ACCELERATE PRODUCTION

Host cell DNA residual assays

We offer PCR-based host cell DNA residual assays with short lead times to accelerate process decisions.

Host cell impurities

DNA from the production host cell increases the risk of infection and oncogenicity. Therefore, safety testing for host cell DNA residuals is required for each batch.

Quality assessment of gene therapy products involves evaluating impurities not intended to be part of the final product. These impurities can be categorized as cellular impurities or process-related impurities, encompassing various elements such as reagents, media components, host cell components, residual DNA, viral vectors, vector-associated impurities, CRISPR-Cas9 ribonucleoproteins (RNPs), RNP-associated impurities, and other materials associated with viral production.

The risks associated with host cell DNA are potential infection and oncogenicity risks. The rep gene, utilized in vector production, possesses helicase and endonuclease activities that may increase mutation rates and promote vector integration in transduced cells.

Among DNA impurities, viral oncogenes represent a significant concern theoretically associated with an increased risk of oncogenesis. These genes are typically compact enough to fit within the viral capsid. Cell lines containing viral oncogenes are often used to produce AAV vectors. For instance, HEK 293 cells carry adenovirus E1, HEK 293T cells have adenovirus E1 and SV40 large T antigen, and HeLa cells harbor human papillomavirus E6 and E7. Plasmids containing the adenovirus E4 region, known for encoding proteins inhibiting the tumor suppressor p53 gene, are frequently used in triple transfection.

The risk to the human body increases as the length of residual host cell DNA fragments increases. Therefore, during the purification process, DNA is intentionally fragmented using nucleases. However, certain impurities may persist even after nuclease treatment, potentially because they are encapsulated within the capsid.

The primary goal of fragmentation is to disrupt the integrity of elements like oncogenes and eliminate infectious units such as integrated retroviruses and other functional sequences. It’s important to note that the AAV capsid shields the packaged nucleic acid from nuclease digestion, making removing or further reducing its size impossible.

Host cell DNA detection employs quantitative PCR methods like digital PCR. A representative segment, such as the 18S rRNA gene found in multiple copies within the HEK 293 cell genome, can serve as a target to identify host cell DNA. Ideally, we measure multiple amplicons of varying sizes to quantify a gene in more than one genome copy. Current guidelines recommend that residual cell-substrate DNA levels should not exceed ≤10 ng per dose, with a median DNA size of 200 bp or less.

Accelerate production with TATAA

We offer short lead times and fast analyses, allowing you to optimize the purification process, provide confidence in your products before GMP analysis, help with deviation control, and ensure trust in GMP results and safe product delivery.

Our well-equipped molecular analysis laboratory features automated platforms, a Laboratory Information Management System (LIMS), and high-throughput instruments for qPCR, dPCR, and Next-Generation Sequencing (NGS). Additionally, our facility includes a Biosafety Level 2 (BSL-2) laboratory that allows us to offer end-to-end solutions, from sample extraction to data transfer.

TATAA Biocenter can offer method development and validation tailored to your specific samples, from extraction to data transfer. We can assist you in measuring 18S rRNA, adenovirus E1, SV40 Large T antigen sequences, the E6/E7 genes, or any other genes you choose.

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.

QUALITY ANALYSES

Accelerate with reliable results

With over 20 years of experience in nucleic acid analysis, we specialize in developing PCR-based assays that offer fast, accurate, and reliable quality testing for process optimization. The rapid results generated by PCR technology make it well-suited for assays on viable products, crucial for cell and gene therapies.

Vector copy number

Quantifying the transgene dosage, the presence of transgenes, the number of integrated vectors, or the number of non-integrated vector genomes in targeted cells provides essential information during production optimization.

Vector Integrity TATAA Biocenter
Vector integrity​

Ensuring consistent characterization of the packaged vector genome is crucial for production process optimizations and comparing results across production batches.

Pathogen Detection TATAA Biocenter
Pathogen detection

Various sequencing technologies provide a fast and reliable tool for evaluating sterility and detecting mycoplasma and endotoxins.

Integation Site Analysis TATAA Biocenter
Integration site analysis

We evaluate the integration site specificity and transduction efficiency, assess safety, and prevent unintended effects on adjacent genes during integration.

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

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