Continuous Processing: Is The Pharma Industry Finally Coming Round To The Idea? - Pharmaceutical Technology

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PharmTech Europe

Continuous Processing: Is The Pharma Industry Finally Coming Round To The Idea?

Pharmaceutical Technology Europe
Volume 22, Issue 9

Q. PTE: What continuous processing technologies does your company specialise in?

Nepveux (Pfizer): At Pfizer, we have active programmes in dry and wet granulation, tablet coating, and several API process stages.

Schoeters (GEA): We specialise in continuous dispensing, dry blending, wet granulation, melt granulation, drying, tabletting and coating.

Weiler (SAFC): At SAFC, we specialise in continuous liquid/liquid synthesis, SMB and thin film evaporation.

Whitfield (Inprotech): As a pharmaceutical engineering consultant and as a direct consequence of my previous "Big Pharma" experience, I have tended to focus on secondary manufacturing applications. However, more recently, as I aim to provide fully integrated solutions for clients, I have been concentrating on the continuous flow or microreactor technologies for small molecule API applications. There have been some exciting developments in this technology area during the last 2 or 3 years that offer the pharmaceutical industry alternative continuous processing options for API manufacturing.

Q. PTE: What process and/or cost improvements have you witnessed with these technologies so far?

Nepveux (Pfizer): On the drug product, side, the paybacks have generally been modest in terms of incremental yield improvement and productivity increases. Unfortunately for continuous processing, there is plenty of excess capacity for traditional, small-molecule processing so capital avoidance is not a powerful driver. If the situation were different, I would expect to see more successful installations.

Schoeters (GEA): We have a number of case studies, which will allow me to explain the different benefits that we have witnessed with continuous processing technologies so far:

Company 1

This company opted to install our ConsiGma technology primarily to help them reduce costs, not only initially, but also in running costs. ConsiGma is a small unit that can be easily installed in existing pharmaceutical production rooms, avoiding the need to invest in an expensive change or extension of the production. It requires only a minimal continuous amount of utilities and avoids energy consumption peaks. Finally, because of continuous on-line monitoring and feedback techniques, generation of out-of-spec materials is kept to a minimum, thereby reducing the generation of toxic waste.

The business case was made for a 1.5 billion tablets/year production. The overall investment cost (building, GMP–space) was two-thirds less than what the cost would have been with conventional technology, only 30% of the manufacturing space was needed, quality costs were drastically reduced (50%) and yield was raised by more than 0.5 %.

Company 2

This company chose to install ConsiGma because there is no need for scale-up with this technology, and thus it can produce any batch size. This attribute was particularly important to this client, who regularly switched between R&D and production batches.

Andreas Weiler
Weiler (SAFC): Most continuous liquid/liquid reactions can be performed at much higher temperatures, delivering an improved product quality so that additional work-up steps, such as distillation or crystallisation, can be avoided.

If chiral phases are used, SMB is not cheap initially but it is often the only method to separate two enantiomers and the better the solvent recovery works, the more significant the reduction in running costs.

Finally, because of the short contact time, we have seen that thin film evaporation can be a cost efficient process for continuous separation of thermally unstable mixtures.

Whitfield (Inprotech): I have worked on two separate OSD continuous processing projects, one at approximately 250 kg/h and the other at 25 kg/h, one for an OTC tablet and the other an Rx tablet, both delivered significant operational benefits when compared with the traditional batch approach. In both cases the factory footprint required was only 20% of that required for the traditional batch approach. Additionally, for the Rx tablet process, two of the dried granule Critical Quality Attributes — moisture level end point and particle size distribution — were incredibly reproducible with very low variability compared with the equivalent, existing batch process.

I have also been involved in a project that delivered a fully continuous process for the manufacture of a toothpaste product at one-tenth and full commercial scales, which again realised highly compelling business benefits versus the existing batch-based process, including a six sigma process capability.

I am also aware of a continuous process for API manufacturing that simplified an extremely complex synthesis route and delivered a reaction chemistry solution that was not achievable by conventional batch reactor technology.


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