1. The development must be place cost-efficient.

2. Short development times enable the early start of clinical studies.

3. High flexibility is required regarding the capacity and type of the processes.

4. The transfer from R&D plants into production facilities must run fast and smoothly.

The requirements mentioned above lead to the development of a concept for our pilot plants that illustrates an alternative to the highly automated hard piped stainless steel plants we built before. In order to expand our capacities for process development and to implement the new concepts for plant operation, an investment project of 172 million € was approved in January 2008 by Roche’s Cooperate Executive Committee. This concept of the pilot plants is based on a process platform of Single Use Equipment working together with classic steel & glass equipment in different modular plants. To ensure fast and efficient process development, tools to increase equipment utilization will be established. All plants and all equipment are working together in one fully electronic “Data Acquisition and Management and Analysis System”. A major component during the elaboration of the new plant concept has been the evaluation of single use bioreactors (SUB). In a joint evaluation study of the sites in Basle and Penzberg, different SUB models were characterized up to a scale of 500 L and their suitability was examined in numerous fermentations. In order to ensure a compatibility of the single use bioreactors with the used media and cells, these tests were performed using our platform technologies for the development and production of antibodies. These platform processes require the realization of

• Short mixing times

• High mass transfer rates and

• Sufficient power input.

In the course of the evaluation, the best suitable SUBs were adapted in co-operation with the vendor to our requirements. Finally we ended up in a Roche-specific bioreactor design that guarantees comparable results to the existing stainless steel bioreactors. Apart from mechanical process engineering the adjustment of the automation systems plays a major role for the acceleration of the development process and increase of the flexibility. The development of an appropriate automation system covers several aspects:

• Reliable and précised single use sensors are needed to operate SUBs in an efficient way.

• The plant control system must integrate analytical devices, classic and single use bioreactors and harvest equipment using different control cabinets from different vendors.

• The plant control and automation system has to integrate the operation of modular plants and research laboratories in different facilities.

• Nevertheless, full remote control of all equipment and the use of advanced control algorithms must be feasible.

• Interfaces of the data acquisition system have to support the use of many other different software tools used in R&D for process design and analysis.

Having a complete electronic documentation & automation system available, we can use the advantages of our platform technologies to accelerate the development process.

In this presentation, we will introduce the new features of this novel disposable bioreactor and then discuss the results from biological tests involving CHO cell lines expressing recombinant monoclonal antibodies.

SUT can bring a lot of advantages such as avoiding cleaning steps, eliminating cross contamination risks, adding flexibility in development and production processes. However, a lot of companies are reluctant to go for SUT because of the work associated with the implementation of technology. How to overcome the challenges of SUT implementation?

In this presentation you will learn about manufacturing of disposables in clean room environment in order to better understand the process. The different production steps will be outlined , highlighting cGMP and Best practices.

The author will also provide an overview of critical documentation required to support the evaluation of SUT. We will show how this information can answer to the risk assessment necessary prior to implementation .Validation tests will be illustrated and examples given. A focus on extractable and leachables studies with their link to customer process will be presented. You will learn about new trends for thorough risk assessment while minimizing work and which added value you might get from your SUT-supplier Finally, the first part of the presentation will be challenged by a case study from a key Biopharmaceutical customer illustrating how the data provided have been supportive and which further expectation he has.