Advanced Therapy Medicinal Products (ATMPs), viral vectors, and other emerging therapeutic modalities are transforming drug development. As these therapies become more complex, understanding how they distribute within the body and whether they can be released into the environment becomes essential for both regulatory compliance and patient safety.
Biodistribution and shedding studies play a critical role throughout preclinical and clinical development. This FAQ-style overview explains their purpose, differences, regulatory expectations, and the analytical approaches commonly used to support these studies.
Key Takeaways
- Biodistribution studies evaluate how therapeutic products distribute throughout the body.
- Shedding studies assess whether a product may be released from treated individuals.
- These studies are particularly important for ATMPs, Virus or Bacteria-Based Therapies.
- Regulatory agencies including FDA, EMA, and ICH provide guidance for biodistribution and shedding assessment.
- Robust analytical methods are essential to support safety and efficacy evaluations.
What is Biodistribution? What is Shedding?
Biodistribution studies consist in the assessment of the dispersion of a compound or therapeutic agent (drug, nanoparticle, viral vector or cell therapy) within the body and organs of the living organism after its administration. The scope of performing Biodistribution studies is to determine if a drug reaches the targeted organ and to verify possible accumulation in different organs and toxicological effects.
Shedding studies consider the evaluation of the excretion of a product or drug from the subject after its administration, mainly through excreta ways (feces), secreta ways (urine, saliva, nasopharyngeal fluids, etc) or even through the skin (pustules, sores, wounds). The scope of shedding studies is to assess the possibility of the product transmission from treated to untreated (healthy) subjects.
What is the difference between Biodistribution and Shedding?
Biodistribution is focused on determining how a product is spread from the administration site through the body. Whereas Shedding describes how the product is excreted or released from the patient’s body implicating possible transmission to healthy population.
| Biodistribution Studies | Shedding Studies | |
|---|---|---|
| Main objective | Evaluate therapeutic agent distribution throughout body organs | Evaluate product release/excretion after treatment |
| Primary concern | Targeting, persistence, safety | Transmission risk |
| Typical samples | Different organs, blood/plasma | Excretion samples: Urine, feces, saliva |
| Common products | ATMPs, viral vectors, oncolytic virus or bacteria and nanoparticles | Virus or Bacteria-Based Gene Therapies (Viral vectors, oncolytic virus or Bacteria) |
| Regulatory focus | Distribution in target/non-target tissues | Environmental and patient safety |
When are Biodistribution and Shedding Studies needed?
Nowadays, Biodistribution Studies are required not only for some Small Molecule products, but also for the now ever-growing field of Advance and New Modality Therapies, having become a crucial step in preclinical and toxicology studies to assess a treatment’s safety, efficacy and clearance pathways.
Extracellular vesicles, Nanoparticles, Cell Therapy Products, Oncolytic Products (Oncolytic Virus or Bacteria) and virus or bacteria-based gene therapy products (VBGT products) including Viral Vectors, are all subjected to Biodistribution studies.
Furthermore, Shedding studies should be conducted on Oncolytic and VBGT products, due to possible risk of transmission to healthy populations. The Shedding study should be conducted during preclinical and clinical development stages. In case of the latter, they can be part of the safety of efficacy trial.
How to assess the Biodistribution of a Product?
- Imaging Techniques (In Vivo & Ex Vivo):
- Nuclear Imaging (PET/SPECT) of labeled agents
- Optical Imaging (Fluorescence/Bioluminescence)
- Magnetic Resonance Imaging (MRI) & Computed Tomography (CT) for labeled agents
- Molecular and Analytical Methods:
- PCR-Based Methods (qPCR, ddPCR)
- Liquid Scintillation Counting (LSC)
- Histology/Microscopy
What is the difference between Biodistribution and Pharmacokinetics (PK) studies?
Pharmacokinetics (PK) studies evaluate the drug interaction and metabolism in the body, they are focused on determining the concentration of the drug in the individuals’ blood at different timepoints over a period of time. Whereas Biodistribution determines the therapeutic agent or compound presence and distribution throughout the entire body and specific organs or tissues.
Which Regulation rules Biodistribution and Shedding Determination?
Several international regulatory agencies provide guidance on biodistribution and shedding assessment for gene therapies, ATMPs, and other advanced therapeutic modalities.
- ICH S12: Nonclinical Biodistribution Considerations for Gene Therapy Products(Draft released June 2021): provides harmonized recommendations for the design of nonclinical BD studies to detect the product and its expression in target/non-target tissues.
- European Medicines Agency (EMA)
- Guideline on quality, nonclinical and clinical requirements for investigational advanced therapy medicinal products (ATMPs): Requires data on persistence, duration of effect, and target organs.
- Guideline on the non-clinical studies required before first clinical use of gene therapy medicinal products: Provides specific, detailed requirements for shedding studies (e.g., in excreta, secreta).
- US. Food and Drug Administration (FDA).
- Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products (August 2015): This is the primary guidance for evaluating the release of products from patients
- Preclinical Assessment of Investigational Cellular and Gene Therapy Products (2013): Addresses early-stage biodistribution.
- The use of Validated or Qualified Methods:
- Validated methods are mainly used when quantifying the therapeutic agent in target tissues
- Qualified methods are suitable when quantifying the therapeutic agent for safety purposes and off-target tissue analysis.
Where to perform Biodistribution and Shedding studies? How can Kymos Group assist?
- Kymos Group has experience in Biodistrobution and Shedding studies with Oncolytic viruses and Viral vectors (AAV, Herpes virus)
- Analytical method Development, Validation or Qualification
- Kymos Group has experience of gene expression in target tissues
- Analytical method Development, Validation or Qualification
- One-Stop-Shop Solutions
Providing our Clients with full-pack assistance on their projects. Our solution merges:
- Preclinical CRO for animal housing and treatment
- Histological Studies
- Biodistribution and Shedding Determination in different biological matrices
Conclusion
The development of Advanced Therapy Medicinal Products (ATMPs) and new modality therapies is a field undergoing a considerably expansion. The use of complex therapeutic vectors, living cells, and organisms raises the necessity of studying not only their efficacy but also safety for both the patients and the broader population. In this context, Biodistribution and Shedding studies are becoming a milestone of preclinical and clinical development. Having robust analytical methods and executing successful and reliable trials are essential for a swift transition from laboratory innovation to global market availability.
