Stability assessment of lyophilized intravenous immunoglobulin after reconstitution in glass containersand poly(vinyl chloride) bags

Abstract

Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2-3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care-giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico-chemical tests (molecularsize distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non-specific binding of complement (anti-complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 degrees C. The reconstituted product was also found to be stable at room temperature (25 degrees C) up to 12 h.

In-use physicochemical and microbiological stability of biological parenteral products

“…3 For lyophilized products, interim storage of the reconstituted solution can also result in physical and chemical instability. 4 Contact of the drug with various surfaces can also affect stability and drug recovery, and care should be taken to ensure that in-use components such as i.v. infusion bags, lines, and filters have been previously evaluated for compatibility.…”

Intravenous immune globulins: an update for clinicians

“…Intravenous immune globulin (IVIG)* is currently the most widely used plasma component in the world 1 . Immunoglobulins provide the body with an important defense mechanism against infectious agents for the patient with hypogammaglobulinemia.…”

Challenges in the intravenous (IV) administration of monoclonal antibodies (mAbs)

“…In particular it was shown that potential aggregation-prone regions and hydrophobic patches in the IgG2 mAb are in close proximity to amino acid residues whose binding with metal ions leads to oxidation and aggregation (Kumar, Zhou, & Singh, 2014). In addition, two studies have been published purporting to show that there was no stability impact to the mAbs tested after dilution into PVC bags (Ikesue, Vermeulen, Hoke, & Kolesar, 2010;Parti & Mankarious, 1997).…”