Leverage the benefits of the unique test system ID.Flow®
BLOOD DONORS
We draw blood from donors directly at our test site allowing us to observe the effects of drugs on fresh, minimally manipulated whole blood. This provide invaluable insights into how drugs affect complex biological systems in the human blood including the complement and cascade system, immune cells, platelets and immunoglobulins.
TEST SYSTEM
ID.Flow is a highly advanced test system that ensures the continuous circulation of human blood and test substance at a regulated temperature of 37°C. Its superior sensitivity and physiological features set it apart from other methods of assessing complement activation.
COMPLIANCE
FDA and EMA encourage the use of New Approach Methodologies (NAMs) to evaluate the immunotoxicity potential of new drugs and urge drug developers to choose non-animal methods when applicable.
Complement Assay
Complement activation should be assessed in human blood with active complement factors.
We have extensive experience assessing complement activation for various drugs. Complement data from ID.Flow can help determine the appropriate starting dose for clinical trials, identify potential immunotoxicity, and overcome the limitations of in vitro or animal studies in this area. For instance, in the case of antisense oligonucleotides (ASOs), non-human primate studies can overestimate complement activation, making assessment in ID.Flow a valuable and relevant resource.
Why complement activation should be a part of the nonclinical safety assessment.
The human complement system comprises upwards of 50 proteins. Although small, these proteins can trigger a massive immune response, starting a cascading reaction that stimulates phagocyte activation, inflammation, and membrane attack complex. In a clinical trial, they can be the source of significant infusion reactions, such as hypersensitivity reactions caused by the complement system. These include reactions based on complement-dependent cytotoxicity (CDC), which can be prevented through antibody modification. However, they also include reactions based on antibody-dependent cell-mediated cytotoxicity (ADCC), which is frequently overlooked. The latter can occur via the alternative pathway, which remains active even when the classical pathway has been blocked.
Based on the FDA Guideline: Nonclinical Evaluation of the Immunotoxic Potential of Pharmaceuticals, June 2023, it is recommended to include complement activation in the non-clinical safety assessment. The ID.Flow system is capable of providing more than 40 readouts from each test condition of fresh whole blood, making it an ideal tool for obtaining a comprehensive understanding of the human immune response to a drug.,l-
The Figure above shows a study of complement activation in ID.Flow. The figure shows the activation of complement subunits C3a and C5a as assessed by ELISA in fresh human blood from five healthy donors. The donor responses are compared to PBS (vehicle) and different monoclonal antibody controls in ID.Flow as compared to blood collected before addition to ID.Flow (zero sample).
The process of working with us
- We work together to set the study design including readouts, controls and timepoints. ID.Flow can assess over 40 readouts from each test condition.
- You send the test substances to our test site in Sweden.
- We recruit blood donors and initiate the analysis immediately upon blood draw.
- The study includes:
- Design and guidance by our Scientific Advisors, Immunology.
- Donor recruitment.
- Ex-vivo assessment.
- Statistical analysis and interpretation.
- Raw data files and scientific report.
Readouts
- Complement activation: C3a, C5a, SC5b-9 and or Bb split product
Additional readouts that can be assessed from the same test conditions:
- Simultaneous evaluation of CDC and ADCC
- Platelet activation and counts
- Cytokine release
- Blood cell counts, hemolysis and clotting
- Immune cell activation
MORE SERVICES
Cytokine Release
Sensitive cytokine release prediction in fresh human whole blood.
White Blood Cells, Count & Activation
Activation of B cells, T cells, NK cells, monocytes, and granulocytes is simultaneously analyzed in fresh human whole blood.
Platelets, Count & Activation
Platelet activation, aggregation, apoptosis, hemolysis and hemagglutination.
ADCC / CDC
Simultaneous study of ADCC and CDC in fresh human whole blood.