The rise of aseptic technology and the manufacturing and regulatory challenges that come with, will inevitably impact project execution. Find out what lies ahead for fill and finish projects in the conflict of market requirements.
In his article, “Aseptic technology on the rise”, Hartmut Schaz provides an interesting account of the future of the pharmaceutical market and the technological and regulatory changes driven by the rise of aseptic processing. In this article, I will pick up where Schaz left off, and look into how the supplier industry, such as machinery and packaging material manufacturers, is expected react to the new market situation. How does the market development effect projects in the future? In what direction will machine delivery times, building construction periods and overall project duration develop? And how will project costs develop?
It would be anticipated that time and costs in fill and finish projects will be influenced negatively. But in fact, the opposite seems to be the truth.
How are equipment suppliers adapting?
Equipment suppliers have been observing the market situation for quite some time and have adjusted their equipment to the requirements of the market in terms of modularity and the level of automation, e.g. by introducing more robotics solutions. Well-known filling line manufacturers such as Bausch + Ströbel or Groninger have been offering modular lines in isolator technology for some time now, and use the variety of modules to maintain the required flexibility with regards to the use of different primary packaging materials. Particularly impressive are filling lines or filling cells from newcomers such as Vanrx or Pharma Integration, whose systems can be used almost without the need of gloves.
Some suppliers of primary packaging material are already able to deliver almost their entire portfolio as RTU (ready-to-use). It is often available both as a bulk (single container) and in a nested arrangement versions. These primary packaging materials are already pre-inspected for damages or other defects. Due to standardised nest sizes, format changes are almost redundant. Early alliances between machinery and packaging manufacturers, mean that both parties have made adaptations to their respective products to match each other’s products. Coordination and standardisation thus clears the way for a fill and finish technology that can be performed by robots only. Thus, as Schaz has already pointed to, people – who are regarded as the greatest risk of contamination – don’t need to perform any critical production process that might result in a viable or non-viable contamination of the product. Instead, they can focus their attention on monitoring and control tasks.
How does this affect delivery times, costs and quality of the equipment?
The technical design of the modules will show a high degree of standardisation, requiring much less effort in the design, engineering and implementation. Also, the consistent design of the modules will drastically reduce both costs and delivery times. A customised filling line has an average delivery time of 20 months. In comparison, suppliers proclaim that they need only 8-10 months to deliver the modular units. Add to this that factory acceptance tests and qualification pre-tests are standardised and significantly less test time is needed.
What does this mean for the overall project plan?
In projects with tailor-made process machines, early development of building planning very often fails due to missing information from the equipment suppliers. They simply do not have the technical information, such as utility connections, layout and dimensions, at this early stage. This leads to delays in both building design and building execution.
Again, the desired modularity and the associated standardisation, providing a much smaller number of interfaces with less complexity to the building and utilities, can remedy this situation: As the information required for the building can be made available almost immediately after purchase order, resulting in shorter delivery times.
With early knowledge of machines and their technical details, commissioning and the associated test phase can be approximately halved. Where several months have been needed so far, it is now possible – even for more complex machines – to complete the preparation work for the qualification within weeks.
It would be anticipated that time and costs in fill and finish projects will be influenced negatively. But in fact, the opposite seems to be the truth."
The modular standardisation also ensures a high degree of planning security during the qualification phase. The procedures for the execution of qualification are tested several times in the same modules and quality assurance has the opportunity to check and accept the qualification plans and qualification documents at a very early stage. If the responsibility for the complete execution of the installation and operational qualification remains exclusively with the machine manufacturer – and the customer is only limited to monitoring and control – the qualification of the process machines has almost no time risk and accordingly no cost risk, like ad hoc shortage of qualification resources.
Depending on the type and scope of the process, we need to consider that the investment costs for a fill and finish project, calculates 35-45% of the TIC for process machines including their qualification. Here, the opportunities arising through modularity inevitably leads to significant cost savings. This is certainly not caused by lower equipment costs itself, but rather by reducing the follow-up costs for setup, commissioning, qualification and the involved time savings.
A significant factor is to be mentioned here: The operating costs of a modular, highly flexible fill and finish production with exclusively RTU packaging (regardless of whether nested or bulk) will obviously be much higher than the operating costs of a conventional production line. Depending on the production quantities, batch sizes and products, this cost difference can vary a lot, but rough calculations lead to a factor of about 1:10 up to 1:20 or more, to the disadvantage of RTU packaging. Since production capacity within the RTU industry is constantly increasing, this ratio is most likely to decline significantly in the future.
However, relating the higher costs of this extremely high production quality to the horrendous values of a single dose of biotech product, this seems quite justifiable.
Image provided by Vanrx Pharmasystems.