Extended stability of the rituximab biosimilar CT-P10 in its opened vials and after dilution and storage in polyolefin bags.

The stability of the rituximab biosimilar CT-P10, in 50mL vials at a concentration of 10mg/mL, and after dilution to final concentrations of 1 and 4mg/mL and storage in polyolefin bags at 4°C and 25°C was studied by several orthogonal and complementary methods. No significant change (as defined by a magnitude greater than the inter-batch variability) was observed, for each of the parameters characterizing physical and chemical stability studied, for the two concentrations and temperatures tested, or for any of the three batches tested. This implies that cold-chain rupture and exposure to room temperature up to 15 days both for vials and diluted bags have no deleterious consequence on the quality of the product. Moreover, this extended stability permits safe in-advance preparation, dose-banding or flat-dose, that to avoid unnecessary delays in the management of the patient, improvement of the pharmacy and nurse workload and money saving by avoiding non justified losses of this expensive drug.

Evaluation of sources to document extended shelf lives of compounded cytostatics.

BACKGROUND: Due to the increasing demand for compounded cytostatics, future compounding of these drugs has to include automated production and improved logistics, and in both cases batch production for stockholding is needed. This set-up would also meet future staff shortages. Stockholding requires documentation of extended shelf lives in the range of minimum 1-3 months. Documentation is often provided by summary of product characteristics, data provided by the industry which is not included in the summary of product characteristics and data from literature. OBJECTIVE: To evaluate the quality of the three main stability data sources used by hospital pharmacies when assessing extended shelf lives of compounded cytostatics. METHODS: A total of 150 summary of product characteristics for fluorouracil, cyclophosphamid, oxaliplatin, cisplatin, doxorubicin, paclitaxel, vincristin, irinotecan, epirubicin, gemcitabin, docetaxel, carboplatin and cytarabin were examined regarding available information on how to handle the compounded product. A survey of literature for shelf lives for cyclophosphamide, fluorouracil, oxaliplatin and gemcitabine has been made. Dialogues with 14 suppliers of cytostatica have been conducted to clarify the possibility of expanding the fluorouracil information on shelf lives to include information on extended shelf lives of compounded products. RESULTS: The analysis showed that often the information on shelf life stated in the summary of product characteristic is very short and sparse in basic information regarding the compounded product. The dialogues with the companies revealed that longer shelf lives will probably not be stated in the summary of product characteristic, and the literature review revealed very different stability data and uncertainty on the validity of the obtained data. CONCLUSION: None of these data sources can be applied as documentation for extended shelf lives and it is crucial to document the extended stability yourself.

A Method for Risk Assessment Evaluating the Safety, Stability and Efficacy in Clinical Practice of Anticancer Drug Preparations in the Centralized Compounding Unit of the Veneto Institute of Oncology-IRCCS.

BACKGROUND: Preparation of injectable anticancer drugs in hospital pharmacies is a high-risk activity that requires a proper risk assessment (RA) and quality assurance system (QAS) to ensure both a decrease in risk associated with chemotherapy compounding and high quality of the final product, especially in terms of its microbiological stability. METHODS: At the centralized compounding unit (UFA) of the Italian Hospital IOV-IRCCS, a quick and deductive method was applied to evaluate the "added value" provided by each prescribed preparation, and its RA was calculated applying a formula that integrates different pharmacological, technological and organizational aspects. According to specific RA range values, the preparations were divided into different risk levels, in order to determine the QAS to be adopted, according to the Italian Ministry of Health guidelines, whose adherence was meticulously evaluated through a specific self-assessment procedure. A review of the scientific literature was carried out to integrate the risk-based predictive extended stability (RBPES) of drugs with data concerning their physiochemical and biological stability. RESULTS: Based on the self-assessment comprising all microbiological validations of the working area, personnel and products, the microbiological risk level within the IOV-IRCCS' UFA was defined through the creation of a transcoding matrix, conferring a microbiological stability to preparations and vial leftovers of a maximum of 7 days. The calculated RBPES were successfully integrated with stability data from the literature, leading to the drafting of a stability table of drugs and preparations in use in our UFA. CONCLUSIONS: Our methods allowed us to perform an in-depth analysis of the highly specific and technical process of anticancer drug compounding in our UFA, ensuring a certain grade of quality and safety to preparations, especially in terms of microbiological stability. The resulting RBPES table represents an invaluable tool with positive repercussions at organizational and economic levels.

