Pharmacokinetics-pharmacodynamics
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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PK/PD​ bioanalysis

General PK/PD Page

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compliant bioanalysis

Accurate and reproducible data

A GLP accredited and GCLP compliant laboratory

TATAA Biocenter is accredited by the Swedish Board of Accreditation and Conformity Assessment (SWEDAC) for complying with Good Laboratory Practice (GLP) standards. We also adhere to Good Clinical Laboratory Practice (GCLP) guidelines, which are international quality standards governing the analysis of samples from clinical trials using GLP.

GLP and GCLP validation is mandatory in preclinical and clinical assays to demonstrate accuracy, reliability, and consistency. These standards cover every aspect of study planning, execution, monitoring, documentation, archiving, and reporting. This rigorous process assures both the sponsors, when submitting data for new drug approvals, and the regulatory authorities, when reviewing the data, that it is generated in a regulated manner.

drug development TATAA Biocenter
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method validation

Accelerate drug development with validated assays

Validated bioanalysis is essential throughout the entire drug development process.

Conducting fit-for-purpose validations in the initial stages of discovery is key. These validations offer valuable insights of expected assay performance before undertaking more comprehensive method validation processes. A validated PCR assay is essential to ensure the accuracy and reliability of results and ensures that the assay meets the client’s needs, study requirements, and assay criteria under defined operating conditions. Our assay validations ensure dependable data for making stage-gate decisions and preparing regulatory filings.

A validated assay is a valuable asset.

BIOANALYTICAL SERVICES

Quantification of viral and transgene RNA and DNA

We offer a comprehensive range of tailored services for drug development programs. With over two decades of expertise in nucleic acid analysis and sample preparation, we excel in sample extraction and quality assessment, method development and validation, and analyzing biomarkers using leading, well-matched technologies.

Shedding TATAA Biocenter
Shedding

We quantify shed viruses, bacteria-based gene therapy products, or oncolytic products in sweat, urine, excreta, and various body fluid.

Biodistribution

We monitor the biodistribution of genetically modified cells, viral vectors, and mRNA vaccines within the body using validated PCR methods.

Transgene expression​ TATAA Biocenter
Transgene expression

We quantify transgene RNA, derived from foreign genetic material, as a surrogate marker for protein expression and correlate it with bioanalysis for dosage optimization.