Or at least the CNBC Anchors think so …
“The Fill Finish process of manufacturing has to be done under aseptic conditions to ensure there is no contamination. That capacity is at a premium. Weird right?” from CNBC on 01 February 2021
Why should it matter to you?
Admittedly, it is not common knowledge but certainly not weird stuff. If you have ever had medication injected via a syringe (think COVID-19 vaccine) chances are it was the product of aseptic fill. I don’t know about you but I’m not interested in a side serving of bacteria injected along with my vaccine. Neither should you be.
What is Aseptic Processing?
A critical feature of injectable drugs is that they are completely free of disease-causing microorganisms, such as bacteria. Unlike other forms of medication (such as pills, capsules, ointments, etc.), injections bypass most of the body’s natural barriers, and therefore sterility, or the complete absence of microorganisms, is crucial.
Generally, there are two methods of producing sterile product. The first is to assemble all the ingredients into the finished dose container (for example, vials or pre-filled syringes), and then sterilize the product, usually using high temperatures or radiation. This method has traditionally been the most common method used. However, many newer products such as biologically-derived materials such as mRNA and proteins, cannot withstand these sterilization conditions and would be irreversibly damaged. Think of how poaching an egg changes its structure. For these fragile materials, aseptic processing is used.
“Aseptic” means free of pathogenic (i.e., disease-causing) microorganisms. For this method, the different components of the finished drug form are each sterilized separately, then brought together and assembled under conditions designed to prevent the potential re-introduction of microorganisms. For example, the containers and closures (e.g., vials, syringes, cartridges, stoppers, caps) may be sterilized ahead of time using heat (either dry or steam heat). Product-contact materials such as bulk containers (carboys), filters, fill tubing, and fill nozzles, can similarly be heat sterilized. The actual drug ingredients, either individually or in a pre-formulated state, are usually sterilized through very fine specialized filters that have been proven to remove bacteria down to 0.22 microns from the product stream as it passes through the filtration media.
These components, separately sterilized, are brought together in a clean room. These rooms have controls such as HEPA (High Efficiency Particulate-free Air)-filtered air to remove bacteria in the air, higher pressures to keep outside air out, and strict controls on operator dress and behavior, that together help to ensure that no microorganisms can be introduced into the product by the operator. In the clean room, the sterile containers are filled with the correct amount of product and then sealed to protect them from future contamination.
A number of additional controls go into ensuring that clean rooms stay “clean”. These rooms are routinely certified to demonstrate that they are performing according to their design. Environmental monitoring is performed during every product batch to make sure that the proper environment is maintained. Operators entering the clean room are highly trained in proper gowning and behavior, and must pass a test before initial entry and routinely thereafter. The aseptic filling method is challenged periodically to ensure that there is nothing within the process that could result in a sterility failure. The entire process is simulated during these challenges, and a special growth media designed to show the presence of any microorganisms within the product container is used. Samples are taken from the operator’s hands and gown in search of microbes. A zero “positive” result is the expected result.
Aseptic processing is an established and well-controlled method for producing quality, sterile drug products. Manufacturers conform to strict guidelines and requirements set forth by regulatory agencies such as the FDA. This method is crucial for manufacturing many of the most critical medicines used to treat diseases in the modern world.