In-vivo and In-vitro biopharma efficacy assays

Bioassay GmbH laboratories possess the expertise and facilities required to perform biopharma efficacy assays, both in-vivo and in-vitro.

Its wide range of validated Bioassay in-vivo and in-vitro efficacy models can accurately characterize the properties of active pharmaceutical ingredients and drugs and their therapeutic efficacy against targeted indications and are particularly applicable to biopharmaceuticals like monoclonal Antibodies, Hormones or Cytokines, along with biosimilars or modified biologics, such as pegylated products.

The Bioassay laboratories also provide specialized models to characterize nephrology and diabetes drug candidates.

In-vitro efficacy bioassays

Analytical teams at Bioassay’s 1000 m2 laboratories at Heidelberg Technology Park use in-vitro facilities with state-of-the-art-equipment to execute and assess efficacy assays within quality control and development regimes for a wide range of active pharmaceutical ingredients (APIs) and drug products.

Further, Bioassay has extended experience in developing and validating new efficacy assays accordingly to ICH-Guidelines as well as in optimizing existing assay formats and transferring data into routine applications.

Bioassay has developed a series of established cGMP in-vitro efficacy assays covering cell-based analysis, FACS-Based Receptor Binding Assays, specific cell line development and neutralizing antibodies.

In-vivo efficacy bioassays

Bioassay has developed an extensive range of validated in-vivo models of human disease to support preclinical drug efficacy testing. This range of efficacy assays can assist clients in choosing the correct pharmacodynamic (PD) or disease-specific model for selecting candidates, optimizing leads or validating targets.

Bioassay’s in-vivo studies are fully supported by expertise in histopathology and bioanalysis to assess and interpret how the studied therapy affects disease pathogenesis. In-vivo efficacy assays cover a series of commercially relevant fields, including:

• Nephrology models
• Immunotoxicology (ITOX3-Panel)
• LLNA

Nephrology Models

Bioassay’s In-vivo Efficacy models use in-house developed technologies that cover key study areas such as:

• Acute Kidney Injury: (ischemia, inflammation, endothelial und tubular cell death)
• 5/6 Nephrectomy: (glomerular hypertension and glomerulosclerosis)
• Unilateral Ureteral Obstruction: (loss of renal parenchyma and fibrosis)
• Renal Artery Stenosis: (hypertension, renal fibrosis and tubular degeneration)
• Renal Transplantation: (acute and chronic allograft rejection)
• Aortic Transplantation: (vascular rejection and neo-intima formation)
• Diabetes Induction: (Streptozotocin > mild diabetic nephropathy, insulin-dependent)
• Diabetes Mutation: (BTBR Ob/Ob mice)

In-vivo analysis

In House In-vivo analyses can cover:

• Direct Organ Function
• Hematology
• Light Cycler PCR (Renal tissue)
• ELISA (biomarkers: e.g. Kim-1, NGAL, NAG)
• FACS (peripheral blood/tissue)
• Multiplex Analysis (cytokines)
• Cell Analysis (inflammatory cells)
• Renal tissue analysis (macrophages)

Immunotoxicity assays

Bioassay’s in-vivo analysis in rat models can establish:

• Immunophenotyping (Flow Cytometry)
• Oral or parenteral administration of test samples)
• Immunophenotyping in target organs: blood, spleen, lymph nodes and bone marrow)
• Standardization by ITOX3-Kit (Beckman Coulter method) )
• Analysis of T-, B- and NK- Cells by CD3, CD4 and CD8 detection)
• Calculation of a cellularity index (comparison to negative and positive Cyclophosphamide control) )

LLNA assays

Bioassay can conduct Local Lymph Node Assay (LLNA) studies for skin sensitization using BrdU-ELISA techniques and conforming to OECD guideline 442B for determination of skin sensitization in the mouse.

These measure lymphocyte proliferation without disposal of radioactivity by a non-radio labelled 5-bromo-2-deoxyuridine (BrdU). BrdU is an analog of thimidine and is similarly incorporated into the DNA of proliferating cells.

Unlike traditional LLNA (429) techniques, the LLNA:BrdU-ELISA model can be used for testing nickel compounds.

These assays have further key advantages including:

• No use of adjuvant required (compared to OECD 442A and 406)
• Reduction and refinement of animal use (compared to OECD 406)

Specialized efficacy assays

For further products or to meet specific customer requirements, Bioassay has a comprehensive library of existing specialized assay formats. Its analysts can also develop customized efficacy assays at short notice.

Biopharma efficacy assays combine standardized processes with flexible organization, adapting constantly to changing needs. Project managers are assigned to each customer at both operative and administrative levels, to accompany the client through all stages of their projects.

This combined approach enables Bioassay to extend the scope of its assay services.

Compliance and transparency

Bioassay conducts and documents all biopharma efficacy assays in conformity with GMP standards, which form the basis for its quality and reliability standards. This compliance guarantees acceptability of data generated for product acceptance and licensing.

Bioassay quality standards are inspected by leading regulatory authorities and in customer audits. These serve to encourage continuous improvement and reinforce transparency.

All customer-specific data and processes are handled and stored with utmost discretion and confidentiality.