Human absorption, distribution, metabolism and excretion (ADME) studies have long been a critical component of drug development.
Evolving regulatory expectations and the increasing complexity of clinical pharmacology programmes mean these studies are becoming far more strategic than they were once considered to be.
In a recent expert Q&A, Iain Shaw, Senior Director of 14C Enabled Drug Development at Quotient Sciences, discusses how the landscape for human ADME studies is changing and what sponsors need to consider when planning their development programmes.
Earlier Planning is Becoming the Norm
Historically, many companies only began detailed ADME planning after obtaining proof-of-concept data in Phase II. Today, ADME requirements are increasingly being discussed much earlier, sometimes as first-in-human studies are nearing completion. This shift reflects growing recognition of the value of understanding human drug disposition earlier in development, alongside the influence of recent FDA guidance on radiolabelled mass balance studies.
While earlier planning can accelerate development decisions, it also introduces new challenges as less clinical pharmacokinetic and safety data may be available to inform study design.
Regulatory Expectations Continue to Shape Study Design
The FDA's 2024 guidance formalised expectations around human ADME programmes, including recommendations on subject numbers, recovery of administered radioactivity, and metabolite profiling approaches. As a result, sponsors are often including additional participants to ensure six evaluable subjects are available and extending collection periods to achieve the required recovery criteria.
These changes can increase study complexity and cost, making robust planning and cross-functional collaboration increasingly important.
More Data from a Single Study
Another notable trend is the growing use of integrated study designs that combine traditional human ADME investigations with assessments of absolute bioavailability using intravenous microtracers (IV microtracers).
Using this approach, sponsors can generate valuable information across several areas (pharmacokinetics, absorption, metabolism, drug disposition) from a single clinical study.
How Arcinova Supports Human ADME Programmes
Successful human ADME studies begin long before the clinical phase. The quality of radiolabelled drug substance and drug product materials can have a significant impact on study success, which is why isotope labelling strategy and CMC planning are increasingly being considered earlier in development.
Arcinova works closely with Quotient Sciences to provide a seamless route from radiolabelled CMC development through to clinical ADME study execution. Our isotope labelling team has delivered more than 500 radiolabelling programmes and supports the synthesis of 14C-labelled drug substances, formulation development and manufacture of fit-for-purpose oral and sterile radiolabelled drug products for ADME and absolute bioavailability studies.
Arcinova's specialist radiolabelling and CMC capabilities connect directly with Quotient Sciences' clinical pharmacology expertise, enabling a holistic Quotient Sciences’ Synthesis-to-Clinic® offering. For sponsors that are looking to simplify their development activities, this approach of working with one, integrated partner helps reduce development handovers, streamline timelines and accelerate the generation of critical ADME data needed to support drug development and regulatory submissions.
Read the Full Expert Q&A
To learn more about the changing regulatory landscape, evolving study designs and what these changes mean for drug developers, read the full expert Q&A from Quotient Sciences: What's Different About Human ADME Study Design Today?