Imagine the scenario: Your new blockbuster drug is making a significant difference to the lives of patients. But then your supply chain fails, taking the product out of circulation. The consequences for patient health – plus the damage to your reputation as a biopharmaceutical manufacturer – would be catastrophic, even before you consider the economic impact.
Given the investment that has been put into the development of a production process – in both time and resources – it’s vital that the process can be implemented in a way that is as repeatable and predictable as possible to minimize the risk of contamination, process failure or production shutdown.
As a biopharmaceutical manufacturer, you may have employed elements of quality by design (QbD) to established limits of operation, taking into account critical quality attributes (CQAs), but is process protection built into your operations? And what does it mean?
Protecting your process from contamination
Contamination is one of the most obvious ways in which a process can be compromised. The presence of a biological contaminant such as a mycoplasma, virus or bacteria can result in a reduced yield or the complete loss of a batch.
However, there are a number of ways in which contamination can be combated including the use of:
- Mycoplasma retentive filters when processing mammalian cell culture media
- Bioburden reduction filters at key stages of the process
- Fully enclosed processing, making use of single-use technology
- Viral risk mitigation treatments such as HTST (high temperature short time)
System failure protection
Mitigating against the risk of production system failure and the resulting unplanned downtime also forms an important part of process protection, resulting in a secure supply chain.
You would not run a car without having it serviced regularly. Biopharmaceutical manufacturers should also have a service support plan in place for identified pieces of critical equipment. This will ensure the system is running in an optimal state.
Also essential – though sometimes overlooked – is the importance of quick access to critical components. The additional investment in critical spares (whether they are components or fully assembled systems ready to be brought into play at a moment’s notice) would normally be at a significantly less cost than that incurred by an unplanned plant shutdown due to component failure and the inability to replace it.
Linked to this is the need to ensure access to source codes for automated equipment. Such systems would ideally run on an industrial platform rather than a vendor’s bespoke solution, allowing support from more than one source.
The purchaser / vendor relationship
As a biopharmaceutical manufacturer, the relationship you have with your vendor can also shape your ability to protect your processes and guarantee operational continuity. Having a supply agreement with the appropriate service level agreement in place is a good starting point. Equally important is ensuring that the vendor has a comprehensive disaster recovery plan in place, which could include (but not be limited to) the flexibility to offer manufacturing at dual sites.
Another factor to consider is that if your plant is made from stainless steel, and a steam in place (SIP) cycle fails, it can be repeated – albeit with consequences for lead times. The use of single-use systems in bioprocessing changes the landscape: no process can be put into operation unless the assemblies that make up the process are available. Put simply, there is no product if there is no process.
In this environment, ensuring that the supply chain is robust is critical, and the relationship between the purchaser and vendor should go beyond placing orders and waiting for deliveries.
Having a two-way conversation and treating the relationship as a partnership, rather than simply viewing the vendor as a commodity supplier, can have significant benefits for process protection.
As a biopharmaceutical manufacturer, sharing information with a vendor on your manufacturing forecasts, for instance, can help the vendor to predict demand for stock, and plan production of key components, part-finished assemblies or indeed, finished systems around this forecast. This will enable the end user to access stock at the appropriate time rather than risking the consequences of a long turnaround time for delivery.
You may also consider holding stock in line with your own production forecasts and putting in place a contingency against product or process failure. Standardization can help here. If common parts are used in more than one process, then the need for a contingency can be reduced.
In addition, a closer vendor/purchaser relationship will help to prevent any issues surrounding unrealistic expectations around delivery times, and support the development of a more holistic approach to the supply chain by all parties ensuring the supply of life saving products
This post was contributed by Guy Matthews, market development manager, Parker Bioscience Division, United Kingdom
Parker Bioscience Division specializes in automating and controlling single-use processes. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively, ensuring the quality of the final product. Find out more at www.parker.com/bioscience