. 2023 Dec 17;58(2):242–257. doi: 10.1007/s43441-023-00593-3

Table 3.

Clinical Trials: Additional regional guidances on lactation studies beyond ICH/CIOMS guidelines

Country/region	Lactation studies
EU	EMA Guideline of GVP Chapter P.III.B.4.3 Clinical Lactation Studies: “In cases where no human data are available on the extent of medicine transfer into breast milk, where use by breastfeeding women is expected to be common, and based on the medicinal product’s pharmacological properties, it is considered plausible that there is a risk to breastfed infants, a PK study amongst breastfeeding women should be considered. This is expected to be the case when a medicinal product is commonly used by women of reproductive age (e.g., antidepressants, anti-infectives, diabetes medications, pain medications) or when there is evidence of use or anticipated use of the medicinal product by lactating women.” “Medicine concentration levels in breast milk samples should be measured and a relative infant dose calculated, to obtain information for supporting the risk assessment and provision of advice on timing of medicine intake relative to breastfeeding where this may be feasible (e.g., for short-term or single-dose treatments). Moreover, data on the effect of the medicine on milk production or composition should be collected, if potentially clinically relevant.” “In the case of a medicine highly used in women who could breastfeed, with an unknown potential for serious adverse reactions in breastfed children, establishing safety information in the post-authorisation phase should be considered as an important source of information. This may include the clinical follow-up of breastfed children whose mothers are treated with a specific medicine. Pregnancy registries in which newborns are further observed could include the collection of information on breastfeeding to allow a comparison of a group of breastfed children to those not breastfed and those breastfed in mothers who are not treated with the product of interest. In case a medicine is used during breastfeeding and questions arise regarding a potential long-term impact on child’s growth, neurodevelopment, or other adverse events with a prolonged latency, it should be considered to carry out long-term follow-up in those children.” [6]
USA	FDA Guidance for Industry—Clinical Lactation Studies—Considerations for Study Design: Detailed design considerations for lactation studies are provided, including sample collection, pharmacokinetic and pharmacodynamic considerations. [19]

Country/region

Lactation studies

EMA Guideline of GVP Chapter P.III.B.4.3 Clinical Lactation Studies:

“In cases where no human data are available on the extent of medicine transfer into breast milk, where use by breastfeeding women is expected to be common, and based on the medicinal product’s pharmacological properties, it is considered plausible that there is a risk to breastfed infants, a PK study amongst breastfeeding women should be considered. This is expected to be the case when a medicinal product is commonly used by women of reproductive age (e.g., antidepressants, anti-infectives, diabetes medications, pain medications) or when there is evidence of use or anticipated use of the medicinal product by lactating women.”

“Medicine concentration levels in breast milk samples should be measured and a relative infant dose calculated, to obtain information for supporting the risk assessment and provision of advice on timing of medicine intake relative to breastfeeding where this may be feasible (e.g., for short-term or single-dose treatments). Moreover, data on the effect of the medicine on milk production or composition should be collected, if potentially clinically relevant.”

“In the case of a medicine highly used in women who could breastfeed, with an unknown potential for serious adverse reactions in breastfed children, establishing safety information in the post-authorisation phase should be considered as an important source of information. This may include the clinical follow-up of breastfed children whose mothers are treated with a specific medicine. Pregnancy registries in which newborns are further observed could include the collection of information on breastfeeding to allow a comparison of a group of breastfed children to those not breastfed and those breastfed in mothers who are not treated with the product of interest. In case a medicine is used during breastfeeding and questions arise regarding a potential long-term impact on child’s growth, neurodevelopment, or other adverse events with a prolonged latency, it should be considered to carry out long-term follow-up in those children.” [6]

USA

FDA Guidance for Industry—Clinical Lactation Studies—Considerations for Study Design:

Detailed design considerations for lactation studies are provided, including sample collection, pharmacokinetic and pharmacodynamic considerations. [19]

CIOMS council for international organizations of medical sciences, EMA European medicines agency, EU European union, FDA food and drug administration, GVP good pharmacovigilance practices, ICH international council for harmonisation of technical requirements for pharmaceuticals for human use, USA United States of America