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Itepekimab, a monoclonal antibody against interleukin‐33, has demonstrated clinical utility in previous studies in patients with asthma and chronic obstructive pulmonary disease. An autoinjector (AI) has been developed for administering itepekimab to facilitate further development. This study compared pharmacokinetics of single 300‐mg itepekimab subcutaneous administration via an AI versus a prefilled syringe (PFS). Of 90 healthy volunteers enrolled in this Phase 1, parallel‐design, randomized study and stratified by body weight (50 to <70 kg, ≥70 to <80 kg, ≥80 to 100 kg) and injection site (abdomen, thigh, or arm), 84 completed the study. Systemic exposure of itepekimab was similar for both groups. Point estimates for geometric mean ratios of pharmacokinetic parameters for AI versus PFS groups were 1.01 for maximum serum concentration, 1.06 for area under the serum concentration‐time curve to the last quantifiable concentration, and 1.04 for area under the serum concentration‐time curve extrapolated to infinity. The exposure was similar for both devices in each body weight and injection site subgroup. Overall, systemic exposure of 300‐mg single‐dose itepekimab in healthy participants was comparable when administered subcutaneously via an AI device and PFS, with an acceptable safety profile in both device groups. [ABSTRACT FROM AUTHOR]

Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were −72.7% (3.9%) for PFS and −71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html. • Ongericimab 150 mg Q2W demonstrated statistically significant reductions in LDL-C level. • Beneficial effects were observed on other lipid parameters, especially in Lp (a). • Treatment with Ongericimab 150 mg Q2W was safe and well tolerated. • Patients demonstrated consistent effects from PFS or AI device. [ABSTRACT FROM AUTHOR]

Shrihari Jathanakodi,1 Charlotte Both,1 Ines Brueckmann,1 Laura Rose,2 Nahal Nasseri,3 Jean-Pierre Raynauld,4 Neeraj Narula5 1Sandoz Group AG, Holzkirchen, Germany; 2Sandoz Inc., Princeton, NJ, USA; 3Sandoz Canada Inc., Boucherville, QC, Canada; 4Division of Rheumatology, Department of Medicine, Montreal Institute of Rheumatology, Université de Montréal, Montreal, QC, Canada; 5Division of Gastroenterology, Department of Medicine, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, CanadaCorrespondence: Neeraj Narula, Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada, Tel +1 905 521 2100, Email neeraj.narula@medportal.caPurpose: Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes that are important to patients, and assessed patient perceptions and preferences between an adalimumab biosimilar autoinjector (Hyrimoz® SensoReady® Pen [SDZ-ADL pen]) and the reference adalimumab autoinjector (Humira® Pen [ref-ADL pen]) in patients with rheumatoid arthritis (RA) or Crohn’s disease (CD) in Canada.Patients and Methods: In this survey, adult patients were recruited for web-assisted telephone interviews. Patients had ≥ 3 months’ experience with the ref-ADL pen and 1– 12 months’ experience with the SDZ-ADL pen.Results: The survey included 120 patients with RA (n = 32) or CD (n = 88). Mean experience with the ref-ADL pen was 7 years for RA or 5 years for CD vs 9 months with the SDZ-ADL pen. The most important autoinjector attributes were the ability to use the pen independently and the ease and simplicity of self-injection. When comparing the two autoinjectors, patients significantly preferred the SDZ-ADL pen over the ref-ADL pen for nearly every attribute evaluated, with the greatest differences reported for visual and audible feedback mechanisms, ease of self-injection, and ability to use the device independently. Overall, 82% of patients preferred the SDZ-ADL pen over the ref-ADL pen, with buttonless activation and less injection pain being the main drivers for this preference.Conclusion: Patients with RA or CD indicated a preference for the SDZ-ADL pen over the ref-ADL pen, independent of the duration of use of the pen. The preference for a biosimilar device within 1 year of switching provides reassurance of rapid patient acceptance of biosimilars and may simplify the switching process. These results confirm the importance of ensuring autoinjector design supports independent self-administration of medication and align with previous data showing high patient satisfaction with the SDZ-ADL pen.Keywords: adalimumab, adherence, autoinjector, biosimilar, patient preference

Omalizumab is an anti‐IgE monoclonal antibody currently approved for the treatment of asthma, nasal polyps/chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria. Omalizumab is available as an injection in a prefilled syringe (PFS) with a needle safety device (NSD). New product configurations were developed to reduce the number of injections per dose administration, improve patient convenience and treatment compliance. The objective of this randomized open‐label 12‐week study was to demonstrate pharmacokinetic bioequivalence between (1) new PFS with autoinjector (PFS‐AI), (2) new PFS‐NSD configuration, and (3) current PFS‐NSD configuration. Each new configuration was considered bioequivalent to the current configuration if the confidence intervals (CIs) for the geometric mean ratios (GMR) were contained in the 0.80‐1.25 range for maximum concentration (Cmax), area under the concentration‐time curve until the last quantifiable measurement (AUClast), and AUC extrapolated to infinity (AUCinf). Safety was assessed throughout the study. In total, 193 healthy volunteers were randomized at 1:1:1 ratio to omalizumab 1×300 mg/2 mL via new PFS‐AI (n = 66), omalizumab 1×300 mg/2 mL via new PFS‐NSD (n = 64), or omalizumab 2×150 mg/1 mL via current PFS‐NSD (n = 63). Comparing new PFS‐AI versus current PFS‐NSD, the GMRs were: Cmax, 1.085; AUClast, 1.093; AUCinf, 1.100. Comparing new PFS‐NSD versus current PFS‐NSD, the GMRs were: Cmax, 1.006; AUClast, 1.016; AUCinf, 1.027. The 95% CIs for all GMR parameters were contained within the 0.80‐1.25 range. Safety findings were consistent with the known safety profile of omalizumab. Single‐dose omalizumab administered as the new PFS‐AI or new PFS‐NSD was bioequivalent to the current PFS‐NSD. [ABSTRACT FROM AUTHOR]

Purpose: Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes that are important to patients, and assessed patient perceptions and preferences between an adalimumab biosimilar autoinjector (Hyrimoz® SensoReady® Pen [SDZ-ADL pen]) and the reference adalimumab autoinjector (Humira® Pen [ref-ADL pen]) in patients with rheumatoid arthritis (RA) or Crohn's disease (CD) in Canada. Patients and Methods: In this survey, adult patients were recruited for web-assisted telephone interviews. Patients had ≥ 3 months' experience with the ref-ADL pen and 1– 12 months' experience with the SDZ-ADL pen. Results: The survey included 120 patients with RA (n = 32) or CD (n = 88). Mean experience with the ref-ADL pen was 7 years for RA or 5 years for CD vs 9 months with the SDZ-ADL pen. The most important autoinjector attributes were the ability to use the pen independently and the ease and simplicity of self-injection. When comparing the two autoinjectors, patients significantly preferred the SDZ-ADL pen over the ref-ADL pen for nearly every attribute evaluated, with the greatest differences reported for visual and audible feedback mechanisms, ease of self-injection, and ability to use the device independently. Overall, 82% of patients preferred the SDZ-ADL pen over the ref-ADL pen, with buttonless activation and less injection pain being the main drivers for this preference. Conclusion: Patients with RA or CD indicated a preference for the SDZ-ADL pen over the ref-ADL pen, independent of the duration of use of the pen. The preference for a biosimilar device within 1 year of switching provides reassurance of rapid patient acceptance of biosimilars and may simplify the switching process. These results confirm the importance of ensuring autoinjector design supports independent self-administration of medication and align with previous data showing high patient satisfaction with the SDZ-ADL pen. [ABSTRACT FROM AUTHOR]

Background: Several biologics for the treatment of severe asthma are available as self-administration devices. Objective: We performed a systematic literature review to understand the use, benefits, and challenges of these self-administration devices. Methods: Electronic databases and conference proceedings were searched using terms for asthma, biologic treatment, and at-home/self-administration (GSK study 213094). Publications were scanned for relevance using prespecified Population, Intervention, Comparison, Outcomes, Study Design (PICOS) criteria. Data on efficacy, safety, patient experience, and economic outcomes were extracted; study quality was assessed. A firsthand patient perspective was obtained. Results: Thirty-five of 504 records met the inclusion criteria. Across four phase 3 studies, ≥95% of biologic self-administrations were successful on the basis of predefined criteria. At-home self-administration was preferred over in-clinic administration by 43-96% of patients across 5 studies. Most patients (≥89%) in two phase 3 studies reported completing self-administration easily without repeated reference to instructions; high proportions of patients (≥98%) were confident in their ability to self-administer their biologic, and ≥96% rated it as extremely, very or moderately easy to self-administer. Across 16 studies reporting efficacy data, there was evidence of reduced blood eosinophil counts and improved asthma control with biologic self-administration, with improved health-related quality of life shown across 6 studies. Economic outcomes data were limited. From a patient perspective, autonomy is the major benefit of self-administration. Conclusion: Although more evidence is needed, this systematic literature review provides consistent evidence of high injection success rates and, supported by a patient perspective, preference for self-administration of biologics among patients with severe asthma.

