مقاله انگلیسی رایگان در مورد تحقیقات ناخالصی توسط مراحل توسعه محصول و دارو (الزویر)

Regulatory expectations for control of impurities in new drugs have been established through ICH guidelines for many years [1]. The Q3 guidelines outline requirements for the registration of new drugs and therefore represent the expectations for knowledge of impurity sources and controls that should be present as development is completed. Little guidance is given regarding expectations by phase of development other than acknowledgement that knowledge should increase and be applied to the manufacture and storage of drug substances and products. Regional guidelines supplement the ICH and sometimes offer more phase-related comments, but usually few specifics [2-4]. Drug development sponsors must determine the nature and depth of impurity investigations to conduct as the development process moves through clinical phases. Cost can be a major factor in the timing of these efforts. The high rate of attrition of new drug candidates entering clinical studies makes complete impurity investigations at early phases impractical. Patient safety is the primary consideration for impurities at all phases. All situations have specific considerations that depend on factors such as intended therapeutic use, dosage form, route of administration, duration of dosing, and patient population. Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6].