Syringe Research Articles

Cost-effectiveness and outcome of ultrasonographically guided clipping of breast mass using metallic clips made from 5 cc disposable syringe needles: introducing new cost-effective technique for LMICs

Cost-effectiveness and outcome of ultrasonographically guided clipping of breast mass using metallic clips made from 5 cc disposable syringe needles: introducing new cost-effective technique for LMICs

Correlation of fasting serum cholesterol level with severity of chronic liver disease.

Objective: To evaluate correlation of fasting serum cholesterol level with severity of chronic liver disease (CLD). Study Design: Cross-sectional Survey. Setting: North Medical Ward, Mayo Hospital Lahore. Period: June 2020 to December 2020. Material & Methods: Patients having chronic liver disease with age 25-85 years and of either gender, were included. After 12 hours of fasting, 5ml of blood was drawn from patients under all aseptic precautions into sterile disposable syringes and blood samples were sent to laboratory for measurement of total cholesterol. Total cholesterol (TC) in mg/dl was noted from their reports. CLD severity patients was defined by using Modified Child Pugh classifications. Data was entered in SPSS version 20 and analyzed by same software. Results: Total 100 cases diagnosed with chronic liver disease (CLD) were studied, with an average age of 53.8±10.76 years. The majority of participants, constituting 72%, were male. Overall average TC was 119.85±31.51mg/dl. Out of all 27% patients belonged to CPT class A, 28% had CPT class B and 45% had CPT class C. Spearman correlation between Child Pugh score and total cholesterol level was calculated. A negative spearman correlation was found as r= -.672. It was significant at the level of 0.01. Conclusion: As per the study conclusion, total serum cholesterol level was observed to be the significantly corelated with degree of liver damage. The significance of this correlation highlights the potential clinical utility of serum total cholesterol as a prognostic tool for evaluating the degree of liver damage.

TVRI Sulbar Program In Preserving Mandar Culture In West Sulawesi

This research uses agenda setting theory as a way to look at the production process of local TVRI West Sulawesi broadcasts, starting from the design process to the broadcast stage and then looking at the public response to cultural broadcasts broadcast by TVRI West Sulawesi, as well as using hypodermic (syringe) theory to look at the factors. supporters and obstacles to TVRI West Sulawesi in broadcasting Mandar cultural content in West Sulawesi. The data sources for this research are employees of TVRI West Sulawesi, KPID West Sulawesi, humanists and broadcasting academics. Data collection methods used in research are observation, interviews and documentation. The data collection technique used is the inductive method. The results of this research show. TVRI West Sulawesi does not yet have a special cultural program, TVRI. The TVRI West Sulawesi program with a cultural theme comes from the national program, namely Indonesian Charm, the theme is dominated by cultural themes, the Indonesian Charm program is broadcast once a month and the program model is a documentary. The supporting factors for TVRI West Sulawesi in its cultural content are program support from TVRI Nasional and the inhibiting factors are human resources, budget and competition.

Assessing the Clinical, Economic, and Health Resource Utilization Impacts of Prefilled Syringes Versus Conventional Medication Administration Methods: Results From a Systematic Literature Review.

The objective of this systematic review was to assess the clinical, economic, and health resource utilization outcomes associated with the use of prefilled syringes in medication administration compared with traditional preparation methods. We conducted a systematic literature review to evaluate outcomes such as medication errors, wastage, time savings, and contamination in prefilled syringes. Our search encompassed multiple databases, including PubMed and Embase, for studies published between January 1, 2017, and November 1, 2022. Peer-reviewed publications meeting our inclusion criteria underwent rigorous screening, including title, abstract, and full-text article assessments, performed by two reviewers. Among reviewed articles, 24 met our eligibility criteria. Selected studies were primarily observational (46%) and conducted in Europe (46%). Our findings indicated that prefilled syringes consistently reduced medication errors (by 10%-73%), adverse events (from 1.1 to 0.275 per 100 administrations), wastage (by up to 80% of drug), and preparation time (from 4.0 to 338.0 seconds) (ranges varied by drug type, setting, and dosage). However, there was limited data on contamination. Economically, prefilled syringes reduced waste and error rates, which may translate into overall savings. This review highlights the value of prefilled syringes, which can streamline medication delivery, save nursing time, and reduce preventable medication errors. Moreover, prefilled syringes have the potential to minimize medication wastage, optimizing resource utilization and efficiency in health care settings. Our findings provide new insights into clinical and economic benefits of prefilled syringe adoption. These benefits include improved medication delivery and safety, which can lead to time and cost reductions for health care departments, hospitals, and health systems. However, further real-world research on clinical and economic outcomes, especially in contamination, is needed to better understand the benefits of prefilled syringes.