End Group Modification for Black Phosphorus: Simultaneous Improvement of Chemical Stability and Gas Sensing Performance.

Black phosphorus (BP) nanosheets have been receiving attention for gas sensing showing superior sensitivity and selectivity among various two-dimensional materials. However, the instability of BP nanosheets due to chemical degradation, especially in humid environments, has severely limited their potential applications. Here, we propose to control the chemical stability of BP nanosheets through modifying their end groups via silanization treatment. Compared with other chemical passivation methods, the end group modification strategy proposed here can be well-controlled and results in little variation in the electronic structure of the puckered phosphorus plane. The results show that modification with fluoroalkylsilane leads the hydrophilic BP to become hydrophobic and exhibits extended chemical stability in oxidizing, humid environments. The sensitivity of fluoroalkylsilane-modified BP (F-BP) to NO2 improved by 3.9-fold in comparison with that of pristine BP nanosheets. More importantly, the NO2 sensing response could remain stable under changing relative humidity ranging from 5% to 95%. Such excellent sensing performance is ascribed to the strong interaction between NO2 and BP decorated with fluoroalkylsilane, as confirmed by density functional theory calculations. This work offers an effective means for preventing degradation of BP in ambient environments and provides a promising solution to solve the issue regarding humidity dependence in gas sensors.

Extended Stability of Reconstituted and Diluted SB3 (Trastuzumab Biosimilar) Assessed by Physicochemical and Biological Properties.

INTRODUCTION: Stability information for the trastuzumab biosimilar SB3 is limited to 48 h at 2-8 °C for the reconstituted solution and 24 h at up to 30 °C for diluted solutions. Extended physicochemical stability and biological activity were assessed to evaluate the advanced preparation of reconstituted and diluted SB3. METHODS: Under controlled and aseptic conditions, the stability of reconstituted and diluted SB3 was evaluated using several assessments and according to the UK's National Health Service guidance. Reconstituted SB3 was stored at 25 ± 2 °C with 60 ± 5% relative humidity for 3 days, and subsequently diluted SB3 (0.32-4 mg/mL) was stored in an infusion bag in the absence of light at 25 ± 2 °C with 60 ± 5% relative humidity for 28 days and 5 ± 3 °C for 28 days, respectively. Physicochemical stability (appearance, pH, protein concentration, size exclusion high-performance liquid chromatography, non-reducing capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity (competitive inhibition binding assay to human epidermal growth factor receptor 2 by fluorescence resonance energy transfer, anti-proliferation assay), and properties with a potential safety impact (subvisible particulates, submicronic aggregation by dynamic light scattering) were determined. RESULTS: No physicochemical instability signs or biological activity changes were observed for either reconstituted or diluted SB3 up to 28 days; all stability acceptance criteria were met. No major change was noted in the proportion of molecular weight variants (high molecular weight impurity, total purity) or relative percentages of acidic, main, and basic charge isoforms of the protein. No increases in particulates or aggregates in terms of a potential safety impact were noted. CONCLUSION: The physicochemical stability and biological activity of reconstituted and diluted SB3 are maintained for extended time periods beyond those denoted in the product labeling, which allows for advanced SB3 preparation and may reduce drug wastage and preparation time. FUNDING: Samsung Bioepis Co., Ltd.

Extended stability study of an extemporaneously analgesic solution of clonidine, ropivacaine and fentanyl

Abstract The aim of this work was to perform an extended stability study for the analgesic containing fentanyl, clonidine and ropivacaine in physiological saline solution 0.9% at different infusion sites, such as infusion bags, epidural infusion sets and syringes. The extended stability was assessed by an HPLC system equipped with a photodiode array detector set at 210 nm. The separation was conducted on a C18 column maintained at 40˚C and using an isocratic mobile phase consisted of buffer solution-methanol-acetonitrile (45:45:10, v/v/v). The presence of particulate matter and the pH of each solution were also investigated. Twenty-four hours after the preparation, the formation of one suspected product was observed and for all drugs, in 24 hours it was observed the concentration decrease in different sets (PVC infusion bags, syringes and epidural infusion administration sets). The pH values of each solution varied no more than 5% during the study and no particle was observed. Conclusion: The extended stability study was applied to the analgesic solution and promoted the detection of an unexpected peak in 24 hours. Based on it, further stability studies are necessary to determine the extended stability data.