Infusion Bags Research Articles

Physicochemical Stability of Nab-Paclitaxel (Pazenir) Infusion Dispersions in Original Glass Vials and EVA Infusion Bags

Background/Objectives: The study objective was to determine the physicochemical stability of nab-paclitaxel (Pazenir) ready-to-use (RTU) dispersion for infusion in original glass vials and ready-to-administer (RTA) infusion dispersion in EVA infusion bags. Methods: Triplicate test dispersions were prepared and stored light protected for a maximum of 28 days either in the original glass vials (RTU) at 2–8 °C or in EVA infusion bags (RTA) at 2–8 °C and at 25 °C. Directly after reconstitution and on days 1, 3, 5, 7, 14, 21, and 28 samples were withdrawn and paclitaxel concentrations assayed by a stability-indicating HPLC method. In parallel, pH and osmolality were measured. In a second series, test dispersions were stored over a 14-day period and inspected daily for visible particles and colour changes. Samples were taken daily for particle size analysis. Integrity and particle size distribution of the nanoparticles were determined by dynamic light scattering (DLS) and albumin monomers, dimers, oligomers, or polymers by size-exclusion-chromatography (SEC). Results: Non-redispersible particles were observed in test dispersions on day 5 (RTA 25 °C), day 7 (RTA 2–8 °C), and day 11 (RTU 2–8 °C). DLS analysis revealed out-of-specification results for the polydispersity index from day 7 (RTA 25 °C) and day 12 (RTU, RTA refrigerated). Paclitaxel concentrations remained >95% of the initial concentrations for 7 days (RTU 2–8 °C, RTA 25 °C) and for 14 days (RTA 2–8 °C). All test dispersions met the specifications regarding the oligomeric status of albumin, pH, and osmolality over the investigation periods. Conclusions: Stability of nab-paclitaxel dispersions is limited by the release of water-insoluble paclitaxel from the nanoparticles and subsequent crystallisation and by formation of insoluble albumin aggregates. Based on our overall results, shelf life of refrigerated RTU and RTA nab-paclitaxel dispersions is limited to 7 days. Shelf life of RTA nab-paclitaxel dispersions stored at room temperature is limited to 4 days. Careful visual inspection of nab-paclitaxel dispersions after reconstitution and prior to administration is highly recommended to detect non-redispersible particles.

An Assessment of Surface Contamination and Dermal Exposure to 5-Fluorouracil in Healthcare Settings by UPLC-MS/MS Using a New Atmospheric Pressure Ionization Source

5-Fluorouracil (5-FU) is a well-known cytostatic drug, which is often used in cancer treatments. Yet, it is also a very dangerous compound for people who are occupationally exposed to it for a long time, such as pharmacy employees, nurses and cleaning staff. We aimed to improve and implement a LC-MS/MS method for 5-FU quantification on surface contamination samples collected with swabs in a pharmacy department and outpatient nursing station of a university hospital. To improve the existing methods to quantify 5-FU, we compared a LC-MS/MS method using the frequently applied electrospray ionization source (ESI) with a UniSpray ionization source (USI). To determine the contamination of 5-FU in a pharmacy department preparing 5-FU infusion bags, which are then given to patients in the outpatient nursing stations, we collected multiple surface swabs of the laminar flow cabinets and frequently touched objects, before the preparation and administration of 5-FU and afterwards. Furthermore, we sampled the protective gloves and the bare hands of employees of the pharmacy department, involved in the preparation of the infusion bags. Using the USI source, we were able to reach the lowest limit of quantification (LOQ). With this technique, we were able to detect 5-FU contamination on the laminar flow cabinets and frequently used objects in the pharmacy department and the outpatient nursing station in the very low ng/cm2 range. This contamination was mostly higher after preparation or administration than before. While we also found 5-FU on the protective gloves, we almost found no 5-FU on the skin of the pharmacy technicians preparing the 5-FU infusion bags. In conclusion, our method was able to detect very low concentrations of 5-FU contamination, but the contamination we found is very unlikely to result in any issues for the personnel working in these areas.

