Women's Health: clinical trials and medicinal product development
For decades, women played only a minor role in medicinal product research. The consequences are still evident today and range from a lack of trial data to medicinal products that have not always been adequately tested for efficacy and safety in women. We must now make up for what has long been neglected. There are fundamental questions to be addressed when it comes to medicinal product development: How can medicinal products be developed and approved that are genuinely tailored to the biological, hormonal and disease-specific features of women?
Fortunately, the subject of Women's Health is increasingly coming to the attention of policymakers in Germany and is, for example, identified by the German Federal Ministry of Health (BMG) as an important topic. Furthermore, the Alliance for Women's Health (Allianz für Frauengesundheit) was recently established, which is committed to ensuring, amongst other things, that women's health needs are systematically taken into account in research. The EMA has also placed this topic on its agenda. For instance, the EMA recently announced initiatives to better embed Women's Health considerations in medicinal product development and regulation and will be meeting to discuss this subject at the end of September 2026. Similarly, the EU's Safe Hearts Plan focuses on gender-specific risks, early detection in women and the reduction of inequalities in cardiovascular care.
This article examines the legal framework currently shaping the development process, from trial design to authorisation, and what stakeholders need to consider right now.
The historical starting point: the gender data gap as a regulatory burden
Right up until the 1990s, women were frequently and systematically excluded from clinical trials, initially for seemingly protective reasons (fear of harm to an unknown foetus) and later for practical reasons aimed at simplifying trial design and analysis. The exclusion of women of childbearing age was generally mandatory under relevant FDA and the EMA regulations. Furthermore, even well into the 1980s, it was widely believed that the female and male bodies were essentially the same and that medicines would have the same effect on both sexes. It was therefore not considered necessary to test medicinal products on women, even though their anatomy and physiology are different. This means that, to this day, much of our understanding of the effects of medicinal products, the progression of diseases and risk factors is based on data from male subjects. Evidence regarding efficacy and safety – particularly in women – is, by contrast, often only generated after the product has been launched through simple observational studies, which do not, however, provide high-quality evidence.
This gender data gap applies to "everyday" medicinal products such as sleeping pills, painkillers and cardiovascular medications equally as much as medicinal products used to treat serious illnesses.
Given that women have somewhat different hormonal cycles to men and also differ in their physical constitution, and in view of the gaps in the evidence described above, it must currently be assumed that, in many cases, medicinal products are not (or cannot be) used optimally in the treatment of women.
However, scientific research into female physiology is still in its infancy in this area, though scientific findings from this research do suggest that the absorption, distribution and metabolism of individual active substances may vary in interaction with sex hormones, or that there are differences in metabolism. Based on the realisation that risk factors and medical conditions differ between men and women, the focus in recent years in the development of medicines has also shifted towards chronic conditions that are more common in women, such as migraines, headaches and anxiety.
The growing, but still insufficient, regulatory significance of Women's Health
Although the legislature has already responded to the growing importance of the topic of "Women's Health", there is still a long way to go to achieve "equal treatment" in the authorisation process.
Under section 25 German Medicinal Products Act (AMG) or Article 12 (1) Regulation (EC) No 726/2024, marketing authorisation under pharmaceutical law will be granted on the basis of the documentation required under section 22 German Medicinal Products Act (AMG) and Article 6 of Regulation (EC) No 726/2024, to the extent specified in the application. The efficacy of the medicinal product must be demonstrated primarily by clinical trials.
The planning and performance of clinical trials are regulated in the EU by Regulation (EU) No 536/2014 (Clinical Trials Regulation, or CTR for short). According to Recital 14 of the CTR, subjects participating in a clinical trial should represent the population groups that are likely to take or be administered the medicinal product being tested in the clinical trial. If a specific gender is excluded, an explanation of the reasons for the exclusion and justification for the exclusion criteria must be provided (see Annex 1 to the CTR, D.17(y)). However, there are no further requirements regarding the consideration of women, for example specifically in relation to the biological, hormonal and disease-specific features of women. Nor do the relevant EMA guidelines (as yet) contain any provisions that explicitly address the specific characteristics of Women's Health and require these to be taken into account. The situation is essentially the same with regard to the ICH Guidelines. The need for a separate guideline concerning women as a specific population in clinical trials was even rejected by the ICH as recently as 2009; the relevant considerations can still be found in this form today, at least on the ICH website. Instead, reference is made primarily to the general requirements regarding gender representation and to the need for subgroup analyses. At the very least, ICH E3 "Structure and Content of Clinical Study Reports" identifies, for example, a woman's menstrual status as a factor that may influence the effects of the medicinal product. In addition, there are a few EMA guidelines concerning the development of medicinal products in areas relevant to Women's Health, including recommendations on the design and performance of relevant clinical trials (e.g. "Guideline on the clinical investigation of steroid contraceptives in women").
