A Comparison of Fed-Batch, Concentrated Fed-Batch, Perfusion and Concentrated Perfusion

When determining how to develop a bioprocess for your drug candidate, there are many key decisions about how to proceed including choosing a cell line, whether to outsource or keep in-house, and what type of bioprocess is most economic.

The old fed-batch and perfusion processes are well known but both have limitations. If you wish to move to a modern production platform, which one is best?

If you already have a facility this will impact significantly your cost base and therefore your choice, but today, most people wish to evaluate all opportunities that could reduce the cost of development and the cost of manufacture. Here is an overview about the four main process options commonly available. (note that batch processing is ignored here)

Typical questions may include:
Should I use fed-batch rather than perfusion? Which is lower cost? Which involves less risk? What about the new concentrated fed-batch or concentrated perfusion processes? How do I know which process option is right for me?

…here are some ideas and answers:

Perfusion, Concentrated Perfusion, Fed-Batch, Concentrated Fed-Batch CFB™

Use Perfusion if you want to:

• keep a low cell density of 30m or less for reasons of cell or product stability, for example because the concentration of a required toxic molecule will be too difficult to control.
• replicate a process that is moving from older style perfusion technology, such as a spin filter or cell settler, and just wish to benefit from the ATF System’s improved reliability and gain a filtered product stream - but wish to maintain a similar cell density as previously.

Use Concentrated Perfusion (ATF-perfusion) if you want to:

• reduce the size of bioreactor required to produce to same amount of product as in fed-batch or perfusion
• reduce the time taken to produce X kilograms of your molecule
• reduce USP development times
• standardize process control and improve the reliability of reactor performance
• reduce the complexity of media development and use only a single medium feed
• remove contaminants and by-products from the reactor and improve product quality
• maintain a constant environment for cell growth and/or product expression
• utilize an existing DSP train that is suited to receive one or two vessel volumes per day of clarified material at 1-2g/L concentration.
• take advantage of moving towards continuous processing in downstream activities.

Use Concentrated Fed-Batch (ATF-fedbatch) if you want to:

• take advantage of all the benefits of concentrated perfusion, but also require a single concentrated product harvest directly from the reactor
• have a short production time comparable to fed-batch, e.g. 12-16 days

Use Fed-Batch if you want to:

• utilize effectively your existing 10,000L or 20,000L reactor

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