Disposable Components in Aseptic Processing

The authors discuss current and future disposable technologies and outline the validation and qualification steps that would be required for a possible disposable process stream.
May 01, 2009
Volume 2009 Supplement, Issue 2

Aseptic processing is of great importance within the biotechnology industry because cold sterilization by membrane filtration is the only method of sterilizing biological solutions. Any heat treatment would destructively affect the drug product and target protein. To ensure sterile filtered products maintain their sterile state, an increasing number of companies are using disposable process solutions to process or store the resulting filtrate. Modern disposable connectivity allows joining the filtrate hold bag with the filling line. If the product must be transported to another facility, then the filtrate could be frozen and thawed after it reaches the filling facility. A controlled freeze–thaw process ensures protein degradation is kept to a minimum as a result of the lack of fluid movements and/or uneven protein concentration within the frozen volume.

In addition, biologics are commonly difficult to remove from fixed, stainless-steel equipment. The cleaning and cleaning qualification process is tedious and must be exceptionally thorough to prevent residues and potential cross-contamination. The cleaning and sterilization down-times for stainless steel vessels, transfer lines, or filter housings might require 8–10 hours and copious amounts of cleaning solutions and water-for-injection (WFI). Calculations have shown that the cleaning and sterilization process of a 1000-L vessel can cost as much as $5000, depending on the WFI costs, whereby a bag of this size is priced at $200–300. The need for shorter cycle times and reduced process-material pushed the development of disposable solutions, which require no set-up times or cleaning. Disposable mixing systems can be connected to capsule membrane filters and a hold bag. These interconnected disposable systems are gamma sterilized and ready to use.

Another benefit of disposable equipment is the fact that the end-user does not come in contact with the product. Therefore, disposable equipment has increasing popularity in cytotoxic drug applications. The drug product is processed from one disposable process step to the next without the need to either dismantle a filter from a filter housing or clean a vessel by hand. Any time a drug product has a potential to harm the user, disposable processes are the equipment of choice.

Disposable equipment development

Figure 1: Small-scale filter capsule devices. (ALL PHOTOS ARE COURTESY OF THE AUTHORS.)
The first disposable units were probably filter capsule devices, which could filter small volumes without the need of a filter housing and required cleaning. These filter capsules incorporated a plastic filter housing and filter cartridge into a one-piece disposable unit (see Figure 1). Capsules nowadays are available in sizes from 100 cm2 to 4 m2. These capsules can be assembled to other equipment and autoclaved, or the capsules are delivered presterilized by the filter manufacturer, including equipment connections (e.g., to a filtrate hold bag).

Figure 2: Example of a bag laminate.
The next development was single-use sterile bags to replace glass bottles, plastic carboys, or stainless-steel containers for small-volume storage, transport of biological solutions, and growth media. Originally, blood and parenteral solution bags were adapted for process use. Because the mechanical stability had to be strengthened, specific polymeric bag films were developed. These films are laminated in various configurations to gain the mechanical strength for large-volume bags, to reduce any leachable release into the product, and to create an oxygen barrier (see Figure 2).

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