Monday, September 14, 2015

The 4Vs framework and its application in Biopharmaceutical manufacturing

Bioprocessing is an endeavor with some specific challenges associated with it, such as how we might implement single-use technologies or gain regulatory approval for new drugs. It seems to me, however, that it is easy to become so focused on topics such as these that we overlook applying established methods and practices used in a broad array of industries to improve our own. One such framework that could be applied to our sector is an analysis of the 4Vs of volume, variety, variation and visibility. Considering these parameters can help us make decisions about how to best organize biopharmaceutical manufacturing operations.

Volume: The number of doses of a biopharmaceutical to be manufactured varies considerably between drug products. Blockbuster products and products used to manage chronic diseases over long periods of time might be manufactured in large volumes. Due to the specific nature of biopharma drugs the patients that will respond to them can be small and the number of doses required not nearly so many. Orphan drugs for treating relatively rare diseases are a good example of products where the number of doses per year to be manufactured might be very low. Taking this to an extreme, personalized medicines and cell therapies are likely to be required is such small volumes that they are challenging existing industry processing technologies, supply networks and regulatory frameworks in order that they can be successfully commercialized.

Variety: Often linked by an inverse relationship to volume, variety refers to the number of different products an operation must deliver. In the above example of personalized medicine the variety of products to be produced may be very high as the products are in essence customized to the patient receiving them. Less variety tends to imply higher volume production and perhaps less operational complexity. Biopharmaceutical companies often strive to develop platform manufacturing processes capable of delivering a variety of products within their portfolio without adding to this complexity.

Variation: The degree to which demand for the product varies can have a significant impact on operation design. This variation can be more predictable, such as with the seasonal flu vaccines or less predictable, perhaps driven by competitor or regulatory activity. Responding to variations in demand can be a significant challenge for the biopharmaceutical industry where making process changes including process scale-up be a slow process with technical and regulatory challenges. Failure to design operations with sufficient agility to respond to demand fluctuations can result in increased lead times and patients not receiving medicines at the time they are required.

Visibility: Biomanufacturing operations are typically exposed to a high level of internal and external scrutiny due to the regulated nature of the industry. Process visibility is a term often used to describe operations that deliver services in which the customer is typically heavily involved in their design and operation. An example in biologics manufacturing are the use of Contract Manufacturing Organizations (CMOs). Once the decision has been made to outsource production, the management of the relationship between customer and contractor must be given significant attention to ensure successful delivery of drugs to patients and the sponsor must address issues such as relinquishing of some control.

Consideration of the 4Vs can help shape the design of biomanufacturing operations. For instance, high volume-low variety operations are typically more repetitive in nature and may suggest continuous biomanufacturing is an appropriate strategy. Companies requiring a small number of doses of a large number of products will need to design operations that permit a greater level of complexity and more intermittent processes. It is a framework worth reviewing when considering the future design of your companies bioprocessing footprint.

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Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.

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