Rapid Detection of Microplastics/Nanoplastics Directly Exposed to Blood During Intravenous Injections via Mie Scattering Spectra

Microplastics/nanoplastics (M/NPs) are pervasive in the environment, leading to inevitable human exposure through various pathways and raising significant public and scientific concern. Understanding the sources and levels of M/NPs in human blood is crucial for environmental health studies. This work examined the content, type, shape, and size of M/NPs released directly into the bloodstream from medical devices via saline solution during intravenous (IV) injection. The results of the Mie scattering spectra method show that the M/NPs content from infusion bags was 1.0 ± 0.7μg/L, mainly fibers, polyethylene, and polypropylene, with fragments being predominant. During a IV process, the initial 12mL of saline from infusion tubes contained 8.4 ± 3.6μg/L of M/NPs, primarily polyvinyl chloride and fibers. These results suggest that M/NPs exposure during IV therapy mainly originates from infusion tubing, necessitating high concern for exposure risks. Recommendations include: 1) reducing non-essential IV treatments, 2) discarding the initial 12mL of saline solution flowing through the tubing during essential IV therapy, and 3) expediting the development of legal requirements and detection standards by national authorities and the healthcare industry to mitigate the risk of M/NPs exposure in the bloodstream.

Impact of pneumatic tube transportation on the aggregation of monoclonal antibodies in clinical practice

Postproduction handling and in-hospital transportation of antibody drugs cause mechanical stress, including interfacial and shear stress, that can induce antibody unfolding and aggregation. The handling practices differ significantly between hospitals and the impact on protein stability is unknown. For example, the mechanical stress caused by transport via pneumatic tube systems (PTS) on therapeutic antibody aggregation is a potential safety and quality gap.The aim of this study was to investigate whether mechanical stress and PTS transportation in a hospital cause aggregation of five commonly used antibody drugs diluted in infusion bags.Orthogonal analytical methods showed that the handling and PTS transportation in this hospital did not cause aggregation of the investigated mAbs. The absence of aggregation could be explained by the reduction of interfacial stress due to headspace removal from the infusion bags and a mechanical sensor indicated that there was also only a moderate amount of mechanical stress caused by transportation with this particular PTS.Although this case study focuses on five antibody drugs and the practices in one hospital, the work demonstrates how to evaluate whether other handling and transportation practices cause significant mechanical stress that could compromise the quality and safety of antibody drugs.

An automated dispensing cabinet alert influences anesthesia provider medication preparation in a remifentanil waste reduction initiative

Study ObjectiveTo decrease the occurrence of remifentanil waste of 1 mg or more (1 full vial) by 25 % in our surgical division while maintaining satisfaction of 60 % of providers by using a remifentanil mixing workflow. DesignA time series–design quality improvement initiative targeted preventable remifentanil waste. A period of active interventions, followed by a pause and reinstatement of a system intervention, was used to validate its effectiveness. SettingAn academic medical center in the US with 1219 inpatient beds, performing 144,418 surgical cases in 2019 and 127,341 surgical cases in 2020, in 148 operating rooms. InterventionsIndividual- and system-level interventions provided education on the issues of preventable waste, access to a remifentanil dose calculator, and an automated dispensing cabinet (ADC) alert to halt wasteful practice. MeasurementsPreventable remifentanil waste was identified as disposing of intravenous infusion bags containing 1 mg or more or 1 full vial or more of unused medication. Data were retrieved from ADC reports. A preimplementation and postimplementation survey of anesthesia providers assessed workflow attitudes, perceptions, and satisfaction surrounding remifentanil mixing. Main ResultsPreventable remifentanil waste (≥1 mg or ≥ 1 full vial) decreased significantly from 22.0 % of cases using remifentanil at baseline to 16.7 % of cases using remifentanil (odds ratio, 0.71; 95 % CI, 0.60–0.84; P < .001) during the final data collection. Individual-level interventions of education, remifentanil dose calculator, and practice champions did not significantly affect waste while unpaired from the system intervention of the ADC alert. ConclusionsThe implementation of an ADC alert reduced preventable remifentanil waste among anesthesia providers.

Prolonged in-use physicochemical and biological stability of nivolumab and pembrolizumab diluted in saline infusion bags and in partially used medication vials.

