Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 129

These often involve many thousands of patients designed to quantify the extent to which the drug is effective and in what patient groups. Given the increase in numbers of patients exposed less common side effects may be seen and the benefit/risk ratio can be more clearly estimated. These are the key regulatory studies, and as such inform the labelling and patient information for the drug when it is marketed. At the same time as these trials are underway, the pharmaceutical company will be investing considerable efforts into scaling up the manufacturing process, and completing the stability studies on the dose form and packaging which will be taken to market. While various formulations can be tested in Phase II, Phase III studies must be conducted using the final formulation. A key challenge with biotechnology products, which are not manufactured using conventional chemistry, is to develop manufacturing processes and robust assay methods which can guarantee consistent levels of biological activity between batches.

During Phase III, the regulatory affairs department within companies will be pulling together the large amount of manufacturing, preclinical and clinical data necessary for making a formal application to the relevant regional and national regulatory authorities for a product licence. Each major regulator requires the data structured in a different way, therefore first priority will usually be given to submissions to the FDA and the EMA. Review times by these regulators vary based on circumstances, but it usually takes approximately 1 year.

Based on the data submitted, each regulatory authority will produce a factual summary of the preclinical and clinical results, including the key safety information and dosing instructions. This document will also state whether the marketing approval is general or restricted, e.g. hospital use only. The relevant document issued by the EMA is called the summary of product characteristics (SPC) and provides the key information required to aid a decision by the prescriber as to whether the drug is indicated. A second valuable document is the European Public Assessment Report (EPAR), found on the EMA website, which provides a more detailed summary of the Agency's review of the data submitted. Over time, the SPC will be updated by the company as key new information becomes available, but clinical publications and treatment guidelines are also invaluable in providing additional detail which will not be found in the SPC.

In the UK, each new drug in the British National Formulary has an inverted triangle symbol next to it reminding doctors that it is a new product and that any suspected adverse effects should be reported to the Commission on Human Medicines (CHM) via the yellow card scheme.