欧盟gmp附件13：研发阶段药物的gmp更新!.pdf

Commission Européenne, B-1049 Bruxelles / Europese Commissie, B-1049 Brussel – Belgium. Telephone: (32-2) 299 11 11 EUROPEAN COMMISSION ENTERPRISE AND INDUSTRY DIRECTORATE-GENERAL Consumer goods Pharmaceuticals Brussels, 03 February 2010 ENTR/F/2/AM/an D(2010) 3374 EudraLex The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use Annex 13 Investigational Medicinal Products Document History Revision to reinforce the principle of independence between production and quality control functions in cases where the number of personnel involved is small. Changes to sections 36 and 37 to supplement, for investigational medicinal products, the guidance for reference and retention samples given in Annex 19. An additional note has been introduced to clarify the meaning of “reconstitution” as referred to in article 9.2 of Directive 2005/28/EC. The content of the Batch Certificate referred to in Art. 13(3) of Directive 2001/20/EC, agreed following a separate public consultation, has been added as an attachment. A few editorial changes have been made to sections not consulted upon in the interests of updating references and consistency with terminology used throughout the GMP Guide. February 2008 Public consultation April 2008 until January 2009 Adopted by the European Commission 31 January 2010 Deadline for coming into operation 31 July 2010 PRINCIPLE Investigational medicinal products should be produced in accordance with the principles and the detailed guidelines of Good Manufacturing Practice for Medicinal Products (The Rules Governing Medicinal Products in The European Community, Volume IV). Other guidelines published by the European Commission should be taken into account where relevant and as appropriate to the stage of development of the product. Procedures need to be flexible to provide for changes as knowledge of the process increases, and appropriate to the stage of development of the product. In clinical trials there may be added risk to participating subjects compared to patients treated with marketed products. The application of GMP to the manufacture of investigational medicinal products is intended to ensure that trial subjects are not placed at risk, and that the results of clinical trials are unaffected by inadequate safety, quality or efficacy arising from unsatisfactory manufacture. Equally, it is intended to ensure that there is consistency between batches of the same investigational medicinal product used in the same or different clinical trials, and that changes during the development of an investigational medicinal product are adequately documented and justified. The production of investigational medicinal products involves added complexity in comparison to marketed products by virtue of the lack of fixed routines, variety of clinical trial designs, consequent packaging designs, and the need, often, for randomisation and blinding and increased risk of product cross-contamination and mix up. Furthermore, there may be incomplete knowledge of the potency and toxicity of the product and a lack of full process validation, or, marketed products may be used which have been re-packaged or modified in some way. These challenges require personnel with a thorough understanding of, and training in, the application of GMP to investigational medicinal products. Co-operation is required with trial sponsors who undertake the ultimate responsibility for all aspects of the clinical trial including the quality of investigational medicinal products. The increased complexity in manufacturing operations requires a highly effective quality system. The Annex also includes guidance on ordering, shipping, and returning clinical supplies, which are at the interface with, and complementary to, guidelines on Good Clinical Practice. Notes Non-investigational medicinal product1 Products other than the test product, placebo or comparator may be supplied to subjects participating in a trial. Such products may be used as support or escape medication for preventative, diagnostic or therapeutic reasons and/or needed to ensure that adequate medical care is provided for the subject. They may also be used in accordance with the protocol to induce a physiological response. These products do not fall within the definition of investigational medicinal products and may be supplied by the sponsor, or the investigator. The sponsor should ensure that they are in accordance with the notification/request for authorisation to conduct the trial and that they are of appropriate quality for the purposes of the trial taking into account the source of the materials, whether or not they are the subject of 1 Further information can be found in the European Commission’s Guidance on Investigational Medicinal Products (IMPs) and other Medicinal Products used in Clinical Trials a marketing authorisat。