Commission Delegated Regulation (EU) No 1252/2014 of 28 May 2014 supplementing Directive 2001/83/EC of the European Parliament and of the Council with regard to principles and guidelines of good manufacturing practice for active substances for medicinal products for human use Text with EEA relevance
Commission Delegated Regulation (EU) No 1252/2014of 28 May 2014supplementing Directive 2001/83/EC of the European Parliament and of the Council with regard to principles and guidelines of good manufacturing practice for active substances for medicinal products for human use(Text with EEA relevance)THE EUROPEAN COMMISSION,Having regard to the Treaty on the Functioning of the European Union,Having regard to Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human useOJ L 311, 28.11.2001, p. 67., and in particular the third paragraph of Article 47 thereof,Whereas:(1)All active substances manufactured in the Union, including active substances intended for export, should be manufactured in accordance with the principles and guidelines of good manufacturing practice for active substances which at present are set out in the technical guidelines on manufacturing of active substances published by the Commission. It is necessary to lay down principles and guidelines of good manufacturing practice for active substances in a legally binding act.(2)In order to promote the use of harmonised standards at global level, principles and guidelines of good manufacturing practice for active substances should be laid down in line with the guidelines for active substances established by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.(3)Principles and guidelines of good manufacturing practice should be set out in relation to all issues, operations and processes that are key to determining the quality of active substances, such as quality management, personnel, premises and equipment, documentation, material management, production, in-process quality controls, packaging, labelling, laboratory controls, returns, complaints and recalls, contracting out and repackaging. In order to ensure compliance with those principles and guidelines, the manufacturers of active substances should be required to establish and implement an effective system for managing the quality of those substances.(4)Personnel in unsanitary conditions, wearing unsuitable clothing or practicing potentially contaminating activities in the manufacturing area may compromise the quality of the active substance. This should be prevented by practicing sanitation and health habits that are appropriate to the manufacturing operations performed. Those practices should be provided for in the quality management system established by the manufacturer of the active substance.(5)In order to ensure an adequate quality of the active substance, it is necessary to minimise potential contamination and cross-contamination by requiring the use of facilities, production processes and containers designed for this purpose, as well as appropriate contamination controls.(6)It is of particular importance to prevent cross-contamination when producing active substances harmful to human health. Contamination of other products with highly sensitising active substances could pose a serious threat to public health since exposure to these substances very often results in the development of hypersensitivity and allergic reactions. For that reason, manufacturing of those active substances should only be allowed to take place in separate production areas. The use of separate production areas may also be necessary for the production of active substances with the potential to be harmful to human health because of their potency or their infective or toxic nature. For those substances, the manufacturer should perform an assessment of the risks to human health and the need for separate production areas.(7)In order to facilitate the tracing, identification and solving of potential quality problems as well as to verify compliance with good manufacturing practice, the manufacturer should keep detailed written records of all processes he performs that relate to the manufacturing of active substances, including of deviations from those processes.(8)In order to ensure that medicinal products have the appropriate standards of quality, safety and efficacy and to protect public health, manufacturers of an active substance should communicate without delay any changes which may affect the quality of the active substance to manufacturers of medicinal products using the active substance.(9)It is necessary to have in place appropriate procedures to record and investigate quality-related complaints and perform product recalls in order to rapidly address quality concerns and remove from the market active substances that do not meet quality standards or pose a serious threat to public health.(10)When the manufacturer of the active substance entrusts any part of the manufacturing to another party, it is important to clarify in writing the responsibilities of that other party with regard to compliance with good manufacturing practices and quality measures.(11)The application of good manufacturing practices to the process of repackaging and relabelling is necessary to avoid that active substances are wrongly labelled or become contaminated in the process,HAS ADOPTED THIS REGULATION: