Analytical Testing for IVIG Drug Products

Intravenous immune globulin (IVIG) drugs are sterilized solutions of antibodies made from human plasma, and are used to treat primary immune deficiency and other immune-related conditions. IVIG drugs have, however, been linked to thrombotic events mediated largely by coagulation factor XI(a), which co-purifies with immune globulin as a contaminant. As a result, IVIG drug manufactures are recommended to routinely test the thrombogenicity of their IVIG product via detection of XI(a) activity in a specially designed thrombin generation assays. In addition, a myriad of testing for identity and impurities is also required for the release of an IVIG lot into the marketplace. HBS performs the following testing on IVIG drug products.

Analytical methods for IVIG

Assay Method	Utility/Intended Use
Thrombin generation assay (TGA)	Quantitative Test for Process-Related Impurities: Factor XIa and “Factor XIa-like” activity
Factor XIa chromogenic assay	Quantitative detection of FXIa present in the sample
NAPTT	Detection of active contaminant clotting Factors with thrombogenic potential
Protein G HPLC	Identification/quantitation test for purity
Size exclusion HPLC (SE-HPLC)	Identity/Molecular Size Distribution
SDS-PAGE, non-reduced	Identification/Quantitative Test for Purity
SDS-PAGE, reduced	Identification/Quantitative Test for Purity
Total protein, Bradford assay	Protein concentration
Na-Caprylate	Quantitative Test for Process-Related Impurity: Sodium Caprylate
Glycine	Quantitative Test for Excipient: Glycine
PKA	Quantitative Test for Process-Related Impurity: PKA
Plasmin	Quantitative Test for Process-Related Impurity: Plasmin
Plasminogen	Quantitative Test for Process-Related Impurity: Plasminogen
Anti-complement activity	Quantitative Test for Process-Related Impurities:  Anti-complement antibodies
Hemagglutination for Anti-A and Anti-B	Quantify levels of anti-A and anti-B antibodies
Anti-D antibodies	Quantify levels of anti-D (Rh factor) antibodies
Fc Function Test	Ensuring that Fc-mediated functions are maintained
Fibrinogen (ELISA)	Quantitative measurement of Fibrinogen
pH	Ensure Correct pH of Drug Product
Osmolality	Ensure Correct Osmolality of Drug Product

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