Industry expert details advantages of continuous manufacturing

While a continuous manufacturing line can yield better quality products with greater efficiency than traditional batch processes, the current business climate and testing requirements are two factors impeding wider adoption, said Eric Jayjock, director of process engineering at Vertex Pharmaceuticals.

Jayjock made these remarks at a continuous manufacturing workshop on 18 July cosponsored by the United States Pharmacopeia (USP) and the Regulatory Affairs Professionals Society (RAPS).

Vertex is a forerunner in the continuous manufacturing space and was the first company to receive US Food and Drug Administration (FDA) approval for a drug manufactured on a continuous line with the approval of its cystic fibrosis drug Orkambi (lumacaftor/ivacaftor) in 2015. The company later received approvals for two other cystic fibrosis drugs – Symdeko (tezacaftor/ivacaftor and ivacaftor) and Trikafta (elexacaftor/tezacaftor/ivacaftor) – that are produced using continuous manufacturing processes.

An FDA official who also spoke at the meeting touted the potential efficiencies with continuous manufacturing while noting the technology’s sluggish uptake in the pharmaceutical space. (RELATED: Advanced manufacturing: FDA official sees room for growth, Regulatory Focus 19 July 2023)

FDA has approved 20 applications using advanced manufacturing methods, which is a small increase over the 16 applications approved as of last October 2022.

Advantages

Jayjock discussed some of the advantages of continuous manufacturing and why this mode of production is better than batch manufacturing. He said that more uniform blending is the number one reason why continuous manufacturing is better.

You can “boil it down to one statement: superior blending. The blenders that we see in the process are fantastic at blending. It is one of these things that we started looking at 15 years ago… this was an important question, the blending works,” he said.

It is also easier to scale up a continuous process than a batch process. He said “continuous is also better because it is a more direct pathway to scale. In continuous, processes are scaled up by time. In batch the process can be scaled up by volume but there are challenges in batch with bigger volumes.”

Another advantage is that continuous allows for nonstop online monitoring of the production process.

Stumbling blocks

Yet despite these greater efficiencies, there are multiple barriers impeding the adoption of the technology. Major international capital investment in the 1990s and early 2000s has led to excess batch capacity for solid oral solid dosage forms, leading to a reduced incentive to build new manufacturing capacity. He also noted that there is not enough incentive to invest in new manufacturing equipment.

There are also limited outsourcing options. “If you produce continuous in-house, your only option for business continuity is to convert to batch,” Jayjock said.

Change the testing paradigm

Jayjock said that a paradigm shift is needed to recognize the differences between products made from batch processes from those made on continuous lines. He added that FDA’s current testing requirements are more aligned to the batch manufacturing.

In a batch process, the process can be stopped, and products are typically pulled and sampled mid-process to evaluate their content uniformity. This is not done in a continuous process where products are running continuously in real time from start to finish, and it is not feasible to stop the process. Instead, products are tested in real time using online testing methods such as Near Infrared Spectroscopy (NIR) methods to ensure content uniformity.

Through this method, products produced through continuous manufacturing have a higher capability compared to batch processes yet still must adhere to the batch testing paradigm. Jayjock said that “the testing burden should be inversely proportionate to the capability of the process, and a highly capable process should require less testing to assure product quality.”

Workshop

Industry expert details advantages of continuous manufacturing

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