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How a risk-based approach to continuous processing will change the face of the pharmaceutical industry (or the Manufacturing Revolution)

An article by Rob Bowen published in BioPharma Asia:

The article considers the opportunities for risk-based change in facility design through quality by design (QbD) and advances in PAT. It suggests that the approach has relevance equally to biopharma and more traditional oral solid dose products based on a manufacturing “dancefloor” concept. The dancefloor principle is based on the potential for using closed process equipment using matrix rather than modular servicing within an open flexibly supplied process hall to provide the opportunity for adaptability of layout, rapid changeovers, varied set-ups, and multi-product manufacturing. Further that both upstream and downstream may be reconsidered and the opportunity for continuous processing without hold steps, using in-process real-time testing and approval taken in location, reducing the risk of product degradation and microbial contamination whilst significantly reducing or withdrawing entirely the need for work-in-progress (WIP) inventory and quarantine storage needed as supply chain management processes integrate.

Upstream and downstream – supply chain, WIP and quarantine

There is a tendency to think about manufacturing as being only the processing stream without considering upstream and downstream operations. At an extreme of efficiency of continuous processing one can see a small container size continuous processing module being supported by a massive warehouse and supplying another massive warehouse. A key issue, therefore, is as much to resolve the intake and dispensing of materials, its intermediate holding, the export of the continuous process stream’s product as it is the operation process and quality of the product in process.

Currently raw material is received, sampled, quarantined, picked and batched for dispensing, dispensed and held prior to use, and, on manufacture of tablet, capsule or vial, packaged and quarantined prior to export. During a batch process there is a need to hold staged work in progress (WIP) prior to the next stage, often because batch sizes do not correlate with equipment sizing and efficiency downstream and otherwise the need for product stage sampling the and quarantine of product awaiting QC testing and release. This inevitably involves labour and transport in transfer to warehousing, space required within an expensive manufacturing building to hold the quarantined material and consequential time delays in this and awaiting final quarantine clearance prior to export from the facility.

Continuous processing through use of PAT at appropriate stages allows that WIP is a thing of the past. It also means that loss in process is significantly reduced as the continuous stream of product is minuscule compared to the amounts retained in batch WIP that go to waste. In supply chain management (SCM) terms this is inventory lost to production. This is, of course, dependent on risk based assessment of the process. Arguably there is no need to test until the final product form is achieved and even then by a use of continuous IPC and PAT techniques that do not slow production other than, subject to any more major fault that would have been picked up through the process using PAT monitoring, in the clearance of the slug of material during a run that showed a defect.

This, when combined with the opportunity to reconsider the sourcing of raw materials and direct end of line clearance, can mean that storage needs become just that, storage and not warehousing, and primarily limited to engineering, reject, operational dry waste, equipment and consumables storage.

The automotive industry involves its suppliers in its manufacturing process with the expectation that materials are supplied to the standard and quality expected. This cuts out a significant proportion of in-house inspection and quality clearance as quality is cleared at source. If the pharmaceutical industry followed similar practices, with the agreement of the regulators following full risk assessment, then raw material clearance should be a matter of simple sourcing checks. This would then allow consideration of a much simpler receipt, automated feed and dispense system for a continuous line. Likewise, at the line end, automated inspection and controlled feed to packaging line focussed needs linked with PAT processes would avoid the need for quarantining, significantly reducing the quality burden both in staffing and retention of inventory.

Subsequent note: The Kiva robotic warehouse system, since the article was written, has been bought and taken in-house by Amazon depriving the benefit of that system from the market. Although other systems are now available. The excellent US on-line publication Robot Report is a good source for current developments.

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