Avrupa Komisyonu, ilaç katkıları için İyi Medikal Üretim taslak kılavuzunu yayımlıyor (İng)
The European Commission Health and Consumers Directorate – General has published draft “GUIDELINES ON THE FORMALISED RISK ASSESSMENT FOR ASCERTAINING THE APPROPRIATE GOOD MANUFACTURING PRACTICE FOR EXCIPIENTS OF MEDICINAL PRODUCTS FOR HUMAN USE” for public consultation.
As per Article 46(f) of Directive 2011/83/EC “The holder of the manufacturing authorisation shall ensure that the excipients are suitable for use in medicinal products by ascertaining what the appropriate good manufacturing practice is. This shall be ascertained on the basis of a formalised risk assessment in accordance with the applicable guidelines referred to in the fifth paragraph of Article 47.
The section 2 of the guideline covers Determination of appropriate GMP based on type of excipient provides guidance on how to assess and rank the risk presented by the excipient. Quality Risk Management principles should be used to assess the risks presented to the quality, safety and function of each excipient and to classify the excipient in question as “low risk”, “medium risk” or “high risk”. Area to be considered include Transmissible Spongiform Encephalopathy,Potential for viral contamination, Potential for microbiological or endotoxin/pyrogen contamination,Potential, in general, for any impurity originating from the raw materials (e.g. aflatoxins, pesticides) or generated as part of the process and carried over (e.g. residual solvents and catalysts), Sterility assurance (for excipients claimed to be sterile), Use of dedicated equipment and/or facilities, and Environmental control and storage conditions.
The section 3 recommends determination of Excipient Manufacturer´s Risk Profile covers identification of appropriate GMP and assessment, ranking and control of the risk profile of the excipient manufacturer. A gap analysis of the required GMP against the activities and capabilities of the excipient manufacturer should then be performed. Any gaps identified between the required GMP and the activities and capabilities of the excipient manufacturer should be documented. Furthermore, the Manufacturing Authorisation Holder should perform a further risk assessment to determine the risk profile (i.e. low risk, medium risk or high risk, for that excipient manufacturer). The Manufacturing Authorisation Holder should have a series of risk mitigation strategies ranging from acceptance through control to unacceptable for the different risk profiles and based on these a control strategy.
Section 4, Confirmation of Application of Appropriate GMP” presents guidance on how to manage the risks of use of the excipient on an on-going basis. Once the “appropriate GMP” for the excipient and the risk profile of the manufacturer has been defined on-going risk review should be performed through mechanisms such as: Number of defects on received batches of excipients, Type/severity of defects on excipients, Loss of relevant quality system accreditation by excipient manufacturer, Observation of trends in drug product quality attributes (this will depend on the nature and role of excipient), Audit (re-audit) of excipient manufacturer.
Stakeholders are invited to comment on this draft by 30 April 2013 at the latest. Responses should be sent preferably by e-mail to email@example.com, or by post to Unit SANCO/D/6, DM24 02/050, BE-1049 Brussels.