The pharmaceutical industry has begun to adopt continuous manufacturing, which can reduce the processing times and footprint of a facility. Significant investments in the production process have been seen as Eli Lilly invested $40m (€35m) into a facility in Ireland, to focus on continuous manufacturing of its active pharmaceutical ingredients (APIs), and the recent partnership between GSK and AstraZeneca.
It was previously believed that this type of manufacture posed uncertainty in quality assurance because regulatory guidances were not immediately developed with the process. However, with secure regulatory guidelines as the US Food and Drug Administration (FDA) recommended the industry to move more manufacturing from batch to continuous, it will become an unavoidable part of the production process, according to certain analysts.
After in-PharmaTechnologist (IPT) spoke with Mauricio Futran (MF), VP of process science and advanced analytics at Johnson & Johnson, and Sarah Nielsen (SN), principal scientist at Janssen, they outlined that this streamlined manufacturing approach, created to mitigate bottlenecks in production, has the ability to both accelerate processes and to provide real-time quality assurance.
IPT: What makes continuous manufacturing an innovative part of drug production?
SN: We in pharmaceuticals consider continuous manufacturing really a revolutionary technology; where we can take what was previously a batch manufactured product, which was many different rooms with many different steps, into a continuous process which can continuously flow materials from powders to raw materials to a drug product within a matter of minutes, as opposed to hours, days or weeks in the previous process.
MF: The beauty of continuous manufacturing is that all the steps are happening simultaneously and essentially in the same room, so you’re constantly aware of the quality of your product and you can control it much more effectively than in a batch process.
IPT: How is it impacting the industry?
SN: I think in a positive way, both types are manufacturing are subject to the same high-quality control standards but with continuous manufacturing, we have ways of automating the process and monitoring the process in real-time – adding a layer of quality assurance that we didn’t previously have. In addition to that, we can make larger batches to potentially reduce drug shortages.
MF: The big advantage is that we have the flexibility to run bigger or smaller batches to match demand. Which, for a variety of reasons, always fluctuates, and we can do that in a very efficient way.
SN: It gives agility to our supply chain that we didn’t previously have.
MF: I would say that I’m not aware of any negative impacts of this on the industry. It is a way of manufacturing that requires more in-depth knowledge of the processing of your materials and your equipment, but I would argue that any manufacturer should have that knowledge anyway.
IPT: Why may be some reasons industry stakeholders may have not yet adopted continuous manufacturing?
MF: Every company has to make its decision based on the installed base that they have on batch equipment and things like that. You need to consider it from that point of view and how it integrates with your manufacturing network. It does require good engineering and understanding of the process. You also have to make an investment in that knowledge and the equipment, and it has to match your pipeline.
IPT: What are Janssen’s plans for the utilization of continuous manufacturing?
MF: We have a goal of having in the future about 70% of our volume made by continuous manufacturing because it has its advantages. We expect, within Janssen, to grow [such processes]. It’s a more efficient way of getting to the quality that we like; you save time because you’re not taking as many samples and, as Sarah said, it provides agility.
IPT: What are some regulatory challenges one faces when looking to implement this type of manufacturing?
MF: I don’t think that there is a big regulatory hurdle;, again, you have to do your homework and know what you’re doing. However, we’ve found that agencies around the world were eager to work with us and make this happen.
IPT: Have there been any recent innovations to improve continuous manufacturing?
SN: We recently had the approval of our dissolution real-time release method, in addition to our other methods we have approval with our first submission. With this, we expect there to be even greater agility in our manufacturing facility. We will be able to monitor the critical quality attribute for dissolution in real time, as the product is being manufactured every 10’s of minutes. We’ll have a profile of our critical quality attributes and, for us, this is really revolutionary and it brings a lot of value to really understand the production and how it's developing in real time.
IPT: What are some ways in which real-time quality assurance benefits the overall process?
SN: Real-time release brings a lot of benefits in that it reduces testing in a quality lab, with that, inherently, a lot of benefits are brought: you’re reducing the amount of solvent, which brings a lot of environmental benefits, and you’re reducing lead time. You’re also able to measure quality and subsets of the batches quality, which brings stability to the supply chain.
We’ll know in real time if our batches are being made in its highest quality without waiting for the test to come back, it brings a lot of assurance in real-time so the batch can be released to the next step almost directly after manufacture.
Mauricio Futran serves as vice president of process science and advanced analytics at Johnson & Johnson. Futran previously held the position of vice president of process and R&D at Bristol Myers Squibb and taught at Rutgers University as a professor and chair of the Chemical and Biochemical Engineering department.
Sarah Nielsen holds the role of principal scientist at Janssen, where she works in process analytical technology development. Nielsen previously worked at Johnson & Johnson where she served as senior scientist.