Despite regulatory and manufacturing complexity, combination drug products continue to gain in popularity.  Many of these products incorporate a sensitive pharmaceutical or biotherapeutic compound with a drug delivery system.  One of the most complicated elements of manufacturing is the sterilization process - both during the process of filling the active drug ingredients and during the final assembly and packaging of the device. 

Many of the active drug ingredients and many of the device designs do not lend themselves to common forms of terminal steriliization, namely EtO gas, steam heat, gamma irradiation or high energy electron beams.  Due to the sensitive nature of biologics, direct exposure to heat or radiation can alter drug efficacy and safety, making validation and cleaning protocols particulary complex.  Furthemore, material selection for primary packaging materials (i.e. packaging that comes into direct contact with the active drug components) is complicated as the properties of many packaging materials are altered once exposed to high heat or radiation. 

Low voltage electron beam sterilization can be an enabling alternative for complex drug packaging challenges.  Already in wide use for sterile transfer of syringe components into barrier isolator filling lines, the technology is well understood by the FDA and appreciated for its efficacy, simplicity, and ease of process control.  While the limited penetration of low voltage electron beam energy prevents its use for most terminal sterilization applications, it can be the ideal solution for sterilization applications where there is a need to not affect the active drug or the interior surfaces of the device that come into contact with the drug.  The graph below shows how the electron beam dose  varies as a function of voltage and depth of penetration (graph is for a unit density material).  Penetration of energy can be controlled by varying the voltage of the system.

Low voltage electron beam technology can be deployed in three basic ways in the manufacture of combination drug products:

1. Surface sterilization of primary packaging components as they are transfered into an isolator for aseptic filling.
2. Creating sterile connections of mated surfaces during the assembly of the device - since the energy penetration is precisely controlled, drug that has already been filled into vials, syringes, or bags is not affected.
3. Sterilizing the exterior of a device through secondary packaging (e.g. a blister pack) without penetrating through the primary packaging (e.g. syringe) - secondary packaging can be designed to be thin enough to allow low voltage electron beam energy to penetrate. 

Get more information about AEB sterilization solutions for combination drug delivery devices by clicking here.