Format and Function: Optimizing Gene Therapy Manufacturing Workflows

Format choice for cell culture media can have a significant logistical impact on gene therapy development. Understanding the suitability of a format for use at commercial scales and making the appropriate choices throughout process development can help streamline operations and reduce the risk of delays.

The use of media in a liquid format is well-established for small-scale gene therapy development because liquid media are ready to use and require few preparation steps. Saving time and reducing in-house workload, the liquid format is ideal for helping developers create a more convenient process.

However, as workflows scale up and liquid media volumes increase, so too do the logistical and financial challenges of shipping and storage. Careful planning and forecasting are required so that media are available when needed and used before expiration. However, liquid media are heavy, which means they can be expensive to ship and challenging to move around facilities. Moreover, large areas of manufacturing facilities may be needed for storage, reducing production space. Using third-party warehousing can lead to substantial additional costs, and storage is further complicated by the relatively short shelf life of liquid media. 

Furthermore, while liquid media do not require reconstitution, the addition of supplements can increase complexity by adding to the number of preparation steps.   

Because of the challenges associated with liquid media, many companies choose to use dry powder media (DPM). DPM is more compact, saving on storage and shipping costs, and leaves more facility capacity for operations, providing the opportunity for greater productivity. DPM also has a longer shelf life, which allows for the stockpiling of supplies and results in less pressure on accurate forecasting – as well as the reliance on supply chains.

However, standard DPM requires a multistep rehydration process before it can be used, which can add to the in-house workload. The need for manual handling steps during the rehydration process, such as pH and osmolality adjustments, can increase the risk of inconsistency. When using DPM, it is important for developers to have strict quality protocols in place to reduce any process variability. 

There is also an alternative option that can bridge the gap between production-ready liquid media and DPM: granulated media formats. Granulated options provide a simpler reconstitution process and lower dust generation without the need for pH or osmolality adjustments, increasing efficiency and reducing the risk of inconsistency. Moreover, supplements can be integrated into a granulated format, effectively resulting in a convenient single-component product. 

By providing similar storage and shipping benefits as DPM, alongside helping support more efficient preparation and improved consistency, granulated media can help many developers reduce operating costs and increase productivity.

Transitioning from liquid to dry powder or granulated media during scale-up can be challenging. Carefully considering the optimal format early during process development is essential to help avoid costly delays, such as reformulation or requalification of a medium. 

Choosing an off-the-shelf medium that is available in multiple formats could prepare a workflow for future changes. Similarly, validating that a proprietary formulation is suitable for conversion can help streamline the transition. This validation step can still be beneficial for developers who plan on using liquid media at all scales. Knowing that a formulation can be used in multiple formats means developers have a backup option should they face complications. 

That said, using the same format at all stages can support the more rapid progression of the therapy. Liquid, dry powder, and granulated media formats offer a variety of benefits and potential drawbacks, depending on the specific process requirements. The challenge is finding a medium that provides consistent quality and performance in a format that can also help optimize logistics. 

Ultimately, developers need to consider scalability, cost-effectiveness, and convenience during process development to find the format that will be most suitable for their current and future needs. By choosing the right format, developers can optimize their development and manufacturing processes to help them accelerate the speed to market for their gene therapy product and confidently meet future demand.