SAFETY ASSAYS

Shedding of cell and gene therapies

We offer PCR-based shedding assays, including extraction, method development, validation, and high-throughput sample analysis.

Shedding assays

Shedding assays presents unique challenges. The analytes released are typically found in very low quantities, and the matrices involved in shedding assays often contain significant levels of PCR inhibitory agents and endogenous DNA.

To assess the risk to individuals in close contact with subjects receiving gene therapy treatments and to track the distribution of genetically modified DNA, monitoring of cell and gene therapy product shedding is required.

Even though AAV viruses have their rep and cap genes responsible for replication depleted, the shedding of viral particles poses an infection risk to individuals in close contact with the treated patient. These genes are supplied separately on helper vectors during AAV production, since the vector is unable to replicate independently. Regulatory agencies require shedding studies due to the potential scenario where a patient sheds virus particles, exposing someone in close contact with the AAV drug, wild-type AAV, and a helper virus in a triple infection. The risk associated with shedding is significantly greater with replication-competent viruses than with replication-incompetent ones.

Shedding is most likely to occur shortly after product administration. Replication-competent products may exhibit a second shedding peak in the days or weeks following administration because of product multiplication within the body.

Bioanalytical approaches use highly sensitive PCR technologies to detect low-copy-number foreign viral or transgene DNA in complex matrices like urine, saliva, and feces. These matrices contain proteases, nucleases, ions, and salts that can interfere with PCR performance. In addition, feces have DNA from natural flora, increasing the potential for non-specific amplification.

SHEDDING ASSAYS AT TATAA

TATAA Biocenter specializes in developing and validating quantitative nucleic acid analysis (qPCR and dPCR) for bioanalysis studies, including shedding assays, while adhering to the regulatory requirements for preclinical and clinical programs. Our services encompass fit-for-purpose assays and fully validated assays.

We have two decades of experience in nucleic acid extraction. This enables us to effectively address challenges associated with shedding assays where the target nucleic acid exists in exceptionally low copy numbers and the matrices often contain high levels of PCR inhibiting agents. Our extensive experience, advanced technical instrumentation, and well-defined workflows also empower us to develop, validate, and execute assays with the specificity required to detect the low copy number range in shedding samples.

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
Lines in Circle Mask - Lg
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.

PK/PD​ TATAA Biocenter
PK/PD

We extract and quantify PK/PD analytes, including vector DNA, transgene DNA, transgene RNA, and expressed RNA, using validated PCR methods to determine the PK and PD profiles.

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.

The Olink Target 96 panels are designed for high throughput, cost efficiency, and low sample consumption, facilitating targeted biomarker research in various disease areas and biological processes. The Olink Target 96 panels simultaneously enable high-multiplex targeting analysis of 92 protein

The Olink Explore 384 panels collectively form the comprehensive Explore 3072 panel. Run one or several of these panels on each sample simultaneously. Each Olinke 384 panel contains carefully selected proteins validated for human plasma and serum samples, making it

The Explore HT panel contains over 5,400+ proteins, almost twice as many as the Explore 3072 panels. The sample volume for Explore HT is 2 µl, compared to 6 µl for Explore 3072. The workflow for Explore HT is four

why work with tataa?

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, we are committed to generating accurate and reproducible data that shortens time-to-market.

Experienced scientists

We are ahead of industry trends and always updated on the regulatory landscape and requirements for gene editing and nucleic acid-based therapies. Our purpose is to provide data that’s easily auditable.

Total project transparency

We maintain transparency and proactively communicate throughout the project, ensuring our clients always stay updated on the progress. Transparency forms the cornerstone of our proven client model.

Have confidence in your data

We use the highest quality reagents, adhere to dedicated controls, and standardize all processes per technical requirements like the MIQE guidelines. We deliver rapid, robust, and reproducible results that are submission ready.

Flexible and scalable

Every project is customized to meet our client’s specific needs. We manage projects of all sizes and all stages, including any or all phases from sample extraction to analysis and data transfer. Your goals are our deliverables.

TECHNOLOGIES

We operate with the latest technologies

TATAA Biocenter comprises highly skilled scientists with extensive expertise in method development, optimization, validation, and optimization of molecular analysis. We leverage market-leading instrumentation and automation platforms, offering expert guidance to choose the most suitable technology for your program.

PCR Analysis TATAA Biocenter
PCR

We use highly sensitive and highly precise quantitative PCR (qPCR) and digital PCR (dPCR) technologies to detect one or multiple DNA/RNA targets in complex samples.

NGS Services TATAA Biocenter
NGS

We use NGS, a powerful tool to sequence entire exomes, genomes, or transcriptomes, and our scientists and bioinformaticians provide comprehensive sequencing data.

Olink service provider TATAA Biocenter
Quantitative proteomics

We are a designated Olink service provider with the latest technologies for running quantitative proteomics using Olink’s panels for biomarker discovery, validation, and screening.

contact us

Let's explore how we can support your drug development program.

PK/PD​ bioanalysis

General Shedding Page

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