Preclinical development programs

Over the past two decades many biotechnology-derived products have been approved in the United States. A selected list of these products is provided in Table 6.2. The products include recombinant endogenous-replacement proteins, cytokines, monoclonal antibodies, and fusion molecules. Other chapters in this book give more detailed product-class-specific descriptions of the preclinical development programs for many of these molecules. 

Comparison of Preclinical Development Programs for Small Molecules (Drugs/Pharmaceuticals) and Large Molecules (Biologics/Biopharmaceuticals) Studies, Timing, Materials, and Costs... 

The objective of this chapter is to compare to the studies, materials, and costs associated with hypothetical preclinical development programs intended to... 

COMPARATIVE PRECLINICAL DEVELOPMENT PROGRAMS FOR A HYPOTHETICAL DRUG AND BIOLOGIC... 

For this hypothetical comparison of the preclinical development programs for a drug and a biologic it was necessary to make some general assumptions about... 

The general assumptions about the preclinical development programs were as follows ... 

The respective preclinical development programs would represent typical, but idealized programs, with the focus being on safety only (e.g., no consideration of pharmacology or DMPK studies). 

Designing an appropriate preclinical development program requires a complete understanding of the therapeutic target, mechanism of action, clinical... 

Design relevant studies to answer relevant questions. The preclinical development program should consist of relevant studies designed to answer relevant concerns about pharmacology, PK/PD, efficacy, and safety, as well as comparability. No study should be conducted if it is not potentially capable of adding useful information to the knowledge of the product. 

While useful for evaluating substrate reduction and tissue distribution, the knockout mouse also presented specific challenges to the preclinical development program. After repeated administration of rhGAA, a predictable hypersensitivity response to the recombinant human protein was observed. Frequently this reaction resulted in morbidity and mortality associated with test article administration. This hypersensitivity reaction responded to diphenhydramine prior to, and as necessary, during dosing however, such intervention complicated interpretation of toxicity studies. 

Preclinical Development Programs with Monoclonal Antibodies 593... 

PRECLINICAL DEVELOPMENT PROGRAMS WITH MONOCLONAL ANTIBODIES 593... 

The FDA refers to a few official documents for guidance in accomplishing a valid preclinical development program. These include International Conference on Harmonization (ICH) accepted guidances as well as US FDA guidance documents ... 

Preclinical development programs are required to establish modeling systems that adequately evaluate and/or detect potential risks associated with cellular differentiation, tissue growth, and organogenesis—all necessary components of a neo-organ regenerative process. Sufficient control studies are... 

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