Evaluation of the Safety of Drugs and Biological Products Used During Lactation: Workshop Summary

Abstract

This report serves as a summary of a 2-day public workshop sponsored by the US Food and Drug Administration (FDA) to discuss the safety of drugs and biological products used during lactation. The aim of the workshop was to provide a forum to discuss the collection of data to inform the potential risks to breastfed infants with maternal use of medications during lactation. Discussions included the review of current approaches to collect data on medications used during lactation, and the considerations for future approaches to design and guide clinical lactation studies. This workshop is part of continuing efforts to raise the awareness of the public for women who choose to breastfeed their infants.

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

“…In the absence of human data, data on DAA exposure in milk are limited to rat studies. They should be interpreted with caution due to species‐specific differences in lactation physiology such as mammary gland anatomy, storage and release of milk into ducts, protein and fat composition of milk and the expression of drug transporters in mammary tissue, as these factors play a major role in the extent passage of drugs into milk . Data obtained from rat studies showed that DAAs are transferred into milk, but no effects on growth and development were observed in nursing pups exposed to DAAs via milk .…”

Opioids in Breast Milk: Pharmacokinetic Principles and Clinical Implications

“…Similarly, in postmarket settings, such milk PK data are difficult to obtain, and information on individual variations of infant exposure is virtually nonexistent, making it impossible to assess the likelihood of reaching certain drug concentrations in milk and infant plasma. Regulatory agencies have become aware of the dire situation, urging efforts from the stakeholders . In this regard, methodological characteristics of the population PK approach with opportunistic sampling schedules, which are advocated for the pediatric population to facilitate PK data generation, appear attractive also for milk PK studies .…”

“…Regulatory agencies have become aware of the dire situation, urging efforts from the stakeholders. 102 In this regard, methodological characteristics of the population PK approach with opportunistic sampling schedules, which are advocated for the pediatric population to facilitate PK data generation, appear attractive also for milk PK studies. 43,103 Although a population PK approach can transform a relatively small number of milk level observations into a large-population data set of predicted milk levels and variations, a final component of the risk assessment requires prediction of plasma drug level distribution in the infants without exposing these otherwise healthy infants to the drug.…”

The pre‐ and post‐authorisation data published by the European medicines agency on the use of biologics during pregnancy and lactation

“…Data were considered adequate for clinical management when they fulfilled the following criteria (shown in green in Tables and ), stratified according to section: Pre‐clinical and/or animal studies: When the amounts and timing of drug concentration in the mother's milk of studied animals are provided . As larger molecules such as immunoglobulins have more chance of being secreted into the milk due to larger gaps in breast alveolar cells during the first postpartum days, the timing of sampling is crucial for adequacy of information in this regard .…”

“…If this is <10% no additional studies are required. If the percentage of weight‐adjusted maternal dose exceeds 10%, breastfed infants' plasmaconcentrations of the medicinal product, it should be studied and follow‐up studies of the breastfed children should be initiated …”