reports, applicable manufacturing conditions were used. Log10 RFs on the order of 4 or more are considered effective for virus clearance in accordance with the Committee for Medicinal Products for Human Use (CHMP, formerly CPMP) guidelines.
b No RF obtained due to immediate neutralization of HAV by the anti-HAV antibodies present in the product.
The Recombinant Human Hyaluronidase of HYQVIA is produced from genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase PH20. The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons [see Mechanism of Action (12.1)]. This component is supplied as a sterile, clear, colorless, ready-for-use solution and has approximate pH of 7.4 and an osmolality of 290 to 350 mOsm. Each vial contains 160 U/mL of recombinant human hyaluronidase with 8.5 mg/mL sodium chloride, 1.78 mg/mL, sodium phosphate dibasic dihydrate, 1.0 mg/mL human albumin, 1.0 mg/mL edentate disodium dihydrate, 0.40 mg/mL calcium chloride dihydrate, and 0.17 mg/mL sodium hydroxide added for pH adjustment. It does not contain preservatives.
Due to comprehensive virus testing at the Master Cell Bank, Working Cell Bank and bulk harvest stage, effective virus reduction during the purification process and the use of pharmaceutical grade human albumin as an excipient with no other materials of human or animal origin involved in the manufacturing process, recombinant human hyaluronidase provides for high margins of safety with respect to viruses.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action The Immune Globulin Infusion 10% (Human) provides the therapeutic effect of HYQVIA. The Recombinant Human Hyaluronidase of HYQVIA increases dispersion and absorption of the Immune Globulin Infusion 10% (Human). The Immune Globulin Infusion 10% (Human) of HYQVIA supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. The Immune Globulin Infusion 10% (Human) also contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. The role of these antibodies and the mechanisms of action of IgG in the Immune Globulin Infusion 10% (Human) of HYQVIA have not been fully elucidated.
Hyaluronan is a polysaccharide found in the extracellular matrix of the connective tissue8. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a very fast turnover with a half-life of approximately 0.5 days. The Recombinant Human Hyaluronidase of HYQVIA increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan.In the doses administered, Recombinant Human Hyaluronidase of HYQVIA acts locally. The effects of the hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours.
12.3 Pharmacokinetics The pharmacokinetics (PK) of HYQVIA was eva luated during a clinical trial of adults with PI after they achieved steady state at their 3 or 4 week dosing interval and underwent individual dose adjustment [see Clinical Studies (14)]. For adults, adjustment of dose was based on comparison of the ratios of the area under the IgG concentration versus time curve (AUC) during in