A Phase 3b, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-Njft (P1101) in Adult Patients with Polycythemia Vera

Background and Significance: Polycythemia vera (PV), the most common chronic myeloproliferative neoplasm in the United States, is a long-term, debilitating, life-threatening cancer with limited treatment options. Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis. Cytoreductive therapy is recommended for high-risk and in some low-risk patients. Ropeginterferon alfa-2b-njft (P1101) is the first and only FDA-approved interferon for treating PV regardless of patients' risk category or past treatment history. The FDA-approved dosing for ropeginterferon alfa-2b-njft in patients with PV is a starting dose of 50 or 100 mcg every 2 weeks, with dose increases of 50 mcg every 2 weeks up to a maximum of 500 mcg. Clinical trial results confirmed high complete hematologic response (CHR) rates and molecular responses to ropeginterferon alfa-2b-njft, however, time to achieve CHR can take 6 months or longer because dose escalation to the highest maintenance dose ranged from 16 to 28 weeks. It is expected that the faster and simpler dosing scheme of 250-350-500 mcg, escalated every 2 weeks may allow patients to achieve complete hematologic responses significantly earlier with acceptable tolerability and safety. This notion was supported in a recently reported clinical study (Jin et al. Exp Hematol Onc 2023). To further assess the 250-350-500 mcg dosing regimen, this Phase 3b, randomized, open-label, parallel group, multicenter study (NCT05481151) of U.S. and Canadian patients will evaluate the efficacy and safety of ropeginterferon alfa-2b-njft when using the above described dose-escalation scheme directly compared with the approved dosing scheme. Study Design and Methods: The planned enrollment for this study is approximately 100 patients with PV aged ≥18 years from the U.S. and Canada. Patients will be randomized (1:1) into either the approved dosing regimen arm or the amended dose-escalation scheme arm (Figure 1). Inclusion criteria include diagnosis of PV according to the WHO 2008 or 2016 criteria, hemoglobin ≥10 g/dL for females, and hemoglobin ≥11 g/dL for males at screening, neutrophil count ≥1.5 × 10 9/L at screening. Exclusion criteria include: any contraindications to interferon alfa or hypersensitivity to interferon alfa, having stopped prior interferon alfa therapy due to low efficacy or poor tolerability, severe or serious diseases or any other diseases that the investigator determines may affect the subject's participation in this study, or the use of any investigational drug <4 weeks prior to the first dose of ropeginterferon alfa-2b-njft. Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included. Patients in the approved dosing arm will undergo HU tapering by 25% for the first 2 weeks, followed by 50% for weeks 3-4, 75% for weeks 5-6, and discontinuing completely during week 7 and onwards. Patients in the amended dose-escalation scheme arm are required to discontinue HU immediately upon initiation of ropeginterferon alfa-2b-njft. The primary efficacy endpoint is CHR (defined as hematocrit <45% in the absence of phlebotomy in the previous 12 weeks, white blood cell count ≤10 × 10 9/L, and platelets ≤400 × 10 9/L) at Week 24. Secondary endpoints include time to CHR, proportion of patients in CHR at Weeks 8, 12, 16, 20, 24, 36, and 48; time to maintenance dose (stable dose for 3 consecutive doses); and time to freedom from phlebotomies. The core treatment period will be 24 weeks followed by a 24-week extension period and a 4-week safety follow-up. Ropeginterferon alfa-2b-njft (P1101) will be provided in single-use 500-mcg prefilled syringes for subcutaneous administration every 2 weeks. The approved dosing arm will initiate with a starting dose of 100 mcg (Day 0) and increase by 50-mcg every 2 weeks up to a maximum dose of 500 mcg. The amended dosing arm will initiate with a starting dose of 250 mcg (Day 0), increase to 350 mcg at Week 2, and increase to a maximum of 500 mcg at Week 4. Dose adjustments will be allowed if safety or tolerability concerns arise. Cochran-Mantal-Haenszel test stratified by investigator sites will be used for analyzing the primary efficacy endpoint at Week 24. General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.

