By: Stephen Moore
The Manufacturing Strategies and Solutions for Gene Therapies session was introduced by Lisa Bradbury PhD, Director of Research & Development of the Proteomics & Cell Therapy Programs at Pall Life Sciences. She briefly spoke of the challenges and innovation that are required in the production of gene therapeutics. She stated that lessons can be taken from the scale-up of antibody production, but reminded the audience that many of the issues with the scaling-up of gene therapies are unique.
Achieving Large-Scale GMP Production of Adenovirus in the iCELLis 500 Fixed-Bed Bioreactor.
The first presentation of the session was given by Dr Hannah Lesch, the Research & Development Director at FinVector Vision Therapies. FinVector Vision Therapies is a Biotechnology company based in Finland that specializes in the research and development of Viral-Based Gene Therapy Products. Dr Lesch started by introducing the layout of their laboratory and production facilities. She then spoke on the steps that they undertook when scaling-up the production of one of their drug candidates, a adenoviral gene therapy vector encoding the gene IFNa2b, which is being tested for use in the treatment of refactory non-muscle invasive bladder cancer. After FinVector Vision Therapies had shown that they could generate the transfected vector, they decided to scale-up production. To do this they turned to the iCELLis bioreactor system produced by Pall Corporation. The iCELLis bioreactor is a single use fixed-bed reactor that is available in two formats, the iCELLis nano and the iCELLis 500. They found for the most part the scale-up was relatively straightforward. Dr Lesch reported that the main issue they found was when it came replacement of media in the bioreactors. She also reported that cell distribution in the fixed-bed bioreactor was relatively even, scalability was good, productivity was improved, and that there was process consistency across the four batches they had produced so far.
Viral-Based Gene Therapy: Manufacturing Considerations, Benefits and Challenges.
The second presentation in the session was given by Bryant Cook, the Senior Director of Facilities, Engineering, and Validation, at uniQure, a biotechnology company in Lexington, Massachusetts. uniQure specializes in pipeline development of adeno-associated virus (AAV) based gene therapies to treat CNS, liver/metabolism, and cardiovascular diseases. Bryant spoke of the considerations needed in the design of a new facility based on the building of uniQure’s own facilities. He addressed the need to understand the scale and capacity of production, not just at the time of construction, but future requirements to enable better planning of space utiliztion. Determining whether clinical or commercial production was the main goal would lead to design that addresses GMP considerations. Other considerations for the design process are whether separate product lines would be needed, type of bioreactors to be used, what the maximum processing scale would be, and whether in-house solution preparation is desired. Furthermore, he spoke of the need to address drug product management, such as sterile filing and packaging, labeling, and clinical supply lines.
As an example, Bryant spoke of the design of a single-use facility. This type of facility would result in reduced cleaning costs, faster product changeover, allows flexible design, and involves lower capital cost. However, he also cautioned that the fitness of purpose and function need to be considered. For instance, compatibility issues need to be addressed, pressure, flow, and temperature limits need to be considered, as well as instrumentation limits and HVAC systems. When considering single-use facilities materials management also need consideration, are materials solo-sourced and will this result in long lead times? All these factors may well result in an increased cost, however, for generation of small batches of multiple products, it may be the preferred option.
Bryant also spoke of the need to build in flexibility when designing the layout of facilities for future needs. For example, ceiling heights should be considered, extra utilities and power outlets should be installed, data collection points should be strategically placed, modular furniture used, and material pass through points installed. Lastly he emphasized the need for a firm that had experience in the design and build-out of commercial clinical/commercial biopharmaceutical facilities.