Ulf Müller-Ladner,1 Christopher J Edwards,2 Andreas Erkens3 1Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Campus Kerckhoff, Bad Nauheim, Germany; 2Musculoskeletal Research Unit, NIHR Southampton Clinical Research Facility, University Hospital Southampton, Southampton, UK; 3Aurum Research GmbH, Lauf a.d., Pegnitz, GermanyCorrespondence: Ulf Müller-Ladner, Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Benekestrasse 2-8, D-61231 Bad Nauheim, Germany, Fax +49 6032-996 2104, Email u.mueller-ladner@kerckhoff-klinik.dePurpose: Prefilled syringes (PFS) and various types of pens are available for subcutaneous injection of methotrexate (MTX) in patients with rheumatoid arthritis or moderate to severe psoriasis. A new MTX pen with modernized button-free autoinjection technology was developed as a successor to a button-activated pen (metoject®/metex® PEN). To assess the needs of users and the relevance of features of the new MTX autoinjector an international online survey was performed.Methods: A structured questionnaire was distributed to physicians, nurses and patients in Germany, France, and the United Kingdom. Participants received illustrations and information about features of the new MTX autoinjector.Results: In total, 189 rheumatologists, 111 dermatologists, 90 nurses, and 180 patients answered the questions. Specific reasons for a preference for the use of MTX pens over PFS could predominantly be assigned to the categories “dosing/administration” and “ease of use”. The first impression of the new MTX autoinjector was positive in 82% of physicians, 87% of nurses, and 76% of patients, respectively. The four most important features of the new MTX autoinjector were 2-step autoinjector mechanism (receiving a mean 14.1 to 18.1 chips of a total of 100 chips), small injection volume (9.7 to 11.7 chips), 10 different doses for dose flexibility (8.0 to 13.2 chips), and short injection time below 5 seconds (8.5 to 11.1 chips).Conclusion: Arguments for the use of MTX pens as opposed to PFS predominantly refer to dosing/administration and ease of use. The new button-free MTX autoinjector combines a number of advantageous features identified by the international survey.Plain Language Summary: Subcutaneous injection of methotrexate (MTX) is an option to treat patients with specific inflammatory diseases. A new MTX autoinjector with button-free activation of the injection and no need to build a skin fold was developed to address some of the reasons for non-adherence. The importance of specific needs of users as well as the relevance of features of the new MTX autoinjector are unknown. Therefore, a structured questionnaire was distributed to physicians, nurses and patients in Germany, France, and the United Kingdom. Illustrations and information about features of the new MTX autoinjector were distributed to the participants. The results of the study show that arguments for the use of MTX pens as opposed to prefilled syringes predominantly affect the categories dosing/administration and ease of use followed by safety/side effects. In addition, the study identified four main advantageous features of the new MTX autoinjector, ie simplicity due to the 2-step button-free autoinjector mechanism, the small injection volume, 10 different doses for dose flexibility, and the short injection time below 5 seconds.Keywords: autoinjector, methotrexate, pen, psoriasis, rheumatoid arthritis, syringe

[Display omitted] • This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. • While prefilled syringes, autoinjectors and pen injectors remain as the mainstay of medical devices, innovative modifications like dual-chamber design and novel devices like on-body injector also emerged as promising presentations. • Insulin related combination products are all delivered by pen injectors with multi-dose cartridges subcutaneously. Vaccine-device combination products are presented with PFS and administered through the intramuscular route. • Around 40 % of products employ high-concentration formulations (≥ 100 mg/mL), and 78 % of mAb products are at high concentrations. With the remarkably strong growth of the biopharmaceutical market, an increasing demand for self-administration and rising competitions attract substantial interest to the biologic-device combination products. The ease-of-use of biologic-device combination products can minimize dosing error, improve patient compliance and add value to the life-cycle management of biological products. As listed in the purple book issued by the U.S. Food and Drug Administration (FDA), a total of 98 brand biologic-device combination products have been approved with Biologic License Application from January 2000 to August 2023, where this review mainly focused on 63 products containing neither insulin nor vaccine. Prefilled syringes (PFS) and autoinjectors are the most widely adopted devices, whereas innovative modifications like needle safety guard and dual-chamber design and novel devices like on-body injector also emerged as promising presentations. All 16 insulin products employ pen injectors, while all 19 vaccine products are delivered by a PFS. This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. In addition, challenges and opportunities associated with biologic-device compatibility, regulatory complexity, and smart connected devices are also discussed. It is believed that evolving technologies will definitely move the boundaries of biologic-device combination product development even further. [ABSTRACT FROM AUTHOR]

Subcutaneous injection of monoclonal antibodies (mAbs) has experienced unprecedented growth in the pharmaceutical industry due to its benefits in patient compliance and cost-effectiveness. However, the impact of different injection techniques and autoinjector devices on the drug's transport and uptake is poorly understood. Here, we develop a biphasic large-deformation chemomechanical model that accounts for the components of the extracellular matrix that govern solid deformation and fluid flow within the subcutaneous tissue: interstitial fluid, collagen fibers and negatively charged proteoglycan aggregates. We use this model to build a high-fidelity representation of a virtual patient performing a subcutaneous injection of mAbs. We analyze the impact of the pinch and stretch methods on the injection dynamics and the use of different handheld autoinjector devices. The results suggest that autoinjector base plates with a larger device-skin contact area cause significantly lower tissue mechanical stress, fluid pressure and fluid velocity during the injection process. Our simulations indicate that the stretch technique presents a higher risk of intramuscular injection for autoinjectors with a relatively long needle insertion depth. [ABSTRACT FROM AUTHOR]

The timely administration of antivenom is the most effective method currently available to reduce the burden of snakebite envenoming (SBE), a neglected tropical disease that most often affects rural agricultural global populations. There is increasing interest in the development of adjunctive small molecule and biologic therapeutics that target the most problematic venom components to bridge the time-gap between initial SBE and the administration antivenom. Unique combinations of these therapeutics could provide relief from the toxic effects of regional groupings of medically relevant snake species. The application a PRISMA/PICO literature search methodology demonstrated an increasing interest in the rapid administration of therapies to improve patient symptoms and outcomes after SBE. Advice from expert interviews and considerations regarding the potential routes of therapy administration, anatomical bite location, and species-specific venom delivery have provided a framework to identify ideal metrics and potential hurdles for the development of a field-based medical device that could be used immediately after SBE to deliver adjunctive therapies. The use of subcutaneous (SC) or intramuscular (IM) injection were identified as potential routes of administration of both small molecule and biologic therapies. The development of a field-based medical device for the delivery of adjunctive SBE therapies presents unique challenges that will require a collaborative and transdisciplinary approach to be successful.