Glucagon fill rates and cost among children and adolescents with type 1 diabetes in the United States, 2011–2021

AimsTo characterize glucagon fill rates and costs among youth with type 1 diabetes mellitus (T1DM). MethodsClaims-based analysis of commercially-insured youth with T1DM included in OptumLabs® Data Warehouse between 2011 and 2021. Glucagon fill rates and costs were calculated overall and by formulation (injectable, intranasal, autoinjector, and pre-filled syringe). Sociodemographic and clinical factors associated with glucagon fills were examined using Cox regression. ResultsWe identified 13,267 children with T1DM (76.4% non-Hispanic White). Over mean follow-up of 2.81 years (SD 2.62), 70.0% filled glucagon, with stable fill rates from 2011 to 2021. Intranasal glucagon had rapid uptake following initial approval, and it accounted for almost half (46.6%) of all glucagon fills by 2021. Family income was positively associated with glucagon fills in a stepwise fashion (HR 1.39 [95% CI 1.27–1.52] for annual household income ≥$200,000 vs. <$40,000), while Black race was negatively associated with fills (HR 0.83 [95% CI 0.76–0.91]) compared to White race). Annual mean out-of-pocket costs ranged from $21-$68 (IQR $29-$44). ConclusionRoughly 30% of commercially-insured youth with T1DM may lack access to unexpired glucagon, with significant disparities among Black and low-income patients. Health systems, clinicians, schools, and caregivers should work together to ensure children have reliable access to this critical medication.

Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties

BackgroundIntravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands).MethodsTo assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)).ResultsFaricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor.ConclusionsWithdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.

The impact of using prefilled syringes on a standard operating procedure for preparing injectable medicines in clinical areas.

The impact of using prefilled syringes on a standard operating procedure for preparing injectable medicines in clinical areas.

Clinical Bridging From Prefilled Syringe to On-body Injector for Risankizumab in Crohn's Disease

This article describes the clinical development bridging strategy and key data to support the marketing application of the risankizumab on-body injection (OBI) system for the treatment of moderately to severely active Crohn's disease (CD), even though the OBI was not evaluated directly in the pivotal Phase III studies in CD. Three studies were conducted as part of the clinical bridging strategy. The pilot pharmacokinetics (PK) study was a Phase I, single-dose, 4-arm, open-label, randomized, parallel-group exploratory PK and tolerability study that assessed the effect of rate and volume of administration on the bioavailability (BA) of risankizumab and the extent of injection site-related pain after subcutaneous (SC) administration in healthy subjects. The pivotal BA/bioequivalence (BE) study was a relative BA/BE bridging study in healthy subjects to assess the relative BA of the to-be-marketed risankizumab OBI compared with the prefilled syringe (PFS) used in the Phase III CD studies. The OBI adhesive study was a randomized, open-label, non-drug interventional study in healthy subjects to assess the OBI adhesive effectiveness and skin tolerability at 2 different locations (abdomen and upper thigh) over different periods of time (5 and 30 minutes). The pilot PK study showed that risankizumab exposures were similar across different rates/volumes of SC administration in healthy subjects, thereby supporting further development of the OBI. Second, a pivotal BA/BE study showed comparability between the OBI and Phase III PFS with bioequivalent risankizumab AUCs and no clinically meaningful difference for Cmax based on the wide therapeutic window of risankizumab. In both studies, no new safety risks were identified. No impact of immunogenicity on PK profile or safety was observed for the OBI. Third, an adhesive OBI (without risankizumab) study showed that there were no differences in adhesion/skin tolerability observed over time (up to 30 minutes) or for location of adhesion, and the OBI device adhesion was well tolerated at both the abdomen and thigh locations. These results supported the risankizumab OBI presentation approval in CD.

