Swiss clinical trial regulation is designed to protect research participants. Its framework of dual approvals, risk categorization, and liability coverage reflects a considered balance between enabling research and safeguarding those who participate in it. For pregnant individuals, however, that protective architecture has produced a different outcome: not safer participation, but systematic exclusion from the evidence base that informs their medical care. The regulatory apparatus that ensures rigorous oversight of clinical research has, in practice, made it operationally difficult to generate the pregnancy-specific data that prescribers and patients need, a gap that an incoming international guideline is poised to expose.
1. The Protective Reflex and Its Consequences
Swiss law does not prohibit clinical trials involving pregnant participants. The Bundesgesetz über die Forschung am Menschen (Humanforschungsgesetz, HFG) and the Verordnung über klinische Versuche mit Ausnahme klinischer Versuche mit Medizinprodukten (KlinV) subject such trials to additional conditions beyond those applicable to the general adult population, a classification that sounds manageable and that most sponsors have treated as a reason not to include pregnant participants at all.1Art. 26 HFG (SR 810.30) (research with pregnant women and embryos/fetuses in vivo); KlinV (SR 810.305). The distinction matters. A legal framework that conditions inclusion on additional requirements is structurally different from one that prohibits inclusion, but the practical effect, for most trial sponsors, has been the same.
The consequences of that practical exclusion extend beyond the individual trial. Products reach the Swiss market (and markets worldwide) without pregnancy-specific safety, efficacy, or dosing data. Prescribers must rely on extrapolation from non-pregnant populations, animal studies, or post-market observational evidence that accumulates slowly and unevenly. One analysis of 172 medicines approved by the United States Food and Drug Administration (FDA) between 2000 and 2010 found teratogenic risk “undetermined” at approval for 97.7% of products, with a mean of approximately 27 years passing before sufficient evidence emerged to assign a confident teratogenic-risk rating.2Adam, Polifka & Friedman (2011) 157C Am J Med Genet C 175; reported in G Guglielmi (2026) 650 Nature 286. Sponsors designing global trials with Swiss arms routinely exclude pregnant participants not because the HFG demands it, but because the surrounding regulatory, insurance, and liability architecture makes inclusion operationally difficult in ways that are rarely documented, rarely escalated, and rarely questioned.
A framework that protects by excluding may generate precisely the evidence gap it was designed to prevent.
The question, then, is not whether Swiss law permits inclusion (it does), but whether the regulatory infrastructure provides sufficient clarity for sponsors to design compliant protocols, and whether the absence of that clarity has itself become a source of risk.
2. What the HFG and KlinV Require, and What They Leave Open
The starting point is the dual-approval process that governs all clinical trials with medicinal products in Switzerland. Art. 54 of the Heilmittelgesetz (HMG) requires Swissmedic authorization; the HFG requires ethics committee approval.3Art. 54 Bundesgesetz über Arzneimittel und Medizinprodukte (HMG) vom 15. Dezember 2000 (SR 812.21). For trials involving pregnant participants, both approvals are subject to additional requirements, but the content of those requirements is specified with considerably less precision than the approval process itself.
The KlinV establishes a risk-based categorization system for clinical trials of medicinal products under Art. 19, classifying such trials into Categories A, B, and C primarily by reference to the Swiss authorisation status of the investigational product and the conformity of its proposed use with the Fachinformation, with case-by-case re-categorisation on safety grounds available under Art. 19 Abs. 4 KlinV.4Art. 19 Verordnung über klinische Versuche (KlinV) vom 20. September 2013 (SR 810.305), as revised 7 June 2024. Lower-risk categories benefit from reduced documentation, simplified ethics review, and potentially lower insurance requirements. Applied to trials enrolling pregnant participants, however, the categorization raises questions the KlinV does not address. Whether fetal exposure to an investigational product elevates the risk category is not specified. Whether a trial that would qualify as Category B in a non-pregnant population automatically becomes Category C when pregnant participants are included is a question for the dual-approval system: Swissmedic leads on the pharmaceutical-safety dimension and the ethics committee on the protective-measures dimension. Neither body has published criteria for that assessment.
The ordinance revisions adopted by the Federal Council on 7 June 2024 (which took effect on 1 November 2024, with transparency provisions following on 1 March 2025) introduced several procedural improvements. Electronic consent (Art. 7c KlinV) became available as of 1 November 2024, potentially easing the logistical burden of obtaining and documenting informed consent in pregnancy trials. Updated notification and reporting duties may improve safety data capture. The Swissmedic fast-track procedure (Pilotprojekt) for qualifying clinical trial applications, launched 1 July 2025, may accelerate review timelines.5Art. 7c KlinV (new); Swissmedic news release on the fast-track procedure (27 June 2025). None of these revisions, however, addressed the substantive gap: what does a compliant protocol for pregnant participant inclusion look like under Swiss law? The procedural machinery has been modernized. The substantive standard remains unspecified.
