Early phase development

Pharmacologically Predictable Adverse Events or Nonresponse Obtained in Early-Phase Development Affect the Risk/Benefit Assessment and Product Labeling . 213... 

If a secondary method is required during early phase development, a level 3 method is developed and validated to support phase 2b or early phase 3 clinical studies. This method should be capable of separating all components of interest identified up to this stage of pharmaceutical development. In cases where the initial primary method is still viable, the level 1-level 2 method may be maintained. As in early development, the use of an orthogonal method to evaluate DS generated via new synthetic schemes and to evaluate new formulations remains an important means of assuring that the primary method is sufficient for characterizing DS and DP. 

During early phase development there is limited knowledge about the chemistry of the new chemical entity (NCE) with respect to synthetic impurities and degradation pathways and kinetics. It is, therefore, desirable to develop an array of methods that show applicability to a broad range of potential impurities, degradation products, and excipients. The methods are intended to provide the information necessary to guide the improvement of a synthesis route or a new drug formulation. 

CE methods are developed and utilized in pharmaceutical QC for early to late phases of drug development. Chapter 4 covers the approaches for late-phase development for small molecules that can be used in early-phase development, as well as for large-molecular-weight compounds. Late-phase method development in pharmaceutical QC is performed for required stability studies and for release of the drug product or drug substance validation batches, and is intended to be transferred to the operational QC laboratories for release testing of the production batches. Preferably, late-phase methods should be fast, robust, reliable, and transferable. Therefore it is crucial to devote adequate time, thought, and resources to the development of such methods. 

The activities in the projects have become increasingly creative and a specialized discipline of Early Phase Development was created here and there. With the challenging goal to become faster and to better predict the chance of success Proof of Concept studies meant to measure surrogate markers, biomarkers, results from functional imaging, creative early clinical readouts and endpoints have been... 

Whereas the other separation methods have been demonstrated to also provide the requisite performance for release and stability testing for select drug substances and drug products, more typically the techniques are applied as supportive methods for HPLC during early-phase development and in niche areas during late-phase development. Because each separation method provides a different mechanism of separation to HPLC, utilization in early-phase development can be used to confirm specificity of HPLC methods. In later phases, both SFC and CE have shown applicability to chiral separations, and GC remains as the unique technique for the determination of residual solvents. 

To provide a forum for information exchange of issues relating to solid- and liquid-state characterization of chemical entities, active pharmaceutical ingredients, excipients, and early-phase development of pharmaceutical dosage forms and delivery systems... 

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