With rapid market growth and over 1220 ongoing clinical trials, the need for flexible alternatives is higher than ever. To meet this demand, advanced therapeutic developers are utilizing flexible manufacturing and single-use technologies.

This is an abridged version of an article first published as part of the BioProcess Insider ebook, entitled: Cell and Gene Therapies — A 2021 Industry Update. To download the full report, click here.

Utilizing flexible systems like premanufactured cleanrooms can reduce costs, construction timelines, and time to market. As a result of the advanced therapy revolution and significant advancements in equipment design, the single-use technology industry is expected to grow to $33 billion by 2027.

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The advantages of flexible manufacturing

Flexible manufacturing is a production method that is designed to easily adapt to changes in the type and quantity of the product being manufactured. In advanced therapies, the ability to stand up a facility with a limited amount of capital and quickly execute product transfer is critical. Advanced therapies get to market quickly by using flexible manufacturing and these key advantages:

• Speed
• Fewer resources
• Smaller footprint
• Rapid product transfer
• Reduced facility cost
• Low contamination risk

Pre-manufactured cleanrooms

One of the most important factors with any build is time. Lead time, build time, and down time are critical and can greatly improve or impact the flow of a project. Forming a strategic and flexible manufacturing plan saves a lot of time, starting with pre-manufactured cleanroom builds.

Overall, pre-manufactured cleanrooms are easy to install, durable, speed up qualification time, and maintain their value. A drawback is that the design must be completed up front. It is a large capital investment with longer lead times for fabrication and require a detailed submittal creation. Ultimately, the benefits of pre-manufactured cleanrooms outweigh those of the traditional stick builds.

Single-use technologies (SUTs)

Single-use manufacturing seems like a new and innovative technology, but it has been around for several decades. It is widely used today to decrease production timelines and allow for rapid scale up.

Single-use systems replace traditional stainless steel or glass equipment with metal frames that house the pre-sterilized disposable components. There are little to no reusable surfaces and these parts are rarely in contact with the product. Single-use systems are often utilized by cell and gene therapy developers due to a reliance on vendor design services and to meet rapid development timelines. An example of a single-use technology that doesn’t come into contact with a product is a temperature probe on a bioreactor which sits in a well that is part of the disposable bioreactor during processing.

Considerations for single-use

Single-use technologies present an opportunity to reduce timelines, cost, and resources. The caveat is that in order to effectively implement SUTs, there are some considerations that must be thought through.

1. Cost

The cost effectiveness of single-use technologies can be viewed from two perspectives. From a capital standpoint, utilizing single-use technologies saves money up front, as it costs less to build a facility optimized for SUTs. From an operating perspective, raw materials and consumables are more costly. However, even though they are called disposables, they can be reused more than once and should be factored into a cost analysis.

2. Logistics

While SUTs remove the need for sterilization protocols and save production time, there are other logistical considerations that need to be accounted for up front and throughout the manufacturing process.

• Longer lead time for consumables
• Ensuring sufficient space to store consumables
• Fire system design for the number of plastics that will be stored and in use
• Plastics rub together and create particulates that need to be filtered before final product

3. Environmental Impact

Because of the amount of plastic used, the seemingly obvious consideration for single-use technologies is that they aren’t sustainable or environmentally friendly. However, when you begin to compare the amount of energy and water utilized during the sterilization processes for stainless steel equipment, the results are surprising

Studies actually show that SUTs reduce the overall environmental footprint of a manufacturing site. Reports have shown that due to the massive amounts of water required to clean facilities utilizing traditional stainless-steel equipment, they are ultimately about 50% more energy intensive than those utilizing SUT. Findings further suggest that making the switch to SUT results in a roughly 85% reduction of both water use and waste generation.

Conclusion

Benefits like reduced cost, footprints, and timelines coupled with increased scalability and ergonomics are pushing the advanced therapy industry towards flexible manufacturing and single-use technologies. Integrating these practices is becoming a standard necessary to meet the demands of the advanced therapy market. Most importantly, integrating flexible manufacturing gets products to market and into the hands of patients who need them faster.

Joe Neroni is a director at Project Farma. Salome Philip is a consultant at Project Farma.