ADVANCED THERAPIES
PK/PD Bioanalysis
We offer PCR-based PK/PD bioanalysis including method development, validation, and high throughput sample analysis.
PK/PD analysis in cell and gene therapies
Cell and gene therapies differ from traditional PK/PD bioanalysis. They involve transgene DNA, vector DNA, and transcribed RNA as analytes, necessitating precise and validated quantitative and digital PCR methods for quantification.
Pharmacokinetics investigates what happens to the drug after administration, while pharmacodynamics explores its effects on the body. Unlike most traditional small molecules administered as finished products, ex vivo modified cells or viral vectors produce therapeutic components within the body, such as proteins or RNA molecules.
The traditional pharmacokinetic terminology of absorption, distribution, metabolism, and excretion (ADME) must be expanded for cell and gene therapies. Instead, distribution, persistence, and clearance describe how viral vectors or modified cells behave.
Gene modifications are conducted either ex vivo within cells before administration to the patient using viruses, CRISPR, or other gene modifying techniques or in vivo through the delivery of viral vectors. One common vector for in vivo administration is the Adeno-associated virus (AAV) vector. The AAV consists of the viral capsid or envelope, the therapeutic DNA known as the transgene, and regulatory elements that control transgene transcription.
The mRNA transcribed from the vector or expressed from a transgene element does not count as a metabolite in contrast to the products of small molecules. In gene therapies, the pharmacodynamic analyte is the synthesized functional protein from the mRNA or the RNA itself if it acts as the therapeutic product, such as siRNA inhibiting pathways.
In this context, the pharmacokinetic analyte comprises the transgene DNA and vector DNA, while the pharmacodynamic analyte is the transgene mRNA, serving as a surrogate marker for protein expression. Reliable quantifications of these analytes are crucial to understanding the mechanisms and efficacy of gene and cell therapies.
We measure transgene mRNA expression for correlation with administration dose, pharmacokinetics (PK), biodistribution, and shedding data. The concentration-time profile of the transgene mRNA reflects turnover and degradation, providing insights into its PK. While the transgene protein is a reliable indicator of transgene expression, mRNA analysis offers greater sensitivity.
PCR ASSAYS AT TATAA
TATAA Biocenter specializes in developing and validating quantitative nucleic acid analysis assays (qPCR and dPCR) for PK/PD studies, adhering to applicable regulatory requirements for different phases. Our services encompass fit-for-purpose assays to fully validated assays.
We utilize qPCR, dPCR, and NGS-based methods to detect therapeutic transgene RNA expression in tissues and biofluids. We tailor the extraction, analysis, and level of validation to meet the sponsor’s and regulatory requirements.
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About us
The power of our approach
Committed to quality, innovation, and fostering strong client relationships, we serve as your trusted partner to accelerate drug development. As a contract research organization, our mission is to push the boundaries of science and technology to generate accurate and reproducible data that shortens time-to-market.
Regulated laboratory environment
We are GLP accredited for qPCR, dPCR, and molecular biology, GCLP compliant, and ISO/IEC 17025 accredited. Our facility features a strict sample management process, a fully integrated LIMS system, backup for all vital systems, temperature and humidity control, and robust IT security.
Purpose-built PCR laboratory
Our purpose-built laboratory in Gothenburg, Sweden, is specifically designed for PCR. It has controlled air pressure, temporal separation, and biosafety cabinets to minimize contamination risk. This setup enables us to achieve the highest sensitivity and robustness required for validated assays. The lab is equipped with market-leading PCR and NGS instruments and advanced liquid handling systems.
Pioneers in assay development and validation
We are a team of 45 employees, with scientists at the forefront of assay development, optimization, and validation. Our team has co-authored key publications in the field, including Recommendations for Method Development and Validation of qPCR and dPCR Assays in Support of Cell and Gene Therapy Drug Development (AAPS J. 2024) and The MIQE Guidelines for qPCR and dPCR.
Flexible, client-centered solutions
We work closely with our clients to find tailored solutions, offering flexibility in sample types, test items, sample volume, and scalability. We prioritize transparency and proactive communication throughout each project, ensuring our clients are continuously updated on the progress.
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