Many articles describe the growing need for and benefits of the replacement of traditional, reusable technologies with disposable, single-use components in the pharmaceutical and biotechnology industries (1–6). Replacing reusable materials (e.g., stainless steel) with disposable products is cost effective and increases operator and product safety (3–6).

For disposable technologies to be accepted by an industry, vendors must show that disposable systems can have equal or better performance than traditional systems. As vendors begin supplying complete sterile, disposable solutions to the pharmaceutical and biotechnology industries, suppliers will be required to have complete validation packages and an in-depth understanding of their products.

The first decision that must be made when designing and manufacturing a disposable assembly is the choice of materials to be used. The materials typically chosen are polymeric materials that must be sterilized using common sterilization methods. Typically, prepackaged, presterilized disposable assemblies are gamma irradiated at >25 kGy. Therefore, the materials of these assemblies must be nontoxic and resist changes to their physical properties after being irradiated.

Validated and guaranteed product sterility is the most critical parameter for disposable systems in final fill and finish. Manufacturers of disposable products that are intended for a Class 100 environment or better must prove sterility throughout the fluid path as well as on the products' outer surfaces.

The validation method must then show that the disposable process is reliable, robust, and safe. The final filling performance of the disposable system must be validated and qualified to show repeatability and robustness. The levels of extractables and particulates for the chosen materials must be quantified, and the major contributing components must be identified. In addition, it must be proven that the final packaged assemblies maintain sterility and integrity during storage.

The final test for any disposable product is to show that it maintains product sterility during actual operating conditions. In the case of final fill and finish, the last step in the process validation is to perform media trials in which the final filling process is interrupted by process interventions while media are dispensed, packaged, and tested for sterility.

Figure 1

Methods, results, and discussion

Biological validation. The choice of materials to use is the first critical step in providing a robust, sterile product. As described in the "Performance validation" section that follows, none of the materials chosen should show significant physical degradation after gamma irradiation. Because the materials used for the disposable assemblies are polymeric, they must conform to safety standards for plastics set forth by the United States, European, and Japanese Pharmacopeias. To ensure this, each material that may come into contact with the drug product must pass United States Pharmacopeia (USP) 27 ‹88› "Biological Reactivity Tests In Vivo" after the samples are gamma irradiated to >40 kGy, the maximum dosage level that the disposable product may experience.