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Drug Regulatory Developments
European Journal of Pharmaceutical Sciences 21 (2004) 101–102
Drug Regulatory Developments The European Regulatory Environment This is the first of a regular update on key regulatory developments in Europe. The topic of this short article is the clinical trials Directive and the impact its implementation will have on the regulation of clinical research in Europe. Background Currently the laws relating to initiating and monitoring clinical trials differ considerably across Europe. For example, there are significant differences in the amount of information on the proposed trial required for submission to the regulatory authorities before the trial starts. Some countries require an approval from the relevant regulatory authorities; other countries only require notification to the regulatory authorities of intent to start the trial. Also, the ethics committee structure and the time taken to obtain an ethics committee opinion varies between countries. This can result in increased costs and delays, particularly when trials are carried out in a number of countries. The European Commission first started work on legislation on clinical trials in 1991, and 10 years later the so-called clinical trials Directive was finalised. Its full title is ’Directive of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States (MSs) relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use’1. Scope of the Directive The Directive has a wide scope, covering in effect the conduct of all clinical trials (from Phase I to Phase IV) on medicinal products within the EU, whether sponsored by industry, Government, academia, research organisation or charity. The only trials outside of the scope are those that are non-interventional. One of the primary aims of the Directive is to protect trial participants by introducing the principles of the existing internationally agreed ICH Good Clinical Practice (GCP) guideline into the legislative framework for the conduct of clinical trials. The Directive sets standards for protecting the rights, safety and well being of trial subjects, including incapacitated adults and children. The Directive is also a harmonising measure for the scientific, administrative and documentary procedures in the conduct of clinical trials. European MSs will be required to establish ethics committees on a legal basis and imposes a timeframe for issuing an opinion. The regulatory authority process is defined by the Directive as an implicit approval system within a maximum of 60 days. There will be a core set of information to be submitted to the regulatory authorities before initiating a clinical trial, although country specific information will still be needed. Standards for the manufacture, import and labelling of investigational medicinal products (IMPs) and provisions for quality assurance of clinical trials and IMPs are covered. Member States will be required to set up inspection systems for Good Manufacturing Practice (GMP) and GCP to ensure compliance with these standards. Pharmacovigilance reporting during clinical trials in the Europe is also covered by the Directive; co-ordination will be required between regulatory authorities and universal standards, processes and procedures for collecting, monitoring and reporting safety information are detailed. The Directive also requires the setting up of a European database of information on clinical trials, accessible only to the regulatory authorities of the MSs, the European Medicines Evaluation Agency (EMEA) and the Commission. The database will provide an overview of clinical trials in the Community and will facilitate communication between the authorities. Impact of the Directive on Regulatory Authorities and Ethics Committees For several MSs most of the procedures and criteria required by the Directive are already part of current practice. For instance, most of the regulatory authorities are currently issuing their decisions more quickly than the Directives’ timeframe. However, in some MS restructuring of the regulatory authorities will be needed, especially in those countries where currently only a simple notification is required. The Directive is clear that the scientific aspects of the protocol should be under the responsibility of the regulatory authority, which is not the case today for countries with a notification process. So this introduces a new review task for several authorities. In many MSs, the Directive brings ethics committees under legislative control for the first time. The Directive also streamlines the process of obtaining an ethics committee opinion by requiring a single opinion be issued per MS on proposed doi:10.1016/S0928-0987(03)00354-3
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Drug Regulatory Developments / European Journal of Pharmaceutical Sciences 21 (2004) 101–102
multi-centred trials; the procedures established to reach this single opinion will be under national responsibility. However, the documents to be reviewed by the ethics committees under the Directive should be very similar to the current situation. Implementation of the Directive Member States are required to transpose the Directive’s requirements into national legislation. A deadline was set of 1st May 2003 to draw up the legislation, however MSs have until 1st of May 2004 to actually apply the requirements. In terms of drawing up national legislation, only a couple of MS have finalised this transposition to date (October 2003). However, it is expected that all MSs will have their legislation in place for the 1st May 2004. The European Commission has published a series of guidance documents that aim to assist with implementation and clarification of various aspects of the Directive. Final guidance on one of the most important areas of the Directive- the principles of GCP- have yet to be published. There is general agreement that the smooth implementation of the Directive across the EU will greatly depend on the way in which it is transposed into national requirements and put into practice. Those involved in clinical research in Europe will be hoping for consistency in the interpretation of the new requirements, so that the Directive can facilitate high standards of patient safety and clinical research without increasing bureaucracy. Reference: 1. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Available at http://pharmacos.eudra.org/F2/eudralex/vol-1/home.htm
