A Brief History of Single-Use Manufacturing

Single-use manufacturing may seem like a new trend, but it has actually been around for almost 30 years, beginning in the early 1980s when filter manufacturers began to make small process-scale plastic filter capsules to replace "junior" size stainless-filter housing assemblies. Small laboratory syringe filters were already being supplied presterilized by gamma radiation, but originally, disposable filter capsules for pharmaceutical production were only available in nonsterile format for autoclaving by the user. Higher area filter capsules for even larger volumes did not become available until the late 1980s to early 1990s, eventually including the large scale 10-inch modular capsule filter assemblies available today. Around the same time, the smaller production-scale filter capsules presterilized by gamma irradiation began to be offered.

Jerold Martin

On a parallel track, the mid-1980s also brought developments in disposable biocontainers. Bioprocessers began to use plastic film bags originally developed for large volume parenterals or food storage for serum and culture media containment as well as for buffers. Similar to the large-scale filter capsule developments, the late 1980s and early 1990s brought the introduction of large-scale single-use processing with 2D bags in volumes from 50 to 1600 L and by mid to late 1990s, 3D bags for process volumes up to 3000 L, along with the first generation of totes to contain them.

As larger-scale capsules and biocontainers became more available, bioprocessers began to request that suppliers assemble early systems with pre-connected tubing, and by the mid-1990s, bag suppliers had begun offering single-use systems with filter capsules that were pre-attached to biocontainers, and filter manufacturers began offering filter capsules with tubing and bags preconnected. Gamma-irradiated systems followed shortly thereafter, and by the mid 2000s, they were being validated as sterile systems. In addition, more advanced totes and biocontainer designs offered reduced leakage risks

Single-use manufacturing was further facilitated in the early 2000s by the introduction of large-scale tube welders and sterile connectors that enabled the connection of two sterilized fluid pathways/systems while maintaining the sterility of both. Availability of larger biocontainers by the early 2000s brought with them the innovative development of the disposable rocking-bag bioreactor, and by the late 2000s, stirred tankliner bioreactors and mixers came to market, with the larger filter capsule formats enabling the development of membrane chromatography units for trace-contaminant polishing.

The mid-late 2000s also brought the industry disposable depth-filtration capsule systems and a new generation of disposable sensors. During that time, the Bio-Process Systems Alliance (BPSA) was established. BPSA has been instrumental in promoting best practices for implementation of single-use technologies. The most recent developments in the 2010s have been sterile disconnectors and single-use tangential-flow filtration systems.

Today, the term "single-use technology" encompasses a broad range of primarily plastic disposable technologies that are suitable for a wide variety of scales and applications, from upscale bioprocessing to final formulation and filling. They can be found in manufacturing processes for licensed drug and vaccine products around the world.

This primer explores these various uses with articles on moving from a fixed system to a single-use system, working with flexible manufacturing facilities, determining carbon footprints, and more.

Acknowledgment: The author wishes to acknowledge Paul Priebe of Sartorius-Stedim Biotech for his input.

Jerold Martin is senior VP of global scientific affairs for Pall Life Sciences, and chairman of Bio-Process Systems Alliance, www.bpsaalliance.org