The demand for sterile injectable drugs has steadily increased through the years and will continue to do so. One key factor of this is the expansion of the market for biological drugs, which can only be delivered through injections. Intravenous infusion has also become popular due to its efficacy and immediate effect as the medication is delivered straight to the bloodstream, with the desired effect evident within minutes. The growing demand for small-molecule drugs can be utilized in a variety of products, including heart medications, antibiotics, and much more.
With this in mind, the pharmaceutical industry is faced with the demand to ensure patients’ safety when delivering these injectable drugs. Various forms of sterilizations were deliberated on, with the deciding factor on the most desirable one: terminal sterilization.
Why Terminal Sterilization?
It is absolutely critical that any drug products remain sterile and without the presence of potential microbial contaminants (fungi, bacteria) before patient use. Terminal sterilization is the process where a product is sterilized within its final packaging. This allows for the evaluation of microbial content through validation processes, and it is the most secure form of sterilization on the market.
Given that the sterilization is completed in the final packaging form, it eliminates any risk of contamination once the sterilization is complete.
All medical, ophthalmic, and parenteral equipment are typically sterilized in batches and usually terminally sterilized using heat. The drug products themselves, however, are not generally thermally sterilized as the heat may damage them. Treatment with gases is also a sterilization alternative. Such gases include ethylene oxide, formaldehyde, glutaraldehyde, propylene oxide, hydrogen peroxide and chlorine dioxide.
Other options include gamma radiation, and also include infrared and ultraviolet radiation and high-velocity electrons. Radiation is typically used for the sterilization of single-use components | systems, but it can be used for packaged drug products.
Sterilization via filtration is the only option if the other processes are not suitable for the specific product or component. In filtration, the final drug product solution is passed through a filter that has been produced under aseptic manufacturing conditions and designed with appropriate pore sizes | surface chemistries that remove bacteria via size exclusion, entrapment, electrostatic attraction and other modalities.
Terminal sterilization is preferred for pharmaceutical products since this type of sterilization takes place after the product has been put in its final packaging (known as the primary packaging). It requires no movement to another package and eliminates any opportunities for contamination due to possible human intervention.
Before terminal sterilization begins, a holding period needs to be established. This is the time the products need to be held at their highest required temperature, or subject to other terminal sterilization methods, to ensure all microbes, pathogens, and possible contaminants are killed.
However, innovation has been required within the terminal sterilization market. E-beam processing, or electron irradiation, is the most advanced sterilization technology on the market. This technique uses beta radiation - a form of high-energy electrons - to penetrate and disrupt the microorganism’s RNA | DNA chains (their genetic material and means of survival). Electron beam provides the highest level of sterility assurance at 10⁻⁶. When these chains are disrupted, it means that the microorganism can no longer survive, and eliminates any risk of their contamination.
Because of the nature of e-beam processing, the time to sterilize is also significantly shortened, making the process less stressful on the product and packaging and ensuring its potency and structure remain intact. Additionally, e-beam terminal sterilization meets all ISO regulations, so its use is widely accepted and known for exceptional quality and consistent results.