Bioanalysis Services | Clinical Bioanalysis

Uniquely built to support studies with small and large molecules

Delivering a full range of bioanalytical services across non-regulated early drug discovery through to regulated pre-clinical and clinical phases (Phases I-IV), we can work with all types of drug products and biomarkers, from small molecules to proteins including antibodies, antibody drug conjugates and oligonucleotides.

We have extensive experience in developing bioanalytical assays in blood, plasma, urine and many other matrices such as tissues, CSF and feces.

Our bioanalytical platform is uniquely built to support studies with small and large molecules.
Leveraging state-of-the-art instrumentation, we create the most robust, sensitive assays possible to solve your most complex bioanalytical challenges and detect analytes of interest to the required quantification level. Our facilities are also equipped with advanced, compliant temperature-controlled biosample storage at 2-8°C, -20°C, 80°C, and lN2.

We deliver results within required timelines to allow rapid decision-making during dose escalation studies with all the results put through rigorous Quality Control (QC) and source verification, conducted by our Quality Assurance (QA) team.

Flow cytometry

Our flow cytometry services offer sensitive measurements of:

Fresh or preserved biological matrices, such as whole blood, PBMCs
Cell cultures
Genetically modified organisms (GMO, Biosafety Level 2)
Single-cell suspension from enzymatically or mechanically dissociated solid tissues.

We provide state-of-the-art flow cytometry for high-throughput single-cell measurements of up to 14 parameters (3 lasers—blue, red and violet—12 fluorescence channels), equipped with a loader for fully automated measurements.

Our instruments have been validated through Installation Qualification (IQ), Operational Qualification (OQ) and daily Performance Qualification (PQ).

Analytical support

During panel design for the 12-color BD FACSLyric flow cytometer, fluorophore-conjugated antibodies are carefully selected based on antigen density, co-expression and spectral overlap of fluorophores. Antibodies are titrated for optimal staining conditions.

Analytical support is conducted at all stages of the drug development process, including:

Immunophenotyping
Immune monitoring
Immunogenicity assessment (ADA & NAb assays)
Receptor occupancy (RO) assays

Clinical trials services (sampling kits, lab manual, logistics)

Quality starts at the point of sample collection so we design and assemble sample collection kits, providing detailed instructions in a laboratory manual customised to each clinical trial.

We supply investigator sites with assay-specific sample collection procedures and transportation kits compliant with IATA packing instructions, accompanied by requisition forms, pre-printed airway bills and instructions describing logistics procedures.

Ensuring that samples are analyzed in a timely and cost-efficient manner for even the most complex clinical trial, we have a dedicated sample management department in place.

Upon receipt, we verify the identity and completeness of each sample, its sample identifiers and the accompanying requisition forms. After unpacking the samples, the documentation is checked and entered into our LIMS system.

Read more about our assays and expertise

hELISA for oligo’s

Oligonucleotides are measured using hybridization ELISA, usually on the MesoScale Discovery platform. We have developed numerous assays detecting oligonucleotides in plasma as well as in several tissues like liver, intestine, muscle, heart and spleen. For several tissues like muscle and spleen, which are difficult to process, we have developed special procedures in house to allow detection of the oligonucleotides in these tissues. Assays are usually optimized for probe annealing temperature, which varies for each probe/oligonucleotide combination and solutions are available for preventing non-specific binding of oligonucleotides, which is a known feature of some oligonucleotides.

Ceramide / sphingosine analysis by LCMS

Analyzing sphingolipids is one of our specialties in the LC-MS/MS group. Especially the ceramide and sphingosine lipid species containing glucosyl or galactosyl residues are notoriously difficult to separate. We have developed several methods in house that enable us to evaluate virtually all lipids in the ceramide/sphingosine pathway, also distinguishing between glucosyl or galactosyl residue containing lipids. Our years of experience culminated in several panels of ceramide and sphingolipids that can be measured at the same time, resulting in efficient analysis of these lipids in plasma, CSF and tissues.

Hybrid MS for ADC

For antibody-drug conjugate (ADC) PK assessments during (pre-)clinical studies we evaluate total antibody, total conjugated ADC and free payload. Depending on the ADC characteristics, assay requirements and Sponsor needs, hybrid LC-MS/MS, ELISA (different platforms) or a combination can be employed, which we all have in house. Assays are typically developed such that total antibody and total conjugated ADC are determined simultaneously, which saves time and costs. In addition, some generic formats are available, which considerably saves assay development time.

NAb by flow cytometry

NAbs are a subset of ADA that unintendedly bind to the drug product and inhibit its pharmacological function. Although complex, cell-based NAb assays are preferred method to detect the presence of NAbs because they more closely mimic the mechanism of action. For example, cellular uptake of enzyme replacement therapy, which needs to be internalized by the cell to exert its action, could potentially be inhibited by NAbs. In our cell-based lab we have developed a Nab assay using fluorophore-conjugated enzyme replacement therapy uptake as read-out on our flow cytometer and we were able to measure the inhibitory effect of NAbs on cellular drug uptake during a clinical trial.

THC + metabolites by LCMS

Cannabinoids are a group of molecules which require very specific expertise. Molecules like THC or CBD are metabolized rapidly and the analysis of these metabolites is complex and extensive, requiring expertise and experience for proper evaluation at a high sensitivity (pg/mL range). At Ardena we have performed over 20 projects evaluating cannabinoids and our facility is licensed for evaluation of controlled substances.

PK and ADA for COVID therapy

For COVID-19 Ardena Bioanalyis has developed PK and ADA assays for a COVID-19 monoclonal antibody therapy. The rapid onset of COVID-19 required a quick development and validation of the assays as well as a rapid turnaround for bioanalysis. For the PK assay three different methods were developed in parallel to ensure employment of a suitable assay timely. Immediately, following method development, the most suitable method was validated, such that samples from a clinical trial could be evaluated in time. For the ADA assay the Sponsor was advised on the fastest ways to obtain the appropriate reference materials and reagents, after which an ADA assay was setup immediately upon reception of reagents, fully validated according the FDA and EMA guidelines and ready for sample analysis before the clinical trial had started.

Nanoparticle bioanalysis

The bioanalytical evaluation of nanoparticles is very complex with usually the presence of multiple active drug substances, major metabolites and derivatives of the nanoparticle as well as impurities. In addition, the API can be measured in its total, free and bound forms. We have performed several projects successfully evaluating all these parameters in an integrated approach.