Faster processing, improved quality assurance, and simplified cleaning validation are critical factors fueling the impetus towards disposable systems for pharmaceuticals and biopharmaceuticals processing. While the concept of a completely disposable manufacturing process would have been considered utopian a few years ago, today it is just another shift in the manufacturing paradigm. New aseptic processing initiatives by FDA have spurred greater interest in disposable processing systems as a way to minimize opportunities for product cross-contamination and to aid in compliance.

Disposable Systems Eclipse Stainless Steel

The elimination of cleaning and cleaning validation is a significant benefit of disposable processing. Cleaning process equipment consumes time and valuable operator resources. Cleaning chemicals require suitable handling systems for the delivery and disposal of the fluids. Care must also be taken to use these chemicals in the appropriate concentrations to ensure that they perform their specified function. In addition, proper handling techniques are needed to ensure that the system is properly cleaned and that the operators are protected from contact with potentially hazardous cleaning fluids.

During the cleaning of stainless steel systems the filter housings are typically dismantled prior to cleaning. Following cleaning, stainless steel hard-piped systems must be rinsed with a suitable amount of water to ensure that the residual cleaning fluid is removed. For some applications, the cost of the cleaning operation increases when water for injection (WFI) is required for the system flush. Following each cleaning and flushing, the systems must be re-assembled and re-sterilized, which adds further time to the operation as well as increases labor costs.

Perhaps the most critical element of cleaning is validation of the process. Complicated cleaning processes are cumbersome to document, and it is even harder to prove that traces of the cleaning chemicals have been removed. Instead of having to prove that the cleaning has been effective, disposable systems are used one time and discarded. Gaps in cleaning validation documentation can cause regulatory scrutiny, and in the worst case, production of new or existing products is delayed. Failure to execute specified cleaning standard operating procedures (SOPs) are a non-compliance. For example, in the case of caustic solutions (often used for cleaning), if the concentration of the caustic is incorrect or if the temperature of the cleaning fluid used is not at the SOP-specified temperature, the validity of the cleaning process may be questioned.

Disposable systems also offer drug developers an alternative in terms of sterilization. While stainless steel systems are confined to steam sterilization processes, either autoclave or steam-in-place (SIP), disposable systems can be purchased pre-sterilized by gamma irradiation. Existing steam sterilization processes can also be used for the disposable capsule filters. Most capsule filters can be subjected to sterilization by autoclave, and some capsules (which have suitable materials of construction) can also be subjected to SIP.

Disposable products that are supplied pre-sterilized by gamma irradiation eliminate the need for sterilization and sterilization validation procedures and can reduce the maintenance of sterilization equipment. The user can essentially remove the product from its package and install it in the process. The disposable product supplier provides validation documentation. While the cost of sterilization by gamma irradiation is comparable to that of traditional steam sterilization methods, the gamma irradiation process reduces labor, and circumvents many of the potential issues associated with in-house steam sterilization. For example, if condensate has not been properly drained from a filter that has been steamed in place, the filter membrane could become wet out. The bubble point of the membrane must be exceeded to expel the fluid from the pores and allow steam penetration. This situation could lead to an extended steam cycle, or in the worst case, damage the filter due to excessive pressure in the forward direction, if an increased pressure is used to expel fluid at an elevated temperature.