Introduction: Pegfilgrastim-cbqv (UDENYCA®; Coherus BioSciences, Redwood City, CA, USA) is a pegfilgrastim (Neulasta®; Amgen, Thousand Oaks, CA, USA) biosimilar approved for administration by prefilled syringe (PFS). The recently approved pegfilgrastim-cbqv prefilled autoinjector (AI) was developed as another method of self-administration and to aid in-office use, providing flexibility in drug delivery. The objectives of the study were to assess the pharmacokinetics (PK) and pharmacodynamics (PD) to determine bioequivalence of the prefilled AI and the PFS for administration of pegfilgrastim-cbqv and to assess the safety profile of the prefilled AI. Methods: During this open-label, two-period crossover study, healthy adult males (N = 155) were randomly assigned (1:1 ratio) to receive a subcutaneous injection of pegfilgrastim-cbqv using a prefilled AI (n = 76) or a PFS (n = 79) in period 1. During period 2, participants received an injection using the other method. Primary PK and secondary PD parameters were calculated to assess the bioequivalence of the treatment as administered by the two delivery methods. Safety and immunogenicity were also assessed. Results: The 90% CIs of the geometric mean ratios for the PK and PD parameters were within the required range (80–125%), demonstrating bioequivalence between the pegfilgrastim-cbqv prefilled AI and PFS. Treatment-emergent adverse events (TEAEs) were reported by 75% and 74.1% of participants in the prefilled AI and PFS groups, respectively. The most common TEAEs in both treatment groups were myalgia, bone pain, and headache. AI-device–related TEAEs were injection site pain (1.4%) and injection site bruising (0.7%). The incidence of antidrug antibodies and neutralizing antibodies was low and was similar in both treatment sequences. Conclusions: The bioequivalence of pegfilgrastim-cbqv administered using a prefilled AI and a PFS was established. The safety, including immunogenicity profiles, of pegfilgrastim-cbqv administered using the prefilled AI and the PFS were similar, with no new safety findings. Plain Language Summary: Pegfilgrastim-cbqv is used 24–96 h after chemotherapy to prevent febrile neutropenia. This is when a patient has a fever and a lower-than-normal number of white blood cells. Pegfilgrastim-cbqv is also used to treat someone who has a fever and a low number of white blood cells after high radiation exposure (hematopoietic acute radiation syndrome). Pegfilgrastim-cbqv is given as an injection by hand. The syringe is already filled with the drug. The US Food and Drug Administration also approved a prefilled autoinjector as another way to give the drug. The autoinjector is a spring-loaded system that delivers pegfilgrastim-cbqv in less than 10 s. A shield covers the needle before and after the drug is given. The autoinjector is safe and effective for patients to give pegfilgrastim-cbqv to themselves and for health care staff to use in-office. This study looked at whether the way in which pegfilgrastim-cbqv moves through the body (pharmacokinetics) and its effects on the body (pharmacodynamics) were similar in healthy adult males when using a prefilled autoinjector and a prefilled syringe. Side effects were also assessed. The two administration methods had very similar pharmacokinetic and pharmacodynamic results for pegfilgrastim-cbqv. The side effects for both groups were also similar. The most common side effects were muscle aches and pains, bone pain, and headaches. Giving pegfilgrastim-cbqv with the prefilled autoinjector was very similar to giving it with the prefilled syringe and the pharmacokinetics, pharmacodynamics, and safety were similar. [ABSTRACT FROM AUTHOR]

Abstract Introduction The SmartClic®/ClicWise® autoinjector is a new reusable, multi-use, single-patient device for the administration of subcutaneously administered biologics in the treatment of chronic conditions, including rheumatoid arthritis. The device will be used in conjunction with a mobile application (app). The aim of this study was to collect feedback on the usability, functionality, and applicability of the device and the companion app from health care professionals (HCPs) who perform injections as part of their role and care for patients with rheumatic conditions. Methods The study was conducted from September to October 2020 in Germany. HCPs participated in a training session for the device and gained experience by performing simulated injections with water. Following the simulations, HCPs answered questions on the ease of use, feature design, effectiveness, and injection speed of the SmartClic/ClicWise device and estimate the patient training time required. They also answered questions on the functionality of the proposed app after attending a storyboard presentation. Responses were recorded as multiple-choice answers, Likert scale ratings (seven-point scale), or open-ended comments. The mean, median, and mode scores were recorded. Results Twenty-five HCPs (mean age, 38.2 years; females, n = 22 [88%]; registered nurses, n = 19 [76%]) participated in the study. HCP feedback on questions related to the SmartClic/ClicWise device was positive overall, with mean scores > 4.50 across questions; mean scores 5.70. Conclusions Initial feedback from HCPs on the SmartClic/ClicWise device and proposed app was generally favorable, suggesting they will provide an acceptable alternative for self-administration of biologics for patients with rheumatoid arthritis and other chronic conditions.

A prototype reusable large-volume (2 mL) autoinjector (LVAI) was designed to compare injection performance of a novel 27 gauge ultra-thin wall (UTW) pre-filled syringe (PFS) cannula (8 mm external cannula length, 14.4 mm total needle length) against an existing 27 gauge special thin wall (STW) PFS cannula (12.7 mm external cannula length, 19 mm total needle length) across a range of injectate viscosities (2.3–30 cP) in a series of in vivo feasibility studies in swine. The UTW cannula had an approximately 30% greater cross-sectional lumen area than the STW cannula. The target exposed needle length was adjusted to ensure appropriate needle penetration depth and achieve injectate deposition in the subcutaneous (SC) tissue. Delivery time and volume, injection site leakage, injectate depot location, and local tissue effects were examined. The STW and UTW cannulae both provided effective SC delivery of contrast placebo solutions, and were able to accommodate injectate viscosity up to 30 cP without quantifiable leakage from the tissue and with minor tissue effects which resolved within 1–2 hours. Delivery times at each viscosity were significantly different between PFS types with the UTW PFS producing faster delivery times. In a histological substudy of the UTW cannula using injectate viscosities up to 50 cP, injection site reactions were rare and, when present, were of minimal severity. This series of studies demonstrates the feasibility of LVAI SC injection and informs autoinjector and PFS design considerations. Use of a UTW cannula may enable more rapid LVAI injections with minimal tissue effects, especially for higher viscosity formulations.

Introduction: The SmartClic®/ClicWise® autoinjector is a new reusable, multi-use, single-patient device for the administration of subcutaneously administered biologics in the treatment of chronic conditions, including rheumatoid arthritis. The device will be used in conjunction with a mobile application (app). The aim of this study was to collect feedback on the usability, functionality, and applicability of the device and the companion app from health care professionals (HCPs) who perform injections as part of their role and care for patients with rheumatic conditions. Methods: The study was conducted from September to October 2020 in Germany. HCPs participated in a training session for the device and gained experience by performing simulated injections with water. Following the simulations, HCPs answered questions on the ease of use, feature design, effectiveness, and injection speed of the SmartClic/ClicWise device and estimate the patient training time required. They also answered questions on the functionality of the proposed app after attending a storyboard presentation. Responses were recorded as multiple-choice answers, Likert scale ratings (seven-point scale), or open-ended comments. The mean, median, and mode scores were recorded. Results: Twenty-five HCPs (mean age, 38.2 years; females, n = 22 [88%]; registered nurses, n = 19 [76%]) participated in the study. HCP feedback on questions related to the SmartClic/ClicWise device was positive overall, with mean scores > 4.50 across questions; mean scores < 5.00 were reported on 2/40 questions. Twenty-four of 25 participants (96%) estimated that a training time of ≤ 20 min would suffice for patients learning to use the device. Positive feedback was also reported on questions related to the companion app, with mean scores > 5.70. Conclusions: Initial feedback from HCPs on the SmartClic/ClicWise device and proposed app was generally favorable, suggesting they will provide an acceptable alternative for self-administration of biologics for patients with rheumatoid arthritis and other chronic conditions. [ABSTRACT FROM AUTHOR]

Objective: evaluation of the pharmacoeconomic feasibility of using benralizumab in the form of autoinjector (pen-injector device) in outpatient facilities compared with its use in the form of a syringe in hospital settings for the treatment of severe asthma (SA).Material and methods. The cost minimization and budget impact analysis methods were used. The current practice of treating patients with SA with benralizumab in hospital settings at the expense of compulsory medical insurance funds was compared with the simulated practice. The simulated price was calculated as half patients receiving benralizumab in the hospital transferred to outpatient facilities at the expense of regional funds for 3 years. Direct medical costs included drug cost and outpatient patient monitoring services cost.Results. The direct medical costs associated with benralizumab therapy in outpatient facilities were lower than the costs required for benralizumab therapy in the hospital settings and amounted to 0.99 million rubles versus 1.17 million rubles per one patient per year, respectively. Thus, the use of benralizumab in outpatient facilities leads to savings of 185 thousand rubles (16%). In 2021, 93 patients were prescribed benralizumab in hospital settings. The expansion of the application of benralizumab use in outpatient facilities will lead to a reduction in medical costs in the first year of therapy (when switching 16.7% of patients) by 5.9 million rubles (4,9%). The consistent expansion of the practice of benralizumab use in outpatient facilities over a 3-year horizon (when switching 50% of patients) will lead to a reduction in medical costs by 46.6 million rubles (12.1%).Conclusion. Expansion of benralizumab use in outpatient facilities with a new form of autoinjector (pen-injector device) will lead to savings in medical costs and reduce the burden on the health care system, thus it is economically feasible.

