During downstream processing, the value of a product increases with every unit step of the operation, designed to both remove impurities and concentrate the biologically active component.
Each of these unit operations involves a significant cost to the biopharmaceutical manufacturer. From cell harvesting and clarification, through affinity chromatography, buffer exchange, cation exchange chromatography, viral reduction, anion exchange chromatography, viral inactivation, concentration, sterile filtration and filling, value is added and is incremental.
Affinity chromatography (such as the Protein A chromatography step), the initial concentration and purification step in downstream processing, is typically the most expensive unit operation – and costs of up to $20,000 per litre of chromatography resin can be incurred. Consider the following scenario: if very wide chromatography columns are used – for instance at 2m diameter x 30cm bed height – this would amount to almost 1000 litres of Protein A resin.
The final cost will depend on the process and volumes, and some processes may use much less. But even a 30cm diameter x 30cm bed height Protein A chromatography column, which would amount to approximately 21 litres of Protein A resin, would mean a consumable cost of more than $400,000.
Each subsequent step in downstream processing inherently increases the value of the final product. And any loss of product or contamination following the Protein A chromatography step would be very costly indeed, given the consumable costs associated with it.
In addition, as well as consumable costs, there are also costs associated with the time and resources allocated to each step, in terms of operator hours and training.
By the time the product reaches the final sterile filtration step, it is highly purified and concentrated and has reached its highest monetary value, It is now ready to be vialled into smaller quantities for use in the medical field. This is typically carried out at another location specially designed for filling vials and therefore needs to be shipped in bulk.
Prior to this, the bulk drug substance has traditionally been manually dispensed into smaller quantities to safeguard the batch. However, this method is prone to human error.
Imagine an operator working in a high-stress, high-pressure situation, manually operating pumps and valves, while struggling to also read a balance – it is easy to see how costly mistakes can be made.
Automating and enclosing bulk fill operations can reduce the risk of human error in the bulk filling process. For instance, by using this method there is no open manual manipulation of tube sets, which is a very real potential source of product loss. In addition, by standardizing the process and simplifying training, variations in the process are eliminated.
After dispense it is crucial that the substance being shipped remains in an optimum condition as it completes the journey from production to the filling site. A poor bottling solution can lead to product loss, even if bulk fill has been successfully completed. Common problems include the tubing from the bottle breaking under impact once frozen or the bottle cap seal leaking.
It is critical to validate each step within the bottle process and implement solutions to alleviate the risk of product loss.
Parker has created an end-to-end automated packaging solution that creates a platform for bulk shipping. We have validated this solution with a focus on bottle filling, bottle integrity and liquid ingression, across the full range of temperatures found in a typical supply chain.
You wouldn’t prospect for gold using a sieve that could let your precious finds fall back into a stream, to be lost forever. Sometimes, simple errors or avoidable mistakes and damage can have huge ramifications if a high-value final product is lost. The SciLog® FD system automates and encloses bulk fill operations to protect the final product and ensure that the great expenses incurred during downstream processing do not go to waste.
This post was contributed by Graeme Proctor, product manager - single-use technologies at Parker Bioscience Filtration, United Kingdom
Parker Bioscience Filtration specializes in automating and controlling bioprocesses. By integrating sensory and automation technology into a process, a biopharmaceutical manufacturer can control the process more effectively ensuring the quality of the final product. Visit www.parker.com/bioscience to find out more.