For biomanufacturers, using a structured, analytical approach to process scale-up will breed confidence and ensure quality.
By adopting robust experimental design, results gleaned during initial experiments to determine an optimum bioprocess arrangement can be scaled-up to reliably predict performance during cGMP production.
An example of this is a case study for determining the correct sizing for a filter utilized in an automated final bulk-fill system for a biopharmaceutical product.
- The manufacturer identifies a target product and the process parameters which a bioprocess must work within to ensure quality.
- Small-scale experiments – using a theoretical selection of filters – will allow the manufacturer to estimate filter system sizes: these can then be tested in pilot-scale and engineering trials.
- Because the capacity is directly proportional to the filter area, data from the smaller scale experiments can be scaled-up to determine the required size for the target process.
- Experimental variability can also be introduced through differing filter formats, drug product batches or process equipment at a pilot scale or during full engineering trials, to confirm the initial findings.
- To ensure scale-up predictability, sizing should be performed using a scale model of the target process.
- Ideally, processing time should be adjusted as a function of test batch volume.Parker domnick hunter’s SciLog FilterTec system can provide a solution in cases like this.
The FilterTec system:
- Measures differential pressure across a filter (or multiple filters) during testing.
- Allows real-time assessment of filter blocking characteristics.
- Allows further optimization through the use of prefiltration stages.
- Performs constant flow testing until the differential pressure reaches a defined, predetermined end point.
In this case study, sterilizing filtration of a high-potency drug was required in order to meet the requirements of cGMP manufacturing. The process was defined by the maximum size of 25 L of bulk product and an upstream pressure limit of 2 barg (29 psig).
The hazardous nature of the product meant that neither mid-batch filter blockage nor damage to the single-use manifold (caused by overpressure) was acceptable.
Small-scale disc testing was performed on Parker domnick hunter’s PROPOR HC sterilizing grade filter at a target flow rate of 10 ml/min with a pressure limited to 1.6 barg (23.2 psig) which gave a 20% safety factor. This established a capacity of 92.4 ml of solution for a 47 mm PROPOR disc at an actual flow rate of 8.5 ml/min.
Scaled-up relative to the effective filtration area, this is the equivalent to 35 L of bulk product through a 10 inch (250mm) filter capsule, which is capable of processing a 25 L batch while incorporating a 40% safety factor in capacity.
A pilot-scale trail confirmed this analysis – and provided further assurance that the results are repeatable on a larger scale and the whole batch could be processed without the risk of filter blockage.
This post was contributed by Andrew Kelly, Filtration Product Manager (Life Sciences), Parker domnick hunter Process Filtration, UK
Parker domnick hunter specialize in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid flow more effectively, ensuring the quality of the final product. Find out more at our dedicated bioprocessing microsite.