The approach to connector technologies used in traditional and disposable systems tends to be different. Traditional bioprocess
manufacturing methods have adopted an almost universal stainless steel sanitary tri-clamp fitting or stainless steel straight
connectors (originally put in place as they could be flamed). Disposables manufacturers, on the other hand, have developed
a wide variety of connector technologies for aseptic and nonaseptic connections, both dry and wet. This means that end-users
often end up evaluating three or more technologies for different parts of their process, all of which have to be subsequently
validated and operators trained.
Guidelines need to be developed to specify the qualification and validation requirements for connector technologies. A risk
analysis approach also must be developed in relation to ergonomics and operator handling of each technology.
Guidelines for bioburden controlled and sterile processing. Appropriate guidelines also will facilitate single-use system selection and implementation in terms of using bioburden controlled
processing, instead of sterile processing. If we look at the ISPE biotech baseline guide for biopharmaceutical manufacturing
facilities,2 we see that typically, low bioburden processing applies to recovery and purification operations. This means that 70–80%
of single-use systems are currently being supplied for low bioburden applications, though all are systematically gamma sterilized
and are often preassembled with aseptic connector technologies.
Of course, if we consider radically changing the way we design facilities, the fact that the single-use systems are gamma
sterilized and offer the possibility of totally closed processing across different zones, this allows room classifications
to be lowered if suitable validation is carried out. Could aseptic processing in a controlled non classified (CNC) environment
become a reality?
While some components of disposable systems, such as silicone tubing, can be recycled, many have to be incinerated. Consideration
must be given to what was contained in the disposable system, what contracting company will deal with waste, and how frequently
the waste will be collected.
Disposables companies have analyzed the relative quantities of water, chemicals, and electricity requirements needed for cleaning
and steaming stainless steel for a given process in comparison with the kilos of plastic to be incinerated. Despite the common
perception that disposables are the worst option from the environmental point of view, this is not necessarily the case. Further
guidelines in the area of waste management will need to be developed by the industry standards committees.
From an economic perspective, a study was carried out to determine the relative costs of plastics incineration for a given
process compared to the average costs of wastewater treatment. The costs were based on a survey of key European biopharmaceutical
industry players. The total amounts of water and bag consumption were multiplied by the unit waste management costs to compute
a total waste treatment cost for one campaign. On an annual basis, the incineration cost of plastics was half the cost of
waste water treatment.3
Workflow and process optimization through process simulation
Process simulation can offer critical insights for developing guidelines and standards for the implementation and operation
of single-use systems.
Figure 2 shows how simulation can be used to assess the impact on personnel and floor space requirements for buffer make-up
strategies with single-use bag systems. The company is a multiproduct contract manufacturer. The simulation tools allowed
the workflow and buffer makeup process to be optimized to suit the multiproduct production schedule. Operator levels were
reduced and contingency time increased under the same storage and makeup area constraints.
Figure 2. Buffer use per day, broken down by volume. Through a simulation, the buffer makeup process and workflows were optimized
for a multiproduct site using disposables.
When process simulation is used for equipment and infrastructure sizing, it often shows that using disposable technologies
can have a big impact. For example, on average 70% of WFI usage in a biotech plant is for cleaning. Many engineering companies
struggle to evaluate the direct impact of disposables on utility requirements and oversizing of WFI systems still occurs frequently.