Protein-based therapeutic manufacturing

By Robert Broeze

Robert J. Broeze is Chief Commercial Officer at Laureate Pharma. He talks to Next Generation Pharmaceutical about manufacturing therapeutic proteins.

What is the current state of protein-based therapeutic manufacturing in the pharmaceutical industry?

Robert Broeze. Outsourcing of protein-based biopharmaceuticals has increased significantly over the last decade due to a number of factors. A major industry driver has been the expansion of the market for biopharmaceutical products. Biopharmaceuticals can be highly effective and potent, can have fewer side effects and can cure diseases rather than merely treat the symptoms. These advantages, combined with the number of diseases treatable with biopharmaceuticals, are driving demand for these drugs worldwide.

In 2009, biopharmaceutical contract manufacturing revenues worldwide were forecasted to reach more than $1.5 billion, with the strongest segment of the market being GMP production. It is estimated that 700 biopharmaceutical products are in clinical trials, with another 900-1000 in pre-clinical or early clinical development. Large pharmaceutical companies are increasing their outsourcing of development, manufacturing, testing and filling of products in their development pipelines.

The strongest growth continues to be from the many biotechnology companies that elect to outsource pre-clinical through commercial development in order to avoid the cost and risk of establishing in-house manufacturing.

Manufacturing therapeutic proteins is an inherently expensive and time-consuming process. How do you reduce cost and time expenditure for the next generation of biotech drugs entering the pipeline?

RB. In the present economic environment, many companies outsourcing the development and manufacture of their biopharmaceutical products are very cost conscious and are sensitive to timing issues. As we develop proposals and project timeline for our clients, we invest considerable time to determine precisely a client’s specific needs for their development program. We work very hard to tailor their program to meet their specific development and financial needs.

In order to reduce development time and keep costs down, it may be necessary to eliminate duplicate or repeat development runs and scale up directly to pilot and clinical scale manufacturing. As an example, instead of performing five runs at the 12 liter scale to demonstrate the robustness of a process, a client may choose to have us perform only one or two 12 liter runs and then move on to the pilot scale.

This presents a degree of risk to the client but many clients are willing to accept this risk in order to keep costs low. In addition, clients may choose to have us produce their clinical material at smaller scale as a way to reduce risks. Producing product to meet only their immediate needs through smaller batch size is a way that clients may choose to reduce cost significantly.

What methods look most promising for providing customers with solutions for advanced APIs?

RB. Fusion proteins are an area of protein therapeutics where we are seeing an increased level of activity. Fusion proteins offer the opportunity to engineer unique targeting properties and, activities into proteins by designing combination molecules that are not found naturally. These hybrid structures can be used to address specific clinical needs. We expect that there will continue to be increased interest in this area as companies develop more and more experience and expertise in working with these novel proteins.

How do you see the area of manufacturing therapeutic proteins developing within the pharmaceutical industry over the next few years?

RB. We see the use of single-use technologies increasing significantly in the next few years and having a tremendous impact on the manufacture of therapeutic proteins. Laureate has utilized single-use technologies in our facility for many years and we view this technology as being applicable for manufacture of clinical as well as commercial protein-based therapeutic products.

Single-use technologies have been developed for all aspects of biopharmaceutical manufacturing activities. Several companies have developed single-use bioreactors within the past five years. Such bioreactors offer a great amount of flexibility that is not available with fixed stainless steel bioreactor.

For example, they offer the advantage of having all product surfaces as disposable and discarded after use. This simplifies the product changeover procedures and significantly decreases the time for these activities.

In addition, single-use technologies are more portable than fixed stainless steel systems. A process can be developed in a pilot facility and the equipment moved to another facility for use for clinical manufacturing. Development of single-use technologies in other manufacturing areas such as down stream processing, buffer preparation, liquid storage and handling solutions and aseptic filling are having a similar impact.

Biography

Robert J. Broeze is Chief Commercial Officer, Laureate Pharma. Broeze has more than 20 years of experience in the biopharmaceutical industry. His technical expertise spans research, development, characterization, validation, testing and cGMP manufacture of biopharmaceutical products, from pilot to phase III clinical and commercial scale with a strong emphasis on monoclonal antibody products for therapeutic and diagnostic use. He is a graduate of Rensselaer Polytechnic Institute, where he earned both his BS and PhD degrees.