co-ordination of GMP inspection.doc

此文档收集于网络，如有侵权，请联系网站删除Co-ordination of good-manufacturing-practice inspectionsUnder European Union (EU) law, all manufacturers and importers of medicines located in the European Economic Area (EEA) must hold a manufacturing authorisation. These authorisations are supervised by medicines regulatory authorities in Member States (the supervisory authorities), which are responsible for issuing authorisations for activities taking place in their territories. The supervisory authorities must perform inspectionsof manufacturing-authorisation holders to ensure that they are adhering to the principles and guidelines of good manufacturing practice (GMP).For products imported from countries outside the EU, the supervisory authority is responsible for verifying that the manufacturer conforms to standards of GMP equivalent to those in force in the EU, unless the country has negotiated an appropriate agreement with the EU establishing mutual recognition of GMP inspections. The supervisory authority for manufacturing sites in countries outside the EU is the regulatory authority that issues the manufacturing authorisation to the importer.The European Medicines Agencys Manufacturing and Quality Compliance Section coordinates GMP inspections of manufacturing sites connected to centrally authorised human and veterinary medicines.For more information, see the standard operating procedure on co-ordination of GMP/GDP inspections.The responsibility for carrying out inspections rests with the regulatory authority the the Member State that is responsible for supervising the manufacturer or importer.Number of inspections performed from 1999 to 2009GMP inspections may take place when an application for a marketing authorisation is received. This is to check the GMP compliance of the manufacturers connected to the medicine concerned or to investigate a specific matter arising from the assessment of the application. Inspections also take place periodically after the granting of a marketing authorisation as part of the ongoing supervision of manufacturers. This graph below shows the numbers of inspections carried out following requests by the Agency between 1999 and 2009. It covers pre- and post-authorisation for human and veterinary medicines.Manufacturers located within the EEA are under the direct supervision of regulatory authorities in Member States. Because of this, the Agency does not specifically request inspections of manufacturers located in the EEA except when the need arises for a specific medicine. This is usually during the pre-authorisation phase of a centralised marketing-authorisation application.This means that most inspections requested by the Agency are in countries outside the EU (third countries).Most inspections are carried out by teams of inspectors from two countries. The lead is usually the supervisory authority, supported by another authority. The supporting authority often shares supervisory responsibility with the lead. This occurs when a medicine from a particular manufacturing site outside the EU is directly imported into more than one Member State.The pattern of commercial activity results in an uneven distribution of responsibility. In the interests of flexibility and better use of resources, the Agency is keen to involve all Member States in its GMP inspection programmes, even if they have no formal supervisory responsibility.International collaborationThe Agency has conducted two pilot programs of inspections with international partners:International active-pharmaceutical-ingredient inspection pilot programmeRepresentatives from authorities in Europe, including the European Medicines Agency, five EU Member States (France, Germany, Ireland, Italy and the United Kingdom) and the European Directorate of the Quality of Medicines and Healthcare (EDQM) conducted a joint initiative with the United States Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) on international GMP inspections of active-pharmaceutical-ingredient (API) manufacturers located outside the participating countries.The objectives of the initiative included sharing of information on inspection planning, policy and inspection reports and joint inspections.The programme began with a pilot, which ran from December 2008 until December 2010. During the pilot, the participants shared their surveillance lists and found 97 sites common to all three regions, resulting in the exchange of nearly 100 inspection reports and in nine joint inspections. This led to increased levels of understanding between the agencies, and a greater number of inspections of value to more than one authority.An interim report on the pilot was published in October 2010 and the final report was published in August 2011.Based on the positive experience, the agencies have agreed to continue with their collaboration, taking into account the experiences and lessons learned during the pilot. This has paved the way for all EU Member States to participate actively in this collaboration. International partners can also become involved, if they meet the criteria outlined in the updated terms of reference published in March 2012.This collaboration is not linked to and is without prejudice to the European Union Falsified Medicines Directive, which adds specific provisions on the import of active substances into the EU. EMA /FDA inspection programme for finished-dosage-form manufacturersThe Agency is conducting a joint inspection programme on finished-dosage-form manufacturers.The programme began with the agencies organising joint pre-authorisation inspections. However, this required simultaneous submissions of marketing-authorisation applications to both agencies, with manufacturing sites in the US or the EU. It also required both applications to trigger pre-authorisation inspections of similar scope. Consequently, the results were limited to two joint inspections conducted in 2009.Because of these limitations, the agencies agreed to extend the scope of this programme to routine surveillance inspections. This involves the exchange of information and planning for possible joint routine surveillance inspections. This began in October 2010. The Agency published a reminder about this collaboration in August 2010, inviting companies to participate in the pilot