3. The Liability and Insurance Circular Problem
The HFG establishes a liability regime for research-related injuries that applies to all clinical trials conducted in Switzerland. The regime’s application to pregnancy trials, however, introduces a specific structural difficulty that neither the statute nor the ordinances resolve. The burden of proof (requiring the participant to demonstrate a causal link between the trial intervention and the adverse outcome) has been the subject of ongoing parliamentary and academic debate, including proposals to reverse it and place the onus on the sponsor to disprove causation. The BAG commissioned the Academy of Swiss Insurance Medicine (asim) at University Hospital Basel to evaluate the liability regime’s practical operation, including an international comparison of burden-of-proof approaches.6BAG, ‘Evaluation of Liability Regulation in the Swiss Human Research Act’ (asim, University Hospital Basel, 2015; updated 2018).
The uncertainty is prospective as much as present. A sponsor designing a pregnancy trial today cannot know whether the liability standard will shift before the trial concludes. Adverse outcomes with long latency periods (fetal exposure effects that manifest in childhood or later) may be assessed under a legal standard that did not exist when the trial was designed. That temporal mismatch between trial design and liability exposure is difficult to address contractually, because it depends on legislative developments neither party controls.
The more immediate obstacle, however, is insurance. Clinical trial insurance in Switzerland must cover research-related injuries (Art. 20 HFG; Art. 13 KlinV), and the KlinV’s risk categorization system influences the minimum required coverage amounts. For pregnancy trials, the actuarial data that insurers rely on to price risk simply does not exist in sufficient quantity. The problem is circular: insufficient trial data because insufficient insurance coverage, and insufficient insurance coverage because insufficient trial data. One estimate from the Concept Foundation in Geneva suggests that developing a medicine specifically for use during pregnancy could cost an additional USD 5.7 million compared with standard therapeutic development, with the majority of that cost attributable to the additional safety and efficacy studies required.7Concept Foundation, AIM market analysis (Geneva); see also Guglielmi (n 2). The insurance component of that cost is difficult to isolate but may be decisive: a sponsor that has budgeted for the additional studies may still be unable to proceed if the insurer refuses to cover the trial, imposes conditions that effectively dictate the protocol’s design, or sets premiums that render the trial commercially unviable.
The clinical trial agreement’s indemnification provisions exist within this context. The allocation of liability between sponsor, contract research organization, and clinical site rests on assumptions about insurance coverage that may not hold. Whether the sponsor’s indemnification obligation is meaningful depends on whether the underlying insurance responds, and the insurance market’s willingness to respond to pregnancy trial claims remains largely untested in Switzerland.
4. Ethics Committee Practice: The Unwritten Standards
Cantonal ethics committees in Switzerland serve as the primary gatekeepers for clinical trial approval involving pregnant participants. The HFG requires that these committees apply specific expertise when assessing such trials, a requirement that mirrors the approach taken in the EU Clinical Trials Regulation and that the incoming ICH E21 Guideline reinforces. The difficulty is that neither the HFG nor the KlinV defines what that expertise entails, how it must be demonstrated, or whether it requires the committee to include a maternal-fetal medicine specialist, consult one, or simply apply a general standard of care informed by obstetric considerations.
The practical consequence is variation. Switzerland’s cantonal ethics committee structure (coordinated through swissethics but operationally independent) means that a protocol submitted in Basel-Stadt may be assessed against different unstated expectations than the same protocol submitted in Zurich, Vaud, or Bern. For multi-site Swiss trials, a single lead ethics committee (Leitkommission) issues the project authorisation while remaining bound by the participating cantonal committees’ statements on local technical and operational conditions, mitigating the variation to some degree. For single-site trials, the sponsor must anticipate the reviewing committee’s approach without a published standard against which to calibrate.
The international context adds a further layer of interpretive uncertainty. The reclassification of pregnant people from “vulnerable” to “complex” in international research ethics discourse (a shift from a category suggesting the need for additional protection, potentially justifying exclusion, to one suggesting the need for additional expertise, potentially requiring inclusion with safeguards) has influenced regulatory thinking. Earlier formulations of international research ethics tended to group pregnant participants among populations requiring additional protective measures, a framing that the 2016 CIOMS International Ethical Guidelines for Health-related Research Involving Humans (notably Guidelines 15 and 19) substantially revised, with the 2018 US PRGLAC Task Force Report reinforcing the shift and the October 2024 revision of the Declaration of Helsinki reframing vulnerability itself as contextual and dynamic rather than a fixed group attribute.8CIOMS, ‘International Ethical Guidelines’ (4th edn 2016) Guidelines 15, 19; PRGLAC, ‘Report to HHS Secretary and Congress’ (NICHD, Sep 2018); WMA Declaration of Helsinki (75th GA, Helsinki, Oct 2024). The ICH E21 Guideline does not invoke the “vulnerable population” framing, treating inclusion of pregnant participants as an expected design consideration rather than a categorical protection issue.