The aim of this study was to determine long-term physicochemical and biological stability of nivolumab and pembrolizumab diluted in saline infusion bags and partially used medication vials. This may enable the prolonged clinical use of these expensive monoclonal antibodies (mAbs) to minimize the economic loss. Sterile nivolumab and pembrolizumab concentrates in partially used medication vials and compounded nivolumab and pembrolizumab infusion solutions were stored for two and four weeks, respectively, at 2-8°C in the dark. Subsequently, concentrates and compounded solutions were stored for an additional two weeks under ambient temperature and light conditions. A panel of validated and complementary methods, consisting of enzyme-linked immunosorbent assay, size exclusion chromatography, and dynamic light scattering, were used to assess the biological and physiochemical stability of these mAbs. All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. Diluted in infusion bags, nivolumab and pembrolizumab remained biologically and physiochemically stable for up to four weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light. Stability in partially used medication vials was demonstrated for at least two weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light. The findings of this study justify the storage and clinical re-use of sterile nivolumab and pembrolizumab in partially used medication vials and compounded IV infusion bags for up to six weeks. This minimizes the risk of economic loss due to waste. Moreover, these findings support the batch-wise compounding of fixed-dose and dose-banded nivolumab and pembrolizumab infusion bags.

Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials

Hospital pharmacy compoundings are crucial for maintaining patient care. They are time- and cost-effective in hospital pharmacy settings because they prevent waste, preparation errors, dosage errors, microbial contamination and breakage due to handling. Unfortunately, the drawbacks of hospital pharmacy compounding include the selection of inappropriate medical devices (MDs) for long-term storage, which could directly impact patients.In this study, three important hospital pharmaceutical compoundings, vancomycin in prefilled syringes (PFSs) made of polypropylene (PP) material, paediatric parenteral nutrition (PN) in ethylene vinyl acetate (EVA) bags and diluted insulin in cyclic olefin copolymer (COC) vials, were selected for leachate study and risk assessment. These compounds were studied via a semiquantitative screening approach by means of an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) with postcolumn infusion and an in-house built database. 17 leachable compounds for the PFS, 25 for the PN, and 10 for the vial were identified, and their concentrations were estimated for toxicological assessments.In conclusion, all MDs used in hospital pharmacy compoundings were observed suitable thanks to risk assessments. However, suitable MDs recommended for long-term storage would remain with polymers like COC, for higher safety when exposed to frail and vulnerable patients like neonates and infants.

Antimicrobial infusion practices within intensive care units: Carbapenem infusion preparation and administration process errors

ObjectiveTo describe nurse preparation and administration of intermittent carbapenem infusions. Research methodology/designThis observational study documented the carbapenem infusion process to adult patients in three general intensive care units. Main outcome measuresTiming and duration of infusions were observed. Volumetric analysis of infusion items was conducted to determine loss of reconstituted carbapenem during preparation and administration phases. ResultsCarbapenem infusions (n = 223) administered to twenty adult patients were observed. Infusion duration guidance was variable, with two ICUs following current literature recommendations, and one ICU referring to medication package insert information. Within these parameters, only 60 % of infusions complied with infusion duration. Non-compliance with planned time of administration impacted on desired dosing intervals. Incomplete delivery of intended dose was found during: sub-optimal reconstitution of vials, incorrect number of vials reconstituted, failure to administer a dose (missed dose), and discarding antibiotic residue in infusion items. Volumetric analysis of infusion items showed mean dose losses of 4.9 % and 1.2 % in discarded vials and syringes. Mean drug losses of 6.3 % and 30.8 % occurred in discarded infusion bags and infusion lines respectively. No flushing guidance or practice was observed. ConclusionIncorrect nurse administration of antibiotics resulted in varying durations of infusions and the non-delivery of prescribed dose. Under-dosing has the potential to contribute to selection pressure for bacterial antibiotic resistance. The increasing frequency of intravenous delivery of antimicrobial agents through infusions requires an understanding of the required duration of administration and how to manage residual drug remaining in the intravenous line once the infusion is completed. Implications for clinical practiceFlushing of administration lines is not common practice following intermittent antimicrobial infusions. Although there are multi-factorial risk factors for antimicrobial resistance in the critical care arena, nurse infusion practice must ensure that patients receive intended antimicrobial treatment. Attention must be given to the potential for antimicrobial resistance from environmental contamination with the disposal of infusion items containing undelivered antimicrobial medication.

