2. General Questions

2.1 Name of Regulatory Authority

Swissmedic – Swiss Agency for Therapeutic Products.

2.2 Name of Ethics Committee

Swissethics - the Swiss Association of Research Ethics Committees.

2.3 Clinical Trial Application Language

The national language of the trial site must be used – see Annex 3 of the Clinical Trials Ordinance (“ClinO”). This means either French, Swiss-German, or Italian, depending on which Canton the trial site falls within. (Canton is the name given to each of the 23 states (or 26, depending on the methodology) comprising the Swiss Confederation.)

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes – approval from both is required before the commencement of a clinical trial.

Both Swissmedic and Swissethics review their respective dossier and issue separate approvals. The trial cannot start before both approvals have been obtained (Art. 45 Human Research Act (HRA); Art. 54 Therapeutic Products Act (TPA)).

2.5 Can regulatory authority and EC submission be done in parallel?

Yes. In Switzerland, clinical trials with drugs and medical devices are classified into the categories A, B, and C. (See Art 10- ClinO)

Category A – When a medicinal product is authorized in Switzerland and its use:

1. Is in accordance with the prescribing information, 
2. Is in an indication or dosage different from that specified in the prescribing information, but in accordance with the following criteria:
   1. The indication is within the same disease group of the International Classification of Diseases (ICD),
   2. The disease in question is self-limiting and the dosage of the medicinal product is lower than that specified in the prescribing information; or
3. Is recognized as standard in guidelines prepared in accordance with internationally accepted quality criteria.

Category B - If a medicinal product:

1. Is authorized in Switzerland; and
2. Is not used as specified above.

Category C - If the medicinal product is not authorized in Switzerland.

Application for clinical trials applications (CTAs) can be made in parallel to Swissmedic and to the lead Ethics Committee for Categories B and C.

Category A clinical trials are exempt from the requirement for authorization from Swissmedic (see: Art 30, Clinical Trials Ordinance (ClinO), RS 810.305. The trial cannot start before the relevant approvals have been obtained (Art. 45, HRA - Art. 45 Human Research Act (HRA).

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

Yes – Swissmedic will grant an authorization of import based on the information provided in the CTA Form. This authorization concerns exclusively the IMP(s) used in the clinical trial and is valid only for the duration of the clinical trial. This authorization for importation is given in the authorization letter for the clinical trial.

For further details, see Swissmedic’s Clinical Trial Application dossier Guideline. Helpful forms and checklists are also available via that webpage.

In section 00F “FO Submission Form”: 

“10. In case the IMP(s) is/are imported from a foreign country and intended to be sent directly to the Swiss center(s) involved in the clinical trial, Swissmedic will grant an authorization of import based on the information provided in the CTA Form. This authorization concerns exclusively the IMP(s) used in the clinical trial and is valid only for the duration of the clinical trial. This authorization of import is given in the authorization letter for the clinical trial.

The same applies for import of auxiliary medicinal products used in the clinical trial, based on the information provided in the cover letter”.

“In case of import of the IMP(s) by a distributor located in Switzerland (for example a hospital pharmacy or packaging company), this distributor must have the appropriate licenses from Swissmedic to import, store, and distribute the IMP(s). In case such a company is not in possession of the licenses required, the license(s) need to be applied for. The instructions and forms for such application are available on www.swissmedic.ch (Section Licensing; “Authorisations - > Forms - > Authorisation“ - Swiss Medic - Authorisation Forms). Meanwhile, this company can pursue its activities [including auxiliary medicinal products] until the decision with regard to licenses has been taken."

“If substances which are under the control of the narcotics law (narcotics like opioids or psychotropics like benzodiazepines) must be imported, an import authorization according to the narcotics law is required for each import. This authorization can only be issued by the Narcotics Division of Swissmedic [see: Import Licence - Narcotics Division.”

“If substances capable of emitting ionizing radiation must be imported, the import for this substance must be covered by the handling license of the Federal Office of Public Health (FOPH).” [FOPH radioactive handling license].

2.7 Biological Specimen Export Requirements

The Health Research Act (HRA) does not require authorization for the export of biological material or health data, including genetic data. However, it does require the informed consent of the participants concerned for the export and further use for research purposes. The participants concerned must also give their informed consent to the transfer for other purposes. 