Whether Swiss ethics committees have adjusted their interpretive lens in response to these developments, and whether that adjustment, if it has occurred, is consistent across cantons, is not publicly documented. The question is not academic: a committee that still applies a protective-exclusion framework will assess the same protocol differently than one that applies an expertise-inclusion framework, and the sponsor’s protocol must satisfy whichever lens the committee applies without knowing in advance which it will be.
5. ICH E21 and What Swissmedic’s Commitment Means
Swissmedic is a Standing Regulatory Member of the Management Committee of the International Council for Harmonisation (ICH), committed to adopting ICH guidelines into its regulatory framework. The ICH E21 Guideline on Inclusion of Pregnant and Breastfeeding Individuals in Clinical Trials reached Step 2 on 14 May 2025 and entered public consultation, with the comment period closing on 15 September 2025. Finalization as a Step 4 document (at which point it becomes available for implementation by ICH regulatory members) is anticipated for the first quarter of 2028.9ICH E21 (Step 2, 14 May 2025), EMA/CHMP/ICH/149462/2025; EMA Press Release (4 June 2025).
The guideline’s scope exceeds what Swiss law presently requires. E21 calls for proactive evidence generation planning from the early stages of drug development, not merely permitting inclusion when a sponsor chooses to pursue it, but establishing an expectation that sponsors consider inclusion as part of their development strategy for any product intended for populations that include people who can become pregnant. The guideline specifies a structured benefit-risk evaluation framework for both the pregnant individual and the fetus, nonclinical data thresholds that should be met before enrollment of pregnant participants, expertise requirements for investigators and oversight bodies, and detailed recommendations for safety monitoring, informed consent, and data collection.
The question for sponsors running trials in Switzerland is not whether Swissmedic will implement E21. As a Standing Regulatory Member of the ICH Management Committee, Swissmedic has committed to doing so. The questions are how and when. The 2024 KlinV revisions already align with certain E21 principles (enhanced transparency, modernized consent mechanisms, updated safety reporting) but that alignment is procedural, not substantive. Three open questions have direct operational implications: whether Swissmedic will issue specific guidance on how E21’s pregnancy-inclusion expectations map onto the HFG’s existing framework, whether ethics committees will revise their assessment criteria in response, and what the transition period between E21 finalization and Swiss implementation means for trials initiated in the interim. A sponsor designing a protocol in 2026 or 2027 must decide whether to anticipate E21 standards that have not yet been finalized, in a jurisdiction that has not yet indicated how it will adopt them. Designing to anticipated standards may prove prescient or premature; designing without them may prove compliant today and inadequate tomorrow.
6. The Questions a Protocol Cannot Answer Alone
The regulatory direction is unmistakable. All three of the ICH regulatory authorities covered in this series (FDA, EMA, and Swissmedic) are moving from a framework that defaults to exclusion toward one that expects justification for exclusion. The EMA, in releasing the draft for public consultation on 4 June 2025, characterised the move as a “change in paradigm”. For the jurisdictional comparison relevant to multi-site global trials designed from Switzerland, this shift creates complexity examined across Insight 28 (EU), Insight 29 (US), and Insight 30 (comparative) in this series.
Within Switzerland specifically, the framework’s gaps are not gaps in the law’s text (the HFG and KlinV provide a coherent structure) but gaps in the interpretive and institutional infrastructure that determines whether that structure can be operationalized for pregnancy trials. What standard of expertise a cantonal ethics committee will apply, and whether that standard is consistent with the committee in the next canton, depends on institutional practice that is not publicly documented. Whether insurance coverage is available at commercially viable terms depends on a market that lacks the actuarial data to price the risk. Whether the clinical trial agreement’s liability allocation protects the parties depends on whether the insurance responds and whether the liability standard itself shifts during the trial’s life cycle. Whether designing a protocol to E21 standards ahead of formal Swiss implementation satisfies or complicates the existing HFG approval process depends on how Swissmedic and the reviewing ethics committee respond to a standard they have committed to adopting but have not yet transposed.
None of these questions have answers that can be derived from the regulatory text. They require analysis that accounts for the specific trial’s design, the specific ethics committee’s approach, the specific insurer’s appetite, and the specific sponsor’s tolerance for regulatory uncertainty, factors that interact in ways a standard protocol template does not capture and that the HFG’s silence leaves to the parties to navigate.