A prototype reusable large-volume (2mL) autoinjector (LVAI) was designed to compare injection performance of a novel 27 gauge ultra-thin wall (UTW) pre-filled syringe (PFS) cannula (8mm external cannula length, 14.4mm total needle length) against an existing 27 gauge special thin wall (STW) PFS cannula (12.7mm external cannula length, 19mm total needle length) across a range of injectate viscosities (2.3-30 cP) in a series of in vivo feasibility studies in swine. The UTW cannula had an approximately 30% greater cross-sectional lumen area than the STW cannula. The target exposed needle length was adjusted to ensure appropriate needle penetration depth and achieve injectate deposition in the subcutaneous (SC) tissue. Delivery time and volume, injection site leakage, injectate depot location, and local tissue effects were examined. The STW and UTW cannulae both provided effective SC delivery of contrast placebo solutions, and were able to accommodate injectate viscosity up to 30 cP without quantifiable leakage from the tissue and with minor tissue effects which resolved within 1-2 hours. Delivery times at each viscosity were significantly different between PFS types with the UTW PFS producing faster delivery times. In a histological substudy of the UTW cannula using injectate viscosities up to 50 cP, injection site reactions were rare and, when present, were of minimal severity. This series of studies demonstrates the feasibility of LVAI SC injection and informs autoinjector and PFS design considerations. Use of a UTW cannula may enable more rapid LVAI injections with minimal tissue effects, especially for higher viscosity formulations. [ABSTRACT FROM AUTHOR]

In the treatment of organophosphate poisoning atropine sulphate monohydrate (AT) and obidoxime dichloride (OB) play a vital role. Currently, the Austrian Armed Forces use the DOUBLEPEN OA two‐chamber autoinjector (ChemProtect) to administer these two drugs. The autoinjector is a part of military standard equipment as a "Basic CBRN‐First Aid Kit" and contains OB and AT with a declared concentration of 220 mg/2 ml and 2 mg/2 ml, respectively. Especially in the two‐chamber autoinjectors, it is highly possible that not all the content of the antidote solution is administered when the autoinjector is triggered. The purpose of the study was to analyze one hundred DOUBLEPEN OA autoinjectors from two different production batches (1707068 and 1707067) for volume loss, drug content and uniformity of dosage unit. Uniformity of dosage units, assessed by the content uniformity method (Chapter 2.9.40 of the European Pharmacopeia), requires the calculation of an acceptable value to quantify the uniformity of the drug product. An acceptance value for the first 10 dosage units of 15.0% or below is considered acceptable. The loss of volume was calculated by determining the density and mass of the solution after triggering the autoinjector. A quantitative high‐performance liquid chromatography method has been developed and in‐house validated for the determination of the content of two drugs. According to International Council for Harmonisation guidelines, the analytical method was proven to be accurate and repeatable. The obtained results show that the average loss of volume after injection was 5%, and the average content of OB and AT for batch 1707068, was 216.5 and 1.9 mg, while for batch 1707067 it was 224.2 and 2.0 mg, respectively. Although the loss of volume and content were observed, the calculated acceptance value for both production batches met the requirements of uniformity of dosage unit by the European Pharmacopeia. [ABSTRACT FROM AUTHOR]

In the world of nuclear medicine, health care professionals face the challenge of safeguarding themselves and their patients from occupational radiation exposure. As the field experiences exponential growth, driven by the surge in approvals of radiopharmaceuticals for diagnostic and therapeutic applications, it becomes vital to delve into the delivery methods of radiopharmaceuticals. Health care professionals take precautions during radiopharmaceutical administration, including maintaining distance from radioactive sources, using shielding, limiting exposure time, and monitoring radiation levels with badges. Regular evaluations provide compliance with recommended exposure limits, yet concerns persist, especially regarding the cumulative radiation exposure from manual injections over time. Understanding the long-term effects of radiation exposure has spurred the development of cutting-edge medical device technologies, such as autoinjectors, designed to administer radiopharmaceuticals accurately while minimizing total radiation dose to health care professionals. The U.S. Pharmacopeia 825 regulation refers to these devices as "direct infusion systems." Nuclear medicine technologists commonly refer to them as "autoinjectors," whereas device manufacturers may use terms such as injection system, radiopharmaceutical injector, or infusion system. Despite variations in terminology, these devices hold a pivotal role in shaping the future of radiopharmaceutical delivery. In an era of escalating demand for PET procedures worldwide, skilled health care professionals ensure the safe and precise dosing of radiopharmaceuticals. This article explores the state-of-the-art medical devices in radiopharmaceutical delivery, spotlighting transformative medical devices currently revolutionizing the nuclear medicine landscape in the global market., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Subcutaneous (SC) drug delivery offers several advantages over intravenous (IV) delivery including: self-administration, improved patient experience, and reduced treatment costs. Unfortunately, each SC delivery is currently limited to ∼ 2.25 mL with IV administration required when the delivery volume exceeds this value. In this work, we explore a new technique for large volume subcutaneous drug delivery that uses microneedles to break through the epidermis then forms the liquid drug into many small jets that penetrate past the ends of the microneedles and into the subcutaneous (or muscle) tissue. By performing multiple simultaneous injections, this delivery approach avoids the volume limitations of SC delivery, and thus may be able to greatly increase the volume we can deliver to this space. Here, we present a novel multi-jet prototype that forms seven simultaneous jets through 30G needles that have been shortened to have an exposed length of just ∼ 1mm. The jet speed, shape, and volume of jets formed through these microneedles are measured to assess the consistency of jet production through the microneedles. We then perform jet injections of volumes up to 3.9 mL into ex vivo porcine tissue. The results demonstrate the successful delivery (>95 %) of 3.9 mL in just 0.3 s using jet injection performed through microneedles. This volume is almost double the maximum volume of current autoinjectors and the perceived limit for subcutaneous injection (2.25 mL). We also find that jet speeds of 70 m/s and below do not achieve complete delivery of 3.9 mL with our prototype system, and that the addition of microneedles leads to more consistent large volume delivery than equivalent needle-free injections. These results demonstrate the promise of multi-jet injection through microneedles to accommodate volumes much greater than current autoinjectors, and thus potentially allow patient self-administration in many more delivery applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases.

