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Translational Medicine Leadership Team
At QPS, translational medicine brings together leading-edge technologies and pharmaceutical R&D experience to create a business service unit that works efficiently to advance your drug development program. Our scientists come from a variety of backgrounds and can confidently perform the pharmacokinetic (PK), pharmacodynamic (PD), immunogenicity assessment or pharmacogenomics (PGx) experiments required by your design.
Projects in translational medicine include method transfer of assays originated from the sponsor's lab, validation of commercially available kits and methods or a collaborative effort between the QPS team and your lab for custom assays. In addition to LBA-based immunoassays for PK, biomarkers and immunogenicity assessment, QPS can help develop cell-based assays for neutralizing antibody activity studies and biomarker evaluation in support of your drug development programs.
QPS maintains four advanced bioanalytical facilities in the USA, Netherlands, Taiwan and India, offering strategic solutions to companies with sites or trials overseas and/or wishing to complete off-shore studies in Asia and/or India. Benefit from our worldwide resources through which a portfolio of assay principles is offered to cover your entire global demand in bioanalysis for your clinical studies.
Translational Medicine Leadership Team
Fit-for-Purpose Validation & Qualification
We have been working diligently with clients to determine best practices for conducting biomarker or other pharmacodynamic studies to support both preclinical studies and clinical trials. As there is no current FDA guidance for pharmacodynamic assays, we have adopted a “fit-for purpose” plan to validate and qualify assay methods. QPS can plan a "fit-for-purpose" method validation or qualification that identifies the key tests needed to ensure the suitability of an assay method on an individual basis.
A full method validation is typically described in a sponsor-approved validation protocol and includes at least six assay runs to determine both inter- and intra-batch precision and accuracy, dilution linearity (hook effect tests), matrix selectivity, matrix effect (n ≥ 6) and necessary stability tests including benchtop (ambient temperature), freeze-thaw and long-term storage.
In a “fit-for-purpose” method validation, the individual biomarker characteristics and the study specifics are used to determine which of these tests are appropriate. Some tests may be eliminated on an individual basis if they are not applicable to the particular biomarker,
not useful for a specific type of assay (e.g. activity assay) or if they are not relevant to the clinical or pre-clinical study our method is supporting. Additional tests may be added given the same considerations.
We can also provide a shorter method qualification, usually performed with a vendor-qualified assay kit. A qualification typically includes 3 or more precision and accuracy runs and matrix testing. In this case, assay specifications including more extensive validation tests are provided by the assay vendor. As a “fit-for-purpose” qualification, additional tests may be added based on the nature of the assay and specific study considerations. In some cases, an inter-laboratory cross validation may be performed for data comparison, using 20-30 samples provided by the sponsor.
The potential of biomarkers to facilitate the development of effective and safe drugs has been well recognized as an integral part of all phases of drug development. As molecular and cell biology science advances, cell-based technologies have become a critical part of biomarker discovery, development and target validation.
At QPS, our scientific team has a wide range of molecular and cell biology experiences, working with both the established cell lines and primary cultures to meet sponsor’s study needs. Since 2002, QPS has supported more than 40 cell-based studies for numerous sponsors. Our expertise ranges from cell banking, cell proliferation assays, on-site cell stimulation followed by cytokine induction analysis and various target specific functional assays. Although cell-based assays do not have current standardized industry guidance, we have developed and validated cell-based assays in GLP environment to assess neutralizing antibody activity in human serum samples in support of the clinical investigation of anti-drug antibodies (ADA) on drug efficacy and safety.
QPS experienced cell-based assays include:
- Endotoxin Stimulation (Cytokine Production)
- Compound Toxicity on Monocytes (Cytokine Induction)
- Uptake Study ( 33 P) Using Primary Cells
- Toxin Neutralizing Assay (Cell Proliferation)
- Neutralizing Antibody (NAb) Assay (Cell Viability)
- Custom Functional Assay
Our cell culture facility is well equipped with BSL2 biosafety hoods, CO2 incubators, automated cell counter, microscopes with cameras and imaging capability, as well as liquid nitrogen tanks for cell banking.
Immunogenicity & Neutralizing Antibodies
Immunogenicity refers to a drug-elicited anti-drug immune response. All macromolecules are potentially immunogenic. Sometimes compounds with molecular weights as low as 1,000 Daltons, such as penicillin or sulfonamides, may also elicit an immune response, but all severe immune responses, including immediate hypersensitivity responses and neutralizing antibody responses, must be avoided.
Immunogenicity can be either non-neutralizing or neutralizing. While a non-neutralizing immunogenicity may not have negative effect on the pharmacodynamics of the drug, neutralizing immunogenicity can deactivate drug activity and alter drug clearance, plasma half-life and tissue distribution. Thus, immunogenicity testing is important both to the safety and efficacy of the product.
Immunogenicity testing and associated services provided by QPS include:
- Preparation of antigen-protein conjugates for plate coating
- Method development and validation using ELISA format
- Screening for positive responses in study samples
- Confirmation test for samples displaying positive responses during screening
- Titering of confirmed positive samples to determine the relative degree of antigenicity
- Detection and determination of various classes of antibodies (e.g., IgG, IgM, etc.)
- Neutralizing antibody assays
Gene expression analysis is a way of monitoring the activity of genes as a result of normal cellular function, disease states or changes in the environment. Expression analysis aids the drug development process by identifying new drug targets, aiding the discovery and validation of clinical biomarkers linked to human disease, monitoring disease progression, predicting the function of novel genes, understanding variability in response to drugs and predicting the toxicity of drugs. Depending on the scale performed, expression profiling can examine one specific gene of interest or thousands of genes at once to create an overall picture of cellular function.
Analysis of gene expression typically involves measuring the relative amount of mRNA expressed in two or more experimental conditions and is generally performed using microarrays or real-time PCR.
There are also methods available to examine epigenetic control of gene expression. With QPS, you are assured of top-quality starting material for successful downstream molecular applications. QPS offers automated RNA isolation and banking from many matrices, including whole blood, plasma, serum, tissues, FFPE biopsy sections or cultural cells. QPS utilizes leading technology platforms for gene expression analysis including Applied Biosystems' TaqMan® platform for real-time PCR (including TaqMan low density arrays), Affymetrix Genechip® microarrays and Pyrosequencing® for identification of DNA methylation status. We also perform western blot analysis, functional assays and cell-based assays.
Genotype testing will provide a genetic basis for target identification, toxicity prediction, dosing determination and for making treatment decisions. Using the focused combination of genetic and protein biomarkers to screen for biological activity increases the likelihood of useful clinical activity. Examples include UGT1A1 genotyping for Irinotecan toxicity prediction, CYP2C9 genotyping for warfarin dosing optimization and CYP2D6 genotyping to help in tamoxifen therapy management for breast cancer patients.
Genetic biomarkers are important in the drug development process because they can provide information about the potential risk associated with specific genes. Some examples include ApoE genotyping, which is used to determine patient inclusion/exclusion, and patient stratification in Alzheimer's disease clinical studies. To support patient inclusion/exclusion decision making, we offer turnaround results in 48-72 hours.