title: Container-content compatibility studies: a pharmaceutical team's integrated approach.
abstract: 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.
authors.affiliation: French Society of Pharmaceutical Science and Technology (SFSTP) Working Group on Container-Content Interaction, 106 rue Monge, Paris, France. Alda.Laschi@sanofipasteur.com
authors.forename: Alda
authors.initials: A
authors.lastname: Laschi
authors.forename: Natacha
authors.initials: N
authors.lastname: Sehnal
authors.forename: Antoine
authors.initials: A
authors.lastname: Alarcon
authors.forename: Beatrice
authors.initials: B
authors.lastname: Barcelo
authors.forename: François
authors.initials: F
authors.lastname: Caire-Maurisier
authors.forename: Myriam
authors.initials: M
authors.lastname: Delaire
authors.forename: Marc
authors.initials: M
authors.lastname: Feuilloley
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Genot
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacaze
authors.forename: Luc
authors.initials: L
authors.lastname: Pisarik
authors.forename: Christophe
authors.initials: C
authors.lastname: Smati
mesh_terms: D003663:Decision Trees; D004340:Drug Contamination; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000379:methods; D004349:Drug Packaging / Q000331:legislation & jurisprudence / Q000592:standards*; D004355:Drug Stability; D004356:Drug Storage; D005060:Europe; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D012957:Societies, Pharmaceutical; D013678:Technology, Pharmaceutical / Q000379:methods*; D014481:United States
chemical_list: D004364:Pharmaceutical Preparations