Depending on what is planned, the following applies according to the HRA:

If biological material and data are to be exported abroad in a non-anonymized form for research purposes, Art. 42 of HRA applies:

Art. 42 “Export

1. Biological material or genetic data may be exported for research purposes if informed consent has been given by the person concerned. For consent, Articles 16 and 22-24 and 32 apply mutatis mutandis.

2. Non-genetic health-related personal data may be disclosed abroad for research purposes if the requirements specified in Article 6 of the Federal Act of 19 June 1992 on Data Protection (SR 235.1) are met.”

If biological material and data are to be disclosed in a non-anonymized form for purposes other than research, Art. 41 of HRA applies:

Art. 41 "Transfer for purposes other than research

Biological material or health-related personal data which has been sampled or collected or of which further use has been made for research purposes may only be passed on for purposes other than research if:

1. a legal basis exists for such a transfer; or
2. in the particular case, informed consent to the transfer has been given by the person concerned.”

If the samples are to be exported in anonymized form, the data subjects must have been informed about the intended anonymization, about their right to dissent, about possible consequences, and also about possible disclosure to third parties (Art. 30 - Human Research Ordinance, HRO):

Art. 30 “Information on the proposed anonymization of biological material and genetic personal data for research purposes

The persons concerned must receive written or oral information on:

1. the proposed anonymization of the biological material and genetic personal data for research purposes;
2. their right to dissent;
3. the consequences of anonymization with regard to results concerning their health;
4. the possibility of the biological material and the data being passed on to third parties for research purposes.”

If the samples are not anonymized, care must be taken to ensure that the provisions of the Data Protection Act (FDPA) are observed with regard to the metadata.

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes – Art. 22 and Art. 35 of the Clinical Trials Ordinance (ClinO), explicitly contemplate the use of GMOs in clinical trials.

Art. 35 – “Clinical trials of gene therapy and clinical trials of genetically modified or pathogenic organisms.

¹ For Category B and C clinical trials of gene therapy and for clinical trials of genetically modified or pathogenic organisms as defined in Article 22, the documents specified in Annex 4 number 4 must be submitted to the Agency. 

² Before granting authorization, the Agency shall seek opinions from the Swiss Expert Committee for Biosafety (SECB), the Federal Office for the Environment (FOEN), and the FOPH. 

³ In addition to the areas specified in Article 32, it shall review whether the quality and biological safety of the product is guaranteed with regard to the participants and to human health and the environment. 

⁴ It shall grant authorization if: 

1. the SECB has confirmed the quality and biological safety of the product with regard to the participants and to human health and the environment; and 
2. no objections to the clinical trial have been raised by the FOPH or by the FOEN, based on the assessment of the environmental data. 

⁵ The Agency shall grant authorization within 60 days of acknowledgment of receipt of the formally correct application documents. The Agency shall inform the competent federal and cantonal authorities of its decision. 

⁶ Authorizations shall remain valid for the duration of the clinical trial, but for no longer than five years after they are granted.”

The Agency, the FOPH, and the FOEN shall jointly issue guidelines on the assessment of risks to human health and the environment.

Additionally, please check the Swissmedic page on clinical trials, where a specific section with related guidance and forms can be found under “Clinical trial on transplant products/gene therapy/genetically modified organism”.

2.9 Is in-country sponsor presence/representation required?

Yes – typically, although “[Swissmedic] authority can also accept that certain aspects of communication with a sponsor based abroad can be dealt with if that sponsor can always be contacted by [Swissmedic]. For legal material correspondence such as (interim) rulings, however, the representative in Switzerland remains the authoritative domicile for service”.

See Swissmedic’s Interpretation guide: Obligations of representatives of foreign sponsors. See page 1: 

“A sponsor, according to the definition in Art. 2c ClinO [Clinical Trials Ordinance (ClinO) is a person or institution headquartered or represented in Switzerland that takes responsibility for organizing a clinical trial in Switzerland. This means that persons or institutions headquartered in another country are acceptable as sponsors only if they have a designated representative in Switzerland. The ordinance does not regulate the specific obligations of such representatives. Given that the sponsor has three main obligations – legal procedural obligations in the approval procedure, responsibility for liability and coverage in relation to patients, and notification and reporting requirements in relation to the supervisory authorities – the tasks of the representative can be specified in greater detail as follows:

Sponsors headquartered in another country must specify a representative in Switzerland in accordance with Art. 2c ClinO. This provision is primarily designed to ensure the availability of a contact for the Swiss authorities in accordance with Art. 11b para. 1 Administrative Procedure Act (APA):

" ¹ Parties who make an application in proceedings must indicate their place of residence or registered office to the authority. If they live abroad, they must indicate an address for service in Switzerland, unless international law or the competent foreign body permits the authority to serve documents directly in the state concerned.

