**Acknowledgement**

The topic dealt with in this chapter was the subject of the author's lecture in his investiture as Doctor Honoris Causa by the University of Valencia (Spain) on March 30, 2011. This work has been supported by grant CTQ2011-23790 of the Spanish Government.

## **6. References**


**Chapter 5** 

© 2012 Krull et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Krull et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Analytical Method Validation for** 

Method validation has a long and productive history in the pharmaceutical and now, biopharmaceutical industries, but it is an evolving discipline which changes with the times. Though much has been written about method validation for conventional, small molecule (SM) pharmaceuticals, less has appeared providing an overview of its application for complex, high molecular weight (MW) biopharmaceuticals (or biotechnology) products. This appears to be satisfyingly changing with the times, and this particular chapter has been designed to address this area of method validation. We hope to address herein the important issues of where do analytical method validation guidelines and directives stand today for biopharmaceutical (protein or related) products. Due to the recognized differences and complexity of biopharmaceuticals relative to small molecule drugs, regulatory agencies have accepted that what is expected of all SM, single molecule entities (even enantiomers), cannot be required for complex protein biopharmaceuticals, such as antibodies. While it is quite a simple matter, in most instances, to characterize and validate methods for SM drug substances, this is not always the case for complex biopharmaceuticals. Biotechnology

products will always be heterogeneous mixtures of product-related species.

While the chapter below focuses on the principles and practice of method validation for biopharmaceuticals in the biotechnology industry, some comments on the topic of "academic method validation," and if and how that differs from what is required by the industry, seem warranted. In general, academics are not required by any regulatory agency or governmental body to perform any degree of method validation. However, one instance where it might be appropriate to do acceptable (whatever that means) method validation is when a reviewer of a grant proposal or manuscript destined for publication demands that some validation be performed. At times, Journal/Book Editors may suggest that some degree of method validation be performed, but in the final analysis, this requirement is at

**Biopharmaceuticals** 

http://dx.doi.org/10.5772/52561

**1. Introduction** 

Izydor Apostol, Ira Krull and Drew Kelner

Additional information is available at the end of the chapter

