A New Manufacturing Framework

As a well-known and well-respected researcher, director, and speaker Fernando Muzzio shares his insights into the significant steps that have led to the "unprecedented" manufacturing industry of today.
Jul 02, 2007

Fernando Muzzio, PhD, started in the pharmaceutical industry in 1991 as a professor at Rutgers University (Piscataway, NJ). His research focused on the engineering and mechanics of blending and mixing systems and the behavior of particles in these operations. After serving as the director of the university's pharmaceutical engineering program, Muzzio now is the director for the new NSF ERC on Structured Organic Particulate Systems and a professor of the Department of Chemical and Biochemical Engineering at Rutgers University. He is also a member of Pharmaceutical Technology's Editorial Advisory Board. Muzzio has conducted numerous presentations on blend uniformity and model-based design. For Pharmaceutical Technology's 30th anniversary, he discussed with us the significant regulatory framework that has shaped the industry, especially process analytical technology (PAT) and quality by design, and how it will change the training and skill set of manufacturing operators.

What significant changes have you seen during your tenure in the industry?
The Food and Drug Administration has moved quite significantly from what was essentially a reactive frame of mind that was making change very difficult to a much more proactive approach to enhance the understanding of products and processes and significantly facilitate and promote continuous process improvement. That has motivated the industry to become much more involved in continuous improvement approaches, design methodologies, and predictive science. Those are major changes.

Besides FDA's CGMPs for the 21st Century document, which regulatory guidances had a major influence on manufacturing?
The 2003 guidance on blend uniformity [Guidance for Industry: Powder Blends and Finished Dosage Units—Stratified In Process Dosage Unit Sampling and Assessment] was an important step forward because it was a result of a very successful dialogue between the industry and the agency with some participation of academia. It was an example of how rather than repeating what we had been doing for years and years, we began to focus on developing new thinking to come up with a science-based approach to determine the best thing. That was an important big step that preceded the process analytical technology initiative.

Have the problems that manufacturers are now facing changed from what they were before this proactive approach?
In many cases, manufacturers are still having the same types of problems they had before, whatever those might be. There are a lot of legacy products that were developed many years before this new framework was put in place, and those products are still manufactured by and large according to those methods and are required to meet the same compliance requirements that were in place before PAT and quality by design. PAT and quality by design are being adopted gradually; it will take a number of years before most of the products in the industry's portfolio are really developed by the PAT approach. And even then, quality problems will appear. But what will change is the methodology of solving these problems and the amount of predictive knowledge that we will accumulate either during development or during manufacturing. I think this is where the big difference is going to be. But I think also there are going to be evolving expectations in terms of quality and performance.

Going forward 10 years from now, how important will PAT and quality by design be?
PAT and quality by design are design and control tools. There is no question that we are going to have some type of standard set of expectations for using these methodologies. How far it goes, what shape it takes in the end, what will end up being the regulatory expectations, and what will end up being the technology standard will depend on what we learn as a community over time. There is a balance that needs to be arrived at between costs and benefits. But there is no question that this is going to be more and more significant. From a regulatory perspective, we have been taking more steps toward facilitating continuous improvement. It is important to realize that quality optimization in general is not achieved with two or three big changes, it typically involves making hundreds of little changes over several years, so to optimize quality we will need a regulatory framework that facilitates change rather than makes it difficult. To the extent that the agency understands that and makes it possible, the benefits will speak for themselves.