There is also a need to recognise the issues surrounding the inclusion of pregnant and breastfeeding women in clinical trials. Traditionally, these groups are regarded as being particularly vulnerable. Their participation in clinical trials is therefore only permitted under the strict conditions set out in Article 33 of the CTR. However, this has (so far) meant that pregnant and breastfeeding women are excluded from taking part in clinical trials for medicinal products that are not specifically indicated for them. If female subjects become pregnant whilst a clinical trial is ongoing, it is not uncommon for the protocol to provide for their exclusion from the trial. The evidence regarding the benefits and risks of administering certain medical products during pregnancy and whilst breastfeeding is therefore generally lacking. Against this background, in 2025 the ICH presented a draft of a new ICH E21 "Guideline on the inclusion of pregnant and breastfeeding individuals in clinical trials", which aims to formulate recommendations for the appropriate inclusion and continued participation of pregnant and breastfeeding women in clinical trials. The FDA had already issued specific guidelines in 2018 on scientific and ethical considerations for the inclusion of pregnant women in clinical trials, emphasising that pregnant women may participate in clinical trials that pose the lowest risk to the foetus.
However, even under the current regulatory requirements, it is important to note that the efficacy of a medicinal product must be sufficiently demonstrated through appropriate clinical trials for all groups of individuals for whose treatment it is to be authorised. However, if new scientific findings suggest that clinical data from clinical trials involving (predominantly) male subjects do not provide sufficient evidence of the medicinal product's efficacy (also) when used in women, this circumstance could therefore constitute grounds for refusing authorisation under section 25 (2) sentence 1 no. 4 German Medicinal Products Act (AMG) in the national authorisation process and grounds for refusal in the centralised EU authorisation process as per Article 12 (1) (b) of Regulation (EC) No 726/2004 (as well as on the grounds of an insufficiently substantiated benefit-risk balance as per Article 12 (1) (a) of Regulation (EC) No 726/2004). Instead of refusing authorisation for a medicinal product altogether, authorisation may be granted solely for use in men, with the consequence that the administration of such a medicinal product to a woman constitutes off-label use and triggers specific responsibilities on the part of the treating doctor. In view of the expected increased focus on women's health and bearing in mind the scientific findings on this topic that are likely to emerge in the future, such an approach on the part of the regulatory authorities cannot be ruled out in the future.
Furthermore, any gender-specific differences identified in a trial must be taken into account accordingly in the product information, provided they have an impact on the use of the medicinal product.
For this reason – but also, more generally, with a view to improving the treatment of women with medicinal products – those initiating clinical trials should therefore give sufficient consideration to aspects of women's health right from the trial planning stage. Fundamentally, this requires sufficient representation of women in clinical trials, but also the selection of appropriate clinical endpoints that adequately reflect women's realities. In addition, further questions arise relating to the distinct physiology of women. For example, to what extent should – or indeed must – phases of the menstrual cycle, female metabolism or the menopause be taken into account in the trial design? However, in the absence of specific regulatory provisions, many issues in this area remain unresolved at present. Nevertheless, the fundamental insights from Women's Health research should already be given due consideration.
For those involved in medicinal product development, it may therefore be worthwhile to seek contact with the regulatory authorities at an early stage and obtain appropriate advice.
Women's Health as a strategic opportunity for the pharmaceutical industry
In addition to the regulatory requirements outlined above, it also appears advisable for the pharmaceutical industry, for market strategy reasons, to position its products at an early stage within the "Women's Health market", which is set to become even more significant in the future. Medicinal products whose effects have been demonstrated (specifically) for women by evidence from relevant clinical trials – and which are therefore tailored to the physiological requirements of women in terms of, for example, dosage and timing of administration – may have a strategic advantage in this market. To this end, it may even be advisable to start as early as the pre-clinical trial stage and to take the sex of the test animals into account within the pre-clinical trial design and when analysing the results. This may reveal whether the results of animal testing are fully transferable to all humans, both men and women, or whether distinctions need to be made in clinical trials and appropriate cohorts defined.
In this context, it cannot be ruled out that such clinical trials may demonstrate an added benefit of the medicinal product specifically for the treatment of women (or a female subgroup) within the relevant area of application. If the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) determines such added benefit as part of the early benefit assessment under section 35a German Social Code (SGB V), the pharmaceutical company may, for example, claim a higher reimbursement amount under section 130b German Social Code, Book V (SGB V) for its medicinal product.
Women's health: changes in the development and regulation of medicinal products
The historical exclusion of women from clinical trials continues to have an impact on the development of medicinal products to this day. In recent times, however, there has been a growing awareness of the issue amongst the relevant stakeholders, foremost among them the EMA. Nevertheless, there is still a considerable amount of ground to make up when it comes to the systematic incorporation of gender-specific differences into research, development and regulatory assessment. It is likely that the topic of women's health will be addressed more prominently by regulatory authorities in future, and that this issue will therefore take on greater significance overall at the regulatory level.
A corresponding shift is also taking place in society: Gender-specific evidence is increasingly seen as a natural component of the development of high-quality medicinal products. Women's Health is thus evolving from a niche segment into a field of innovation within the life sciences that is of strategic importance to the pharmaceutical industry, thereby also reflecting, not least, the considerable economic significance of the topic.
This article is part of a series dealing with the legal aspects of Women's Health. The previous article discussed M&A transactions and due diligence issues in the Women's Health segment. Subsequent articles will focus on topics such as reimbursement, data protection issues and the law on advertising in the field of health within the context of Women's Health.