Introduction: The aim of this sub-study was to evaluate injection success of patients with rheumatoid arthritis (RA) and their caregivers administering the adalimumab (ADL) biosimilar, PF-06410293 (ADL-PF: adalimumab-afzb; Abrilada®/Amsparity®/Xilbrilada®) by prefilled pen (PFP) during the open-label treatment period in year two (weeks 52–78) of a phase 3 multinational, double-blind, clinical study (NCT02480153) comparing ADL-PF and reference ADL (Humira®) sourced from the EU. Methods: This sub-study included adult patients with active RA not adequately controlled by methotrexate. Patients received subcutaneous ADL-PF 40 mg by prefilled syringe (PFS) at weeks 52 and 54, then six biweekly doses (weeks 56–66) of ADL-PF 40 mg each via a single-use PFP device. Training was given on first injection at week 56; all injections were given by patients/caregivers. The primary endpoint was delivery system success rate (DSSR): the percentage of participants (i.e., actual PFP user) achieving delivery success for each of the six attempted PFP injections. Injection success was recorded by the observer (Observer Assessment Tool) and participant (Participant Assessment Tool). Results: In total, 50 patients with no experience self-injecting with an autoinjector/injection pen were included (74.0% female; mean age at screening, 54.9 years; mean RA duration, 8.0 years). Of these, 49 (98.0%) completed the sub-study and 46 (92.0%) received all six PFP injections. Overall DSSR (n = 294 injections) across visits was 100% (95% CI 92.0–100.0%). Complete injection was confirmed following inspection of 292 used and returned PFPs. A total of 47/49 (95.9%) participants who completed the sub-study elected to continue study treatment using PFP injections, rather than switching back to the PFS. Conclusions: All actual PFP users could safely and effectively administer ADL-PF by PFP at each visit, and nearly all participants who completed the sub-study elected to continue study treatment using PFP injections. Trial registration: ClinicalTrials.gov identifier: NCT02480153; EudraCT number: 2014-000352-29. [ABSTRACT FROM AUTHOR]

Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis. To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI). Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were investigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter, randomized, double-blinded, placebo-controlled study that investigated 150 mg/mL risankizumab PFS; study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI. At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and Severity Index ≥90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment (sPGA) 0/1, 78.1% vs. 9.6%; both p<.001) in study 1; in study 2, PASI 90 and sPGA 0/1 were 66.7%, and 81.5%, respectively. All patients successfully self-administered study treatments via PFS or AI. Acceptability of self-injection was high in both studies. Efficacy and safety of risankizumab 150 mg/mL were comparable with results from previous risankizumab phase 3 studies using the 90 mg/mL formulation. The efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS or AI injection support use of this new formulation in patients with moderate to severe plaque psoriasis. NCT03875482 and NCT0387508 [ABSTRACT FROM AUTHOR]

Sady Alpizar,1 Ayman Megally,2 Claudia Chen,3 Abhi Raj,4 John Downie,5 Gene Colice2 1Clinical Research Trials of Florida, Inc., Tampa, FL, USA; 2Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 3Biostatistics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 4Device Development, AstraZeneca, South San Francisco, CA, USA; 5Global Development Inflammation, Amgen, Thousand Oaks, CA, USACorrespondence: Ayman MegallyLate-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +1703334-1796Fax +1301917-3211Email ayman.megally@astrazeneca.comBackground: Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody in development for the treatment of severe asthma. This study assessed the functionality and performance of an accessorized pre-filled syringe (APFS) and an autoinjector (AI) for administration of tezepelumab in the clinic and at home.Methods: This phase 3, multicenter, randomized, open-label, parallel-group study (PATH-HOME, ClinicalTrials.gov identifier: NCT03968978) was conducted in patients aged 12– 80 years with asthma that was uncontrolled despite treatment with medium- to high-dose inhaled corticosteroids plus at least one additional controller medication. Patients received six subcutaneous doses of tezepelumab 210 mg via APFS or AI. The first dose was administered by a healthcare professional, and patients or caregivers administered subsequent doses. First, second, third and final doses were administered in the clinic; fourth and fifth doses were administered at home. The primary endpoint was the proportion of successful administrations of tezepelumab. Secondary endpoints included the functionality and performance of the devices, Asthma Control Questionnaire (ACQ)-6 score, pharmacokinetics and safety.Results: Overall, 216 patients were randomized (APFS, n=111; AI, n=105). Tezepelumab was successfully administered via APFS by 91.7% of the participants (100/109) and via AI by 92.4% (97/105). Overall, 95.4– 97.1% of at-home administrations were successful across device groups. Malfunction occurred in 6 of 655 dispensed APFSs and 5 of 624 dispensed AIs. Clinically meaningful improvements in ACQ-6 score were observed after 24 weeks in 81.1% and 76.2% of the patients in the APFS and AI groups, respectively. Tezepelumab pharmacokinetics were consistent between device groups and with previous studies. The most common adverse event was nasopharyngitis (9.3%). Injection-site reactions occurred in 5.7% and 0% of the patients in the AI and APFS groups, respectively.Conclusion: This study demonstrated that the APFS and AI were functional and reliable, and performed equally well at home and in the clinic.Keywords: accessorized pre-filled syringe, at-home administration, autoinjector, severe asthma, tezepelumab

Abstract Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in Cmax and AUC0-20 when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster Cmax. Two discernable Cmax’s were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher Cmax. There is a dose dependent increase in plasma concentration and AUC0-20. Most investigators found two Cmax’s with Tmax 5–10 min and 30–50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Introduction: The aim of the study was to demonstrate the bioequivalence, and compare the safety and tolerability of MSB11022, a proposed biosimilar of adalimumab, when delivered by either an autoinjector (AI) or a pre-filled syringe (PFS). Methods: In this pharmacokinetic (PK), parallel group, open-label study, 216 healthy volunteers were randomised 1:1 to receive a single subcutaneous injection of a 40 mg/0.8 mL dose of MSB11022 administered via AI or PFS. Coprimary PK endpoints were maximum observed concentration (Cmax), area under the concentration–time curve (AUC) from time 0 to the last quantifiable concentration (AUC0–t), and AUC from time 0 extrapolated to infinity (AUC0–inf). PK equivalence between the AI and PFS administration methods was declared if the 90% confidence intervals (CIs) for the ratio of geometric least square means was entirely contained within the 80–125% equivalence margin for all coprimary endpoints. Safety and tolerability were also evaluated. Results: The 90% CI for the three coprimary PK endpoints (Cmax, AUC0–t and AUC0–inf) were entirely contained within the predefined equivalence margins of 80–125%. Mean serum concentration–time profiles were similar following injection via AI or PFS. Treatment-emergent adverse events (TEAEs) were comparable across both treatment groups. Study device-related TEAEs were reported by 11.3% and 13.1% of subjects in the AI and PFS treatment groups, respectively. Study drug-related TEAEs were reported by 28.3% and 34.6% of subjects in the AI and PFS treatment groups, respectively. Few subjects experienced injection-site reactions, mainly pain and erythema, regardless of the administration method. Conclusion: Delivery of MSB11022 via an AI is bioequivalent to delivery via a PFS. The safety and tolerability profile of MSB11022 was comparable across administration methods. The development of an AI for MSB11022 provides a choice of self-injection devices available to patients, potentially improving treatment compliance. Trial Registration: ClinicalTrials.gov trial identifier: NCT04018599. [ABSTRACT FROM AUTHOR]

Background: Severe hypoglycemic episodes are life-threatening events demanding rapid administration of glucagon by a caregiver or bystander. The glucagon analog dasiglucagon is stable in aqueous formulation and therefore suitable for delivery in a ready-to-use autoinjector, potentially increasing speed and ease of use compared with standard glucagon emergency kits (GEKs). Methods: In an open label, randomized, crossover, comparative device handling study, trained caregivers and untrained bystanders administered the dasiglucagon autoinjector or Eli Lilly GEK to manikins in a simulated emergency hypoglycemia situation. Results: In total, 54 participants were randomized (18 patient-caregiver pairs and 18 bystanders). Overall, 94% of trained caregivers were able to administer the dasiglucagon autoinjector successfully within 15 min, compared with 56% for the GEK (P < 0.05). A greater proportion of trained caregivers and untrained bystanders successfully prepared and administered the dasiglucagon autoinjector within 2 min compared with the GEK (P < 0.005 and P < 0.05, respectively). Time to successful completion was also significantly faster with the dasiglucagon autoinjector than with the GEK (P < 0.005 for both groups). Most study participants preferred the dasiglucagon autoinjector over the GEK (94%, P < 0.001) and rated it as easier (90%, P < 0.001) and less stressful to use (94%, P < 0.001) than the GEK. Conclusion: Dasiglucagon autoinjector was more rapidly and reliably administered, and users reported greater ease of use and usage satisfaction than with the GEK. Thus, dasiglucagon autoinjector has the potential to improve speed and ease of treatment in severe hypoglycemic events, providing a better usage experience for rescuing individuals and enabling faster recovery for patients. [ABSTRACT FROM AUTHOR]

