Michael B. Mitchell

Risk Management in the Pharmaceutical Product Development Process

Abstract“The manufacture and use of a drug product, including its components, necessarily entail some degree of risk.”—International Conference for Harmonization (ICH) Q9. This paper examines the role of risk management in pharmaceutical product development in the context of patient safety and drug efficacy. Its objective is to contribute to building a common understanding of this quality risk management among the various functional groups involved in developing, testing, manufacturing, and approving of drug products within pharmaceutical companies and regulatory agencies. Selected aspects of drug substance and drug product development are used to demonstrate principles of risk management in action and presented as case studies.

A novel synthesis of guanine PDE inhibitors via tricyclic imidazopyrimidines

A new method for the preparation of developmental tetracyclic guanine PDE inhibitors via a common tricyclic pyrimidine intermediate is described.

Use of Potassium tert-Butoxide to Increase the Nucleophilicity of an Imine Stabilized o-Tolyl Lithium Derivative

Abstract Addition of a solution of potassium tert-butoxide in THF to a mixture of LDA and an o-tolylimine caused the resultant anion to be alkylated quickly by the relatively unreactive l-chloro-7-phenylheptane. Significant β-elimination to 7-phenylhepta-1-ene did not occur.