The regulatory framework for compliance with research procedures has essentially developed on an international basis only in the last two decades, except for the US where rules were first established in the 1930s. Today, most countries in the European Union, other countries in Europe (e.g. Hungary, Poland and Switzerland) and Japan have regulations on GCP. Other countries have regulations controlling clinical studies, with guidelines on GCP, such as Australia and Canada. In the 1990s, an attempt was made to harmonise GCP requirements in the form of the ICH GCP document which has since been adapted in regulation by many countries. Some countries have no guidelines or regulations, but guidance for researchers has been provided by oragnisations such as the Council for the International Oragnizations of Medical Sciences (CIOMS) and the World Health Organization (WHO). (A brief list of existing regulations and guidelines is presented at the end of this chapter.) Regulatory authority review and/or approval is usually necesary in all countries before, during, and after clinical studies.
In the last few years, there has been increasing interest in regulatory inspection of GCP compliance to ensure validity of the data and protection of study subjects, and to compare the practices and procedures of the investigator and the sponsor/ CRO with the commitment made in the application for marketing. Although inspection has been a regulatory requirement in the USA for many years, inspectorates have only just started in countries such as Austria, Denmark, France, Finland, Germany, Japan, The Netherlands, Norway and Sweden. There are problems in finding good inspectors, in deciding on the final standards for inspections, and in imposing sanctions for non-compliance. An interesting recent development has been the initiation of inspections in Europe by the central regulatory authority, the European Medicines Evaluation Agency (EMEA). Regulation of compliance with requirements by ethics committees is also developing in some parts of the world (e.g. France and Denmark). To date, the US Food and Drug Administration (FDA) is the only authority that is actively checking on the activities of institutional review boards (IRBs) by inspection and licensing.
For non-compliance with regulations, only the USA has imposed serious sanctions to date. The 'blacklist' (list of all investigators who have been found to be non-compliant and were barred from clinical research for FDA submissions) is publicly available through freedom of information rules.
The USA has vast experience (thousands of inspections) compared to the handful of inspections in other countries.
Within a research organization, other independent review, auditing, is undertaken internally to check on compliance with standards and basically to pre-empt the inspectors. Auditing may be conducted at any time during a clinical study to ensure continued compliance with GCP. Almost all aspects of GCP could be audited. Auditing, by definition, must be undertaken by personnel who are independent of the research being audited.
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