After a year in which flexibility and efficiency were the keys to success in the biopharma industry, the true value of process intensification (PI) has become increasingly clear. Process intensification is a framework to maximize overall productivity that can be accomplished by implementing process changes that increase volumetric productivity, reduce timelines, decrease footprints, lower costs, or improve flexibility. But with all the benefits PI offers, it may not be the right choice for every biopharma, and a hybrid approach may be better for some. Below, we walk through the benefits and key factors to consider during this decision-making process.
 
How to implement process intensification
When applying process intensification, there are five main things that can be achieved.  
 
1.     Increase volumetric productivity: This can be accomplished in multiple ways. One of the more popular options is investing in intensified bioreactor technology. Perfusion bioreactors retain viable cells while continuously replacing cell media, allowing the product to be constantly harvested. These bioreactors can improve volumetric productivity three to tenfold in comparison to traditional fed-batch bioreactors where media is fed once and product is harvested once at the end of the bioreactor run.   
 
2.     Reduce timelines: Faster timelines mean biopharmas can be more competitive as they race to be the first to market with a new product. One way to accomplish this is to transition from stainless steel bioreactors to single-use products. These products eliminate difficult and lengthy cleaning steps, necessitating less downtime in between batches and allowing for a quicker scale-up in later stages.  
 
3.     Decrease footprint: There a myriad of ways to reduce the overall footprint. For example, for perfusion processes, the overall bioreactor volumes are small, which leads to lower upfront capex investment and thus smaller footprint. This also results in decreased overhead costs resulting in increased profitability in revenue. To further reduce footprint, another common approach is securing media and buffers from outside suppliers rather than making them in-house. This allows the company to get rid of the clean room space, which is one of the major costs for running a facility. Another option to decrease footprint is to use concentrated media and buffers with in-line dilution because this reduces the size of tanks needed to store the media and buffers.  
 
4.     Lower cost of goods: Saving money on the materials to create the product will ultimately translate into a cheaper product. This can increase profit margins and allow patients to access life-saving therapeutics at lower prices. One example of cost-saving strategies is switching to multi-column chromatography, which requires lower quantities of expensive resins. Another important tactic is data modeling, which can help show teams how different changes will quantitatively impact the bioprocess and thereby highlight areas where investments will pay off the most. 
 
5.     Increase flexibility: As we’ve seen throughout the COVID-19 pandemic, maintaining the ability to pivot directions easily is crucial to success in the biopharma industry. Single-use products, such as rapid cycle chromatography with single-use membranes, are an efficient way to make this flexibility possible. Even in the absence of global crises, there are many reasons to build agility into your manufacturing facilities. For example, if a therapeutic does not make it to market, it is important to move on quickly to the next promising candidate. 
     
Challenges of implementation 
All these potential benefits of process intensification also come challenges that may prevent the biopharma from actually realizing those benefits. There are upfront investments that may seem daunting at first, so it is important to consider how long those investments will take to pay off. Some of the areas that are important to think through include upfront costs and training, regulatory concerns and integration of new technologies.  
 
1.     Upfront costs and training: The initial transition may be a large barrier for biopharmas deciding to implement any type of PI strategy. First, there are the costs for new equipment that may not seem feasible. We would advise these companies to invest in process modeling tools, as previously mentioned, that can provide insight into how changes will impact return and allow your team to make smarter decisions. There also may be a concern about providing the proper training. This is a valid concern; if employees are not trained on the new technology, the initial increase in productivity may be lost as bottlenecks develop. Specifically, smaller biopharmas will likely not have the existing expertise on their team. For this reason, it is important to recognize gaps upfront and partner with external groups that have the necessary expertise and capabilities.  
 
2.     Regulatory concerns: If a biopharma is in the late stage of clinical research, there may be concerns that any major PI changes will disrupt the regulatory approval process. We have found that minor changes may not cause significant delays. But when dealing with larger change, it is important to have appropriate data and solid reasoning to back up the change. While this still may cause delays, the FDA will likely be more willing to work with you to minimize the impact. Even if this is not the case, make sure to weigh the overall benefits. An initial delay could still pay off in the end.  
 
3.     Integration: Many biopharmas may decide to implement PI only in part of their workflow. Alternatively, they may choose to intensify the entire process but use different technologies from multiple vendors. Integrating all these tools can present several difficulties. If a bioprocess is fully automated, but the tools cannot “talk” to each other, many of the benefits are lost. This is a major challenge that vendors are moving to address. For example, we are seeing some collaborations between different vendors that allow technologies to communicate even if they come from separate companies. When deciding to invest in a technology, make sure to understand whether it will be able to integrate with the other tools in your bioprocess.  
       
There are many approaches to achieve PI. From decreasing your footprint to allowing your company more flexibility within your workflow, there is no one-size-fits-all solution. Some companies will choose to implement as many PI tactics as possible. For others, a stepwise solution may be the best approach.  
 
With so many decision points, the task may seem daunting. Working with a good bioprocessing partner can help you understand where you may receive the most benefits based on your product, current facility, capacity, research stage and expertise.