SINGLE-USE PROCESS DESIGN
The continued innovation and availability of disposable technologies now allows for the design of complete single-use unit
operations that can be combined into single-use manufacturing process platforms. Companies such as Sartorius Stedim Biotech
(SSB), have engineered generic process platforms by using disposable technologies within its own broad product portfolio.
SSB's Process4Success platform is currently established for mAb processes across a range of batch sizes and product titers.
With the exception of the resin-based chromatography technologies used in the downstream purification process, SSB's platform
incorporates complete single-use technologies for all unit operations through bulk filling and controlled freeze/thaw.
For the purpose of this article, the discussion will focus on the conceptual design for a 500-L starting batch size. Table
I summarizes the process steps and equipment/disposable technologies for the upstream process and downstream processes as
well as the support process operations. For the Chromatography I and II steps, any manufacturers' column, resin, and skid,
as defined by the customer, can be integrated.
Table I: Single-use platform process.
The Process4Success platform is designed to be used as a starting point for working with a customer and can be modified as
needed to meet a customer's specific process requirements.
The development of facilities for biopharmaceutical production has been met with certain challenges in the past. In some cases,
the process constrained the facility design, and in others the facility constrained the process. Variables such as total volume
of space, classification requirements, and decontamination, among others, were part of this matrix. With the advancement of
totally modular, autonomous cleanrooms, and single-use technologies many of these problems can now be addressed. Higher yields
and more targeted market focus have also lowered the total amount of material needed to serve the marketplace.
Facilities need to be designed to meet some if not all of the following requirements:
- Lower capital expenditure
- Provide a platform for rapid transition between product development and commercialization
- Provide rapid start-up and ease of compliance
- Be reusable and flexible as process and products change.
No longer can companies afford $500 million facilities expenditures that are locked into only one product and that will have
to be abandoned or scrapped after the production capacity is no longer required. The idea of using a totally autonomous, flexible,
and reusable cleanroom serves as a basis to address these requirements if designed with the following features and attributes:
- Procured (and depreciated) like process equipment
- Easily movable
- Easily integrated into the host facility and process systems
- Requires only basic gray space
- Able to be decontaminated, recommissioned, and re-used
- Addresses all normal ranges of classification
- Self-contained heating, ventilation, and air conditioning (HVAC) and filtration.
THE POD APPROACH
G-CON has developed a series of autonomous cleanrooms or "pods" that meet these criteria. The typical pod is 24' x 42' and
is transportable to the facility site by flatbed truck in two 12' sections. The pod forms a large working space of over 760
ft2 and is shown in Figure 1.
Figure 1: The interior of a G-CON pod.
The pods are equipped with air bearings and can be moved into place effortlessly as they "fly" on a layer of compressed air.
No special rigging is required to move the facilities into place within the gray space. Process piping is completed at the
factory and process equipment can be pre-installed at the factory or at the site. The utilities are connected via umbilicals
with quick connectors to a service chase as shown in Figure 2. Services such as water-for-injection (WFI) and USP water are
prepiped into the pods and provide the required zero-dead volume drops.
Figure 2: The exterior of a G-CON pod showing the utilities connections.
The cleanrooms are typically attached to an access corridor to provide an interface to the building and provide another level
of pressure cascade for containment. Pods have on-board inlet and exit filtration in addition to the HEPA filtration in the
workspace, which effectively isolates the cleanroom from the gray space and allows the pod to be used in either positive or
negative pressure modes and in constant volume or variable volume mode. Pods have on-board fire suppression so that hard connections
to building sprinkler systems are not necessary.
Materials of construction are consistent for use with and resistant to the major disinfectants and decontamination systems
including vapor-phase hydrogen peroxide. Pods are also equipped with a complete and robust control system featuring Rockwell
Control Logix PLC controllers with additional digital input/outputs. All sensors and control systems are internet protocol
(IP) addressable. The pod is connected to the local area net work via Ethernet and a single cable connection. I/O protocols
are provided to the recipient and facilitate the integration of the environmental monitoring and control.