ABSTRACT
I. INTRODUCTION The quality of active pharmaceutical ingredients (APIs) intended for development and commercial products is defined as meeting the appropriate specifications for the APIs and being produced in an appropriate facility. Requirements for this type of API can be found in International Conference on Harmonization (ICH) guideline Q7 and the Food and Drug Administration’s (FDA) current good manufacturing practices (cGMPs) regulations. Most countries regulate the manufacture of these types of APIs. These regulations require a total systems approach to ensuring an API has the appropriate level of quality. Current guidelines and emerging regulations now indicate that the control of API quality should start with the manufacturing of material intended for the first preclinical toxicology studies. In early development, the applicable regulations and guidance are limited to a brief section within the FDA’s Good Laboratory Practice (GLP) regulation, 21 CFR 58, and internationally in the nonbinding Organisation for Economic Co-operation and Development (OECD) GLP guidelines. As the regulators continue the refinement of requirements for early-stage API and drug product candidates, it makes good business sense to ensure that all components in the quality system are properly designed, validated or qualified, maintained, and operated to ensure the API consistently meets quality requirements for the corresponding stage of development. The general components of the system are the process, the facilities, and the people. This chapter addresses these components in the context of the domestic and international regulatory landscape, including ICH guidelines Q9, “Quality Risk Management,” and Q10, “Pharmaceutical Quality System,” and the FDA’s guidance for the industry, “CGMP for Phase 1 Investigational Drugs.” These newly developed guidelines, resulting from an international effort of concerned pharmaceutical manufacturers and the associated regulators, have required companies to reexamine their policies, management’s responsibilities, and how risk is measured andmanaged across all phases of development and commercialization.
