Laschi Alda, Sehnal Natacha, Alarcon Antoine, Barcelo Beatrice, Caire-Maurisier François, Delaire Myriam, Feuilloley Marc, Genot Stéphanie, Lacaze Catherine, Pisarik Luc, Smati Christophe
French Society of Pharmaceutical Science and Technology (SFSTP) Working Group on Container-Content Interaction, 106 rue Monge, Paris, France.
PDA J Pharm Sci Technol. 2009 Jul-Aug;63(4):285-93.
Container-content compatibility studies are required as part of the submission of a new product market authorization file or for a change relating to the primary product-contact packaging. Many regulatory publications and guidances are available in the USA, Europe, and Japan. However these publications and guidances are not sufficiently precise enough to allow for consistent interpretation and implementation of the technical requirements. A working group has been formed by the French Society of Pharmaceutical Science and Technology (SFSTP) in order to propose guidance for container-content interaction studies that meet both European and US requirements, and allows consistent and standardized information to be presented by the industry to the regulators. When a pharmaceutical drug product remains in prolonged contact with a material, the two critical points to consider are the drug product's quality and safety. A pharmaceutical evaluation of the container-content relationship should be done based on the knowledge of the contact material (e.g., type, physicochemical properties), its manufacturing processes (e.g., the type of sterilization that could potentially alter the interactions), and the formulation components involved in contact with this material (e.g., physicochemical properties, pharmaceutical presentation, route of administration). Quality is evaluated using the stability study performed on the product. Safety is partially evaluated with the stability study and is analyzed in conjunction with toxicity testing, specifically with cytotoxicity testing. The toxicity aspect is the key point of the container-content compatibility study and of patient safety. Migration tests are conducted when an interaction is suspected, or found based on previous results, to identify the component responsible for this interaction and to help select a new material if needed. Therefore, such tests are perhaps not the best ones to use for the purpose of safety evaluation. Consequently, a decision tree based mainly on the toxicity aspect is proposed in order to support the pharmaceutical companies' container-content interaction approach and filing.
作为新产品上市许可申请文件的一部分，或者对于与主要产品接触包装相关的变更，需要进行容器-内容物相容性研究。在美国、欧洲和日本，有许多监管出版物和指南可供参考。然而，这些出版物和指南不够精确，无法对技术要求进行一致的解释和实施。法国制药科学与技术协会（SFSTP）成立了一个工作组，旨在为符合欧洲和美国要求的容器-内容物相互作用研究提供指导，并使行业能够向监管机构提供一致且标准化的信息。当药品与一种材料长时间接触时，需要考虑的两个关键点是药品的质量和安全性。应基于对接触材料（如类型、理化性质）、其制造工艺（如可能改变相互作用的灭菌类型）以及与该材料接触的制剂成分（如理化性质、药物剂型、给药途径）的了解，对容器-内容物关系进行药学评估。使用对产品进行的稳定性研究来评估质量。通过稳定性研究对安全性进行部分评估，并结合毒性测试，特别是细胞毒性测试进行分析。毒性方面是容器-内容物相容性研究和患者安全的关键点。当怀疑存在相互作用或根据先前结果发现存在相互作用时，进行迁移测试，以确定导致这种相互作用的成分，并在需要时帮助选择新材料。因此，此类测试可能并非用于安全性评估的最佳测试。因此，提出了一个主要基于毒性方面的决策树，以支持制药公司的容器-内容物相互作用方法和申报。