Provided by: Carolyn Hynes, PhD, Johnson & Johnson Pharmaceutical R&D E-mail: [email protected]
Drug Regulatory Developments The European Regulatory Environment This is the first of a regular update on key regulatory developments in Europe. The topic of this short article is the clinical trials Directive and the impact its implementation will have on the regulation of clinical research in Europe. Background Currently the laws relating to initiating and monitoring clinical trials differ considerably across Europe. For example, there are significant differences in the amount of information on the proposed trial required for submission to the regulatory authorities before the trial starts. Some countries require an approval from the relevant regulatory authorities; other countries only require notification to the regulatory authorities of intent to start the trial. Also, the ethics committee structure and the time taken to obtain an ethics committee opinion varies between countries. This can result in increased costs and delays, particularly when trials are carried out in a number of countries. The European Commission first started work on legislation on clinical trials in 1991, and 10 years later the so-called clinical trials Directive was finalised. Its full title is ’Directive of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States (MSs) relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use’1. Scope of the Directive The Directive has a wide scope, covering in effect the conduct of all clinical trials (from Phase I to Phase IV) on medicinal products within the EU, whether sponsored by industry, Government, academia, research organisation or charity. The only trials outside of the scope are those that are non-interventional. One of the primary aims of the Directive is to protect trial participants by introducing the principles of the existing internationally agreed ICH Good Clinical Practice (GCP) guideline into the legislative framework for the conduct of clinical trials. The Directive sets standards for protecting the rights, safety and well being of trial subjects, including incapacitated adults and children. The Directive is also a harmonising measure for the scientific, administrative and documentary procedures in the conduct of clinical trials. European MSs will be required to establish ethics committees on a legal basis and imposes a timeframe for issuing an opinion. The regulatory authority process is defined by the Directive as an implicit approval system within a maximum of 60 days. There will be a core set of information to be submitted to the regulatory authorities before initiating a clinical trial, although country specific information will still be needed. Standards for the manufacture, import and labelling of investigational medicinal products (IMPs) and provisions for quality assurance of clinical trials and IMPs are covered. Member States will be required to set up inspection systems for Good Manufacturing Practice (GMP) and GCP to ensure compliance with these standards. Pharmacovigilance reporting during clinical trials in the Europe is also covered by the Directive; co-ordination will be required between regulatory authorities and universal standards, processes and procedures for collecting, monitoring and reporting safety information are detailed. The Directive also requires the setting up of a European database of information on clinical trials, accessible only to the regulatory authorities of the MSs, the European Medicines Evaluation Agency (EMEA) and the Commission. The database will provide an overview of clinical trials in the Community and will facilitate communication between the authorities. Impact of the Directive on Regulatory Authorities and Ethics Committees For several MSs most of the procedures and criteria required by the Directive are already part of current practice. For instance, most of the regulatory authorities are currently issuing their decisions more quickly than the Directives’ timeframe. However, in some MS restructuring of the regulatory authorities will be needed, especially in those countries where currently only a simple notification is required. The Directive is clear that the scientific aspects of the protocol should be under the responsibility of the regulatory authority, which is not the case today for countries with a notification process. So this introduces a new review task for several authorities. In many MSs, the Directive brings ethics committees under legislative control for the first time. The Directive also streamlines the process of obtaining an ethics committee opinion by requiring a single opinion be issued per MS on proposed doi:10.1016/S0928-0987(03)00354-3
102
Drug Regulatory Developments / European Journal of Pharmaceutical Sciences 21 (2004) 101–102
multi-centred trials; the procedures established to reach this single opinion will be under national responsibility. However, the documents to be reviewed by the ethics committees under the Directive should be very similar to the current situation. Implementation of the Directive Member States are required to transpose the Directive’s requirements into national legislation. A deadline was set of 1st May 2003 to draw up the legislation, however MSs have until 1st of May 2004 to actually apply the requirements. In terms of drawing up national legislation, only a couple of MS have finalised this transposition to date (October 2003). However, it is expected that all MSs will have their legislation in place for the 1st May 2004. The European Commission has published a series of guidance documents that aim to assist with implementation and clarification of various aspects of the Directive. Final guidance on one of the most important areas of the Directive- the principles of GCP- have yet to be published. There is general agreement that the smooth implementation of the Directive across the EU will greatly depend on the way in which it is transposed into national requirements and put into practice. Those involved in clinical research in Europe will be hoping for consistency in the interpretation of the new requirements, so that the Directive can facilitate high standards of patient safety and clinical research without increasing bureaucracy. Reference: 1. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Available at http://pharmacos.eudra.org/F2/eudralex/vol-1/home.htm
Provided by: Carolyn Hynes, PhD, Johnson & Johnson Pharmaceutical R&D E-mail: [email protected]