Biopharma Demands Better Analytical Assays

An example of a product failure related to analytical testing and biosimilarity/comparability issues is the experience of Genzyme in seeking FDA approval for manufacture of recombinant glucosidase alpha (now Lumizyme) at a new facility using a 2,000 L bioreactor(s) while the original product (Myozyme) was approved and long-marketed as manufactured in 160 L bioreactors. Despite Genzyme (now merged into Sanofi) filing a for supplemental approval with analytical data that it believed showed comparability between the enzymes manufactured at different facilities and scales, FDA perceived significant differences and required the scaled-up product to be approved through a full BLA application, with the scaled-up product simply considered to be a different product. This caused considerable delays and problems for the company.

Analytical Methods are Advancing
Methods and equipment for chemical and physical analysis of biopharmaceuticals continue to advance. New technologies are being developed, existing technologies are being improved, and new applications are being found. For example, Raman, mid-infrared, and mass spectrometers are being directly interfaced with process streams, and various analytical probes, such as for pH, dissolved O2 and CO2 levels, are coming out in single-use/disposable versions. These advances are providing increased options for improved process control, enabling steady-state control of bioprocesses, including better real-time monitoring and control of glycosylation and other structure-related parameters.

With advancing technology, regulatory agencies demand more clearly defined methods for characterizing active agents and products to ensure safety and efficacy. Structural aspects and charge heterogeneity are among the most crucial attributes to monitor throughout the product development process. The sheer numbers of samples that need to be processed as a result of increased testing requirements in a short period of time is forcing industry to invest and innovate in its analytical support infrastructure, including seeking higher sample throughput and automation.

Advances in methods and equipment provide opportunities for cost-saving, driving industry adoption of more and new analytical methods. For example, with equipment capabilities rapidly increasing and prices going down with advancing technology and larger markets, analytical testing that formerly was sent out to contract testing labs can now be cost-effectively done in-house and many more analyses can be performed. But increased adoption of analytical technology also poses many potential problems. Besides the cost of equipment and dedicated staff, new and improved technology may spot problems with bioprocessing and products that were not known before. Also, the proliferation of advanced methods and equipment makes it increasingly difficult to figure out which ones need to be used, which ones are expected by regulatory agencies, and which are most cost-effective and relevant to improved bioprocessing monitoring, control and product testing. With biosimilars entering the market, new assays being developed, a growing approvals pipeline, and increased regulatory scrutiny, industry awareness and adoption of new analytical technologies will surely accelerate. 

Eric S. Langer is president and managing partner at BioPlan Associates, Inc., a Rockville, Maryland-based biotechnology and life sciences marketing research and publishing firm established in 1989. He can be reached at elanger@bioplanassociates.com.

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References
1.    Langer, E., 8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production:  BioPlan Associates, April 2011, 490 pages, www.bioplanassociates.com
2.    Rader, R.A., BIOPHARMA: Biopharmaceutical Products in the U.S. and European Markets, online database, www.bioplanassociates.com/biopharma