Kigelia africana improves libido in phenyl hydrazine induced anaemic female Wistar rats

Background and Objective: Anaemia is a global public health challenge affecting adolescent girls, women of reproductive age, pregnant women and children in low and middle income countries. This study therefore was designed to evaluate the effect of extract of Kigelia africana on female sexual hormones following phenyl hydrazine induced anaemia. Materials and Methods: This research work was carried out using twenty five (25) female Wistar rats. The experimental rats were randomly divided into five (5) groups, with five animals per group .Group A served as Normal control (non-anaemic control), group B: Anaemic control(induced with phenyhdrazine) without treatment ,group C; anaemic rats treated with feroton (Standard control), group D; Anaemic rats co-administered with 200mg/kg petroleum ether leaf extract Kigelia africana extract (PETLETKG1), and group E; Anaemic rats treated with 200mg/kg between petroleum ether leaf extract Kigelia africana extract (PETLETKG2) .All administrations were done orally using oropharyngeal cannula once per day for 14 days (2 week). Blood was collected by cardiac puncture using disposable syringe and needle to draw blood into plane sterile tubes. Thereafter, the samples were analyzed using standard methods. Results: The result depicts the significant (p&lt;0.05) increase in serum follicle stimulating hormone, prolactin, progesterone, oestrogen when compared with both normal and standard control. More so, the petroleum ether extract of K. africana showed no significant (P&lt;0.05) difference on L.H hormone when compared with both the standard and the normal control. Contrastingly, the extract of K. africana decreases serum testosterone significantly (P&lt;0.05) when compared with both the standard and normal control. Conclusion: The result suggests that the extract might be useful in improving the sexual health and libido of female animals following phenyl hydrazine induced anaemia.

Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation.

To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS). Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30 s. Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p = 0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2-24.1; p = 0.0298). There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.

In-use stability of ready-to-administer daratumumab subcutaneous injection solution in plastic syringes

ObjectiveIn multiple myeloma patients, daratumumab is preferably injected subcutaneously. The summary of product characteristics of daratumumab subcutaneous injection solution specifies physicochemical stability for the prepared syringe for 24 hours at...

Development of a systematic social observation tool for monitoring use of harm reduction supplies

BackgroundHarm reduction services such as safer injection supply distribution are essential to reducing morbidity and mortality among people who use drugs (PWUD); however, local use of harm reduction supplies (e.g., tourniquets, saline solution) is difficult to routinely and systematically monitor. The purpose of this study was to develop and validate a systematic social observation tool designed to assess use of harm reduction supplies at the street block level. MethodsData collection took place on a random sample of 150 blocks located throughout the Kensington neighborhood of North Philadelphia from November 2021 to January 2022. We measured inter-rater reliability by two-way mixed-effects intra-class correlation coefficients (ICC) with the consistency agreement definition and internal consistency reliability using Cronbach's alpha and McDonald's omega. Exploratory factor analysis with principal component extraction and promax rotation assessed internal consistency. We validated scales against locations of public syringe disposal boxes, a proxy measure for areas of concentrated drug use, using logistic regression. ResultsNaloxone canisters, syringe caps, saline and sterile water solution bottles showed the highest reliability (ICC≥0.7). Items also showed high internal consistency (alpha, omega>0.7). Exploratory factor analysis identified one, three-item scale with high internal consistency: syringe caps, vials, and baggies (alpha = 0.85; omega = 0.85)—all supplies used concurrently with drug injection but not discarded in syringe disposal boxes. Drug use (OR = 1.78, 95 % CI = (1.48, 2.23)), harm reduction (OR = 3.53, 95 % CI = (2.20, 6.12)), and EFA scales (OR = 1.85, 95 %CI = (1.51, 2.34)) were significantly and positively associated with being within walking distance (≤0.25 miles or 0.4 km) of a syringe disposal box. ConclusionThis study provides an efficient tool with high reliability and validity metrics to assess community uptake of harm reduction supplies designed for use by community organizations, policy makers, or other groups providing resources to PWUD.

Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.

The Adherence and Outcomes Benefits of Using a Connected, Reusable Auto-Injector for Self-Injecting Biologics: A Narrative Review.

Many biologics are now self-administered by patients at home. A variety of self-injection devices are available, including vials and syringes, prefilled syringes, and spring-driven prefilled pens or auto-injectors. Each has advantages and drawbacks, and different devices suit different patients. For example, some patients have difficulty achieving consistent and successful self-injection due to poor manual dexterity, or experience anxiety at the prospect of self-injection or injection-site pain. These factors can reduce patients' medication adherence and overall experience. Furthermore, while self-injection brings patients many benefits, the proliferation of single-use injection devices has implications for environmental sustainability, including the reliance on single-use plastics, repeated freighting requirements, and need for incineration as hazardous waste. Recently developed, innovative electromechanical auto-injector devices offer technological enhancements over existing devices to overcome some of these issues. Features include customisable injection speeds or durations, consistent rate of injection, electronic injection logs and reminders, and step-by-step, real-time instructions. Indeed, a growing body of evidence points to higher adherence rates among patients using electromechanical devices compared with other devices. Further, with time, the reusability of electromechanical devices may prove to lighten the environmental impact compared with disposable devices, especially as research continues to optimise their sustainability, driven by increased consumer demands for environmental responsibility. This narrative review discusses the differences between prefilled syringes, spring-driven prefilled pens, and electromechanical devices. It also explores how these features may help reduce injection-associated pain and anxiety, improve patient experience, connectivity and adherence, and drive sustainability of biologic drugs in future.

