Göbel Claus, Baier Dieter, Ruhfus Birgit, Hundt Ferdinand
Pfizer Pharma GmbH, Berlin, Germany.
Ger Med Sci. 2009 Mar 31;7:Doc01. doi: 10.3205/000060.
The implementation of the Clinical Trials Directive 2001/20/EC and the Good Clinical Practice Directive 2005/28/EC fundamentally restructured and harmonized the conduct of clinical trials in Europe. GCP inspections - which affect study sites, laboratories, sponsors and contract research organizations (CRO) alike - make up an important part of these regulations. A common understanding of how these regulations apply in daily life is however not always ensured.
A working group of the Clinical Research/Quality Assurance subcommittee of the German Association of Research-Based Pharmaceutical Companies (VFA) was established to outline the regulatory requirements, the experience gathered with inspections by means of a survey and to set up guidance on how to manage an inspection.
The survey, conducted with the help of 15 pharmaceutical companies within the VFA, included a total of 224 inspections (74 inspections in Germany, 150 from other European countries). Most frequent findings in and outside Germany were related to "documentation" (40.5% vs. 21.3%), "investigational new drugs" (16.2% vs. 14.7%), "drug safety" (13.5% vs. 8%) and "application for a clinical trial authorization" (5.4% vs. 12%). From a German perspective, key findings of this working group were the necessity for a clear differentiation of responsibilities between national and federal as well as international authorities, a harmonization of inspection procedures and topics, and a clarification of whether pre-study/on-study and pre-approval/post-approval GCP inspections of the federal higher authority are included in the "Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten" (ZLG) requirements. The survey illustrated, that inspections usually are conducted at the investigational site, and that most of the findings are well known and thus could be prevented by communicating and discussing audit results more intensely within study groups. Again, the survey illustrated, that a harmonization of inspections appears warranted. Finally a code of practice is provided that considers these findings and delivers a basis for a successful inspection whether at the sponsor or the GCP site.
《2001/20/EC临床试验指令》和《2005/28/EC药物临床试验质量管理规范指令》的实施从根本上对欧洲临床试验的开展进行了重组和协调。药物临床试验质量管理规范检查——对研究机构、实验室、申办者和合同研究组织（CRO）均有影响——是这些法规的重要组成部分。然而，对于这些法规在日常生活中的应用并非总能达成共识。
德国创新药物研究与制造商协会（VFA）临床研究/质量保证小组委员会成立了一个工作组，以概述监管要求，通过一项调查收集检查方面的经验，并制定关于如何应对检查的指南。
在VFA内15家制药公司的协助下进行的这项调查共涵盖224次检查（德国境内74次，其他欧洲国家150次）。德国境内外最常见的检查结果涉及“文件记录”（40.5%对21.3%）、“研究用新药”（16.2%对14.7%）、“药物安全性”（13.5%对8%）以及“临床试验授权申请”（5.4%对12%）。从德国的角度来看，该工作组的主要检查结果包括有必要明确区分国家和联邦以及国际当局之间的职责，统一检查程序和主题，以及澄清联邦高等当局在研究前/研究期间和批准前/批准后的药物临床试验质量管理规范检查是否包含在“州药物和医疗产品健康保护中心”（ZLG）的要求中。该调查表明，检查通常在研究机构进行，而且大多数检查结果是已知的，因此通过在研究小组内更深入地交流和讨论审核结果是可以预防的。该调查再次表明，统一检查似乎很有必要。最后提供了一份实践准则，该准则考虑了这些检查结果，并为在申办者或药物临床试验质量管理规范机构进行成功检查提供了依据。