² The parties may also indicate an electronic mail address and declare that they consent to service by electronic mail. The Federal Council may provide that for electronic mail service further details of the parties are required.”

The same is true for the ethics committee: “Where a foreign sponsor is the applicant in the procedure for obtaining approval from a cantonal ethics committee (see Art. 24 para. 3 [Clinical Trials Ordinance, a representative should similarly be appointed in order to ensure that the approval decision can be delivered”.

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

No and yes, respectively.

See Art. 6 Clinical Trials Ordinance, ClinO, which sets out the requirements for an investigator’s professional qualifications, none of which explicitly necessitates a local qualification and/or domicile:

“1. The clinical trial investigator must:

a. be adequately trained in Good Clinical Practice and have the professional knowledge and experience required for the clinical trial; and

b. be conversant with the legal requirements for clinical trials or be able to ensure compliance by calling in appropriate expertise.

2. In addition, the investigator in a clinical trial of medicinal products, products under Article 2a paragraph 2 TPA or transplantation must be entitled to practice the medical profession independently.

3. For clinical trials covered by Chapter 4, a person without medical qualifications may also serve as an investigator, provided that this person is entitled to practice independently the profession specifically qualifying him or her to conduct the clinical trial.

4. The other persons conducting the clinical trial must have the professional knowledge and experience appropriate to the activities in question.”

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

Yes, a “Coordinating investigator” must be appointed for clinical trials conducted at more than one site in Switzerland.

Art 27 (2) of the Clinical Trials Ordinance (ClinO), indicates:

“The coordinating investigator is the person responsible in Switzerland for coordination of the investigators responsible at the individual sites.”

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled?

No, no transfer of obligations needs to be shown to Swissmedic. See Swissmedic’s Clinical Trial Application Dossier.

Section 00F-FO Submission forms, paragraph 5 includes the statement that “[t]he CTA form must be dated and signed by the sponsor or by the sponsor representative, or by the CRO as per contractual authorization. Contractual authorizations do not have to be submitted to Swissmedic. Swiss Affiliates of a foreign Sponsor may sign the notification form without contractual authorization. Swissmedic does not need to receive the delegation log for signatures.”

2.13 Is there a requirement to register clinical trials on a local registry or database?

Yes. Art. 64 of the Clinical Trials Ordinance (ClinO) requires that the sponsor must register the clinical trial in both a primary registry recognized by the World Health Organization (WHO) or in the registry of the U.S. National Library of Medicine. Additionally, the sponsor must enter the data specified in Annex 5 number 2 in the supplementary federal database (Kofam), using a Swiss national language (French, German, or Italian). The data must be entered in the form authorized by the responsible ethics committee.

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

In general terms, 10 years from the completion or discontinuation of the clinical trial and 15 years in the case of implantable products.

Art. 45 of the Clinical Trials Ordinance, ClinO, specifies the data retention requirements:

“1. The sponsor must retain all data relating to the clinical trial until the expiry date of the last batch supplied of the medicinal product under investigation or of the last product under Article 2a paragraph 2 [Therapeutic Products Act (TPA)] manufactured, but at least for ten years after the completion or discontinuation of the clinical trial.  In the case of products under Article 2a paragraph 2 TPA that can be implanted, the retention period amounts to a minimum of 15 years.” 

“2. The investigator must retain all documents required for the identification and follow-up of participants, and all other original data, for at least ten years after the completion or discontinuation of the clinical trial. In the case of products under Article 2a paragraph 2 TPA that can be implanted, the retention period amounts to a minimum of 15 years.” 

“3. For clinical trials of transplant products and for clinical trials of blood and blood products, the retention requirements are governed by Article 40 paragraph 1 TPA [30 years].”

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

Art. 37 of the Clinical Trials Ordinance (ClinO) provides that:

“1. If immediate safety and protective measures have to be taken during the conduct of a clinical trial, the investigator shall notify the ethics committee of these measures, and of the circumstances necessitating them, within 7 days.” 

