The major adoption drivers for the biopharmaceutical industry were the availability of manufacturing-grade and scaled-up single-use
systems, the opportunity to reduce CAPEX and OPEX costs, the acceleration of construction projects, and the reduction of the
overall qualification and validation effort. Multiple publications comparing traditional with single-use technology have calculated
a CAPEX saving of up to 60–70% and an OPEX saving up to 20–25% (4–6).
The flexibility of the disposable options available on the market makes their implementation seamless since they can easily
be customized to meet the requirements of an already designed facility. In addition, the high number of different disposable
options in various functional areas allows the Pilot Plant to be a very flexible production unit and to respond to different
project requirements (7).
The evolution of single-use technology was developed in parallel with new modular facility construction concepts made up of
pre-assembled modules. The main advantage of modular construction is the significant reduction of construction time compared
with traditional construction techniques.
Interestingly, despite adopting new single-use technologies, the biopharmaceutical industry has maintained the basic facility
layout stemming from the traditional stainless-steel facilities. This statement holds true even for facilities built out of
pre-assembled modules. The drivers for choosing the traditional layout are based on regulatory requirements, risk mitigation
in hybrid approaches between single-use and traditional technologies, and simply following past behaviors (8).
This traditional approach still results in complex facility layouts, which require multiple heating, ventilation, and air
conditioning (HVAC) systems and elaborate flows of goods and personnel. Hence, the benefits offered by single-use systems
and modular facility construction techniques were and are only partially realized.
Today, the evolution of single-use technologies offers the possibility to close the entire upstream process and downstream
process up to the isolation of the drug substance. Hence, no open handling steps are required in facilities operating either
with traditional stainless-steel technology or with hybrid approaches using traditional and single-use technologies. The only
remaining open handling step is the thawing of a cell vial at the start of the process, although some researchers are already
investigating the possibility of storing cells in bags.
The possibility of isolating the entire manufacturing process from the environment primes a major paradigm shift in the biopharmaceutical
industry. While in the past, individual groups developed their processes for the unit operation they were responsible for
(i.e., a silo approach), today, the new approach is to integrate all unit operations into one end-to-end manufacturing process
(i.e., a holistic approach). The holistic approach enables the architecture of the manufacturing process and the integrated
single-use technologies to be installed such that risks to the process stemming from operator interaction can be minimized.
This is a major breakthrough when taking into consideration that the operator is the primary source for contamination and
process deviations. In that sense, the process itself becomes the product.
This paradigm shift should prompt a review of the traditional facility layout to translate the benefits stemming from entirely
closing the manufacturing process and the reduction of operator-linked risks into major CAPEX and OPEX reductions, which will
dramatically affect the COGS of a drug.