General questions
What is your name, company name and position?
My name is Karol Lacki and I’m Vice President of Technology Development at Avitide. At Avitide we develop and manufacture custom affinity resins.
Would you classify yourself as a beginner, intermediate, or expert user of BioSolve Process?
I would say I’m an intermediate user.
Which version of BioSolve Process do you use currently?
I am quite familiar with BioSolve Process 7.5, but the first time I used BioSolve Process was around six years ago.
What do you like most about BioSolve Process?
For me, the flexibility of BioSolve Process, along with the ability to create and add new unit operations are the highlights of the tool. You can easily see all of the important functions, making it very accessible, and I find it useful to see how unit operations are modelled for it helps in writing own functions describing new, or custom versions of existing, unit operation, but I would say it is more beneficial to be an advanced end user to do this type of changes.
Biopharm Services: Yes, we know about this issue and are planning a solution for the next release.
How steep did you find the learning curve for BioSolve Process? Were there any specific aspects of the tool that you found more difficult to learn than others?
Anyone who has done cost modelling of bioprocessing would have a pretty good idea of how such a modelling should be done, so their learning would be minimal. Having said that, adding unit operations in table-form and working out how the unit operations interact and which parameters are input and which are output values require some learning.
A new generation of users would benefit from the addition of ‘drag and drop’ functionality, and I think it would make the platform more intuitive.
Biopharm Services: Drag and drop is definitely available in BioSolve Connect currently. However, it still requires work around it. Any other thoughts?
Specifying parameters was the most difficult aspect to learn – large number of different sheets for data input could intimidate users. But as I said, if you have previously used a similar Excel-based model of your own, it is easy to use. As long as you know what you need and why, you will be fine.
Continuous Process
What is your definition of continuous processing?
My definition of continuous downstream processing is the type of processing where the feed is applied continuously to the first unit operation in the downstream processing train. A continuous unit operation is an operation where either the feed stream or the product stream, or both, are continuously delivered or collected, respectively, over a defined, preferably longer, operating time. If a downstream process is based on combination of batch and continuous operations I would call it a hybrid process.
What is your thought on the optimum number of columns in a multi-column chromatography (MCC) type system?
It depends – you can do continuous chromatography with two columns applying what I call a swing chromatography concept where each of the column is operated in a batch mode, but of sync, ie., one column is loaded while the other is regenerated. If you are using periodic counter-current chromatography (PCC) approach, the number of columns you need would depend on the process conditions, but you’d need a minimum of two. From a capacity utilization perspective, two columns in the loading zone is enough for majority of operation, and the total number of columns will depend on the duration of one column regeneration phase, where by regeneration I mean elution, strip, CIP, and re-equilibration. For a PCC operation, the rate limiting step is the regeneration phase. In other words, for an uninterrupted operation and when the feed concentration is constant (not periodically diluted with a wash stream), the minimum number of columns is three, two in the loading zone and one in the regeneration zone. More columns can be required if the load phase is too quick as compared to the regeneration phase.
What are your thoughts on column free continuous purification technologies, e.g. the use of membranes or counter-current tangential chromatography?
I would say that the adsorptive membranes can be seen as prepacked columns, and thus still enables counter current chromatography. However, at least till now, membranes suffered from low capacity so therefore they were more suitable for continuous operations for low titre processes. It all comes down to a ratio between capacity and titre – if the ratio is high and you can regenerate a prepacked cartridge, for instance a membrane adsorber, quickly enough, such adsorbers can be used successfully in continuous operations.
In the case of counter current tangential chromatography, the lack of column packing, and also pressure flow limitations associated with columns packed with small particles, is the biggest advantage. Negative side is that the operation requires multiple membrane cartridges and that the eluted product pools have a lower concentration as compared to pools from a packed column.
Do you feel that automation and continuous processing go hand in hand?
They must go hand in hand – continuous processing requires a high level of automation, Process control strategies might prove more complex, and may require changes to be performed at various points in the process simultaneously. For that reason, some companies use break-up tanks to enable process control. At the same time it could be said that from the process control perspective, but not only, technologies that would secure a more robust operation should always be considered first. For instance, affinity chromatography as a capture step, e.g., Protein A in case of monoclonal antibodies, can be seen as a intrinsic control node from the process control perspective. With the right affinity chromatography resin almost any variations in the process stream coming from upstream, will be taken care of and the polishing stage of downstream processing will be performed, more or less, on the same composition of process stream.
Do you think that continuous processing will be applied at the clinical scale to produce material for clinical trials or do you think it is more applicable to commercial scales?
With the recent technology developments, it could certainly be rolled out at a clinical scale. For commercial manufacturing, it is a more complex question and the answer will depend on several factors, such as scale of operation, upstream technology used, new or existing facility, etc. From the scale of operation perspective, I do not see any reason for why a commercial manufacturing cannot be done in a continuous mode.
Final questions
What developments, changes or upgrades would you like to see in future versions of BioSolve Process?
I’d like to see more of the optimisation tool and also have the ability to set some constraints to the parameters within the unit operation.
What three words would you use to describe BioSolve Process?
Three Ps: Potential, Process, and Platform. The standardised approach gives BioSolve Process great potential to become a good platform, or a communication tool, for discussing manufacturing strategies and even for process design discussions both internally and with colleagues from other companies.
