14. Stability of Immune Globulin Intravenous, Human-stwk, 10% Liquid Following Pooling and Storage in Flexible Containers

Background: Immune globulin intravenous, human-stwk, 10% liquid is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. Unopened immune globulin intravenous, human-stwk, 10% liquid in its original container is to be stored under refrigerated conditions at (2-8C/36-46F) for 36 months or may be stored for 24 months at room temperature (25C/77F) from the date it was manufactured. However, pooling intravenous immunoglobulin (IVIG) offers streamlining of administration for the infusion nurse, improves the patient’s ability to ambulate freely during the infusion, and provides reduced risk of container breakage during shipment and administration. Therefore, it is common practice to pool vials of IVIG into a single flexible container under aseptic conditions. Although the United States Pharmacopeia (USP), a scientific nonprofit organization, regulates the compounding of sterile products via the USP < 797> Compounding Standards, it is important to understand individual product stability under these common conditions.

Purpose: The purpose of this study was to determine the effects of pooling immune globulin intravenous, human-stwk, 10% liquid in three types of flexible containers under aseptic conditions.

Methods: Pooling of the immune globulin intravenous, human-stwk, 10% liquid was performed aseptically under a laminar flow hood. 210 mL of the product was pooled into separate flexible containers made by three different manufacturers: the Empty IntraVia Container (Baxter), EVA 2 -port Container (The Metrix Company), and 3-in-1 EVA Mixing Container (B. Braun). These pooled samples were compared to samples obtained from product in the original manufacturer containers, and whenever possible, the original release specifications. The following attributes were evaluated to determine product stability and quality at days 0, 1, 7, and 14: pH, total protein composition, osmolality, molecular size distribution (IgG monomers plus dimers, IgG fragments, IgG polymers), anti-complement activity, hepatitis B antibody titer, appearance, particle matter, and TGA. After completion of the study, sterility testing was performed to verify that aseptic technique was maintained throughout the entire study.

Results: Pooled immune globulin intravenous, human-stwk, 10% liquid remained within release specifications (which are the FDA-Approved requirements for immune globulin intravenous, human-stwk, 10% liquid) for all parameters evaluated for 14 days when stored under refrigerated conditions (2-8C/36-46F).

Discussion: Pooled IVIG products fall into USP < 797> Category 2, which indicates that when product pooling takes place in a modern clean room equipped with an ISO Class 5 Primary Engineering Control (PEC), an ISO Class 7 buffer area, and an ISO Class 8 ante-room, the assigned beyond use date for that product is 4 days at controlled room temperature and 10 days when refrigerated. Nonetheless, it is important to understand individual product characteristics under these conditions.

Conclusions: In this in vitro study, immune globulin intravenous, human-stwk, 10% liquid remained within FDA approved release specifications for all parameters evaluated for 14 days when stored under refrigerated conditions (2-8C/36-46F).