Academics and industry leaders partner to implement continuous manufacturing--the next step in QbD.

BALTIMORE, MD -- A crucial element of Quality by Design (QbD) is the application of knowledge gained throughout a drug product's lifecycle. The acquisition and use of this information is a cyclical practice, one that will ideally improve each step of the manufacturing procedure.

But traditional manufacturing is at times a disconnected process, ungoverned by the QbD principles that support a streamlined, integrated system. During a Jan. 26 presentation at IFPAC--2009, Bernhardt Trout, Ph.D., a professor of chemical engineering at the Massachusetts Institute of Technology (MIT), explained the concept of continuous manufacturing (CM), the answer to fragmented batch processing and the ultimate development in QbD.

"Batches are disconnected in terms of integration," said Trout, whose team is working toward a seamlessly integrated process. "The effect of one step may not be taken into account in the design of all the other steps."

Pharmaceutical companies worldwide are researching the benefits of adopting a continuous manufacturing process. In 2007, MIT teamed up with Novartis, who will invest $65 million over a 10-year period to establish and support the Novartis-MIT Center for Continuous Manufacturing.

Using critical process parameters and mathematical models, continuous manufacturing (or processing) aims to lower throughput time and speed drug production. The end goal is a smaller operational "footprint" achieved by waste minimization, energy conservation and reduced capital expenditures.

CM doesn't intend to replace batch processing entirely. As economically efficient as it may be for large volumes, batch processing is still considered the best approach for small quantities. Equipment flexibility is an aspect of batch manufacturing that MIT developers will strive to maintain.

On the other hand, batch processing often incurs high labor costs and excess inventory, which leads to still higher production costs. Time and effort also add up using batch, where extensive validation is often necessary.

The project could easily exceed its 10-year research phase and may encounter other challenges, not the least of which could be skepticism from organizational heads. "Once we start developing these technologies and create excitement, it will help change the mindsets of organizations," said Trout. "We've been working with FDA, so regulatory is a challenge, but not a major one."

Continuous processing is very much on par with FDA's Process Analytical Technology, QbD and Critical Path Initiative--all developed to help drugmakers assess critical quality attributes. Knowing how significantly these factors affect a product and manufacturing procedure can enhance process understanding and moderate risks.

By Carrie Nathans

Managing Editor