Flexibility in Biopharmaceutical Manufacturing

There is a high degree of consensus in the biomanufacturing industry that product quality, customer service, and cost efficiency are fundamentals for success. Flexibility is another must-have attribute, and although everyone wants it, you're likely to get a wide spectrum of definitions when you ask what it is.

Simon Chalk

With such a diverse view on what flexibility means, the possibility of confusion and dissipated organizational focus is high. So what are the different meanings of flexibility and what is best practice for creating a clear vision that can be implemented?

MULTIPRODUCT FACILITIES

For some, flexibility means the ability to switch between campaigns quickly and easily in a multiproduct facility or even to manufacture different products concurrently. The history of bioprocessing drug substances has been such that mono-facilities were built to produce large volumes of single blockbuster products. The business environment has changed and biofacilities now need to be capable of adopting a more diverse role. Many mono-facilities have been converted to multiproduct use. With shorter changeover times and faster clean-down routines, utilization increases and facilities become more responsive to demand signals.

Creating reconfigurable processes or providing a wider range of options to produce drugs in the same facility using different scales, technology platforms, and upstream and downstream flow balances can also exhibit greater flexibility. Making clinical and commercial batches in the same facility is an additional dimension of flexibility where greater deftness in application of quality policy and compliance is required. Many CMOs have become skilled at this and trade on their flexibility. Innovator firms are heading in the same direction.

STAINLESS STEEL VERSUS SINGLE USE

For many, the use of disposable or single-use equipment offers a route to enhanced flexibility that traditional stainless steel, fixed installations cannot. The choice between stainless steel and single use is influenced not just by the economics of batch size and cost of goods but also by the speed by which processes can be configured and started up. This takes operational flexibility to a different level and provides options when capital investment is at risk because of marketing forecast changes and approval uncertainty. Long construction and start-up lead times for stainless-steel plants have been an uncomfortable reality for the industry when demand volumes fail to materialize and new drugs have failed in the clinic. The ability to install capacity within a horizon of near certainty is a very valuable position to be in.

KEEPING UP WITH DEMAND

At plant level, capacity will have to be flexible not just to changing product variety but also demand levels. Compared to other industries, biopharmaceutical supply chains have been stuffed with inventory that effectively decouples manufacturing supply from customer demand. This makes the job of running the plant easier because the plant manager can run a level load. This luxury is no longer affordable, and plant managers will have to flex plant load to more closely synchronize with supply-chain demand patterns. Workers and their shift routines will need to become more flexible and responsive. Business processes like materials management will need to be more agile, too. At network level, particularly larger companies that have absorbed other companies and comprise multiple legacy facilities, adaptability to reconfigure networks has become an ongoing and continuous activity for senior management. Technology transfer processes are not always fit for purpose in this new reality and will often need to be streamlined. Facilities will have to be designed and operated on the assumption that they will change use more frequently.

EMERGING MARKETS

If business growth hinges on rapid facility deployment for the reasons of capital expenditure deferral and risk mitigation in mature markets, then it also hinges on an additional set of reasons in emerged and emerging markets. Security and risk extend to intellectual property (IP) protection, workforce turnover, and political volatility. By swiftly setting up and, if necessary, removing facilities, risk can be minimized. A new generation of modular units partially completed away from site are becoming available.

Flexibility can place new requirements on tactical, operational, and strategic thinking and affect every function in the business. Taking on board all of these concepts can be daunting and, at worst, counterproductive. Caution should be exercised when deciding what flexibility gives the most leverage for the goals of the business. Senior managers should establish boundaries for beneficial flexibility and rule out where further levels of flexibility will produce diminishing returns. Underpinning built-in flexibility is the need to have a corporate mindset that responds quickly to any challenge placed on the business. It is not too difficult to see how proposed flexible approaches can be analyzed for cost benefit and applied to the known unknowns, but what about the unknown unknowns? Flexibility to cover every possible eventuality would be unlikely to make sense.

Diverse mixes of capacity are emerging in the industry even within a given corporations network. Existing large-scale stainless steel plants, medium-volume launch facilities, and low-volume disposable units, complimented by specialized emerging market service units are all in evidence.

Other intelligent thinkers are developing enterprise-wide philosophies, like the well-known Toyota Production System to guide exactly how facilities, process technologies, human performance systems, and supply-chain planning methodologies come together in concert to deliver the right level of flexibility. By this route, the flexible biomanufacturing system will perhaps deliver transformative change that many in the industry are hoping to witness.

Simon Chalk is director of the BioPhorum Operations Group, simon@biophorum.com

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