proposed dosage and indication; 
3. the risk assessment and risk management based on the medicinal product safety data; 
4. the quality of the medicinal product and compliance with Good Manufacturing Practice (GMP); 
5. other areas, where this is necessary to assess the safety or quality of the medicinal product. 

Detailed instructions for submission and requirements can be found on the Swissmedic “Clinical Trial Application” page.

4.6 Does the RA/CA provide written acknowledgment of the submitted application? If not, describe how the application is tracked.

Yes, Swissmedic provides a written acknowledgment of the application. See Art. 33 of the Clinical Trials Ordinance (ClinO).

4.7 What is the relevant RA/CA fee in local currency/USD? Please provide as much information as possible (e.g. if the fee is different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, etc.)

See Annex 110 Art IV of the decree of the Swiss Institute for Therapeutic Products which sets out the fees:

4.8 Does RA/CA accept checks or can payment be made electronically? Please provide details on (1) A/C number; (2) A/C Name; (3) Sort Code; (4) Swift Code; (5) Bank address, etc. Where can remittance advice notices be sent?

This information does not appear to be publicly available – Swissmedic invoices the sponsor/the sponsor’s representative in Switzerland (as applicable) (See: Swissmedic’s Clinical Trial Application dossier Guideline, Section 00F/4, on page 4).

4.9 Is there any guidance tool available for making an electronic application? If yes, provide the link and/or step-by-step instructions.

Yes – see Swissmedic’s Clinical Trial Application Dossier Guideline. Forms and checklists are also available via that webpage.

4.10 Does RA/CA require any screenshots/mock screens for participant-facing materials?

No, not that we have been able to determine. See Section 4.1 above – materials required to be submitted to Swissmedic do not include patient-facing materials, but please see Section 3.11 in relation to materials to be submitted to the ethics committee(s), which do include patient-facing materials (and therefore probably mock-ups).