New biological entities

Most of the analyses of R D cosfs for new dug entities and their generic imitators have focused on small molecule NCES. This reflecfs the relative youth of the biotech industry. New biologic entities were first introduced in the 1980s. By 1994, only 29 new biological entities had been introduced into the U.S. market, but this number has increased dramatically since then. In this regard, 41 new biological introductions occurred between 1995 and 2001. 

Cell culture, particularly mammalian cell culture, processes enable the production of new, hitherto unknown drugs, the biopharmaceuticals. The year 2001 marked a turning point in the development of biopharmaceuticals, insofar as it was the first time that more new biological entities (NBEs) than... 

This chapter will attempt to describe the various options available to validate commercial assays used in chug development appropriately to meet the expectations and requirements of each study in which they may be used. In particular, we will examine the use of commercial kits for pharmacodynamic (PD), efficacy and toxicity (biomarkers), and pharmacokinetic (PK) assessments. The PK assessment assays will focus on those molecules that are developed as therapeutic chugs, but which are also compounds that exist endogenously in humans. These chugs are often called new biological entities (NBEs) and examples include growth hormone, insulin, and erythropoietin. 

Failures such as those described above can ruin a company financially, or at least shatter its faith in biotechnology, as the development costs for a new biological entity are usually in the range of US 500-800 million, with late-stage clinical trials consuming the majority of this money (see Part IV, Chapter 16 Part VII, Chapter 4 and Part VIII, Chapter 1). 

Finally, the advanced drag delivery systems to be used for the new biological entities will have to make the transition from research to market with the associated issues, including product stability, large-scale production of both drags and formulations, and also the regulatory require-... 

Now, as we have discussed in detail the required analytical methods to thoroughly characterize a biopharmaceutical, including the importance of, for example, drag-drug interactions, we wiU now look into the requirements from a regulatory authority perspective to finally approve such a new biological entity. 

Development of a stable antibody formulation is often challenging due to conflicting requirements of stability, cost of goods, limitations associated with the route of administration, clinical or administration convenience, and lack of robust models to predict long-term stability. One key difference in formulation development of mAbs and other proteins (referred to as NBEs, new biological entities), compared to traditional small molecules (referred to as NCEs, new chemical entities), is focus on physical stability in addition to chemical integrity of the molecule. Table 26.2 summarizes various degradation pathways for mAbs. 

The numbers in Figure 19.1 refer to new molecular entities (NMEs). These figures represent a composite of both small molecule therapeutics, or NCEs (for new chemical entities), and large biopolymer products, or NBEs (for new biological entities) that entered the marketplace each year. Eactors responsible for the trends shovm in Eigures 19.2 and 19.3 will be discussed in greater detail as this chapter proceeds. 

We shall concentrate on the area of new chemical entities (NCEs) rather that new biological entities or biopharmaceuticals. These latter materials are governed by very similar regulations and quality requirements, but are somewhat outside of the experience of the author. The focus will be on regulatory requirements in the USA and Europe. 

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