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The 'Regs'-- 21 CFR 812, EN540, and ICH GCP
While most medical device manufacturers faced with the prospect
of clinical trials may be familiar with 21 CFR 812, Investigational
Device Exemption, they may not be aware that the regulation, intended to regulate how
companies conduct trials for the protection of human subjects was revised recently, and
now contains several requirements previously in similar documents for the EU and globally.
EN540 is a European standard on the conduct of clinical trials which has been harmonized or accepted by every member state of the EU and is applicable to the AIMD (Active Implantable Medical Device) and MDD (Medical Devices) Directives for CE Marking. The only provisionsof EN540 that remain subject to national policy relate to the legal status,composition and regulatory requirements for Independent Ethics Committees (also known as IECs). With our experience setting up trials running in Europe, The CRO Group can guide you as to which member state IEC policies may be more conducive for a trial involving your type of device. For example, recently implantable trial devices involving bovine sourced materials have been the subject of controversy by certain IECs of member states with serious BSE fears and political pressure. In reality, EN540 compliance for clinical trials is expected by Notified Bodies for all MDD Class III devices and AIMDs since 1993 to support CE Mark registrations, and USA clinical trials documented per 21 CFR 812 will not be acceptable without amendment ) which takes time and sometimes forces an extension to the trial).. However, because some requirements of EN540 are presented without extensive elaboration and certain GCP issues are implied but not specified, this standard is generally considered to represent the minimum acceptable requirements. This standard is not sufficient for clinical studies to support US registrations, and sole reliance on EN540 by inexperienced sponsors can lead to costly omissions that result in clinical studies lacking in certain key features, such as adequate documentation and a sufficiently rigorous statistical analysis plan. The recent publication of a Draft Guideline on GCP (Good Clinical Practices) from the International Conference on Harmonization (ICH) is a useful supplement to EN540, and is recognized in most countries where it may be required to conduct a trial either for device registration or reimbursement, including Japan, Russia, and Canada. Although developed for pharmaceutical trials, the scope and content is in almost every respect applicable to the design, conduct, analysis and reporting of clinical studies for medical devices. The ICH guideline elaborates on the basic features of GCPs as does EN540, but provides additional guidance absent from EN540. The ICH Guidance provides more detail on the necessary components of a clinical protocol. including some that are not required by EN540 such as: descriptions of methods used to reduce bias, methods to be used for statistical analysis of results, procedures for handling data that is "missing, unused or spurious;" discontinuation criteria, monitoring and audit procedures, randomization procedures and trial discontinuation procedures. EN540 describes the role of the sponsor in identifying qualified investigators, maintaining study records, providing adequate information to subjects and investigatorson the nature of the risks and possible benefits of the device. The ICH guidance articulates additional responsibilities for the sponsor that enhance the integrity of the clinical experiment. These include developing written procedures for quality assurance and quality control of the study, written procedures for data handling and record keeping and control of the investigational product packaging, shipping and dispensing. Both documents rely on the Declaration of Helsinki to define the rigorous criteria applied to protect the rights of human subjectsparticipating in research. The ICH guidance provides more detail on policies and procedures to ensure that subjects rights are adequately protected. |
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