Simplifying Validation of Disposable Technologies with Presterilization by Gamma Irradiation

Nov 02, 2006

From the elimination of cleaning and cleaning validation to a reduction in capital costs, labor, and space requirements, the myriad benefits of using disposable systems are well-established. However, presterilization is one area that deserves more attention. Presterilization goes to the heart of the disposables concept, which is to minimize opportunities for contamination, whether through operator error, the process, or the product.

As the size and complexity of disposable systems continue to increase, presterilization will become increasingly advantageous and, in some cases, necessary. For example, conventional sterilization techniques such as autoclaving do not always fit a manufacturer's timeline, especially in the case of campaign-based vaccine production. Steam used during autoclaving is also known to damage paper, some plastics, and other heat-labile products and does not always ensure complete sterilization.

In addition to providing validation strategies for presterilization using gamma irradiation, this article addresses the overall benefits of disposables and explains how to minimize revalidation during scale-up.

Validation: An Important Early Process Consideration

Figure 1. A fully integrated, single-use filtration system
Regulatory agencies around the world are focusing on validation, and it is becoming an increasingly important topic to consider early in the drug development process. For example, Annex 13 in Eudralex, the European Union's source for governing medical products, affirms that for investigational medicinal products, the manufacturing process should be validated in its entirety; it also focuses on critical steps, such as sterilization. Annex 13 further defines the process in the following manner:

The different production operations shall be carried out in accordance with GMP; manufacturing facilities must be laid out to allow effective cleaning and reduce cross-contamination risk; equipment used for manufacturing operation, which are critical to the quality of the product, shall be subjected to appropriate qualification and validation.

Example: Virus Particle Filtration
In North America, FDA's January 2006 draft guidance INDs — Approaches to Complying with CGMP During Phase I — states that there are a number of technologies and resources available for use that can facilitate conformance with current good manufacturing practices (cGMPs) and help streamline product development. More specifically, these include the use of disposable equipment and process aids, prepackaged Water for Injection (WFI) and presterilized containers, and process equipment that is not exposed to the environment during processing.

Presterilized Filtration Systems

Filtration systems exemplify disposable technologies that can be presterilized. Disposable filtration systems are offered in a range of sizes, so that corresponding filters and bags are available for every stage of development, ensuring that the most appropriate and economical disposable filter scheme is used. By using the same materials of construction, these systems also generate reproducible results during scale up. Also, like presterilized filter cartridges, the entire single-use filtration system can be gamma irradiated before delivery to the biopharmaceutical manufacturing site. These systems, which generally comprise disposable bags, capsule filters, tubing, clamps, adaptors, and connection devices, also simplify many biopharmaceutical processes, such as preuse filter integrity testing.

Simplifying Scale-Up

To make certain that the process is scaled up with minimal material revalidation, biotechnology and pharmaceutical companies should use components that are made from the same materials from small scale-up to manufacturing scale.

A variety of capsule filter configurations are available to support processes as they are scaled up. Ideally, these differently-sized capsules contain identical filter media and hardware materials. This helps ensure that scale-up and scale-down studies yield relevant information and minimum requalification for various batch sizes.

The availability of a variety of capsules for small-scale operations is especially beneficial for new product development. Since all new biopharmaceutical products may not become commercialized, capital investment can be a concern. Single-use capsules and systems make it possible to produce new products during the early development stages without a large capital investment. Together, these factors can streamline drug development to increase manufacturing capacity, while meeting validation requirements.

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