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The Qualification of Small-Scale Models Workstream addresses the gap in industry alignment and regulatory guidance

Small-scale models and their qualification are important steps of biopharmaceutical process development, characterization, and validation. Despite being required by regulatory bodies, there is no guidance on current best practices and companies use many different qualification approaches throughout the industry.

Prasad Pathange, Director at Bayer, explained the challenges the industry faces when trying to implement small-scale models. “The challenge with small-scale model qualification is that it is a topic that everyone approaches differently. There is a scientific aspect to it and a quality aspect to it; therefore, there are two different teams that do not always have the same thought process. There is a misalignment, so it takes a long time to overcome this. Additionally, there is no industry standard on how to do small-scale models and their qualification,” said Pathange.

Building on existing practices across the industry

To overcome these hurdles and provide guidance on how to implement and qualify small-scale models, the Qualification of Small-Scale Models Workstream has produced an extensive paper called Justification of small-scale models: an industry perspective (to be published in April). Robert Luo, Scientific Director in Downstream Processing Development at GlaxoSmithKline, explained the process of writing the paper and how it took perspectives and practices from all member companies. “Before we wrote the paper, we shared our own practices. Then we did survey work while the paper was being written, which was then organized and clarified.” With varied approaches among different companies, achieving a cohesive paper was quite challenging.

According to Valerie Pferdeort, Senior Engineer I, Cell Culture Development at Biogen, “Getting these conversations going and working with a cross-organizational team was no small feat. Crafting a cohesive message with many ideas from so many great scientists, engineers and statisticians, with such a diverse range of input coming from all the companies involved, has been good, but it has also been challenging.”

Despite the varied approaches, the team collaborated to produce an extensive paper that will provide alignment across the industry, including regulatory authorities. To raise awareness of the paper and its value, the workstream will produce a series of webinars and present their findings at conferences.

“Our group has 28 companies, and we are growing at every meeting. We have a global range now, all from different continents – the US, Europe, and Asia. This is really beneficial to the entire industry.” – Robert Luo

Improving knowledge and driving alignment while maintaining flexibility

The paper will benefit the entire industry by increasing its overall knowledge and subsequently improving the use of resources and providing a faster implementation of technologies. However, it allows for flexibility as well, as companies can use what they learn as a guide to develop their own processes.“This paper is much more of a tangible tool that will give companies a real starting point of where to go. They will need to do their own research and develop details, but people won’t have to start in the woods anymore. They now have a sense of what has been done and what has been accepted in development activities,” said Pferdeort.

The paper will allow larger companies to ensure they are on track with industry practices and it will also benefit smaller biotech companies. “At small or mid-size companies, there is limited knowledge within the company when challenges arise. This paper is a good resource to understand what the current practices and possible solutions are,” explained Kiran Andra, Development Scientist at Alexion Pharmaceuticals, Inc.

Being a part of the workstream has been beneficial to the participants and their companies and enabled networks to grow that would not have been possible without BioPhorum. Joschka Buyel, Process & Knowledge Management Scientist at Bayer AG, explained, “One company used a multivariate approach for small-scale model qualification in the upstream region, and we brought in several experts who were able to share information and help solve the problem. These connections would not have been possible without this network.”

“When participating companies were surveyed to establish a common standpoint on how to do small-scale model qualification, we ultimately came up with a best practice in the field. This is one of the greatest benefits that this paper has.” – Kiran Andra