Manufacturers must consider sterilization during the design phase of the product, explains Lisa Foster, vice president of SteriPro Services for Sterigenics International. “Otherwise, the product may fail after the sterilization phase, which can be very costly when introducing a new product to market and can delay time to market.”
Many biologics and combination products are now being sent to Sterigenics for sterilization, she reports. Methods commonly used for medical device sterilization can be adapted to fit the needs of these temperature-sensitive products.
“The main concern during the terminal sterilization process, whether it be ethylene oxide (EtO) or radiation sterilization of biologics or drug products, is the temperature to which the product is exposed during the sterilization process,” she says. “Both methods of sterilization induce heat, which can cause degradation of the active pharmaceutical ingredient (API).”
Overexposure to heat can be controlled in different ways, depending on the sterilization method, Foster says. “When using radiation, the product can be packaged with cooling agents, such as dry ice or cold gel packs. Another issue when using radiation is dose magnitude and, with some products, dose rate—some proteins may be sensitive to high doses or dose rates. Dose magnitude and rate can be reduced by providing additional shielding during the sterilization process or other mechanical means in the irradiation cell.” She advises manufacturers to perform feasibility tests on the biologic or API to determine the effect of sterilization.
When using EtO, a “cold” cycle (in which gas dwell temperature does not exceed 47ºC) can be developed and applied, as long as the “cold” cycle will provide adequate sterilization of the product, Foster explains. “Heat is a component of success for the EtO gas to deliver kill to the microorganisms.”
Regardless of the product, whether it is a biologic or combination product with an API, packaging is always something to consider during the sterilization process, Foster adds.
“Certain polymers should be avoided, such as polypropylene and Teflon for radiation sterilization owing to the discoloration or brittleness that can be caused by exposure of the polymer to radiation,” she says. “When using EtO, the design of the product and packaging has to be considered as well. The design must allow the permeation of the EtO gas into the device and package; otherwise, the sterilant cannot penetrate the product.”