Protein-based biologic drugs encounter a variety of stress factors during drug substance (DS) and drug product (DP) manufacturing, and the subsequent steps that result in clinical administration by the end user. This article is the third in a series of commentaries on these stress factors and their effects on biotherapeutics. It focuses on assessing the potential negative impact from primary packaging, transportation, and handling on the quality of the DP. The risk factors include ingress of hazardous materials such as oxidizing residuals from the sterilization process, delamination- or rubber stopper-derived particles, silicone oil droplets, and leachables into the formulation, as well as surface interactions between the protein and packaging materials, all of which may cause protein degradation. The type of primary packaging container used (such as vials and prefilled syringes) may substantially influence the impact of transportation and handling stresses on DP Critical Quality Attributes (CQAs). Mitigations via process development and robustness studies as well as control strategies for DP CQAs are discussed, along with current industry best practices for scale-down and in-use stability studies. We conclude that more research is needed on postproduction transportation and handling practices and their implications for protein DP quality. [ABSTRACT FROM AUTHOR]

Convenient administration is an important factor for treatment adherence in patients with psoriasis. MATURE study reports the efficacy, safety, tolerability, and pharmacokinetics (PKs) of secukinumab 300 mg 2 ml autoinjector (AI) from MATURE trial (NCT03589885). Eligible patients were randomized to secukinumab 300 mg 2 ml AI or 2× 1 ml prefilled syringe (PFS) or placebo. The co‐primary endpoints were psoriasis area and severity index (PASI) 75 and investigator's global assessment (IGA) 0/1 response rates at Week 12 versus placebo. Other endpoints included PASI90/100 response, dermatology life quality index (DLQI) 0/1, PKs, 2 ml AI usability rated using self‐injection assessment questionnaire (SIAQ), and safety. The study met both co‐primary and secondary endpoints (p < 0.0001). Secukinumab 300 mg 2 ml AI and 2× 1 ml PFS treatments led to superior PASI75/90/100 (2 ml AI: 95.1%/75.6%/43.9%; 2× 1 mL PFS: 83.2%/62.6%/37.5% and placebo: 10%/5.0%/0.0%, respectively), IGA, and DLQI 0/1 responses compared with placebo, and efficacy was sustained through 52 weeks. SIAQ results showed high usability of self‐injection with 2 mL AI device. No new safety signals were observed. Study design may bias the interpretation of safety profile after Week 12, due to different exposure of secukinumab versus placebo. Secukinumab 300 mg administered with the 2 mL AI demonstrated superior efficacy over placebo, good tolerability, and convenient administration. [ABSTRACT FROM AUTHOR]

BackgroundAnaphylaxis is a life-threatening event, but it is frequently undertreated in pediatric patients with food allergies. Previous studies showed that auto-injectable adrenaline (AAI) is underused by patients and parents. This is especially troubling since fatal anaphylaxis has been associated with delayed adrenaline administration.ObjectivesThis study aimed to investigate parental practice and knowledge in anaphylaxis management, and perceived barriers and facilitators in using AAI.ResultsA retrospective survey was completed by 75 parents (41 mothers, 34 fathers) of children with food allergy and AAI prescription attending the Food Allergy Referral Center of Veneto, Italy. Results showed poor parental preparedness and reluctance to use AAI despite a high/moderate self-rated knowledge (median total score of 23–min. 3, max. 30). Most parents (77%) declared they were carrying AAI but only 20% used it in case of a severe reaction. Most reported Fear/Fear of making mistakes (46 parents) and Concern about possible side effects as barriers (35), while Poor knowledge of the correct AAI use (1) and Lack of knowledge/ incorrect assessment of symptoms (2) were reported less frequently. Theoretical-practical courses for parents on AAI use (65), Psycho-education/Psychological support (3) for better dealing with the emotional aspects of anaphylaxis and Written instructions (1) have been suggested as main facilitators.ConclusionUnderstanding parents' experience and perspective on managing anaphylaxis is crucial to implement effective educational programs. A multidisciplinary approach should be considered.

Abstract Background Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems. Methods Twenty-three patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 – April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test. Results 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe (p

Jennifer Mead, Ryan Dammerman, Soeren Rasmussen Amgen Inc., Thousand Oaks, CA, USACorrespondence: Jennifer MeadAmgen Inc., One Amgen Center Dr, Thousand Oaks, CA 91320– 1799 Email meadj@amgen.comPurpose: Erenumab-aooe (erenumab, Aimovig®)—a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor—is approved for the prevention of migraine in adults in a number of countries. The approved monthly dosage of erenumab (70 and/or 140 mg, depending on the country) is available as a single, prefilled autoinjector for subcutaneous administration in most countries where it is approved. This study evaluated the patient-reported ease-of-use, ability to learn self-injection, confidence in performing a simulated self-injection, and ergonomics of a prefilled autoinjector device for erenumab (SureClick® autoinjector) in individuals in the US with migraine.Patients and Methods: Participants with migraine headaches, all of whom were naïve to the use of an autoinjector for migraine or another condition and CGRP therapy, were recruited from three US-based headache centers. Each participant received a supervised demonstration of the autoinjector during a 30-minute one-on-one session using a standard protocol-driven script. Participants then practiced a simulated injection into an artificial tissue pad using the autoinjector and were asked to rate their agreement with 19 statements about the device on a 5-point Likert scale (1 = completely disagree, 2 = somewhat disagree, 3 = neutral, 4 = somewhat agree, 5 = completely agree).Results: Participants who completed the study and provided responses (n = 204) were between 21 and 85 years of age, inclusive, and 73% were female. More than 90% of the participants completely or somewhat agreed with 16/19 statements relating to the device, including ease-of-use, ability to self-inject, and confidence in using the device, with an average rating of > 4.5 on the 5-point Likert scale. Participants rated the size of the device and the compactness of the device as 4.23/5 and 4.26/5, respectively.Conclusion: The erenumab-prefilled disposable autoinjector was consistently highly rated across categories by individuals with migraine, with an average rating of > 4.5 on the 5-point Likert scale; results were consistent across the three study centers.Keywords: autoinjector, erenumab, migraine, subcutaneous injection, ease of use, calcitonin gene-related peptide

Francesco Patti,1 María Luisa Martínez Ginés,2 Christiane Norenberg,3 Fernando Duarte Caron4 1Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia; Multiple Sclerosis Center, University of Catania, Catania, Italy; 2Department of Neurology, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 3Bayer AG, Wuppertal, Germany; 4Bayer, Whippany, New Jersey, NY, USACorrespondence: Francesco PattiMultiple Sclerosis Center, University of Catania, Piazza Università, 2, Catania 95131, ItalyEmail patti@unict.itPurpose: Patients with multiple sclerosis (MS) would benefit from continued long-term treatment with disease-modifying therapies, and autoinjectors may help improve patients’ satisfaction with therapy, thereby increasing adherence rates. BETACONNECT® is an autoinjector for interferon beta-1b designed to improve the injection experience for patients. The BetaEval Global study assessed medication intake in patients using BETACONNECT to further investigate the value of this autoinjector.Patients and Methods: The BetaEval Global study was a prospective, non-interventional cohort study across multiple European countries in patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) who were starting interferon beta-1b treatment. The decision to administer interferon beta-1b was made independently of the study. Patients were assessed at the initial visits and planned follow-up visits at Weeks 4, 12, and 24. The primary outcome variable was compliance with therapy based on the medication possession ratio (MPR). Injections were automatically recorded by the BETACONNECT device or, in some instances, self-reported by the patients. This allowed for a complete dataset that could be used in the calculation of the MPR.Results: Four hundred ninety-eight patients were enrolled and completed 93.9%, 95.2%, and 95.4% of prescribed injections at Weeks 4, 12, and 24, respectively. Similarly, 76.4% (n=318), 76.6% (n=297), and 81.1% (n=284) of patients completed at least 80% of their prescribed injections. Median scores assessing patient satisfaction with the autoinjector were consistently high across the study.Conclusion: Overall, the results from BetaEval Global demonstrated that in this cohort of patients with RRMS or CIS on interferon beta-1b, use of the BETACONNECT autoinjector was associated with high rates of compliance, adherence, and patient satisfaction.Keywords: multiple sclerosis, interferon beta-1b, autoinjector, adherence, disease-modifying therapy

