On the run: Merck's approach to bioprocessing

European Pharmaceutical Manufacturer editor Reece Armstrong sits down with Andrew Bulpin - head of process solutions at the life science business of Merck - to discuss the industry and the company’s new platform for ‘contiGuous’ manufacturing in bioprocessing.

What’s the current state of the bioprocessing industry?

The industry is at a very interesting turning point. The number of different modalities and therapies on the market, as well as globalisation, has picked up the pace over the past several years. Chronic diseases are prevalent and the onus is on the industry to help develop treatments that are more effective, safer and to do so more quickly.

Next-generation processing is gaining traction in the industry because of the significant impact it will have on bringing therapies to patients. The manufacturing template for monoclonal antibodies needs updating, as the same templated manufacturing process has been used for 30 years and the manufacturing equipment is also ready for updating. This manufacturing evolution will intensify the manufacturing template down to a continuous process involving just a few steps. This intensification brings benefits of smaller footprints for equipment and the manufacturing facilities, requiring less capital. There are additional efficiencies gained in the flexibility of producing drugs in smaller batches versus big, stainless steel vats.

However, this is a journey and we cannot do it alone. This manufacturing evolution requires a triangular collaboration between suppliers, biomanufacturers and regulators - and sometimes even beyond by including academia and industry associations.

Are there any regulatory barriers to new bioprocessing technologies?

Bioprocessing is heavily-regulated, which has created a conservatism within the industry. Adoption of new technologies and novel approaches are slow as a result. There is a hesitation to be the first to go to the FDA with a new manufacturing approach. In many cases, the established players in the industry have a certain culture and risk aversion. Nevertheless, it’s clear to me that the benefits of next-generation bioprocessing are there.

One of the major challenges is precedence from a regulatory standpoint. Nobody wants to be the first company to put in a new manufacturing process and get that through the regulatory agencies, hence there is a natural inertia to bring innovation into manufacturing. The FDA now encourages the industry to adopt continuous processing for small molecules and eventually, the continuous approach to manufacturing biologicals will gain more ground. However, any delay in getting a molecule to market can cost a company millions of dollars, so you can understand the caution on being an early adopter of an innovative manufacturing approach. Continuous processing offers clear benefits. Collaborative consortiums such as the Biophorum Operations Group (BPOG) and The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) can help advance the technology and innovation so there is more acceptance.

Could you explain a bit about Merck’s approach to continuous manufacturing and the benefits its BioContinuum Platform offers to manufacturers?

This manufacturing evolution brings with it process challenges. Manufacturers are looking to suppliers for integrated solutions as they think holistically about their process and visualise future scale up. The industry is buzzing about continuous processing because it will have a significant impact on how our customers bring therapies to market, delivering them to patients faster and more cost-effectively than ever before.

When we think about Merck’s role in leading the manufacturing evolution, we start with process intensification by updating and upgrading outdated unit operations, then connecting these processes to run in a connected and then continuous, flow-through fashion ultimately, reaching “contiGuous” manufacturing – a process that is continuous, connected and digitally-enabled with all the suitable software and automation, run as an orchestrated production train.

ContiGuous takes continuous processing to the next level by going beyond just connecting the individual unit operations to include the orchestration and management of all the processing steps (materials, production, testing and analytics) with an industry-leading streamlined and optimised approach. Our vision is that the entire process is controlled, orchestrated and digitally managed through one manufacturing execution software system.

Merck is ideally positioned to offer contiGuous bioprocessing because we own all of the unit operations and are designing the BioContinuum Platform to achieve contiGuous bioprocessing - the seamless physical and digital integration of our BioContinuum Platform building blocks.

What are the differences between Merck’s approach to ‘ContiGuous’ manufacturing and current continuous manufacturing technologies and their implementation?

While continuous processing is the future of drug manufacturing, customers face challenges today in terms of speed-to-market, facility flexibility or cost of goods sold (COGS). A fully connected, fully continuous process is not necessary for customers to see benefits. That’s why we’ve designed the BioContinuum Platform to feature next generation technologies that provide incremental process benefits now, with a mind to the continuous process of the future. Our unique holistic approach to process intensification allows us to realise benefits of process intensification over the entire process, not gained by focusing on one area at a time.

Is the launch of the BioContinuum Buffer Delivery Platform evidence of a wider strategy for Merck in regard to continuous manufacturing?

The BioContinuum Buffer Delivery Platform is one of those building blocks and a perfect example of the high degree of connectivity that contiGuous biomanufacturing can achieve. The BioContinuum Buffer Delivery Platform is a highly accurate and precise buffer dilution system that utilises buffer concentrates and in-line dilution delivering buffer directly into the system. This streamlines the buffer delivery step and reduces the process footprint by eliminating the massive buffer holding tanks.

How prepared is the pharma manufacturing industry for digitalisation?

For certain, future innovation lies with analytics and process monitoring. Initially, that will evolve to be at-line, but progressively as more technologies advance and the industry moves towards continuous manufacturing, analytics will evolve to be included in-line.

Improvements in the manufacturing template and expression levels allow production on a much smaller scale, while delivering higher yields and more potent drugs. The manufacturing facility of the future will be highly digitalised (cybernated), multi-product or multi-modality facilities. Artificial intelligence and algorithms will not only control production, but also run better processes.

Both BioContinuum Platform & BioContinuum Buffer Delivery Platform are trademarks of Merck.