Continuous Processing: Moving with or against the Manufacturing Flow - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Continuous Processing: Moving with or against the Manufacturing Flow
Fueled by a need to reduce costs and improve efficiencies, continuous processing may be the next paradigm shift in pharmaceutical manufacturing.


Pharmaceutical Technology
Volume 9, Issue 32, pp. 5258

Continuous processing at work

As economic and technical concerns are considered, companies are advancing projects in continuous processing.

Novartis. Novartis Pharma AG (Basel, Switzerland) is proceeding with what it terms its "Blue Sky Vision" for continuous processing, in which process steps are reduced to a minimum, and a product is made from start to finish, from drug substance to finished drug-product, on a continuous basis in one facility. Novartis has teamed with the Massachusetts Institute of Technology (MIT) to help realize that goal. As part of a 10-year collaborative effort, Novartis is investing $65 million in the Novartis-MIT Center for Continuous Manufacturing, which was formed in September 2007.

"We have a pretty ambitious view on continuous manufacturing," says Walter Bisson, global program manager of technical operations at Novartis. The company's focus on continuous processing is not to simply convert existing processes from batch to continuous, as this would be "a very traditional approach," he says. "We're trying to invent new methodologies, which lead to new technologies, which can then be translated into new equipment." Equipment manufacturers have been involved since the early stages of the group's research.

Continuous processing would further involve integrating separate process steps into one process. Bisson offers an example of reducing the throughput time, or the time it takes to go from a chemical intermediate to the final drug product. Chemical and drug-product manufacturing usually occurs at different facilities, locations, and countries, and the entire process can take 300-plus days, he explains. With a continuous process, non-value-added steps such as transportation could be eliminated because all the steps are performed at one facility. "In the Blue Sky Vision, we can envisage a 10-day throughput time—even if it turns out to be 30 days, this would be a tremendous improvement over what it is today."

He says that although the industry has invested heavily in the past 30 years in improving processes, reducing throughput times, and increasing operational efficiencies, it has always done with batch thinking. "We believe the quantum-leap improvements with the batch concept have been done in the past. Looking forward, we will have improvements, but they will be marginal—probably 3% here or 5% there," says Bisson. "With the improvements we have in mind, we really want to take quantum leaps where we improve by 30%, 40% or more. It sounds aggressive, but yes, our program is ambitious," he says. "If you envisage a 50-day throughput time, or even a 10-day throughput time, just calculate the reduction."

Bernhardt L. Trout, director of the Novartis-MIT Center for Continuous Manufacturing and professor in MIT's Department of Chemical Engineering, explains that the goal of the partnership is to develop a portfolio of technologies to allow the implementation of this integrative approach. Eleven research activities are underway at the center, which involve chemical synthesis, new reactor approaches, including microreactors, and new approaches for separations, crystallization, and final finishing. Forty students and postdoctorate associates, along with 10 professors from MIT's chemical engineering, chemistry, and mechanical engineering departments, are working at the center.

The MIT team aims to have a full-end, bench-scale unit for continuous processing within the next two years. The bench-unit will be scaled up into a pilot-scale unit and transferred to Novartis for development into commercial scale.

Trout says the partnership's goal of a fully integrated process that incorporates both drug-substance and finished- product manufacturing is "the ultimate lean technology." This new, integrative approach will "make the quantum leap, the big jump, or the paradigm shift," in pharmaceutical manufacturing, he says.

Pfizer. Pfizer (New York) is evaluating continuous processing for drug-substance, biologics, and drug-product manufacturing, says Maddaluna. Its manufacturing division is working with its research and development group for:

  • Development of internal capabilities by working with vendors and academia to develop methodology and continuous processes
  • Expanding expertise in chemical engineering and in laboratory and pilot facilities
  • Adopting new process-design methodology. For example, Pfizer is a member of Britest, a 21-member company consortium developing innovative approaches to manufacturing and process design, including continuous manufacturing.
  • Identifying continuous unit operations that could be applicable to a wide range of manufacturing processes and developing expertise in their applications and capabilities in R&D and manufacturing.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
27%
Attracting a skilled workforce
27%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
32%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here