“2. In the case of clinical trials of products under Article 2a paragraph 2 [Therapeutic Products Act (TPA)] (devitalized human tissues or cells), this notification shall be made within 2 days.” 

“3. For Category B [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 Category C [where the product is not licensed for use in Switzerland], the notifications specified in paragraphs 1 and 2 shall be made to [Swissmedic]. This obligation rests on the sponsor.” 

Art. 38 of the Clinical Trials Ordinance (ClinO) provides the requirements for “notification and reporting upon completion, discontinuation or interruption of a clinical trial”:

“1. The investigator shall notify the ethics committee of the completion of the clinical trial in Switzerland within 90 days. Completion of a clinical trial is marked by the last participant’s final follow-up visit, in the absence of provisions to the contrary in the protocol.” 

“2. The investigator shall notify the ethics committee of the discontinuation or interruption of the clinical trial within 15 days. In the notification, the reasons for the discontinuation or interruption shall be stated.”

“3. The investigator shall submit a final report to the ethics committee within a year after completion or discontinuation of the clinical trial unless a longer period is specified in the protocol.” 

Art. 39 of the ClinO provides the requirements for “documentation of adverse events (AE) in clinical trials of medicinal products”: 

“1. If, in the course of a Category C clinical trial of medicinal products [ie where the product is not licensed for use in Switzerland], adverse events which are not to be classified as serious occur in participants, they must be documented by the investigator in a standardized manner.”

“2. Adverse events occurring in the course of a Category B clinical trial [ie 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] must be documented in a standardized manner if this is envisaged in the protocol or was requested by the authorities responsible for authorization.” 

“3. For Category A clinical trials [i.e. where the product is licensed for use in Switzerland and the proposed clinical trial is within its licensed indication], there is no obligation to document adverse events.” 

Whilst Art. 40 of the ClinO provides that, for serious adverse events (SAE) in clinical trials of medicinal products: 

“1. If, in the course of a clinical trial, serious adverse events occur in participants, the investigator must document these in a standardized manner and notify the sponsor within 24 hours after they become known. Events which are not to be reported according to the protocol are exempted.” 

“2. In the absence of provisions to the contrary in the protocol, the investigator shall notify the responsible ethics committee of a fatal serious adverse event occurring at a trial site in Switzerland within 7 days.” 

“3. In the case of a multicentre clinical trial, the coordinating investigator shall also report events as specified in paragraph 2 to the responsible ethics committee concerned within the same period.”  

Art. 41 of the ClinO provides that, re suspected unexpected serious adverse reactions (SUSAR) in clinical trials of medicinal products: 

“1. If, in the course of a clinical trial, a suspected unexpected serious adverse reaction occurs in participants, the investigator must document this in a standardized manner and notify the sponsor within 24 hours after it becomes known.” 

“2. The investigator shall notify the responsible ethics committee of a fatal suspected unexpected serious adverse reaction occurring in Switzerland within 7 days and of any other suspected unexpected serious adverse reaction within 15 days.” 

“3. If, in the case of a multicentre clinical trial, a suspected unexpected serious adverse reaction occurs at one of the trial sites, the coordinating investigator shall also notify the responsible ethics committee concerned in accordance with paragraph 2, within the same period.” 

“4. For Category B [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 C [ie where the product is not licensed for use in Switzerland] clinical trials, the notifications specified in paragraph 2 shall also be made to [Swissmedic]. This obligation rests on the sponsor. For Category A clinical trials [ie where the product is licensed for use in Switzerland and the proposed clinical trial is within its licensed indication], the sponsor is subject to the notification requirements specified in Article 59 paragraphs 1 and 2 Therapeutic Products Act (TPA)  “Any person manufacturing or distributing ready-to-use therapeutic products must put in place a system of notification”). 

Additionally, under Art 63 of the Clinical Trials Ordinance (ClinO), if, “in the course of a clinical trial, serious adverse events occur in participants in Switzerland, and it cannot be excluded that the events are attributable to the intervention under investigation, the investigator must document them in a standardized manner, also reporting these events to (a) the sponsor within 24 hours after they become known; and (b) to the responsible ethics committee within 15 days.” 

