title: Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.
abstract: MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original packaging container and strict aseptic handling conditions need to be followed.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mueller
authors.forename: Elke
authors.initials: E
authors.lastname: Dietel
authors.forename: Severin R
authors.initials: SR
authors.lastname: Heynen
authors.forename: Heiko
authors.initials: H
authors.lastname: Nalenz
authors.forename: Pierre
authors.initials: P
authors.lastname: Goldbach
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmidt
authors.forename: Ulla
authors.initials: U
authors.lastname: Grauschopf
authors.forename: Karin
authors.initials: K
authors.lastname: Schoenhamnmer
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards; D001207:Asepsis; D002626:Chemistry, Pharmaceutical; D003116:Color; D004339:Drug Compounding; D004340:Drug Contamination / Q000517:prevention & control; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D017408:Guidelines as Topic; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D009994:Osmolar Concentration; D019999:Pharmaceutical Solutions; D011786:Quality Control; D000069283:Rituximab / Q000008:administration & dosage / Q000737:chemistry*; D013594:Syringes; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D019999:Pharmaceutical Solutions; D000069283:Rituximab