Combined nefopam-fentanyl use in PCA for postoperative analgesia in spinal surgery patients: a randomized, controlled, single-blind trial

Background &amp; objective: The use of fentanyl to manage postoperative pain in spinal surgery patients is common, although there have been concerns about potential of drug abuse and dependence. We investigated the effects of the combined administration of nefopam and fentanyl through intravenous (IV) patient-controlled analgesia (PCA) on early postoperative pain and possible side effects in patients undergoing spinal surgeries. Methodology: In this randomized, controlled study, 70 patients were allocated to receive either fentanyl 10 µg/mL (Group F) or fentanyl 10 µg/mL with nefopam 1.2 mg/mL (Group FN), with a total PCA volume of 100 mL per infusion bag. Patients received a background dose of 0.25 µg/kg/h and bolus dose of 0.5 mL SOS (fentanyl 5 µg). The lockout interval was set at 10 min and upper limit was set at 15 mL/4 h. The PCA parameters were set according to the body weight of each patient. Results: The cumulative postoperative fentanyl consumptions after 48 h for Group F and Group NF were reported as 744.6 ± 94.2 µg and 631 ± 62.5 µg (P &lt; 0.05) respectively. The average number of bolus doses requested by the patients in Group F and FN were 20.8 ± 11.0, and NF 11.4± 7.6). The A/D ratio of both groups for the bolus doses were 70%. Group NF consistently scored a lower VAS and VAS-D score during the 48-hour postoperative period. However, the VAS scores significantly differ statistically between groups at 1, 6, 9, and 12 hours. Within group differences, the VAS score differed significantly statistically during the 0-1, 1-2, and 2-3 hours for Group F, while 24-36 hours for Group NF. Conclusion: The inclusion of nefopam in patient-controlled analgesia for spine surgery patients significantly reduced total use of fentanyl within the 48 hours postoperatively after the surgery. Patients receiving fentanyl with nefopam consistently had lower VAS scores at different time points. Abbreviations: PCA - patient-controlled analgesia; VAS - Visual Analogue Scale Keywords: postoperative pain, fentanyl, nefopam, patient-controlled analgesia Citation: Le XD, Nguyen ML, Nguyen DT, Do TH, Nguyen HG. Combined nefopam-fentanyl use in PCA for postoperative analgesia in spinal surgery patients: a randomized, controlled, single-blind trial. Anaesth. pain intensive care 2024;28(4):687−691; DOI: 10.35975/apic.v28i4.2370 Received: January 06, 2024; Reviewed: April 14, 2024; Accepted: April 14, 2024

Development of an organic polymer monolith column for the nano liquid chromatography fast analysis of monoclonal antibody in infusion bags prepared in a hospital pharmacy.

Poly(butyl methacrylate-co-ethylene dimethacrylate) monolith was in situ prepared in a liquid chromatography capillary column with a 75 μm internal diameter. This monolith offered high permeability (5.3 ± 10-14m2) and good peak capacity (140 for a 15 cm column length at 300 nl/min with a 20 min gradient time). This is exemplified by its separation ability in reversed mode for subunit analysis of monoclonal antibodies after IdeS digestion (middle-up analysis). The potential of this column was also illustrated for the fast analytical control of therapeutic monoclonal antibodies in standardized infusion bags prepared in advance in a pharmacy department. Linearity analysis revealed the column's capability for accurate quantification analysis of the different dose bandings (in mg) of monoclonal antibodies in <2min. In addition, lifetime analysis data indicated that the column can be highly reproducible and has a long lifetime with stable and low back pressure. The variations observed on the peak shape and area between unstressed (intact) and stressed monoclonal antibodies indicated that our nano liquid chromatographic method was stability indicating. In addition, using a gradient elution mode, the presence of minor components in the infusion bags was visualized.

Impact of continuous-infusion meropenem degradation and infusion bag changes on bacterial killing of Pseudomonas aeruginosa based on model-informed translation

BackgroundContinuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of P. aeruginosa given different continuous-infusion solutions. MethodsA semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (CMEM) and bacterial counts of a resistant P. aeruginosa strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate in vitro antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. CMEM, fT>MIC (time that concentrations exceed the MIC) and total bacterial load (BTOT) after 24 h were simulated for different scenarios (n = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L). ResultsHighest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with CMEM_24h close to the MIC, with differences (Δ) in CMEM_24h up to 4.9 mg/L, ΔfT>MIC≤65.7%, and ΔBTOT_24h≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached. ConclusionsIn summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.