Excipient and Packaging Material Impact on Glass and Polymer-Based Prefilled Syringe Functionality.

Compared to glass prefilled syringes (PFSs), cyclic olefin polymer (COP) PFS showed more consistent and predictable extrusion forces when exposed to a variety of excipient combinations (buffers, tonicity agents, and surfactants) at various accelerated storage conditions. Furthermore, COP PFSs also showed significantly less variance in extrusion forces within each individual stroke, which is critical for precision applications. Observed performance differences can be explained by fundamental differences in the stability and homogeneity of the primary packaging materials (i.e., COP vs siliconized glass) and their physicochemical interactions with excipients.

Pyrolysis-catalysis of medical waste over metal-doping porous biochar to co-harvest jet fuel range hydrocarbons and H2-rich fuel gas

This study developed a dual-stage pyrolysis-catalysis pathway to valorize disposal syringe waste into liquid hydrocarbons and H2-rich fuel gas. Two typical biomass sources (corn stover and cotton stalk) were used to synthesize metal-doping porous biochar catalysts through in situ carbothermal reduction treatment. For corn stover-derived biochar catalysts, Fe/C1 (Fe-doping corn stover biochar catalyst) presented a high yield (61.06 wt%) of liquid hydrocarbons with over 78% of jet fuel range (C8 – C16) hydrocarbons, and the 2,4-dimethyl-1-heptene (C9H18) yield reached 101.6 mg/gsyringe. Bimetallic Zn-Fe/C1 (Zn-Fe co-doped corn stover biochar catalyst) was in favor of H2 production, with a proportion of over 37 vol%. Among the cotton stalk-derived biochar catalysts, bimetallic Zn-Fe/C2 (Zn-Fe co-doped cotton stalk biochar catalyst) achieved a highest yield (62.76 wt%) of liquid hydrocarbons, indicating a positive synergistic effect of bimetallic Zn-Fe composite on liquid hydrocarbons production. However, Fe/C2 (Fe-doping cotton stalk biochar catalyst) was responsible for a high yield (over 93 mg/gsyringe) of 2,4-dimethyl-1-heptene and a high selectivity (over 76%) of jet fuel range hydrocarbons. Additionally, a logical reaction mechanism was provided for dual-stage pyrolysis-catalysis of syringe waste over metal-doping porous biochar catalysts. Briefly, this work provides a green route by using metal-doping biochar for valorization of medical wastes into liquid hydrocarbons and H2-rich fuel gas.

Comprehensive Assessment of Pharmacokinetics, Pharmacodynamics, and Tolerability of Ligelizumab in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria to Optimize Its Subcutaneous Delivery System.

Ligelizumab is a highly potent, humanized IgG1, anti-IgE monoclonal antibody. To explore its optimal subcutaneous delivery, the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patients with chronic spontaneous urticaria (CSU) were assessed. Using different injection volumes or durations of a liquid-in-vial (LIVI) formulation or different formulations (LIVI vs. prefilled syringe (PFS)), single-dose ligelizumab showed comparable PK exposure in HVs. Steady-state exposure of ligelizumab was also comparable between LIVI and PFS following multiple dosing in CSU patients. The total IgE level (a PD marker) and tolerability were similar between the two formulations in both HVs and patients. Furthermore, the PK, total IgE, and tolerability were comparable for PFS administered either by patients or healthcare providers (HCPs). Collective evidence demonstrated that the injection duration or volume, formulation, or administrator had no apparent impact on the PK, PD, and tolerability of ligelizumab, supporting no clinically relevant difference between LIVI and PFS, and that PFS can be administered by patients or HCPs. This report provides a comprehensive assessment based on data of multiple clinical endpoints from both HVs and patients to inform formulation development and commercial use of a monoclonal antibody.

First Report of Pantoea agglomerans Causing a Leaf Blight and Bulb Rot of Onion in Chile.

