“Disposable technology is a philosophical change,” Hardy emphasized.
Companies must be open to new ideas and be prepared for additional work. They must agree with their customers about cutting-edge ideas and technologies. That requires a thorough understanding of the process. “Once the process is fixed, you have a very limited scope in which to change it, but clients don’t necessarily know the process, and aren’t necessarily aware of the regulatory aspects,” Dr. Stockbridge pointed out.
Generally, more time must be spent upfront on process design to ensure regulatory and client approval. That includes performing validation and extractable studies, stability, and expiration testing.
Because many plastics migrate from the plastic to the product, regulatory bodies often are requiring companies that plan to use disposable manufacturing systems to also use disposables throughout their testing phases. Because many processes run in a CMO are similar, however, validation and extractable studies from similar processes can be leveraged, thus decreasing the number of validations required for new processes.
Switching from fixed to disposable manufacturing facilities complicates the supply chain by sometimes increasing lead times and by allowing the potential for overstocks or custom parts designs. In terms of supply, it now becomes critical to ensure you have guaranteed sources for customized parts and that convenient items haven’t become critical raw materials. Dr. Stockbridge advised working with companies that can ensure delivery because secondary sources aren’t always possible.
With that in mind, just-in-time delivery may not be an option, as “some processes for a CMO may require you to have 1,000 bioprocess containers on hand to maintain a six-week supply,” Hardy said.
After Avecia expanded, it found it needed additional buffer hold bags, which may eventually require more space in the process areas of the facility. If space or the personnel to track supplies and ensure quality are in short supply, disposables may not be a good choice.
Williams recommended managing the buffer supply in a way that ensures an always-available supply and planning for in-line dilution of buffers. Doing this, and handling caustics separately, roughly doubled productivity, he said.
Disposable manufacturing limitations become particularly evident as the product scale increases. “It’s easier to scale up buying two 500-L bags than installing and validating one 1,000-L tank,” O’Hagan said.
The point at which fixed equipment becomes more practical, however, is open to discussion. O’Hagan likes a 1,000-L limit. Dr. Hermansen doubles that, while Avecia’s facility scales up to 3,500 L.
Flexible facilities clearly have their merits but they’re not right for every situation. “There is a break-even point,” O’Hagan said, beyond which flexibility decreases productivity. Where that point lies depends on the overall use of the facility.