Patent expirations, stiff competition, plant utilization, product safety, and supply assurance are some of the challenges
facing the biopharmaceutical industry. The manufacturing landscape has changed dramatically during the past several years—and
it's still evolving.
Figure 1: Single-use cell culture system. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
Novel approaches for treating specific diseases such as cancer are very promising. However, the days of biotechnology innovations
being measured purely on gaining blockuster status (i.e., reaching more than $1 billion in revenues) are largely gone. The
capacity constraints predicted in the late 1990s, combined with insufficient development pipelines and tougher regulations,
caused a major market consolidation, evidenced by acquisitions, alliances, and outsourcing.
Similar to what the semiconductor industry already experienced, drug manufacturers face a changing environment that requires
innovation and efficiency. They must manufacture products economically and efficiently while also improving quality and safety.
Understanding cost drivers within the manufacturing and development processes is key to assessing the impact of new business
models and technologies.
The costs associated with constructing and operating manufacturing capacities as applied to clinical phases and large-scale
manufacturing call for challenging current paradigms. Single-use technologies represent one option to achieve operational
excellence without compromising quality.
Single-use technologies are being used more in biopharmaceutical manufacturing and that use is expected to increase substantially
in the coming years. With the further penetration of disposables into larger volumes and more critical areas of the biomanufacturing
process, however, companies involved in biopharmaceutical development and the production of new molecules must closely examine
the advantages, limitations, and facility implications of single-use manufacturing scenarios.
The challenge is to design and implement application-specific, integrated-process solutions that follow the same principles
as conventional process designs regarding quality, engineering, automation, and control. Single-use technologies are not an
"one-size-fits-all" solution. They must be intelligently integrated into process designs.
Process analytical technologies (PAT) and quality by design (QbD) are major initiatives in the industry that will influence
the future technology penetration significantly. It's important to examine additional improvement opportunities offered by
the increased implementation of single-use solutions to exploit advantages. Production facilities, traditionally, were built
to house stainless steel-based production scenarios. Does this mean that new facilities are required to be built the same
way? What about cleanroom classifications to operate individual process units? Single-use solutions are presterilized, closed
systems that can reduce, if not eliminate the need for extensive cleaning and steaming utilities. Aseptic-processing requirements
that benefit from single-use solutions through the reduction of cross-contamination successfully support the shift to multipurpose
manufacturing designs and concepts. One might think that disposing such solutions adversely affects carbon-footprint evaluation.
However, there is no standardized approach to such calculations and studies published in the past two years demonstrate that
the opposite is true. The authors contend that understanding the advantages provided by single-use technologies, mitigating
the limitations, and exploring new opportunities is the most-appropriate approach for operational excellence.
Figure 2: Single-use unit operation.