Designing a PEI-Compliant Adenovirus Shedding Study

The PEI places significant emphasis on the environmental risk assessment portion of a gene therapy dossier. A preclinical vector shedding study is a foundational component of this assessment. The objective is to quantify the amount, duration, and route of vector shedding to understand the potential for transmission to non-treated individuals. Our approach focuses on developing a study design that prospectively addresses German regulatory questions.

Key design considerations include:

• Model Selection: The choice of animal model is guided by its ability to recapitulate human biological responses to the specific adenovirus vector.

• Dosing Route: The study must utilize the clinically intended route of administration to generate relevant shedding data.

• Sample Collection Schedule: A robust time-course is established, with intensive early sampling followed by spaced-out later time points to accurately define the clearance kinetics.

Quantitative Bioanalysis and Data Interpretation

The core of the analysis is a validated quantitative polymerase chain reaction (qPCR) assay. This method provides the sensitivity and specificity required to detect low levels of vector DNA in complex biological matrices. Understanding vector fate is a key part of the safety assessment. For instance, sensitive molecular assays have been instrumental in confirming the absence of adenoviral vector DNA in subject tissues long after initial gene transfer, directly addressing concerns about long-term persistence and potential oncogenic risk (PMID: 24010702).

The interpretation of shedding data requires a comprehensive analysis of the kinetics for each matrix, including peak shedding time points and clearance rates. This quantitative profile is contextualized with biodistribution data to build a comprehensive safety narrative for the regulatory submission.

“We started collaborating with UPenn Vector core in 2023 and the AAV vector which they manufactured laid a foundation for development of a gene therapy candidate which will enter soon preclinical studies. The key people from UPenn Vector Core joined Franklin Biolabs and our partnership transitioned without interruption from UPenn Vecor Core to Franklin Biolabs Research Vector Division. Franklin Biolabs is our trusted partner in our AAV-vector based gene therapy candidate development and we hope to continue the partnership for years to come.”
— Biotech Partner

Commitment to Animal Welfare in Preclinical Research

Our protocols are designed to maximize scientific value while adhering to the principles of the 3Rs (Replacement, Reduction, and Refinement).

Our >100,000 sq ft facility network and strategic partners, including Bioculture Group, ensure that all research is performed in compliance with the highest ethical and regulatory standards. All animal studies are conducted at facilities fully accredited by AAALAC International and registered with the USDA.