Research Scientist PPD a Part of Thermofisher, United States
Background: In May 2019, the FDA released guidance on the conduct of post-marketing approval lactation studies which included considerations for overall design, sampling, and PK analysis. However, there is no information provided to guide the decision to use healthy volunteers or patients receiving a product therapeutically.
Objectives: To highlight differences between lactation studies in healthy volunteers versus patient populations.
Methods: We reviewed 12 lactation studies undertaken from 2014 to 2023 and compared healthy volunteer (n=6) and patient-based studies (n=6) in terms of design and product characteristics.
Results: Among the healthy volunteer lactation studies that were reviewed, sample sizes ranged from 8 to 16. Breastmilk sampling occurred after a single dose was administered, and all breast milk from both breasts was collected over 24-240 hours. These studies investigated oral formulations in a variety of indications, mostly in the neurology therapeutic area. Product terminal half-life ranged from 7 to 52 hours. Among the patient-based studies, sample sizes ranged from 12 to 25. These studies investigated intravenous or subcutaneously administered formulations and breast milk sampling occurred over 1 to 2 months. These studies investigated biologics with indications in the immunology therapeutic area. Terminal half-lives ranged from 11 to 28 days.
Conclusions: Products with short half-lives and low risks associated with a single dose may be candidates for healthy volunteer lactation studies. Healthy volunteer studies significantly increase the participant pool and can result in substantially more rapid recruitment and study completion. Products with long half-lives and/or biologics/immunomodulatory medications, as well as indications associated with altered metabolism and/or drug absorption, will typically require lactation studies among patients receiving the treatment therapeutically.