Donghoon Shin,1 Younsoo Kim,1 Ahra Go,1 Maria Velinova2 1Samsung Bioepis Co., Ltd., Incheon, Republic of Korea; 2PRA International, Groningen, the NetherlandsCorrespondence: Donghoon ShinSamsung Bioepis Co., Ltd, 107, Cheomdan-daero, Yeonsu-gu, Incheon 21987, Republic of KoreaTel +82-31-8061-4534Fax +82-31-8061-4393Email dh01.shin@samsung.comPurpose: SB4 is an etanercept biosimilar, approved by the European Commission (EC) and the US Food and Drug Administration (FDA) following a demonstration of equivalent efficacy and safety and comparable quality data to the reference product. This study aimed to demonstrate equivalent pharmacokinetic (PK) profiles, safety, and tolerability between SB4 autoinjector (AI) and SB4 pre-filled syringe (PFS).Patients and methods: This was an open-label, two-period, two-sequence, single-dose, cross-over study to evaluate bioequivalence of PK profiles, safety, and tolerability between SB4 AI and PFS in healthy adults. Treatment periods were separated by 14 days resulting in a 35-day washout between investigational product (IP) administration in Periods 1 and 2.Results: A total of 50 subjects were randomized: 24 subjects in Sequence I and 26 in Sequence II, and 6 subjects discontinued from the study. The primary PK endpoints including area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax) were all within the equivalence margin of 80.00–125.00%. Safety and tolerability were comparable between the two treatments.Conclusion: PK profiles showed that SB4 AI and PFS were bioequivalent in healthy subjects. Safety assessment was also comparable between the two treatments.Keywords: biosimilar, etanercept, bioequivalence, autoinjector, pre-filled syringe

Background: Several biologics for the treatment of severe asthma are available as self-administration devices., Objective: We performed a systematic literature review to understand the use, benefits, and challenges of these self-administration devices., Methods: Electronic databases and conference proceedings were searched using terms for asthma, biologic treatment, and at-home/self-administration (GSK study 213094). Publications were scanned for relevance using prespecified Population, Intervention, Comparison, Outcomes, Study Design (PICOS) criteria. Data on efficacy, safety, patient experience, and economic outcomes were extracted; study quality was assessed. A firsthand patient perspective was obtained., Results: Thirty-five of 504 records met the inclusion criteria. Across four phase 3 studies, ≥95% of biologic self-administrations were successful on the basis of predefined criteria. At-home self-administration was preferred over in-clinic administration by 43-96% of patients across 5 studies. Most patients (≥89%) in two phase 3 studies reported completing self-administration easily without repeated reference to instructions; high proportions of patients (≥98%) were confident in their ability to self-administer their biologic, and ≥96% rated it as extremely, very or moderately easy to self-administer. Across 16 studies reporting efficacy data, there was evidence of reduced blood eosinophil counts and improved asthma control with biologic self-administration, with improved health-related quality of life shown across 6 studies. Economic outcomes data were limited. From a patient perspective, autonomy is the major benefit of self-administration., Conclusion: Although more evidence is needed, this systematic literature review provides consistent evidence of high injection success rates and, supported by a patient perspective, preference for self-administration of biologics among patients with severe asthma., Competing Interests: Funded by GSK (study 213094). Disclosure of potential conflict of interest: S. Boccaletti at the time of the study was a GSK employee. R. Alfonso-Cristancho and W. Ahmed are employees of GSK and hold stocks and shares. A. Eze, L. Badgujar, N. Halfpenny, and D. Heldt are employees of OPEN Health which received payment from GSK to conduct this study. P. Auti and C. Alleman at the time of the study were employees of OPEN 10.13039/100018696Health who received funding from GSK to conduct this study. L. Sergison declares no relevant conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.)

Background: Anaphylaxis is a serious allergic reaction that is effectively treated with epinephrine. Epinephrine autoinjectors are devices that contain fixed doses of medication that can be carried by patients at risk for anaphylaxis so that ready access to first line medication is available outside the medical setting., Methods: This review will discuss recent studies evaluating patient characteristics to consider when prescribing epinephrine autoinjectors., Results: Decisions regarding who should be prescribed epinephrine autoinjectors will depend on the type of allergy, as well as co-morbidities and other risk factors that can increase a patient's risk for poor outcomes., Conclusion: Shared decision-making is essential when developing guidance regarding post-epinephrine management. Regular education during routine follow-up visits can reinforce knowledge and skills for managing food allergy reactions., Competing Interests: J. Wang receives consultancy fees from ALK Abello and Novartis; royalty payments from Up To Date, (Copyright © 2024, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Purpose: Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes that are important to patients, and assessed patient perceptions and preferences between an adalimumab biosimilar autoinjector (Hyrimoz ® SensoReady ® Pen [SDZ-ADL pen]) and the reference adalimumab autoinjector (Humira ® Pen [ref-ADL pen]) in patients with rheumatoid arthritis (RA) or Crohn's disease (CD) in Canada., Patients and Methods: In this survey, adult patients were recruited for web-assisted telephone interviews. Patients had ≥ 3 months' experience with the ref-ADL pen and 1-12 months' experience with the SDZ-ADL pen., Results: The survey included 120 patients with RA (n = 32) or CD (n = 88). Mean experience with the ref-ADL pen was 7 years for RA or 5 years for CD vs 9 months with the SDZ-ADL pen. The most important autoinjector attributes were the ability to use the pen independently and the ease and simplicity of self-injection. When comparing the two autoinjectors, patients significantly preferred the SDZ-ADL pen over the ref-ADL pen for nearly every attribute evaluated, with the greatest differences reported for visual and audible feedback mechanisms, ease of self-injection, and ability to use the device independently. Overall, 82% of patients preferred the SDZ-ADL pen over the ref-ADL pen, with buttonless activation and less injection pain being the main drivers for this preference., Conclusion: Patients with RA or CD indicated a preference for the SDZ-ADL pen over the ref-ADL pen, independent of the duration of use of the pen. The preference for a biosimilar device within 1 year of switching provides reassurance of rapid patient acceptance of biosimilars and may simplify the switching process. These results confirm the importance of ensuring autoinjector design supports independent self-administration of medication and align with previous data showing high patient satisfaction with the SDZ-ADL pen., Competing Interests: Shrihari Jathanakodi and Charlotte Both were employees of Sandoz Group AG. Ines Brueckmann is an employee of Sandoz Group AG. Laura Rose is an employee of Sandoz Inc. Nahal Nasseri is an employee of Sandoz Canada Inc. Jean-Pierre Raynauld has been a speaker or advisor for AbbVie, Amgen, BIOJAMP, Janssen, Novartis, Organon, Orimed, Pfizer, Sandoz, Sanofi, and UCB. Neeraj Narula has been a speaker or advisor for AbbVie, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Innomar Strategies, Iterative Health, Janssen, Merck, Pfizer, Sandoz, Takeda, and Viatris. The authors report no other conflicts of interest in this work., (© 2024 Jathanakodi et al.)

Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases. [ABSTRACT FROM AUTHOR]

Fremanezumab (AJOVY; Teva Pharmaceutical Industries Ltd, Netanya, Israel), approved for the preventive treatment of migraine, is available as a subcutaneous injection either once a month or once every 3 months using an autoinjector or a prefilled syringe. The present study evaluated the pharmacokinetic (PK) bioequivalence of a single subcutaneous injection of fremanezumab 225 mg administered using an autoinjector compared to a prefilled syringe in healthy volunteers. Blood samples for PK and antidrug antibodies were collected before and after dosing. Safety and tolerability assessments included physical examinations, adverse event reporting, laboratory evaluations, and immunogenicity. Following single‐dose administration, the mean concentration‐time profiles for the 2 treatment groups (autoinjector, n = 106; and prefilled syringe, n = 110) were similar. The point estimates for the back‐transformed ratio (autoinjector/prefilled syringe) of geometric least squares means of maximum plasma concentration, area under the plasma concentration–time curve from time 0 to the time of the last measurable drug concentration, and area under the plasma concentration–time curve from time 0 extrapolated to infinity were 1.03, 1.04, and 1.05, respectively, with the 90% confidence intervals entirely contained within bioequivalence margins of 0.8 to 1.25. For both groups, median time to maximum observed concentration was 5 days and mean terminal elimination half‐life was approximately 29 days. Treatment‐related adverse events were reported by 39 (36%) subjects in the autoinjector group and 26 (24%) in the prefilled syringe group, and the majority were nonserious injection site reactions. The incidence of treatment‐emergent antidrug antibody response was low and evenly distributed between the autoinjector (n = 3; 3%) and prefilled syringe (n = 4; 4%) groups. These results indicate that the fremanezumab autoinjector presentation provides an easy‐to‐use bioequivalent PK profile with a similar safety and tolerability profile to that of the prefilled syringe. [ABSTRACT FROM AUTHOR]

Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients’ catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations.

Background: Despite its life-saving potential in anaphylaxis, self-injectable epinephrine (SIE) is frequently not administered by caregivers prior to arrival in the emergency department (ED). Prescriptions from the ED often go unfilled which may contribute to the failure to receive SIE when needed.Objective: To determine the prescription filling rate and accessibility of SIE devices among families discharged from the Pediatric ED with an SIE prescription.Methods: A phone survey was administered to parents of children <18 years of age prescribed SIE in the pediatric ED over 12 months. The survey inquired if they own an SIE device, the device's expiration date as confirmation, and details of their child's allergy. Variables were analyzed for association with owning SIE, having SIE accessible when prompted, and having unexpired SIE accessible.Results: 170 children received prescriptions for SIE and 100 (59%) completed the survey. Eighty-four of 100 (84%) had filled the initial SIE prescription. Sixty-five of 100 (65%) had proof of having SIE, of which 29% (19/65) were expired. Only 46% (46/100) of all respondents had an accessible unexpired SIE. Patients with food allergies and those who'd visited an allergist after their ED visit had higher odds of having unexpired accessible devices.Conclusion: A majority of patients prescribed SIE from the ED fill their prescription; however, less than half have unexpired SIE readily available despite high rates of recurrent anaphylactic emergencies. Focusing on post-discharge planning, particularly follow-up, may prevent children with allergies from being left dangerously unprepared. [ABSTRACT FROM AUTHOR]

Gary T Ferguson,1 Jeremy Cole,2 Magnus Aurivillius,3 Paul Roussel,4 Peter Barker,4 Ubaldo J Martin4 On behalf of the GRECO study investigators1Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 2OK Clinical Research, LLC, Edmond, OK, USA; 3AstraZeneca, Mölndal, Sweden; 4AstraZeneca, Gaithersburg, MD, USACorrespondence: Gary T FergusonPulmonary Research Institute of Southeast Michigan, 29255 West 10 Mile Road, Suite A, Farmington Hills, MI 48336, USATel +1-248-478-6806Fax +1-248-478-6908Email garytferguson@msn.comPurpose: Accessorized prefilled syringes (APFS) have demonstrated functionality and reliability for subcutaneous (SC) delivery, including self-administration, of benralizumab 30 mg in the clinic or at home. The multicenter, open-label GRECO study (NCT02918071) assessed functionality and reliability of a single-use autoinjector (AI) for at-home benralizumab administration by patients or their caregivers.Patients and methods: Adults with severe asthma received benralizumab SC injections at the study site at Weeks 0, 4, and 8. The first dose was administered by health care providers. Patients/caregivers had the option of administering the second dose and were required to administer the third dose under supervision. At Weeks 12 and 16, patients/caregivers administered benralizumab via AI at home. After each administration, patients/caregivers completed questionnaires concerning administration and device functioning. All AI devices used were returned for evaluation.Results: A total of 595 AIs were used for 121 patients (mean age 48.5 years; 64% female) in the clinic and at home. Of 116 participants, 113 (97.4%; 95% confidence interval [CI]: 92.63–99.46) and 112 (96.6%; 95% CI: 91.41–99.05) successfully administered benralizumab at home at Weeks 12 and 16, respectively; 108 (93.1%; 95% CI: 86.86–96.98) were successful on both occasions. Throughout the study, 10 (1.7%) AI administrations were unsuccessful: 8 (1.3%) because of user error, 1 (0.2%) with undetermined cause, and 1 (0.2%) because of a manufacturing defect. Benralizumab efficacy (assessed by Asthma Control Questionnaire 6 score) and pharmacokinetics for patients using the AI were comparable to published results for patients receiving benralizumab via syringe in a clinical setting. No new or unexpected safety findings were observed.Conclusion: AIs were functional, reliable, and performed well in the clinic and at home. Nearly all patients and caregivers successfully administered SC benralizumab via AI. Benralizumab availability in AI and APFS could provide patients with choices for self-administration.Keywords: Autoinjector, benralizumab, biologic, clinical trial, delivery system, eosinophil, prefilled syringe, subcutaneous

Today, there is a need to introduce medical devices into everyday medical practice with the goal to self-administer injectional drugs. The speed and safety of auto-injectors / pre-filled syringe pens use (AI/PFS) is the introduction of an injectional form drug in a special medical device, which allows patients to enter a pre-designated therapeutic dose due to the characteristics of the structure of the product, automatic dosing, data of the interactive display on some devices, comfortable design, etc. Considering that AI/PFS were developed to improve the quality of life of patients with various pathological conditions, therefore the creation of affordable medical devices for low-income groups of the population is relevant today. Also an actual issue is the provision of high-quality first-aid kits for soldiers, which is a vital component for medical care in the context of active combat conditions and the lack of the required number of field hospitals.The speed of administration, the onset of effect and ease of use provides significant advantages for AI / PFS. Therefore, the issue of affordability for the low-income groups of the population and the army with the necessary drugs should be sufficiently supported by state regulation.Purpose of study – study of the international experience in the implementation and use of drugs (drugs) in the form of affordable, safe and effective modern dosage forms in the form of autoinjectors.Materials and methods – foreign and domestic literature on the use of AI/PFS in complex and monotherapy treatment of various diseases. State registries of medicines of Ukraine, the USA and some EU countries. The study used systematic, statistical and comparative analyzes, as well as the generalization of information. The data used is freely available among various medical scientific and metric bases, the Internet and international scientific conferences.The analysis of the use of AI/PFS indicates that today the world market of medicines and medical devices contains a large number of drugs under different trade names. However, many patients in the world refrain from using these dosage forms due to the significant cost of medical devices, which makes impossible the required regular use of such drugs for the low-income population groups. This is a significant disadvantage, since AI / PFS is implemented to correct not only chronic diseases such as rheumatoid arthritis, multiple sclerosis, but also to provide emergency careinurgent conditions (anaphylactic reactions, intense pain, etc.).In the global market for drugs and medical devices, injectable medicines in the form of AI/PFS are widely represented. The effectiveness of the use of such devices indicates the advantages and prospects for the use of existing AI/PFS on the global market for patients and medical personnel. Today, the most commonly used drugs in AI/PFSare for the treatment of diabetes, emergency conditions in civil and military medicine, chronic diseases of various etiologies, pediatric practice. The use of AI /PFS significantly improves patient compliance for the treatment of chronic diseases due to ease of use and reduction of adverse reactions at the site of administration. Most of the analyzed sources indicate a low level of economic affordability of drugs in the form of AI/PFS for the population and the government sector of drug supply due to the high cost of the medical devices, compared to traditional syringes. But the results of the study indicate a high level of advantages and prospects in the use of drugs in AI/PFS in medical practice for both medical personnel and patients.