Although we may not realize it, everyone in the world may be affected by the use of sterile products. This may include the use of needles to inject vaccines, the use of life-saving prescription drugs such as insulin or epinephrine, or in 2020 hopefully rare but very real situations, inserting a ventilator tube to enable patients with Covid-19 to breathe.
Many parenteral or sterile products may be produced in a clean but non-sterile environment and then terminally sterilized, but there are also many other parenteral or sterile products that cannot be terminally sterilized.
Common disinfection activities may include moist heat (ie, autoclaving), dry heat (ie, depyrogenation oven), the use of hydrogen peroxide vapor, and the application of surface-acting chemicals commonly called surfactants (such as 70% isopropanol [ IPA] or sodium hypochlorite [bleach] ), or gamma irradiation using cobalt 60 isotope.
In some cases, the use of these methods may result in damage, degradation or inactivation of the final product. The cost of these methods will also have a significant impact on the choice of sterilization method, because the manufacturer must consider the impact of this on the cost of the final product. For example, a competitor may weaken the output value of the product, so it can subsequently be sold at a lower price. This is not to say that this sterilization technology cannot be used where aseptic processing is used, but it will bring new challenges.
The first challenge of aseptic processing is the facility where the product is produced. The facility must be constructed in a way that minimizes enclosed surfaces, uses high-efficiency particulate air filters (called HEPA) for good ventilation, and is easy to clean, maintain, and decontaminate.
The second challenge is that the equipment used to produce components, intermediates, or final products in the room must also be easy to clean, maintain, and not fall off (release particles through interaction with objects or airflow). In a constantly improving industry, when innovating, whether you should buy the latest equipment or stick to old technologies that have proven effective, there will be a cost-benefit balance. As the equipment ages, it may be susceptible to damage, failure, lubricant leakage, or part shear (even on a microscopic level), which may cause potential contamination of the facility. This is why the regular maintenance and recertification system is so important, because if the equipment is installed and maintained correctly, these problems can be minimized and easier to control.
Then the introduction of specific equipment (such as tools for maintenance or extraction of materials and component materials required to manufacture the finished product) creates further challenges. All of these items must be moved from an initially open and uncontrolled environment to an aseptic production environment, such as a delivery vehicle, storage warehouse, or pre-production facility. For this reason, the materials must be purified before entering the packaging in the aseptic processing zone, and the outer layer of the packaging must be sterilized immediately before entering.
Similarly, decontamination methods may cause damage to items entering the aseptic production facility or may be too costly. Examples of this may include heat sterilization of active pharmaceutical ingredients, which may denature proteins or molecular bonds, thereby deactivating the compound. The use of radiation is very expensive because moist heat sterilization is a faster and more cost-effective option for non-porous materials.
The effectiveness and robustness of each method must be periodically reassessed, usually called revalidation.
The biggest challenge is that the processing process will involve interpersonal interaction at some stage. This can be minimized by using barriers such as glove mouths or by using mechanization, but even if the process is intended to be completely isolated, any errors or malfunctions require human intervention.
The human body usually carries a large number of bacteria. According to reports, an average person is composed of 1-3% of bacteria. In fact, the ratio of the number of bacteria to the number of human cells is about 10:1.1
Since bacteria are ubiquitous in the human body, it is impossible to completely eliminate them. When the body moves, it will constantly shed its skin, through wear and tear and the passage of airflow. In a lifetime, this may reach about 35 kg. 2
All shed skin and bacteria will pose a great threat of contamination during aseptic processing, and must be controlled by minimizing the interaction with the process, and by using barriers and non-shedding clothes to maximize shielding. So far, the human body itself is the weakest factor in the pollution control chain. Therefore, it is necessary to limit the number of people participating in aseptic activities and monitor the environmental trend of microbial contamination in the production area. In addition to effective cleaning and disinfection procedures, this helps to keep the bioburden of the aseptic processing area at a relatively low level and allows early intervention in the event of any “peaks” of contaminants.
In short, where feasible, many possible measures can be taken to reduce the risk of contamination entering the aseptic process. These actions include controlling and monitoring the environment, maintaining the facilities and machinery used, sterilizing input materials, and providing precise guidance for the process. There are many other control measures, including the use of differential pressure to remove air, particles, and bacteria from the production process area. Not mentioned here, but human interaction will lead to the biggest problem of pollution control failure. Therefore, no matter what process is used, continuous monitoring and continuous review of the control measures used are always required to ensure that critically ill patients will continue to obtain a safe and regulated supply chain of aseptic production products.