生物类似药的注册法规思考Regulatory Considerations for the Development of Novel Antibody.docx

Regulatory Considerations for the Development of Novel Antibody-Related Products/1429-AuthorProfile/5696-Qing-Zhou-PhD/Qing Zhou, PhD /1429-AuthorProfile/5697-Marjorie-Shapiro-PhD/Marjorie Shapiro, PhD /10314-FDA/FDAAbstractMonoclonal antibodies (mAbs) are widely recognized as invaluable biologic tools for diagnostic and research investigations and have also become a leading class of therapeutic molecules. Tremendous efforts have been made to improve the safety and efficacy of antibody based therapeutics by obtaining a better understanding of the molecular basis of diseases and selecting appropriate targets, as well as developing novel antibody related products as new options for clinical applications. Although a great amount of knowledge regarding the quality attributes, manufacture and control strategies for antibody products is gained as a result of these efforts, the regulation of therapeutic antibody related products continues to be challenging for both the pharmaceutical industry and regulatory authorities. This article provides an overview of the general regulatory considerations from a quality perspective for mAb products, and outlines the current thinking regarding special considerations for several types of novel antibody related products.IntroductionSince the development of anti-diphtheria antitoxins in the 19th century, researchers and physicians have investigated antibodies due to their remarkable characteristics and great potential for clinical applications. After hybridoma technology was introduced in the 1970’s, the first therapeutic uses of hybridoma-derived mAbs in the 1980’s showed sporadic promise, but overall resulted in disappointment. The first mAb, Orthoclone, approved in the US in 1986, was a murine mAb. Although Orthoclone has been withdrawn from the market, its approval represents the beginning of an era in the development of a new class of therapeutic proteins for clinical applications.Early therapeutic mAbs derived from rodents were larg