Fast quantitative determination of monoclonal antibody in infusion bags using protein A nano liquid chromatography

AbstractStaphylococcus aureus Protein A was immobilized on an in‐house made neutravidin poly (glycidyl methacrylate‐co‐ethylene dimethacrylate) capillary column with a 25 µm internal diameter, a length of 30 mm and a mass loadability of 60 ng. The immobilized quantity of protein A on the organic monolith was very low, in the pico mole range (1.80 pmol). This was of significance importance when working with less available or expensive purified enzyme. This capillary column was integrated into a nano liquid chromatographic system and used for the fast determination without dilution of the doses of therapeutic monoclonal antibodies (mAbs) in standardized infusion bags prepared in advance in a pharmacy department. This chromatographic method was linear in the studied concentration range with good precision and accuracy. Heat stressed studies indicated that the protein A affinity capillary column was able to monitor degraded mAbs. As well, the high specificity of this column to capture immunoglobulin G2 in cell culture supernatant was visualized. As the mAbs are produced through genetic engineering of animal cells this last result demonstrated that this novel protein A column could be used in the feature for rapid screening of immunoglobulin G concentration in cell culture.

Development and validation of a HPLC method simultaneously assisted with diode array and evaporative light scattering detection for the quantification of clinical mAb infusion bags in hospital pharmacy

To secure the supply chain of the monoclonal antibody (mAb) standardized infusion bags, a reversed phase (RP) HPLC analytical method assisted with a diode array detector (DAD) and an evaporative light scattering detector (ELSD) was implemented in the pharmacy department of the university hospital center of Besançon (UHCB). For a well-defined batch, the concordance between the two detections evaluated using the Lin’s concordance correlation coefficient (CCC) (Lin’s CCC = 0.9858) and a Bland–Altman plot was excellent. The analytical quantification of the different dose-banded (DB) of the infusion bags prepared in advance were achieved using this new reversed HPLC-DAD/ELSD analytical method in less than 4 min. For a same batch of mAbs, DAD generated nearly uniform response and showed a slightly superior accuracy than did ELSD. Their agreement in terms of calculated dose is excellent. In the event of a breakdown of one of the two detectors, this allowed the mAb infusion bags to continue to be monitored and thus improved the drug supply chain safety. As well our optimized method was able to monitor degradation mAbs created by accidental stress during the time period of stockage.

Rates of paclitaxel hypersensitivity reactions using a modified Markman’s infusion protocol as primary prophylaxis

PurposeMarkman’s desensitisation protocol allows successful retreatment of patients who have had significant paclitaxel hypersensitivity reactions. We aimed to reduce the risk and severity of paclitaxel hypersensitivity reactions by introducing this protocol as primary prophylaxis.MethodsWe evaluated all patients with a gynaecological malignancy receiving paclitaxel before (December 2018 to September 2019) and after (October 2019 to July 2020) the implementation of a modified Markman’s desensitisation protocol. The pre-implementation group received paclitaxel over a gradually up-titrated rate from 60 to 180 ml/h. The post-implementation group received paclitaxel via 3 fixed-dose infusion bags in the first 2 cycles. Rates and severity of paclitaxel hypersensitivity reactions were compared.ResultsA total of 426 paclitaxel infusions were administered to 78 patients. The median age was 64 years (range 34–81), and the most common diagnosis was ovarian, fallopian tube and primary peritoneal cancer (67%, n = 52/78). Paclitaxel hypersensitivity reaction rates were similar in the pre-implementation (8%, n = 16/195) and post-implementation groups (9%, n = 20/231; p = 0.87). Most paclitaxel hypersensitivity reactions occurred within 30 min (pre- vs. post-implementation, 88% [n = 14/16] vs. 75% [n = 15/20]; p = 0.45) and were grade 2 in severity (pre- vs. post-implementation, 81% [n = 13/16] vs. 75% [n = 15/20]; p = 0.37). There was one grade 3 paclitaxel hypersensitivity reaction in the pre-implementation group. All patients were successfully rechallenged in the post-implementation group compared to 81% (n = 13/16) in the pre-implementation group (p = 0.43).ConclusionThe modified Markman’s desensitisation protocol as primary prophylaxis did not reduce the rate or severity of paclitaxel hypersensitivity reactions, although all patients could be successfully rechallenged.

Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia

BackgroundAccidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37–42°, as fluid temperature can decrease the patient’s body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care.MethodsIn this experimental simulation study, temperature changes in crystalloids preheated to 39 °C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between − 4 and 28 °C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm.ResultsThe flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid.ConclusionThis study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 °C is to remain above 37 °C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.

