Process Efficiency in Biomanufacturing:
Biomanufacturing companies are constantly seeking out new ways to lower their cost of goods, improve process efficiency, gain operational flexibility and upgrade their facilities. In today’s bioprocessing industry, there is a demand to cut manufacturing costs while maintaining product safety and quality; flexibility needs to be increased and time to market reduced. Ahead of his workshop at Disposable Solutions for Biomanufacturing 2018, we spoke exclusively with Dr Philipp Hess, Managing Partner at PHA, to discuss the key elements of process optimisation and efficiency used in single-use technology solutions.
There has been a growing interest in using continuous concepts in biomanufacturing as it has been successfully implemented in other industries, “as the development current stands, continuous processing definitely has cost advantages” comments Dr Hess. Other benefits of continuous include productivity gains, reduced equipment, facility size and improved product quality. In downstream processes, there are significant advantages to using continuous processing, for example, intensification in mAB production.
Implementing an end-to-end continuous process in biomanufacturing may still be years away for most companies, but Dr Hess believes that “we will see the first true continuous processes within the next three years”. He adds that “my organisation is looking at implementing some continuous processes together with larger companies”.
When working with cells in upstream bioprocessing, Dr Hess comments that improving the number of cells within a reactor is possible with continuous, but “there is a limit to how much a cell can do”. “I don’t believe there will be a significant increase in efficiency from a production perspective” says Dr Hess, adding that ”this will come from products where the quantities needed can be significantly reduced, for example three normal 2,000 litre bioreactors will be able to make a year’s worth of production”.
“Automation is challenging, but it can be implemented successfully” says Dr Hess, noting that it is also a major protector of company profits. Strategic and economical automation can result in ultimate process control capability; this is a useful way of ensuring there are fewer elements of the process which can be delayed through error. However, Dr Hess also notes that there is a limit to the extent which automation can be beneficial, as it is also important to ensure personnel are sufficiently trained and invested in the processes. Retaining a loyal and efficient workforce is critical to protecting company finances ‘on the shop-floor’.
Significant progress has been made in recent years to achieve higher levels of sustainability in biomanufacturing. A study by GE in 2017 found that single-use technologies usually result in lower environmental impacts compared to traditional stainless steel and that end-of-life disposal of single-use components has minimal impact compared with other factors such as energy and water use in the production phase. When exploring the sustainability element of a biomanufacturing processes Dr Hess believes that the key elements to consider are how many man hours it takes to make the disposable bag and the way in which the single-use system will be disposed of. “The ultimate comparison between stainless steel and single-use is looking at the entire lifetime of the plant” says Dr Hess, he also notes that is it highly dependent on what you need from the system as to which is a more sustainable choice for your plant.
Cost and efficiency
Asset utilisation and avoiding over-investment are key elements of maintain cost-efficiency. “You need to make the process of investment something your organisation can do quickly” advises Dr Hess, as reducing the time between investment and return minimises risks for an organisation. According to Dr Hess, a real ‘quantum jump’ in lowering costs can be expected from product technology improvements, as this can result in a significant reduction in the amount of materials needed.
Utilising single-use facilities also extends the reach capacity of a facility, as “you can start with less investment and move to quickly increase capacity” says Dr Hess, noting that this is particularly important in the early stages of scaling up capacity. Low initial investment, portability and flexible add-on capacity are the key to a successful manufacturing strategy. “There are a unbelievable number of super-optimised, small, single-use systems for bio similar products in Asia with the potential to make profit on the market” says Dr Hess, he puts this down to the fact that big stainless steel facilities require a large amount of learning and therefore some organisations do not have a capacity to use these systems.
Scaling up and scaling out
A limitation that comes with single-use systems is the fact that they cannot be scaled up beyond 2,000 litre containers. While this is a considerable size and as Dr Hess points out “probably bigger than many organisations need”, it does mean the advantages of the economy of scale that come with using a 5,000 or 10,000litre unit cannot be experienced. Additionally, the advantage of scaling out with single-use systems is that a network of smaller facilities mitigates challenges in the supply chain such as globalisation.
According to Dr Hess, a clear risk mitigation strategy which is brought about single-use systems is the use of standardisation and consistency across the production network. Building a clear, vendor-independent sourcing strategy with two or three strategic vendors means that control and automation systems can run vendor-independently, and are not locked into a single-use vendor by the automation system. Other methods for mitigating risks outlined by Dr Hess include simple facility design, pre-set expandability routes to ensure operational continuity when expanding the facility and strategies to adapt in-route. Investing in personnel and providing them with adequate training is also a fundamental method to mitigate risk as involving key individuals in the process as early as possible means that they will be more willing and able to protect again risks when directly handling the materials.
The pharmaceutical biomanufacturing industry are looking to maximize yield, use existing assets more flexibly, and reduce variability, all while increasing process efficiency and quality. Single-use technologies have enabled manufacturing professional to achieve many of these outcomes, offering benefits of flexibility and minimal cleaning. Dr Hess confirms that increasing levels of continuous processing reduces cycle times and can lower investment needs, making the entire operation more efficient, but process efficiency must be understood on an operation and strategic level in order to maximise capacity.
Additionally, potential concerns around sustainability are now widely assumed to be inaccurate when comparing single use system to stainless-steel systems across the entire life cycle of the biomanufacturing process. The technology shift away from stainless steel and towards single-use equipment in biomanufacturing has provided an opportunity for the industry to better understand the environmental impacts of products and communicate them to stakeholders.