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Automated Processing Techniques and Lean Principles Are the Future

Roel Gordijn
Michael Schoeb, Dipl. Ing. FH EMBA
Automated Processing Techniques and Lean Principles Are the Future - ISPE Pharmaceutical Engineering

Why new processing technology and automated processing is key to driving down costs and boosting facility efficiency

One of the key drivers for a technology change in the biopharma industry is the need for leaner, more automated manufacturing processes with the target to reduce costs of goods sold. Most other manufacturing industries have already examined their costs and implemented new technologies, manufacturing techniques and process automation to make their work flows more efficient and cost effective. Biopharma has lagged behind in this field. Most new innovative drugs today require smaller batch sizes because they are targeted at smaller patient populations and tailored to specific market demands. This can make manufacturing using traditional technologies and equipment set up expensive. Scientifically, however, it is an exciting time for medicine. We’ve moved from chemical APIs, to tailored and potent biopharmaceuticals, to ingenious cell and gene therapies that can offer real cures for unmet needs. For the latter therapies, there is a lot of promising activity and clinical trials, but few therapies have been designed with commercial scale in mind. As an industry, we need to find a way to manufacture both traditional biopharmaceuticals and new personalized medicines in a more cost-effective way. The focus on costs will only continue and we need new manufacturing techniques, automated processing and lean principles to be implemented.

Costs have been a key driver for the wider implementation of single-use technologies. Single-use, amongst other benefits, reduces the costs associated with cleaning and makes it less expensive to build a facility, especially for smaller batch sizes and high variation of different drugs within the same facility. Changeover and cleaning validation is generally faster, which means critical decisions about a product’s future and manufacturing capacity can be postponed until more data is available. Single-use is particularly compelling for drugs with smaller patient populations, smaller batch sizes and high changeovers from one to another product - where it’s not economically viable to use stainless steel infrastructure. It is a different scenario for large scale batches with low changeovers. With blockbuster patents expiring, more and more biosimilar products are being developed, and in many cases, multiple biosimilars are being developed for the same innovator drugs with the largest profits. Given the heavy competition, biosimilar developers are keen to reduce their costs as much as possible to make their product that little bit more attractive to payers. Therefore, the technologies chosen for each manufacturing set up are key to drive towards the optimal economical model. In most scenarios, hybrid configurations with a combination of new and traditional technology are the result of these evaluations.

The Early Bird

Initially, the industry was cautious about single-use, but has since found that the approach can be highly successful for certain products and/or markets. Single-use has become more viable thanks to developments in cell culture media and other areas, but higher titers have in turn led to bottlenecks downstream (particularly the chromatography step and cleaning). There is the potential to address these issues using next generation processing technologies, such as continuous bioprocessing, and automation. Continuous isn’t all that different to batch processing – and is a technology that regulators are encouraging biopharma manufacturers to explore.

If you are going to use new technologies for a product then they need to be introduced early on in the process. Products currently on the market or in late-stage trials that are made in batch will be challenging and costly to switch to continuous. On the other hand, there is a lot of interest in using continuous technologies for products at the pre-clinical phase. Not everyone is willing to switch into a fully continuous train immediately; some companies are continually running just one or two steps and seeing huge benefits. The leaner your manufacturing process becomes, the more costs can be saved. In many cases, the systems for continuous bioprocessing are based on single-use, but some companies are choosing to use a mix of single-use and stainless steel in a hybrid approach.

There are two different approaches that you can take when building a new plant and rolling out new technologies with automation. The first approach involves mixing and matching equipment from different vendors, and then using an automation and engineering firm to help put it all together in a seamless flow. In this situation, you need to ensure that the different systems fit together and that the consumables you plan to use are compatible. Depending on the systems you are using, making sure everything “plays nicely” and functions smoothly as a complete line can create some challenges, but it is a viable approach for companies that are adamant about using specific systems from different vendors and do not want to rely on a fully integrated automation set up.

The alternative solution is to work with an end-to-end solution provider. It’s a very efficient approach because the provider will select the equipment based on the process needs. The provider will then check if the required equipment fits into your clean room design and recommend automation concepts. This approach ensures you start first with the process by selecting the equipment based on process needs rather than fitting the process to the selected equipment with subsequent automation. Consumables will also come from the same provider, so everything will be compatible. The downside of this approach? You’re dependent on one supplier, which some companies prefer to avoid. The largest biopharma companies tend to keep their expertise in house and will often ask suppliers not to provide any kind of fully integrated solution because they will implement it themselves.

Smaller companies cannot usually afford to hire such in-depth expertise in house. For them, supplier partnerships are crucial to achieve successful documentation and data collection for drug submissions. In many cases, suppliers can help adapt a customer’s process and scale it up to large-scale manufacturing. If the supplier is rolling out an integrated process line for the biopharma customer, there will always be a higher dependency on the supplier, who needs to ensure that the full process line functions and meets the process needs from the customer.

Focus on Processing Resulting in Reduced Costs

Globally, healthcare costs continue to increase. If you want to dramatically reduce the cost of goods, you need to improve the output of the facility and the team that is making the product. Product titers upstream have already been boosted, but now the industry needs to find a way to efficiently process and purify these high titers downstream. Interestingly the technology does exist! Biopharma may, in some ways, lag behind other manufacturing industries, but there has always been a drive to improve. In the old days, as drugs were developed, production lines were built accordingly, but it didn’t take long for the industry to realize that they should develop drug families on certain platform technologies because individual development and manufacture was not sustainable. We now need to push this even further with a move to smaller, flexible facilities that can be rapidly deployed. Such facilities are particularly compelling where drugs are needed for an epidemic, but there is also a global trend for more localized production – many governments in emerging markets are investing to attract pharma companies because they want local production content for their population; effectively made in the region for the region. This especially as the geopolitical situation may change and uncertainties of supply are raised.

Whether you use stainless steel, single-use or hybrid will depend on your batch size, the number of batches, the age of the drug, and what markets you are targeting, but all of us – whether drug producer or supplier – should be focusing on how we can reduce the overall costs of our healthcare systems, and how new processing techniques and technologies combined with automation can help.

Advantages of Lean Manufacturing and Automated Processing

  • Different processing techniques drive lower production costs
  • Higher volume production
  • More consistent quality and reproducibility
  • Improved floor space utilization
  • Less chance for human error
  • Improved safety
  • Higher process reproducibility and consistency
  • Quality by Design (QbD) with automation
  • Reduced waste
  • Faster processing
  • Less employees required
  • Competitive edge over other companies
 
For more insights from industry opinion leaders to help you choose the best path for your bioprocess, download the new ebook,  The Right Choices in Biomanufacturing.

About the Sponsor

Pall Biotech provides cutting-edge products and services to meet the demanding needs of customers discovering, developing and producing mAbs, recombinant proteins, viral vaccines and gene therapies as well as classic pharmaceuticals. Our portfolio of standard configurable single-use, stainless steel and hybrid technologies for fed-batch and continuous processes across upstream, downstream and formulation and filling applications enables customers to accelerate time to market by selecting cost effective, robust and reliable integrated solutions. The company's Scientific and Laboratory Services (SLS), Technical Services and Validation Laboratories have been a cornerstone of customer support for more than 30 years, supporting customers at both a local and global level. www.pall.com/biotech

This article was originally published in a supplement created by The Medicine Maker. www.themedicinemaker.com