For most drug programs, a key step for inclusion in a successful global regulatory filing is to conduct a human absorption, distribution, metabolism, and excretion (ADME) study. Regulatory agencies require ADME studies to describe the disposition of a drug after it has been dosed in human subjects providing data to explain the pharmacokinetics (PK), metabolism, and safety of the drug. Traditionally, these types of studies usually take place towards the end of Phase II development, as developers are gearing up for Phase III and beyond. However, recently there has been a clear shift occurring within the industry, moving these types of studies earlier in clinical development due to integrated delivery platforms and the use of accelerator mass spectrometry in this field.
At Quotient Sciences, our integrated Synthesis-to-Clinic® programs support human ADME studies from radiosynthesis to the final clinical study report, all under a single program manager and single contract. This approach allows for 14C drug substances to be efficiently synthesized to support non-clinical and clinical requirements. Integrated pharmaceutical sciences facilities provide formulation development, real-time Good Manufacturing Practice (GMP) manufacturing, and qualified person (QP) release of 14C drug products, which enable us to seamlessly supply formulations for ADME studies to healthy volunteers at our in-house clinic or to patients at specialist clinics.
In a typical microtracer study, the radioactive 14C drug dose is generally in the order of about 0.8-1 µCi, and thus a quantitative whole-body autoradiography (QWBA) is not required. Having human ADME data available as early as Phase I can be instrumental in making better and more informed decisions during further clinical development. Another advantage is that early human ADME data reduces the requirement to conduct radiolabelled ADME studies in animals. The 0.8-1 µCi radioactive dose is 100 times lower than in a classical mass balance study, and therefore such a low dose requires substantially better bioanalytical sensitivities than conventional liquid scintillation counting can provide.
Quotient Sciences works with the Netherlands Organization for Applied Scientific Research (TNO), the largest accelerator mass spectrometer (AMS) service provider worldwide, where there are three operational AMSs, all equipped with TNO’s unique rapid sample preparation technology, which reduces sample preparation time from several days to minutes. With this technology, TNO can provide pharmaceutical and biotech companies with all the analytical support that is required for a two-arm microtracer study design. TNO provides AMS services for mass balance and metabolite profiling, and is also equipped for all metabolite identification, using liquid chromatography with high-resolution tandem mass spectrometry (LC-hrMS/MS). For the absolute bioavailability (AB) arm of such a study, TNO provides robust data to derive the %AB, while also providing an estimate for the fraction absorbed. During the webinar, these advantages will be highlighted and discussed.
Join Quotient Sciences’ Senior Director of 14C Enabled Drug Development, Iain Shaw, and TNO’s microtracer expert, Wouter Vaes, along with a panel of synthesis, regulatory and clinical pharmacology experts, for a Q&A roundtable focused on streamlining human ADME studies. Learn more about Quotient Sciences’ unique Synthesis-to-Clinic approach and TNO’s wide range of tools for predicting and measuring ADME/DMPK (drug metabolism and pharmacokinetics) in human subjects, at an early stage. Engage with our panelists as they discuss such topics as efficient ADME study design, common challenges that can occur and mistakes to avoid, and how ADME studies can improve decision-making at critical drug development milestones.
Key Learning Objectives
- Challenges & considerations for developers when conducting a human ADME study
- Regulatory requirements for human ADME studies
- Utilizing a U-tracer study vs a classical human ADME study approach
- Key advantages in conducting microtracer AMS studies in early clinical development
- Benefits in using an integrated Synthesis-to-Clinic approach in delivering ADME studies
About TNO
The Netherlands Organization for Applied Scientific Research (TNO) is an independent research organization. We connect people and knowledge to create innovations that boost the sustainable competitive strength of industry and well-being of society. Now and in the future. This is our mission, and it is what drives us, and the over 3.500 professionals at TNO, in our work every day. We work in collaboration with partners and focus on transitions or changes in nine social themes that we have identified together with our stakeholders. For more information, please visit tno.nl/en/.
About Quotient Sciences
Quotient Sciences is a drug development and manufacturing accelerator providing integrated programs and tailored services across the entire development pathway. Cutting through silos across a range of drug development capabilities, we save precious time and money in getting drugs to patients. Everything we do for our customers is driven by an unswerving belief that ideas need to become solutions, and molecules need to become cures, fast. Because humanity needs solutions, fast. For more information, please visit quotientsciences.com.
