Ensuring the safety and efficacy of IVIG therapies, which are often life-saving for patients with immunodeficiencies and autoimmune disorders, depends on a rigorous battery of assays. Each test, from basic identity confirmation and pH measurements to advanced assays such as Factor XIa activity and Fc-function, plays a pivotal role in verifying that the product is pure, potent, and free from contaminants.
For instance, assays that assess total protein, protein composition, and molecular size distribution confirm the presence of the correct IgG profile without unwanted aggregates or fragments, while tests for IgG subclasses, IgA, and IgM ensure the therapeutic balance that underpins immune protection. Additional measurements of osmolality, chloride, and sodium guarantee that the formulation mimics physiological conditions, reducing the risk of adverse reactions.
Safety is further reinforced by monitoring residual substances—such as glycine, ethanol, tri-n-butyl phosphate, Triton X-100, and aluminium—and evaluating immunological risks with assays for ACA, prekallikrein activator, and anti-A/anti-B haemagglutinins.
Moreover, specialized tests like anti-HAV activity confirm the product’s ability to offer passive immunity against hepatitis A, and assessments of Fc-function validate that the IgG molecules can effectively interact with immune cells.
Together, these assays ensure that IVIG therapies remain consistently safe and effective, providing critical life-saving support to patients by preventing infections and modulating aberrant immune responses.
Discover the full details behind each assay and learn how they safeguard the quality and efficacy of life-saving IVIG therapies. Scroll down to explore the comprehensive descriptions below.
Identification
This assay confirms the unique protein fingerprint of the IVIG product by comparing its characteristics to a known reference. Accurate identification is crucial to ensure that the product is indeed the intended immunoglobulin preparation and free from misidentified or contaminant proteins.
pH
Measuring the pH ensures that the IVIG formulation falls within the optimal range for both stability and compatibility with human physiology. An appropriate pH is essential to prevent protein degradation and to minimize irritation upon administration.
Protein Composition
This test analyzes the specific makeup of proteins in the IVIG sample, confirming the predominance of IgG and detecting any unwanted contaminants. A precise protein composition ensures consistency, safety, and proper immunological activity in the final product.
Glycine
Glycine is commonly used as a stabilizer in IVIG formulations. Its quantification helps verify that the correct amount is present to maintain protein stability during storage and administration, thereby ensuring the product’s safety and effectiveness.
Molecular Size Distribution
By assessing the molecular size distribution, this assay detects aggregates, fragments, or other molecular species. Maintaining a narrow distribution of monomeric IgG is essential since aggregates can provoke immunogenic responses and reduce therapeutic efficacy.
IgG Subclasses
Evaluating the distribution of IgG subclasses (IgG1, IgG2, IgG3, and IgG4) is important because each subclass contributes differently to immune defense. Consistent subclass distribution helps ensure that the IVIG product provides broad-spectrum immunomodulatory and protective effects.
IgA
Measuring IgA levels in an IVIG product is important because excess IgA may trigger adverse reactions, particularly in IgA-deficient individuals. Keeping IgA within acceptable limits reduces the risk of anaphylaxis and other immune-mediated complications.
IgM
Although IVIG is primarily composed of IgG, detecting trace amounts of IgM is also necessary since higher levels can be associated with increased risks of complement activation and adverse reactions. This assay helps in ensuring product safety by monitoring unwanted immunoglobulin isotypes.
Osmolality
Determining osmolality verifies that the IVIG formulation is isotonic, which is essential for patient comfort and to prevent cell damage at the injection site. Proper osmolality ensures that the product is well tolerated upon administration.
Chloride
The chloride assay monitors the ionic balance of the formulation. As chloride levels can influence osmolality and overall product stability, this test ensures that the electrolyte composition meets the required specifications for safe infusion.
Sodium
Sodium concentration is measured to confirm that the IVIG product is formulated to mimic physiological conditions. Maintaining appropriate sodium levels supports osmolality and helps prevent potential electrolyte imbalances in patients.
Aluminum
This assay detects trace levels of aluminium, which might leach from manufacturing equipment or be present as a contaminant. Low aluminium levels are essential to avoid potential neurotoxicity or other adverse health effects in patients.
Ethanol
Residual ethanol, sometimes used during manufacturing or viral inactivation processes, is measured to ensure it is below acceptable limits. Ensuring low ethanol levels helps protect patients from potential toxicity and side effects.
ACA
The ACA assay (which may refer to a test for anti-complement activity or related antibody activities) helps monitor the product for any unintended immunological activities that could activate the complement system. This is important to prevent inflammatory or adverse immune reactions upon infusion.
Prekallikrein Activator
This test measures the potential of the IVIG product to activate prekallikrein, which is part of the kallikrein-kinin system. Elevated levels could lead to hypotension or other adverse reactions, so controlling this activity is key for patient safety.
Anti-A and Anti-B Haemagglutinins
Screening for anti-A and anti-B haemagglutinins is critical, especially for products destined for a diverse patient population. These antibodies can cause hemolysis in recipients with incompatible blood types, making this assay vital for preventing transfusion-related complications.
Tri-n-butyl Phosphate
Tri-n-butyl phosphate is used as a solvent during viral inactivation. The assay ensures that any residual amounts in the final product are within safe limits, protecting patients from potential solvent-related toxicity.
Triton X-100
This non-ionic detergent is also used in viral inactivation processes. Residual Triton X-100 must be quantified to confirm that its concentration is below the threshold that could cause cellular toxicity, ensuring overall product safety.
Factor XIa Activity (e-CAT)
This assay detects the presence of active Factor XIa, a procoagulant that can predispose patients to thrombosis. Monitoring Factor XIa activity is essential to minimize the risk of coagulation-related adverse events following IVIG administration.
Anti-HAV Activity
Evaluating anti-hepatitis A virus (HAV) activity confirms that the IVIG product contains antibodies that can neutralize HAV, which is beneficial for providing passive immunity. This assay supports both the safety and added protective value of the product.
Fc-Function
Testing Fc-function assesses the ability of the IgG molecules to interact with Fc receptors on immune cells. This interaction is key to the immunomodulatory effects of IVIG, ensuring that the product not only neutralizes pathogens but also modulates immune responses effectively.