The creation of sterile products usually requires the most intense regulatory inspection of all product types, because mistakes made during production can be disastrous and manufacturers are expected to make use of the best sterilisation method possible, to reduce the probability of this happening.
Nonetheless, aseptic processing, which is not a conventional manufacturing method, is constantly used in the manufacture of sensitive products, because it’s the only possible way to achieve sterility.
During aseptic processing, the product is created using terminally sterilised components. Sterility is maintained throughout the entire process through the use of conditions and facilities, specially designed to retard microbial growth and contamination.
Over the years, aseptic processing has been criticized due to the tendency of undetected microbial infiltration during the manipulation of sterile components. However, the introduction of isolator systems has proven to be an improvement to the already-existing standard cleanroom technologies, and the problem of microbial ingress during aseptic processing is now almost a thing of the past.
From a microbiological perspective, only two types of products exist; the sterile and non-sterile. The non-sterile products make up a large percentage of products sold in the market. A good example of a non-sterile product is tablets. On the other hand, sterile products constitute a small percentage of products sold in the market, but they undergo intense regulatory scrutiny. Examples of sterile products include injections and infusions. Now, let’s take a look at the meaning of sterility.
Sterility can have varied definitions, depending on the subject being discussed. In this article, we’ll be using the simple definition given by Brown and Gilbert. According to them, sterility is not an absolute concept. The sterility status of a medicinal product is unavoidably a matter of probability.
The latter part leads us to the statistics of exterminating or eliminating microorganisms from a product during manufacture or sterilisation. The statistics totally depend on the amount of microorganisms present at the beginning of the process (bioburden) and the sterilisation method and conditions which were used.
Test For Sterility
A test for sterility is important because just like drug content and end product quality control, sterility is also a product quality attribute. However, sterility is a bit different from other product quality attributes. This is because, microorganisms aren’t equally distributed throughout a product, and because the test is going to be a destructive one, just a little sample from a batch undergoes analysis.
- Terminal Sterilisation
Presently, the regulatory authorities demands that all producers must apply a sterilisation decision tree to determine which sterilisation method may be used for the manufacture of a particular product. The best way to carry out terminal sterilisation is by sealing the product into its final bacteria proof container and then subjecting it to the sterilisation process proper. During terminal sterilisation processes, heat (steam or dry heat) is most the preferred source of energy, followed by radiation and gas (e.g ethylene oxide).
According to the regulatory requirements, the terminal sterilisation method should be able to provide a SAL that guarantees a one in a million chance of a contaminated container still existing after sterilisation. Practically, a properly-controlled terminal sterilisation process with minimal bioburden will produce a SAL that actually exceeds one in a million. This SAL level is way above the provided detection limit of the test for sterility. As a result, the terminally sterilised products are approved and released based on the measured parameters obtained during production and process validation.
- Traditional Sterilization
The traditional sterilisation method cannot be used universally and a large number of products cannot be processed using terminal sterilisation because of the sensitivity of certain nutrients in products. For instance, protein solutions cannot undergo heat treatment and drugs that are hydrolytically sensitive will need to be lyophilised.
Aseptic Processing And Risk Based Quality Management
A new development in pharmaceutical production is the use of “quality risk management” in pharmaceutical quality systems. When this method is used for the production of sterile products, it identifies aseptic processing as the area that most needs risk management and assessment. However, this discovery is not new. Since the early ’60s, it has been established that during aseptic processing, exposure to air should be reduced to the barest minimum and operators need to be dressed properly.
Consequently, aseptic processing is always trying to attain absolute quality by controlling microbial infiltration which usually happens through the operator or environment. The sterility assurance gap (SAG) between terminal sterilisation and aseptic processing is the main reason why there are sterilisation decision trees. The rationale behind this concept is to reduce the risk of microbial infiltration through the operator or environment.
Aseptic processing requires a very sterile environment. Clean air technology which was formerly used only in the microelectronics industry, is now being used in the manufacture of sterile products, through the aid of clean rooms and unidirectional laminar airflow systems.
Regardless of the major improvements in clean air technology, the human operator has remained the same; no biological or technological advancement. This makes the human operator the greatest risk to sterility during aseptic processing. Therefore, the human operator must dress properly during aseptic processing, to prevent microbial infiltration.
Finally, it is important to note that aseptic processing plays a huge role in the manufacture of sterile products. However, the best results can only be achieved when the environment is controlled and the human operators dress properly.
You can get the best of aseptic processing solutions from steriline.it. They develop, manufacture and supply a comprehensive range of solutions, including both mechanic and robotic applications for the aseptic processing of toxic or non-toxic products, liquid or powders, in vials, ampoules, cartridges or syringes.
Also, as a single-source provider of equipment solutions for the primary packaging of injectable drugs, Steriline develops, manufactures and supplies complete lines for the aseptic processing of toxic or non-toxic products, liquid or powders, in vials, ampoules, cartridges or syringes, including both mechanic and robotic applications. The Steriline aseptic filling lines cover all operations and types of equipment spanning from washing machines, depyrogenation tunnels, filling and capping machines to external decontamination machines.
Lastly, Steriline portfolio includes a comprehensive range of barrier systems (such as LAF, oRABS, cRABS) and fully in-house engineered and manufactured Isolators.