Onion (Allium cepa L) is an important vegetable crop in Chile with 3.675 ha (ODEPA, www.odepa.gob.cl). Since 2017, a series of symptoms has been increasingly observed, mainly in mature bulbs which include water-soaked lesions on mature leaves and external and central cataphylls, which evolve to necrotic lesions and rot, reducing yields and affecting the postharvest life. As the season progresses over 90% incidence has been estimated in severely affected fields. Symptomatic plants were collected for disease identification in summer (February 2022) in Santa Cruz, O´Higgins, Chile, (34º41'32"S and 71º27'17"W). Isolations were done on semi-selective OEM medium (Zaid et al. 2012) and isolated colonies were transferred and maintained on King's B (KB) medium. Colonies on OEM medium were yellow slightly green in the center, circular to irregular shape, elevated, smooth margin, and mucoid texture (Tho et al. 2015). On KB medium colonies were yellow cream, slightly darker in the center, with smooth margins and circular or slightly irregular. Two isolates (CHS B3, CHS B1), obtaining in three different onion fields, were further identified by PCR amplification of partial 16S rRNA using primers 27F/1492R (Frank et al., 2008). The resulting sequencing were deposited in GenBank under accession numbers OP934962.1 and OP934961.1. A BLAST search of GenBank showed that these sequences exhibited 99,89 to 100 % nucleotides similarities with multiple Pantoea agglomerans sequences. Three isolates were used to test pathogenicity on detached cataphylls and onion plants tests in the laboratory and greenhouse, respectively. Cataphylls (n=10) were surface disinfected with 2% NaOCl for 2 min, placed in sterile Petri dishes, and injected with 50 µL (106 UFC/mL) inoculum suspension with the aid of a hypodermic syringe. Cataphylls were incubated in humid chamber at 22 + 2ºC for 14 days. Additionally, three-month-old onion plants (n=10), growing in pod, were inoculated by injecting leaves with 1 mL inoculum suspension (106 UFC/mL). Plant were incubated under greenhouse for 30 days to 28ºC. An equal number of cataphylls and onion plants, injected with sterile water, were left as controls. Water soaked lesions on inoculated cataphylls appeared five days after inoculation. While onions plants develop water soaked lesion 1- 4 days after inoculation. Blight and bulb rot were observed only on inoculated plants. Symptoms were identical to those previously observed in the field. Reisolations were accomplished for 100% of the inoculated cataphylls and leaves fulfilling Koch's postulates (Biochemical characterization and PCR amplification of partial 16S rRNA). Previously, Pectobacterium carotovorum was reported causing a similar disease in Chile (Acuña 2008). However, to our knowledge this is the first report of P. agglomerans causing onion leaf blight and bulb rot in O'Higgins Region, Chile. In agreement with other reports (De Armas et al. 2015, Tho et al. 2015), leaf blight and bulb has been a very aggressive disease in Chile. These results do not exclude the possibility that other Pantoea species (Armas et al. 2015) may be involved in the leaf blight and bulb rot of onions.

Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic-Device Using Prefilled Syringes and Autoinjectors.

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration-time curve (AUC) and the maximum concentration (Cmax ). For biologics with a long half-life, a PK comparability study may be long in duration and costly to conduct. The goal of this study was to evaluate whether a truncated AUC (tAUC) can be used to assess PK comparability when bridging prefilled syringe (PFS) and autoinjector (AI) treatment options for biologics with a long half-life. Fifteen biologics license applications (BLAs) were included to determine the concordance and geometric percent coefficient of variation (%CV) between tAUCs evaluated on days7, 14, 21, and 28 and AUC evaluated to infinity (AUC0-inf ). Concordance is established if the tAUCs are comparable with AUC0-inf . Trial simulation was performed to examine the effect of the absorption rate constant (ka ) and sample size on the concordance of tAUCs. The tAUCs evaluated on day14, 21, and 28 had 100% concordance with AUC0-inf for all 15 BLAs. The concordance of tAUC evaluated at day7 was 87.5%. Based on the trial simulation, tAUC evaluated to day28 post-dose can achieve high concordance (≥85%) for biologics exhibiting linear or nonlinear elimination with a ka of ≥0.1/day and with a sample size of 70 subjects per arm. tAUC appears to be a promising alternative PK measure, relative to AUC0-inf , for PK comparability assessments.