Roundtable Part 1: Current Levels of Continuous Processing Adoption

For many reasons associated with efficiency, productivity, and smaller footprints, etc, continuous bioprocessing is clearly a direction most industries, including bio/pharma seek to take, theoretically. However, at present, to be fully continuous, the unit operations must generally all be continuous. Upstream continuous processes have been around for decades, but downstream processes continue to evolve into more efficient continuous operations.

We believe that adoption of continuous manufacturing is trending positively and that different companies are at different points in their journey, experience or plans for adoption.

There is misconception that continuous manufacturing is an off the shelf technology that can be applied in the API manufacturing and formulations of products. That is not true. Process technology selection decisions are made on the basis of “SINGLE” product demand and process economics. Generally, continuous process equipment due to chemistry is designed for a specific API product. Companies may not be able this equipment for other products. There are exceptions but they are rare. However, for continuous formulation same equipment could be used but again, it has to operate and produce products (same API has to be formulated in different dosages using the same equipment) for more than 7,000 hours per year.

The FDA is seeing an increased level of interest in continuous manufacturing of pharmaceuticals. Companies are developing continuous processes for the manufacture of drug substance and drug product. Continuous processes are being used for new products as well as for post-approval change of the approved batch process. Several drug products manufactured with continuous processes have been approved by the FDA. We also see companies building on their experience with the first approved continuous process to develop their next continuous process in the product pipeline.

We see that this is an evolution beginning with process intensification and growing over the next five to ten years into a continuous manufacturing process, and is already taking place in the industry. Most of the major bio- and pharmaceutical customers as well as some CMOs clearly see the vast benefits of process intensification and have active programs and dedicated teams in place. According to our market research, it is estimated that roughly 35% of today’s commercial molecules will utilize process intensification methods in the near and mid-term. Our research suggests a larger adoption rate for new molecules in development, with cell line/media optimization and flow-through chromatography being well-established. However, lifecycle products may only adopt elements of intensification to optimize current processes. While many of the companies interviewed for our research have adopted elements of intensification, very few considered their processes fully intensified or continuous.

Continuous processing is still in early adoption phases across the drug manufacturing industry, but there is already a great deal of progress for such early phases. Regulatory bodies, such as the US FDA, have been supportive, and even encouraging of, the advancement of continuous processes to enable further innovation in the drug treatments and therapies being developed for end users. In fact, small molecule drug manufacturers, such as Janssen (Prezista) have already successfully implemented commercial-scale continuous production processes.

As demand grows for safer, higher-quality and more efficacious drugs that are also more affordable, industry has been forced to find new ways to improve the production process. Even just ten to fifteen years ago, manufacturers were hesitant to accept/apply single-use technologies. But market demand helped make single-use technologies an innovation enabler, and while they are not yet fully standardized, adoption is increasing. We expect a similar trajectory for continuous processes across the drug manufacturing market but predict that industry will adopt it more quickly.

There is a significant increase in interest and activity in the biopharmaceutical industry to adopt continuous bioprocessing. Unlike in the pharma industry, there is the need for robust cell lines, viability for extended periods (up to three months) and the ability to express proteins for extended periods of time. This successful combination defines a successful implementation of continuous bioprocessing in biopharma. Though downstream processing was a bottleneck until now, the use of multiple chromatography columns to achieve continuous operation seems to be one of the paths forward. Most of the molecules that are being developed using continuous processing are still in preclinical or initial phases of clinical manufacturing. I expect to see some developed processes for commercialization in the next four to five years.