Roundtable Part 5: Will Continuous Processing Become the Preferred Method for Pharmaceutical Manufacturing?

The BioPlan annual report evaluates the trends associated with adoption of various bioreactor types at clinical scale for new production.  This is an indication of the trends associated with broad adoption atcommercial scale.  We find relative stability in terms of adoption rates over time, except with single-use perfusion bioreactors.  These devices have shown a rather consistent increase over each of the past 5 years.  In comparison, for batch-fed stainless steel bioreactors, the trends are flat or slightly declining for adoption at clinical scale.

We can project that, similarly, we will see continuous devices increasing in adoption, as long as their use meets the demands of the facility, especially in terms of cost, operations, and productivity.

There are a number of advantages for this technology, which provide compelling reasons for adoption. For example, we have found that our continuous direct compression platform provides additional robustness that shows continuous processes may be advantageous for an even wider range of products than batch process platforms. However, there may be certain situations where continuous is not possible or less preferred due to specific technical limitations or other non-technical (e.g., business) reasons. Additionally, adoption and broadening the use of this technology will take time. That means continuous process should remain part of set of available technology platforms. However, as experience, familiarity and expertise grow in continuous technologies, we expect it to be used across an increasing number of products and portfolios.

For API the answer is NO.

For formulations there is a distinct possibility but the business model will have to change. “Creative destruction” could do that, but possibilities are minimal at this point.

Industry has not realized the ramifications of “continuous manufacturing” and its impact on the total pharma landscape when it comes to contract manufacturing. Companies practicing “continuous manufacturing” will keep the technology in-house and that means the number of overall contract batch manufacturing companies will significantly change. The impact of this is going to change the landscape and reduce pharma employment. No one is thinking of the short-term ramifications/impact of the technology. Unless the industry opens its thinking to other ideas, the downside impact might not be pleasant.

There is plenty of room for batch processing and other technologies in pharmaceutical manufacturing. Many factors impact the selection of the manufacturing process for a given pharmaceutical. For example, the dosage form, formulation, unique attributes of the drug molecule, operational ease and safety, number of units needed, quality attributes necessary for clinical performance, etc. It seems unlikely that any one approach would be suitable for the wide variety of the current and future pharmaceuticals. As previously mentioned, it is up to each company to determine whether continuous manufacturing is a practical approach for them and for the specific drug under consideration.

The industry needs to be much more efficient in how it manufactures and supplies products. Pharmaceutical manufacturing platforms need to be agile, able to adapt to specific requirements, extend capacity rapidly, and able to react to market demand quickly. However, it is critical to remember that continuous processing is not always the goal. Continuous processing is only one potential solution in an effort to increase process flexibility, speed, and quality while lowering cost. We must offer a set of solutions from which the proper technology can be selected to meet the end-user’s goals. The final choice of which process technology or manufacturing approach to take, whether it be hybrid, semi continuous, fully continuous, fed-batch, batch, depends heavily on the desired outcomes and specific situation of each customer. Within our Next Generation Processing program, we truly consider what makes the most sense for our customer’s set of circumstances.

We see it as an evolution of technologies. A lot of the fundamental building blocks of the process and theories of application remain the same. Generally, a continuous process will use the same buffers, chromatography media, membranes etc., that are used in a current batch process only they are used in a slightly different way. It is a misperception that the transition from batch to continuous processing is challenging—that is not actually the case.

As an industry, we must look to innovate across the board, and introduce technologies that can help change the direction of processes for the better. There is no point in seeking to implement continuous processes for drug production if they can only be used in the lab—scalability is critical.

As mentioned earlier, affordable drugs drive demand (quantity), demand drives innovation and adoptability. In my opinion, demand defines manufacturing method for bio-pharmaceuticals. I think continuous processing is one of the answers to derive economical bio-processing strategy and demand defines biological manufacturing.