Investigating the Impact of Drone Transport on the Stability of Monoclonal Antibodies for Inter-Hospital Transportation

In the field of healthcare logistics, the reliance on conventional transport methods such as cars for the delivery of monoclonal antibodies (mAbs) is susceptible to challenges posed by traffic and infrastructure, leading to increased and unpredictable transport times. Recognizing the potential role of drones in mitigating these challenges, we aimed to investigate the impact of medical drone transport on the stability of mAbs. Compromised stability could lead to aggregation and immunogenicity, thereby jeopardizing the efficacy and safety of mAbs. We studied the transportation of vials as well as ready-to-administer infusion bags with blinatumomab, tocilizumab, and daratumumab. The methodology involved the measurement of both temperature and mechanical shock during drone transport. Moreover, the analytical techniques High Performance Size-Exclusion Chromatography (HP-SEC), Dynamic Light Scattering (DLS), Light Obscuration (LO), Micro-Flow Imaging (MFI), and Nanoparticle Tracking Analysis (NTA) were employed to comprehensively assess the presence of aggregates and particle formation. The key findings revealed no significant differences between car and drone transport, indicating that the stability of mAbs in both vials and infusion bags was adequately maintained during drone transport. This suggests that medical drones are a viable and reliable means for the inter-hospital transport of mAbs, paving the way for more efficient and predictable logistics in healthcare delivery.

Protocolized oxytocin infusion for elective cesarean delivery: a retrospective before-and-after study

PurposeTo elucidate the clinical impact of the novel oxytocin protocol using a syringe pump with a stratified dose compared with the conventional practice of putting oxytocin into the bag.MethodsThis is a retrospective cohort study. We collected the data of the patients who underwent elective cesarean delivery under neuraxial anesthesia between June 2019 and May 2020. The patients were allocated to two groups according to oxytocin administration methods; the control group (the attending anesthesiologist put oxytocin 5–10 units in the infusion bag and adjusted manually after childbirth) and the protocol group (the oxytocin protocol gave oxytocin bolus 1 or 3 units depending on the PPH risk, followed by 5 or 10 unit h−1 via a syringe pump). We compared the total amount of oxytocin within 24 h postpartum, estimated blood loss, and adverse clinical events within 24 h postpartum between the two groups.ResultsDuring the study period, 262 parturients were included. Oxytocin doses of intraoperative and postoperative were significantly lower in the protocol group (9.7 vs. 11.7 units, intraoperative, 15.9 vs. 18 units, postoperative). The subgroup analyses showed that the impact was more remarkable in the low PPH risk than in the high PPH risk. The multivariate linear regression analyses also confirmed the difference. The groups had no significant difference in blood loss, requirement of additional uterotonics, and other adverse events.ConclusionsOur oxytocin infusion protocol significantly reduced oxytocin requirements in elective cesarean delivery under neuraxial anesthesia without increasing blood loss. However, we could not find other clinical benefits of the novel protocol.

Physicochemical stability of pevonedistat at 50, 100 and 200 µg/mL diluted in 0.9% sodium chloride and at 10 mg/mL in partially used vials

ObjectivesPevonedistat is a new cytotoxic used in association with azacitidine for the treatment of acute myeloid leukaemia and high-risk myelodysplastic syndromes. The manufacturer indicates an 18-hour stability after dilution in...

Impact of NaCl on Monoclonal Antibody Aggregation Induced by Agitation.

Monoclonal antibodies (mAbs) are a successful class of therapeutics, but their development can be challenging due to the risk of degradation that could happen during manufacturing, storage, and clinical use. One of the common causes of degradation is agitation stress from transportation and clinical handling, which increases interfacial stresses to mAbs. For example, the preparation of the dose solution prior to administration often requires diluting therapeutic mAbs in intravenous (IV) infusion bags containing normal saline, which can substantially reduce the level of protective surfactant and increase the level of salt in mAb solutions. Then the interfacial stress in the subsequent transportation of IV bags can cause mAb aggregation or even particle formation. To better understand the complex interplay between dilution, interfacial stress, and salt, we studied the impact of sodium chloride (NaCl) on the aggregation of two mAbs under agitation stress. We found that the presence of NaCl accelerates the aggregation of both mAbs, but the aggregation mechanism, morphology, and reversibility are very different. Our results clearly highlight the impact of salt on mAb stability at the clinical in-use condition. We believe this study further increases our understanding of protein aggregation mediated by interfacial stresses and brings valuable insights to support development of mAb formulations for patients.

Physicochemical and biological stability of diluted vedolizumab in intravenous infusion bags

IntroductionIntravenous vedolizumab is a widely used monoclonal antibody for outpatients with inflammatory bowel disease. Drug preparation is performed on the day of administration, but is time consuming, causing unnecessary in-hospital...