Cristina Salcianu on the Growing Importance of Lactation Studies for Drug Safety

For decades, pregnant and lactating women have remained among the most underrepresented populations in clinical research, despite the fact that many women require ongoing treatment for chronic and acute medical conditions during pregnancy and the postpartum period. As a result, physicians are often forced to make prescribing decisions with limited information regarding the extent to which medications transfer into breast milk and the potential implications for the breastfed infant.

According to Cristina Salcianu, MSc., a Clinical Pharmacology and Pharmacokinetics (PK) Scientist at ICON plc with a background in pharmacy and regulatory science, this evidence gap is becoming increasingly difficult for the pharmaceutical industry and regulators to ignore. Salcianu currently supports multiple clinical pharmacology programs, including lactation, oncology, and hepatic and renal impairment studies involving pharmacokinetic characterization and exposure assessment to support regulatory and clinical decision-making.

"From a clinical pharmacology perspective, lactation studies provide critical quantitative data needed to assess drug transfer into breast milk and estimate infant exposure," Salcianu explains. This information plays an important role in supporting clinical decision-making and informing drug labeling during breastfeeding.

In recent years, regulatory agencies have strengthened expectations around the generation of lactation-specific safety and clinical pharmacology data, particularly as precision medicine, evidence-based prescribing, and patient-focused drug development continue to shape modern regulatory frameworks. Despite this shift, many therapies still receive regulatory approval without dedicated lactation studies completed during clinical development.

Salcianu explains that this evidence gap is largely rooted in the historical exclusion of lactating women from clinical trials, due to ethical, operational, and safety considerations. Therefore, key pharmacokinetic and maternal-infant exposure questions are often addressed only after a drug has already been approved and introduced into clinical use.

"To address this evidence gap, the FDA may require postmarketing studies when additional lactation data are needed," Salcianu says. "In some cases, sponsors may also proactively initiate lactation studies when there is scientific rationale suggesting that a drug may transfer into breast milk."

These postmarketing requirements, commonly referred to as PMRs, have become an important regulatory pathway for addressing remaining questions related to drug transfer into breast milk and potential infant exposure following regulatory approval. In the context of lactation, such studies frequently focus on quantifying infant exposure and supporting evidence-based labeling recommendations.

At the center of these studies is pharmacokinetics (PK)—the science of how drugs are absorbed, distributed, and eliminated over time. In lactation studies, plasma and breast milk samples are collected over multiple timepoints to generate concentration–time profiles, followed by noncompartmental analyses (NCA) to estimate exposure parameters such as Cmax and area under the concentration–time curve (AUC). These analyses help characterize drug transfer into breast milk and quantify potential infant exposure using clinically relevant metrics such as milk-to-plasma ratios and relative infant dose (RID).

"The key distinction in lactation studies is that we are not only characterizing maternal pharmacokinetics but also evaluating potential infant exposure through breast milk," Salcianu explains. "Without robust pharmacokinetic analyses, the quantitative exposure data needed to support regulatory decision-making and labeling recommendations cannot be adequately generated."

The work is scientifically complex. Breast milk itself is a highly dynamic biological matrix influenced by maternal physiology, milk composition, underlying clinical conditions, and variability in collection intervals and milk volume. "Salcianu notes that several simplified assumptions historically used to predict drug transfer into breast milk—such as relying primarily on molecular weight, lipophilicity, or passive diffusion principles—are no longer considered sufficiently reliable as standalone predictors of drug transfer into breast milk."

"Salcianu adds that recent research suggests drug transfer into breast milk is influenced by multiple biological and pharmacokinetic factors, including active transport mechanisms, maternal clearance, and drug-specific characteristics."

Operationally, these studies present additional challenges. Unlike conventional plasma sampling in clinical trials, breast milk collection must account for real-world breastfeeding patterns, participant burden, variability in milk volume, and deviations from scheduled collection timepoints.

"Participants may not be able to express sufficient milk at predefined timepoints, which is why breast milk is often collected over defined intervals to obtain adequate sample volumes for pharmacokinetic analysis," Salcianu explains. "Variability in milk collection intervals and sample volume can introduce additional complexity when aligning matched plasma and breast milk concentration data and may directly affect the estimation and interpretation of pharmacokinetic exposure parameters."

"Addressing these challenges requires careful consideration during study design, including predefined collection intervals, appropriate sampling windows, and sufficiently intensive pharmacokinetic sampling to ensure robust characterization of maternal plasma and breast milk concentration–time profiles for reliable estimation of maternal and infant exposure parameters."

The pharmaceutical industry is increasingly turning toward model-informed approaches to address these limitations. Techniques such as physiologically based pharmacokinetic (PBPK) modeling and population pharmacokinetic (popPK) analyses can support the characterization and prediction of maternal and infant exposure, particularly when clinical data are limited or sampling is sparse.

"According to Salcianu, these approaches reflect a broader industry shift toward model-informed drug development, where pharmacokinetic modeling and computational methods are increasingly used alongside clinical data to support regulatory assessments and clinical decision-making."

"These approaches allow us to integrate clinical observations with mechanistic understanding, simulate exposure scenarios, and evaluate variability across both maternal and infant populations," she says.

The implications extend directly into prescribing information and patient care. When sufficient lactation data are available, drug labeling can provide more precise, evidence-based recommendations regarding breastfeeding safety. Without these data, labels often default to precautionary language that offers limited practical guidance to clinicians and patients.

"From a regulatory perspective, the objective is to reduce uncertainty through data-driven assessment and evidence-based conclusions," Salcianu says.

As regulatory agencies continue emphasizing inclusion, real-world evidence, and patient-focused drug development, experts believe lactation clinical pharmacology will play an increasingly important role in addressing longstanding gaps in women's health research.

For Salcianu, the broader goal is ultimately straightforward: generating the evidence needed to support regulatory approval and informed treatment decisions in lactating populations, so mothers and their physicians have viable, evidence-based treatment options, and are not forced to choose between necessary therapies, protecting maternal health, and continuing breastfeeding.