Posted on January 7, 2020
Hélène Pora, Vice President Technical Communication & Regulatory Strategy
Hélène Pora, Vice President Technical Communication & Regulatory Strategy
How can we reduce process risk and development times, streamline supply chains, lower costs and improve quality? The short answer: the standardization of single-use processing equipment – but end-users, suppliers and industry organizations must all work together to make that happen.
Single-use processing equipment now dominates pre-commercial biomanufacturing and is becoming an increasingly popular option at the commercial scale. The benefits are clear: pre-sterilized single-use systems can reduce setup and changeover times, while eliminating the costs associated with cleaning and its validation and they are associated with a high degree of flexibility to accelerate time to market. As demand for single use has grown, so too has the number of single-use systems on the market – with a wide variety of components, consumables and sensors. But the proliferation of choice has also led to a need for some degree of standardization. This question is more difficult than it first appears, as there many interpretations of what standardization really means in the world of single-use technology.
Single-use systems contain tubes, bags and filters, and different vendors will use different types of materials of construction for their components. The lack of standardization means that end-users may have to go through complex validation testing protocols for the combination of components they use. To complicate matters further, biopharmaceutical manufacturers often use different single-use systems and components, in different combinations, at different sites – or even within the same site at separate buildings. And that can make extractables and leachables studies complex and expensive.
A degree of standardization would reduce the risk inherent in the process, streamline the supply chain and reduce development times, thereby reducing costs and improving product quality. Of course, standardization does not mean everyone in the industry uses the same pieces of equipment, with the same designs – flexibility and using the right equipment for the process is important. A lot can already be achieved by using similar practices and standardizing the components used. Systems have a tendency to drift apart over time, and it’s important not to let entropy take over – new single-use systems or stock keeping units (SKU) shouldn’t be put in place unless there is a clear need to do so. A central benefit of this approach is that it makes validation much easier. If the components have been used before within a company or a manufacturing site, the validation documentation should already exist or can at least be adapted – much easier than starting from scratch. Using the same SKUs for multiple applications can also reduce inventory size, which in turn can reduce the warehouse space required – a big bonus given the space requirements of single-use systems. All of this can lead to reduced costs and lead times.
No man(ufacturer) is an island
The sector will not reach its potential if standardization is left to end-users – they must work together with suppliers. The Bio-Process System Alliance (BPSA) has led the way in getting competing suppliers to collaborate, along with end-users. Ideas are exchanged through white papers, which can be taken further and developed into agreed-upon standards. On the website (http://bpsalliance.org), you can find white papers on quality matrices that record how components could be characterized or validated. Pall Biotech has contributed to BPSA white papers on particulates and assurance of integrity – an area of importance when it comes to applying single-use technology to cell and gene therapies as well as more traditional monoclonal antibody manufacturing processes.
The BioPhorum Operations Group (BPOG) has also been instrumental in promoting standardization in single-use technologies. BPOG was originally an enduser organization but, around three years ago, suppliers were invited to participate and they also collaborate with other organizations such as the BPSA. BPOG focuses heavily on what can be described as the business aspects, such as supply chain and change control management as well as technical matters. They have been vocal about their recommended approach to extractables and leachables testing, prompting suppliers to keep to a common standard so that when end-users are conducting risk assessments, they can use the same principles. And this raises an important point: standardization isn’t just about components and everyone using the same system. Rather, it’s about common business and technological practices that can help streamline the work that everyone does in the field.
Such streamlining also applies to training. Single-use systems involve a lot of manual interventions, which can lead to operator mistakes, if individuals aren’t well trained. Single-use stirred tanks, for example, are heavy and require significant handling, while also containing several complex tubing assemblies and inlets/outlets. In fact, one company found through root cause analysis that single-use bag failures were caused by three factors: handling (46 percent), supplier defects (28 percent) and operator errors (26 percent). They recommended a combination of system design improvements and training to reduce failures.
Successful training material should be easy to learn, easy to understand, easy to recall and easy to apply. If operators are forced to use different single-use systems that work in different ways, then they will need to be trained to use each of the various systems, making the whole process more difficult to learn, recall and apply. Standardization can reduce this problem and make training less cumbersome. It also facilitates video-based training, where guidance must directly relate to what is in the operator’s hands.
The benefits of standardization extend well beyond single-use components and system design. And we need to work together to collectively reap the benefits.
Pall Biotech has developed a proprietary web-based system to organize information pertaining to the everincreasing number of single-use systems and components on the market.
One major problem for end-users and suppliers is that it can be very difficult to keep track of which combinations of components have already been validated. Pall Biotech found that there was no advanced information management system available that could store all the data related to the increasing number of single-use components on the marketplace. In the early days of single use, this wasn’t a problem, as there were only a limited number of single-use systems, with few components – we just used Excel spreadsheets! But as the number of systems and components grew rapidly, we realized that we needed a better approach. We, therefore, set out to create our own solution: the Allegro™ Central Management System (ACMS).
ACMS categorizes components into preferred, nonpreferred and restricted. Preferred components have been extensively evaluated. Nonpreferred components are the next step down: these satisfy regulatory requirements but are not as well validated as preferred components. Restricted components are typically specialized, custom, components. Customers can therefore reduce validation and lead times by choosing preferred components for their singleuse system design. The system allows for instantaneous compliance reports and has a built-in configurator that can select components operating within a chosen processing window. It also stores all the designs made for any end-user, which allows the ACMS’s advanced search function to find all existing systems which could satisfy additional applications.
The system also stores customer URS documents, including the desired system, project specifications, operating conditions and other project details. We can then use that information to determine whether the enquiry can go ahead. Once approved, the information is used to ensure all materials and designs are fit for purpose, providing traceability for all involved.
We began implementing the ACMS around seven years ago and it is continually evolving as the marketplace develops.
This article was first published in The Medicine Maker
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