Downloaded by 80.82.77.83 on April 6, 2017 | http://pubs.acs.org Publication Date (Web): December 16, 2014 | doi: 10.1021/bk-2014-1176.pr001
Preface Monoclonal antibodies (mAbs) are an important class of therapeutic that has greatly expanded our ability to treat a variety of indications, including cancer, autoimmune disorders, and infectious diseases. The cost of developing these molecules and ensuring that they are fit for purpose is much higher than for small-molecule drugs. Although some of these costs are due in part to the nature of production, a major cost is incurred because of the complexity of the molecule itself. Extensive analytical testing regimes are needed for in-depth characterization and to ensure product stability, proper in-process controls, safety, and efficacy. The next generation of product understanding will require highly complex, orthogonal technologies to elucidate interdependent structure-function relationships. Despite high development costs, the growth of mAb therapeutics continues to soar, with sales of mAb-based therapeutics accounting for ~$50 billion U.S. annually and for seven of the top-ten selling biologic drugs. In anticipation of patent expiry for seven major mAb therapeutics prior to 2020, the U.S. Food and Drug Administration (FDA) released draft guidance on biosimilar approval in 2012. A landmark approval of the first mAb biosimilar occurred in 2013 when the European Commission approved two biosimilar versions of infliximab. It appears likely that the extensive pipeline of biosimilar products will soon become a commercial reality on a global scale. The need for critical assessment of therapeutic mAb characterization is therefore at a precipice, as it is expected that analytical and biophysical characterization strategies will play an ever-increasing role in biosimilarity assessment. Regardless of the pathway to market, the pursuit of improved public health drives therapeutic development. Ultimately, assurance of public safety is of the highest priority. Considering the entirety of a drug’s lifecycle, there is no greater need than for a suite of technologies capable of verifying mechanism of actions (MoAs), identity, and the product and process consistency of such life-saving medicines. Although characterization methods for mAbs continue to mature, a holistic approach combining a multitude of scientific backgrounds is required for the characterization of various attributes of each individual drug candidate. To that end, a manufacturer-specific repository of each drug must be retained as a comparator to ensure consistent production over time. Although this approach is indispensable, it also limits the ability for cross-agency harmonization of industry best practices and limits collaboration across industry, government agencies, academia, and instrument manufacturers. The unique challenge of protein therapeutics resulted in a consolidated effort between industry, academia, and federal agencies to identify a means to better progress from drug target to ix Schiel et al.; State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 1. ... ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
Downloaded by 80.82.77.83 on April 6, 2017 | http://pubs.acs.org Publication Date (Web): December 16, 2014 | doi: 10.1021/bk-2014-1176.pr001
therapy. A group of forward-thinking individuals testified before the U.S. House of Representatives Committee on Science and Technology in 2009 on behalf of the biotherapeutic community regarding the need for better tools and the role that standards can play. The seed was planted for a concerted effort toward the development of appropriate standards and has continued to grow through numerous workshops, seminars, and round-table discussions. Throughout this time, it has become clear that researchers and regulators share a passion for producing the highest quality products through controlled production and robust characterization. The rigors of biotherapeutic development and analysis have clearly indicated a need for control over every stage of development. Critical evaluation of process steps and final product requires technique-specific standards to supplement the in-house repository of specific drug substances. Constant dialogue between industry, regulatory bodies, and standards organizations has identified the need for standards and associated data to better define method performance. The informal consortium referenced above, along with years of testing potential method-specific standards, has shown that a class-specific molecule that embodies all of the technical challenges of that class is necessary. Therefore, an IgG1κ was selected as the premier target capable of covering the broadest range of applications and drug development targets. The mere presence of such a standard will not guarantee success; it will take the unified effort of all involved to incorporate such a material into an already robust pipeline. The NISTmAb IgG1κ, as described throughout this series, is being introduced as a collaborative tool to critically evaluate current characterization strategies. The proposed reference material shows promise as a mechanism for accelerating next-generation technology into the routine development environment. Scientific and health care advances have arisen throughout history, due in part to both directed scientific approaches and a small dose of luck. Inevitably, it is the collaborative effort of many who have advanced this field to a refined state capable of meeting the global capacity and needs of the populous. The current book series represents a defining moment in the development of technologies for characterizing mAbs. A multitude of experts in the field have come together around a single molecule for the first time to demonstrate both current and future practices involved in the characterization of a biotherapeutic. The current series presents an open discussion of current best practices, a multitude of intuitive research, and a collaborative philosophy on where the field needs to move to satisfy future scientific and regulatory needs. Throughout this effort, a first-of-a-kind repository of regulatory considerations, experimental methods, and data—as well as a widely available “reference” mAb—are now available to industry, academia, regulatory personnel, and instrument manufacturers. We hope that this compilation serves as a baseline for many years of future collaboration, continued development, and ultimately a routine analytical pipeline for rapid time-to-market for mAb therapeutics. The editors acknowledge Jane Ladner for preparation of the NISTmAb model structure featured on the cover. This model was built as described in the Higher Order Structure chapter/Volume 3, Chapter 2. x
Schiel et al.; State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 1. ... ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
Downloaded by 80.82.77.83 on April 6, 2017 | http://pubs.acs.org Publication Date (Web): December 16, 2014 | doi: 10.1021/bk-2014-1176.pr001
John E. Schiel Research Chemist Biomolecular Measurement Division National Institute of Standards and Technology Gaithersburg, Maryland 20899, United States
[email protected] (e-mail)
Darryl L. Davis Associate Scientific Director Janssen Research and Development, LLC Spring House, Pennsyvania 19002, United States
[email protected] (e-mail)
Oleg V. Borisov Associate Director Novavax, Inc. Gaithersburg, Maryland 20878, United States
[email protected] (e-mail)
xi Schiel et al.; State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization Volume 1. ... ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
