Converting to a “Batch-less” World: Quality Implications of Continuous Manufacturing

Pharmaceutical processing is typically handled in a “batch” system, which consists of a step-by-step process for manufacturing products. With this process, once one “batch” is completed, the next begins, so on and so forth. This means that to complete the process, each step must be complete for the next to commence. There can be up to six or seven steps in each batch of production, requiring up to six or seven different machines, manufacturing lines and teams to create a batch. When a recall occurs, industry professionals can trace back to the batch where an issue occurred and ameliorate issues for future batches. Batch production is time consuming, but also a popular and time-tested method used in the pharma industry today.

In recent years, however, we have started to see the disruption of these processes. In 2016, Orkambi was the first manufacturer to go “batch-less” on their production lines¹, soon followed by Vertex.² In the manufacturing industry, this is called continuous manufacturing. This is when a drug is taken from its beginning stages, all the way through to the final product, without a stop during its production. This does not require shut down of equipment between “batches” and eliminates down time.

What is Continuous Manufacturing and Where Has It Come From?

Continuous manufacturing is driven by the smart, sensor technology that we have access to on our manufacturing lines. It’s happening always, with the incentive of limiting laboratory testing and making quality control standard.

This batch-less manufacturing process is popular in the automotive, food and electronics industries, and in pharma is used to primarily produce over-the-counter products like personal care items. These other industries have found this process to be quicker and more productive, while the pharmaceutical industry has been a bit slower to convert completely. In many cases, this is due to the high cost in setting this batch-less system up.

The FDA estimates that with continuous manufacturing, a drug can take merely a day to produce³, while batch manufacturing can take up to a month due to the constant set up and break down of processes between batches to ensure quality. Ensuring quality in a continuous process is crucial, as it is not as easily checked for error as batch-manufacturing is.

Benefits and Challenges of Going Batch-less

Batch-processing costs the pharmaceutical manufacturing industry about $50 billion each year⁴ due to inefficiencies, losses, contamination and expenses that come along with product recalls.

Conversely, continuous manufacturing is more time efficient, reduces energy needs, increases productivity and reduces waste. With continuous manufacturing, we also see a reduction in human error, as fewer people are involved in the processes and there is no need for interruption of the system.

According to the National Science and Technology Council, manufacturing can cost 40 to 50 percent less if the continuous method is inputted into an organization.⁵ This batch-less method can also lead to more affordable pharmaceuticals and medicines and prevent shortages in drugs with the lack of time needed to create each batch in processing. When error occurs, the cost goes up, so it’s important to be able to trace back to the origination of an error and fix specific areas in production where the issue occurred.

In the pharmaceutical industry, quality is imperative, and there is room for error within both batch-manufacturing and continuous manufacturing. With batch-manufacturing, there is set up and break down as well as re-setting of each batch. This means that it’s important to maintain quality throughout each step but is easier to trace back to a specific lot. In continuous manufacturing, without the check of each batch, errors can occur while being far more difficult to trace back, which is often where we see major product recalls.

With recalls in the batch-process, it’s easier to trace back to the batch that the recall or error is coming from to make changes. But if the product is continuously manufactured, 24/7 without batches, our quality management systems must enable this tracking and back-tracing to avoid a major issue.

Adapting to the Continuous Way

Even though manufacturing changes and evolves with time and technology, quality teams always need to focus on safety, efficacy, compliance, supply chain and quality continuity while producing products.

Introducing or implementing processes to trace back to recalls and find issues within current processes is crucial. In 2002, the FDA requested that manufacturing and pharmaceutical production companies modernize the supply chain to reduce product failures and enhance product quality.⁶ Ongoing risk assessments come into play here too, to ensure that processes put in place are working for the company and becoming beneficial to the overall business.

With this comes challenges, and having the appropriate training processes for quality professionals is important to the success of continuous manufacturing. Having employees properly trained ensures that everyone is prepared in the event of a recall, for example. Implementing training off the bat will assist with a smooth transition and will allow for the company to adapt quicker and easier. Additionally, cleaning and risk assessment processes must be fully understood by everyone involved.

Modernizing the supply chain within your manufacturing company proves to be a productive use of resources in the industry. There needs to be understanding of each process across the board, which often means running old processes while implementing and adapting to new, continuous processes.

While introducing a new process such as continuous manufacturing has proven to be successful for many organizations and can greatly improve cost, time and production, it’s vitally important to take into account each aspect of quality to experience its full benefits and steer clear of ultra-costly recalls.

References

1. https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2016/4/fda-allows-first-switch-from-batch-to-continuous-manufacturing-for-hiv-drug
2. http://www.pharmtech.com/vertex-receives-fda-approval-continuously-manufactured-drug-product
3. https://www.fda.gov/newsevents/newsroom/fdavoices/default.htm
4. https://www.generalkinematics.com/blog/batch-vs-continuous-pharmaceutical-manufacturing/
5. https://www.whitehouse.gov/sites/whitehouse.gov/files/images/Blog/NSTC%20SAM%20technology%20areas%20snapshot.pdf
6. https://www.europeanpharmaceuticalreview.com/article/72418/continuous-manufacturing-regulatory-and-quality-assurance-challenges/

Stephen McCarthy serves as VP of digital innovation at Sparta Systems. He has nearly three decades of experience within the healthcare industry and was previously a VP of quality management systems for Johnson & Johnson. He is passionate about helping companies improve patient safety, supply chain continuity and speed-to-market.