Parker domnick hunter is committed to increasing productivity and customer satisfaction through application-driven new product development, and collaboration is a highly effective way in which to achieve this.
The development of the PROPOR HC – a high capacity sterilizing-grade PES filter – shows just what can be achieved through partnership.
PROPOR HC was developed by Parker domnick hunter in conjunction with a multinational insulin manufacturer, which was experiencing premature filter blockage when filtering a product intermediate.
The intermediate was being manufactured via a microbial fermentation. Downstream processing of the product involved multiple crystallization steps, which in some cases produced an intermediate that proved extremely difficult to filter.
It became impossible to guarantee that a batch of product could be processed through the existing sterile filtration stage. This led to a need to accommodate change out of filters mid-batch or having to quarantine a complete batch.
The cause of the filtration variability was identified as the production of small fibrils during the crystallization stages. While analysis of the final product showed that the fibrils did not affect the drug quality, the processing difficulties were substantially impacting on shipments and revenues.
Developing a solution
A team from Parker domnick hunter worked with the manufacturer to identify the cause of the problem and develop solutions that were used on a production scale.
- Samples of problematic batches tested in conjunction with the customer at Parker domnick hunter laboratories
- Product re-constituted using customer’s protocol
- Small-scale filterability studies conducted to ascertain the optimum filtration train and membrane configuration
- Evaluation of Parker domnick hunter’s highly asymmetric membranes (specifically designed to maximize throughputs on complex protein solutions)
- Studies showed performance advantages of dual layer construction incorporating a prefilter and a sterilizing grade membrane
- Evaluation of the most appropriate filtration solution against the existing system – the Parker domnick hunter dual layer product (PROPOR HC) showed dramatic improvement compared with the previously used single layer PVDF membrane filter
The performance advantages were achieved by the combination of expert optimization and the use of our new range of PES membranes, which combine a highly asymmetric structure with a very well controlled retentive layer on the downstream face of the membrane. Compared to other membranes, this provides substantially increased dirt holding capacity and flow rates, coupled with absolute microbial retention characteristics.
The filterability studies conducted were invaluable in ensuring the filter configuration was optimized. The dual layer membrane construction incorporating a highly asymmetric prefilter layer has been shown to increase throughputs of proteinaceous solutions by up to ten times.
The significant benefits have also been realised with other protein based solutions such as serum free CHO-K1 medium and a 0.5 mg / ml protein concentration of dust mite serum. In both cases, system size was reduced more than 4 fold.
The efficacy of the membrane prefilter also allows the possibility of simplifying filter trains by replacing a discrete prefilter stage, thus providing further benefits.
By involving the customer directly in product development, we ensured that the filter solved the customer’s problem: the use of PROPOR HC, means that the costly requirement to reprocess batches due to filtration difficulties was eliminated.
Plus, it took just six months for this process to reach a successful conclusion, from the initial filterability trials to on-site tests and full product validation. This forms an excellent example of the benefits of collaboration.
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This post was contributed by Andrew Kelly, Filtration Product Manager (Life Sciences), Parker domnick hunter Process Filtration, UK.
Read the full application note Optimized Sterile Filtration of Pharmaceutical Solutions