Disposable Biopharmaceutical Processes–Myth or Reality? - - BioPharm International

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Disposable Biopharmaceutical Processes–Myth or Reality?


BioPharm International


Stainless steel components, particularly those in contact with the processing fluid, must be cleaned and sterilized before use. In addition to the 1.5 to 2.5 hours required to clean vessels from 100 L to 1,000 L,2 massive volumes of WFI and steam are also required. These utilities are sometimes in high demand and can create an operational bottleneck. Vessel cleaning costs are in part a function of WFI cost per liter (varies by facility), vessel size, and flush volume required. Depending on these variables, WFI costs alone can be up to several thousand dollars per cleaning per vessel.

Since single-use components are typically presterilized by the supplier, utility systems and sterilizing equipment, such as autoclaves, can be reduced in number and size. This has a large impact on capital expenditures during new plant construction, not to mention commissioning and validation of the systems.

Biotechnology companies often build pilot plants in order to manufacture the volumes of drug product required for clinical phases. If the drug shows commercial promise and receives marketing approval from the regulatory agencies, increased demand will often require a commercial-scale manufacturing facility. Unlike stainless steel equipment which depreciates rapidly, disposable components are customizable: designed and made for a specific use, at a specific volume, at a specific time. Scale-up costs are incremental, not capital intensive. If the process is scaled either up or down, disposable components can be redesigned and supplied ready-to-use in a matter of weeks, not years. Furthermore, revalidation requirements are minimal so long as the process conditions, drug product or intermediate, and product contact surfaces remain unchanged.

Disposable solutions result in faster design, construction, and commissioning of facilities, with the operational benefits of "flexible manufacturing." As disposables continue to be used in more applications, they are evolving from isolated solutions into a holistic value proposition for small and large biotech companies alike.

The Promise of Complete Disposability

In light of the trends discussed above, equipment suppliers are allocating increasingly more development resources to disposable technologies. A widely discussed question lately has been, "Is a completely disposable bioprocessing facility possible and practical?" At the current moment, disposable (product-contact) solutions are available for all unit operations at smaller scales (<50 L harvest reactor volume). Even at mid- or pilot- scale production, most unit operations remain practical, using single-use technologies. As processes scale up to commercial manufacturing volumes, certain unit operations become practical only with reusable operations. However, there is a noticeable trend toward larger disposable equipment availability; once a technology gains acceptance at smaller scales, suppliers commonly focus on development for larger volumes.


Figure 2. Simplified MAb process with disposable unit operations shown in blue; reusable equipment shown in red.
In order to discuss disposable solutions to individual unit operations, a simplified, 500 liter monoclonal antibody (MAb) process is considered (Figure 2). The equipment specified in this model is for the purposes of illustrating disposable capabilities and potential. Specific equipment selection and sizing is specific to the drug manufacturer's product and process. Proper selection can only be based upon scientific trials, data collected, and optimization studies.

Upstream Processing


Figure 3. Example of a disposable mixing system
Disposable mixing systems (Figure 3) for media preparation are currently available using impeller, rocking motion, stir bar, and perforated septum platforms. In all instances, the drive units, controllers, and weighing platforms are reusable, while all product contact surfaces are disposable. Systems are installed providing repeatable mixing results for media preparation from 20–1,000 liter working volumes. Sterile bags are provided in customizable designs to fit the specific application, and are delivered presterilized by gamma irradiation and ready-to-use. Moreover, the mixing units can be re-used without lengthy downtime, often being the bottleneck in the upstream process. Cleaning and set-up times are reduced to minutes instead of hours. Such fast turnaround supports equipment and facility utilization.


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