In the case of a multicentre clinical trial, if serious adverse events occur at one of the trial sites, the coordinating investigator must also report the events as specified above to the responsible ethics committee concerned, within the same period.

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)? 

See Swissmedic’s AW-Information sheet FAQ on clinical trials with medicinal products.

Other adverse drug reactions than those referred to in Section 2.15 above must be notified to Swissmedic in the sponsor’s Annual Safety Report (ASR), including “[i]n the case of clinical trials also conducted abroad according to the same protocol, the events or adverse reactions occurring abroad must be included in the Annual Safety Report. The sponsor is also obliged to submit to Swissmedic, once a year, a list of all undesirable side-effects, SUSARs, and a report on the safety of trial subjects, together with a re-evaluation of the risk-benefit ratio.”

Instructions and forms can be found on the Swissmedic webpage “Safety measures in clinical trials.” 

Both Swissmedic and the Swiss Clinical Trial Organization (SCTO) provide template forms for ASRs. Although both are explicitly stated to be for Investigator Initiated Trials (IITs), they are thought to be of use for sponsor-initiated trials and the SCTO’s website includes a statement to that effect (“These forms can be used by any investigator performing clinical research in Switzerland, in particular, sponsor-investigators”). 

See:

• Swissethics ASR Template
• SCTO ASR Template 

2.17 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol? 

No, such notification is not required.

See Swissmedic’s information sheet “Clinical Trial Application (CTA) Questions and Answers” dated 11 May 2023:

“In Switzerland, it is not required by law to notify serious breaches in clinical trials to the competent authority. However, if the serious breach is systematic and it results in safety concerns for the subjects enrolled in the clinical trial, then the sponsor should implement Urgent Safety Measures to minimize this risk immediately. Urgent Safety Measures must be reported to Swissmedic according to Art 47 [of Clinical Trials Ordinance (ClinO), which may revoke or suspend the authorization granted or make the continuation of the clinical trial subject to additional conditions, in particular if the clinical trial is not conducted in accordance with the application documents approved by it or by the ethics committee." 

2.18 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

Yes – insurance or its equivalent is required, using a Swiss insurance company, or a foreign insurance company with a branch office in Switzerland.

Swissmedic’s interpretation guide “Obligations of Representatives of Foreign Sponsors” provides that:

“The person or institution that organizes the clinical trial is responsible for the liability and coverage described in Art. 19 - 20 Human Research Act (HRA), “Liability must be appropriately covered through insurance or in some other manner…”, even if it is not headquartered in Switzerland. The law does not provide for any delegation of the above-mentioned obligations to a third party. This order is not fundamentally affected by Art. 2c Clinical Trials Ordinance (ClinO).”

The wording of this provision does not mean that the representative must accept responsibility for the liability and coverage of the foreign sponsor, although it must be ensured at all times that injured participants are not disadvantaged by the fact that the sponsor is based in another country.

“During the approval procedure before an ethics committee, evidence must be provided to show that liability is covered by insurance or some other provision (Art. 25f [Clinical Trials Ordinance (ClinO). Under the relevant insurance oversight legislation, coverage in the form of insurance is in particular only acceptable if it is provided by an insurance company headquartered in Switzerland or by foreign insurance company with a branch office in Switzerland. This ensures that patients are able to assert both their right of direct claim (Art. 20 para. 3a [Human Research Act (HRA), Art. 14 para. 2 [Clinical Trials Ordinance (ClinO) and associated legal enforcement claims in Switzerland.” 

“If liability is not covered by insurance, but by the provision of security of equivalent value in accordance with Art. 13 para. 1b Clinical Trials Ordinance (ClinO), the ethics committee must require the granting of a right of direct claim towards a person based in Switzerland Art. 14 para. 4, Clinical Trials Ordinance (ClinO). The Ordinance does not specify whether this is implemented by the "representative" according to Art. 2c, Clinical Trials Ordinance (ClinO) or by a third party. 

“If, exceptionally, liability does not need to be covered by insurance or equivalent securities (Art. 12b, Clinical Trials Ordinance (ClinO)), injured persons must direct their claim for damages to the sponsor. Under international private law, injured persons resident in Switzerland can bring an action against a sponsor domiciled in another European country in Switzerland.”

According to Article 13 of the Clinical Trials Ordinance (ClinO), liability coverage must cover damage occurring up to ten years after the completion of the clinical trial.