Trends in GMP Biotherapeutic Facility Design are being discussed on a daily basis in engineering conference rooms around the world. How can the next project:

  • minimise upfront capital cost?
  • maximise flexibility?
  • become a scaleable operation?
  • incorporate modular design?

One option that provides many of these advantages is known as the flexible factory concept. This gives manufacturers the ability to produce any drug at any facility, allows them to take advantage of worldwide production networks with minimal technology transfer, and removes the risk of building a unique and expensive facility. The flexible facility features single-use disposable technologies. Pharmaceutical and biotechnology companies are claiming beneficial results already. When the flex factory concept is combined with modular design, speed to market may also be attained. One recent project engineered by Foster Wheeler Biokinetics went from inception to mechanical completion in eight months, including upstream, harvest and downstream modifications to an existing operating facility. The average greenfield facility takes 18-24 months to complete, according to GCon, a US manufacturer of cleanroom pod designs, and a partner with Foster Wheeler.

There are challenges, however. There is a learning curve for single-use implementation, hire a firm with experience to help you manage the safety, facility design, commissioning, qualifications and automation challenges of disposables. This is where an engineering firm, familiar with all suppliers, can objectively evaluate the options, remaining one true agnostic voice for owner companies. Some of the other challenges with embracing the flexible factory model are described below.

The role of the P&id

With the wide variety of disposable fittings on the market, the need exists for a new piping and instrumentation diagram (P&ID) leadsheet to capture this diversity. However, clients are steering towards less complex information on the P&ID. The details of disposable components can be shown on other documents, avoiding continuous rework of complex drawings, as suppliers and technologies change.

Long-term cost and lead time of disposables

Disposable bag costs are variable, but complex disposable bags can cost up to 15,000. The cost of the reusable components is not insignificant. To receive discounts, clients often need to place large orders. The problem with this is that owners are then locked in to a specific design and vendor. This ties into another issue…

Newer and smaller vendors

Many of the vendors creating the technology of the future are relatively small and focused on productised solutions, as opposed to the custom solutions clients have typically sought. This also means they tend to have less experience with quality assurance and control. Vendor audits become critical and are recommended by Foster Wheeler when engaging in any new vendor relationship.

Media and buffer prep

Even though disposable technologies are available to support media and buffer preparation, at the production scale, clients may find that it is not economically feasible to use them.

The use of hybrid single use/traditional systems is often a workable solution for clients with a bit of an appetite for the flexible factory model, but whose operating budgets could not sustain the media buffer prep single use solutions. Foster Wheeler has experience performing detailed costs analyses to support clients in choosing the right technologies for their specific needs.

Traceability

An active effort and conversation needs to occur with the supplier of single-use components to ensure a manufacturer can tell regulatory agencies exactly what product contact surfaces were exposed to the process, and to help clients prove that they are acceptable.

Tubing management

Standardise, standardise, standardise; this will minimise use of many different bags or assemblies that must be stored and managed. The engineering group must work closely with the architect and client to anticipate the future uses of the space and develop tubing logistics plans for efficient and safe operations.

Environmental health and safety

Design teams need to think about disposable components as part of the facility waste stream. Many manual operations, loading and unloading of heavy bags, and awkward working positions must be mitigated. Equipment interactions, tube set and bag diagrams are an increasingly important part of project safety.

The benefit

Competition in the biologics marketplace is on the rise. The drive for efficiency while maintaining quality is critical. The company that makes the best of today’s technology will be in a position to supply the needs of the ultimate customers, the patients.