Ray O'Connor, Operations Consultant, at the National Institute for Bioprocessing Research and Training (NIBRT) discusses the
basics of biopharmaceutical facility design and operation. NIBRT provides training, educational and research solutions for
the international bioprocessing industry in state-of-the-art facilities. Located in South Dublin (Ireland), it is based on
an innovative collaboration between University College Dublin, Trinity College Dublin, Dublin City University and the Institute
of Technology Sligo.
Q PTE: Why is aseptic processing crucial for injectables, such as vaccines and other biologic-based products?
O'Connor: Certain pharmaceutical products must be sterile as they're introduced to the patient by injection because this mode of drug
delivery bypasses the body's natural defences. Therefore, with biologics, there is an increased risk of infection being introduced
to the patient. Sterile drug products can be manufactured using two techniques: terminal sterilisation or true aseptic processing.
Terminal sterilisation usually involves heat or irradiation; however, quite a large proportion of vaccines and biological-based
drugs can be destroyed by exposure to heat or irradiation; hence, the requirement to manufacture in an aseptic manner.
According to the FDA's guidance for industry on sterilised drug products produced by aseptic processing issued in September
2004, in an aseptic process, the drug product and container–closure are subjected to sterilisation methods separately, as
appropriate, and then brought together. Because there is no process to sterilise the product in its final container, it is
crucial the containers be filled and sealed in an extremely high-quality environment. Therefore, aseptic processing involves
more variables than just terminal sterilisation. Before aseptic assembly into a final product, the individual parts of the
final product must be subjected to various sterilisation processes.
Similarly, in the EU, GMP guidelines state that the manufacture of sterile products is subject to special requirements to
minimise the risk of microbial contamination and of particulate and pyrogen contaminant. So, as a result, much of the aseptic
process depends on the scale of training and attitudes of the people involved.
It's particularly important that this type of manufacture strictly follow established and validated methods of preparation
and procedure. Sole reliance for sterility or other quality aspects would not be placed on any terminal process or finished
product testing. To summarise, aseptic processing is minimising the risk of introducing any microbial contaminant into your
product as you move it through the manufacturing process.
Q PTE: Aseptic processing and the term 'fill–finish' are often used interchangeably throughout the industry. Are these two
terms truly the same or are there unique steps for each?
O'Connor: Fill–finish is a discrete part of the manufacturing process. If you have an upstream or downstream process, that will be
where you manufacture your active ingredient. Fill–finish is the filling and packaging part of this process. It comes after
the product has been manufactured and is ready to be put into its final package container that the patient will see.
Aseptic processing refers to the various techniques that go into ensuring that the product is free of contaminants, thereby
reducing the risk of infection to the patient. Aseptic processing is the processing of drug components, drug product containers
and excipients in a manner that precludes microbial contamination of the final sealed product.