Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Unraveling Pre-filled Syringe Needle Clogging: Exploring a Fresh Outlook Through Innovative Techniques.

OBJECTIVE: This study aimed to investigate the movement of liquid in the needle region of staked-in-needle pre-filled syringes using neutron imaging and synchrotron X-ray tomography. The objective was to gain insights into the dynamics of liquid presence and understand the factors contributing to needle clogging. METHODS: Staked-in-needle pre-filled syringes were examined using neutron radiography and synchrotron X-ray phase-contrast computed tomography. Neutron radiography provided a 2D visualization of liquid presence in the needle, while synchrotron X-ray tomography offered high-resolution 3D imaging to study detailed morphological features of the liquid. RESULTS: Neutron radiography revealed liquid presence in the needle region for as-received samples and after temperature and pressure cycling. Pressure cycling had a more pronounced effect on liquid formation. Synchrotron X-ray tomography confirmed the presence of liquid and revealed various morphologies, including droplets of different sizes, liquid segments blocking sections of the needle, and a thin layer covering the needle wall. Liquid presence was also observed between the steel needle and the glass barrel. CONCLUSIONS: The combination of neutron imaging and synchrotron X-ray tomography provided valuable insights into the dynamics of liquid movement in staked-in-needle pre-filled syringes. Temperature and pressure cycling were found to contribute to additional liquid formation, with pressure changes playing a significant role. The detailed morphological analysis enhanced the understanding of microstructural arrangements within the needle. This research contributes to addressing the issue of needle clogging and can guide the development of strategies to improve pre-filled syringe performance.

"Fabrication of pellets via extrusion-spheronization for engineered delivery of Famotidine through specialized straws for Paediatrics".

OBJECTIVE: A simple and efficient drug delivery device was designed, viz. specialized straw comprising of famotidine-loaded fast disintegrating pellets. SIGNIFICANCE: Pediatric dosage forms are designed and developed considering the palatability in children of all ages. This specialized straw was intended for pediatrics presenting with dysphagia or associated symptoms. METHODS: The pellets were formulated using an extruder spheronization technique incorporated with Kyron T-314 as a super disintegrant. These pellets were characterized for their micromeritic properties, disintegration, and in vitro drug release. The specialized straw was evaluated for various parameters like flow rate of water siphoned through the straw and solvation volume. RESULTS: Pellets were found to have excellent flow properties, disintegration time was found to be 25-30s, and dissolution studies showed 96.1% drug release in 45min. In vitro flow rate was determined to simulate sipping action through this specialized straw. The results indicated that water flowing through the hollow straw at the rate of 13.8±1.3 mLs-1, when tested in prefilled specialized straw, 6.3±1.1 mLs-1 flow rate was observed to be sufficient to dissolve the pellets. CONCLUSION: Finally, the fast-disintegrating pellets demonstrated excellent in vitro performance and relative ease of manufacturing as compared to other solid dosage forms. Furthermore, the developed specialized straw can be used as a convenient and attractive drug delivery device for pediatrics.

Characterizing Silicone Oil-Induced Protein Aggregation with Stimulated Raman Scattering Imaging.

Particles in biopharmaceutical products present high risks due to their detrimental impacts on product quality and safety. Identification and quantification of particles in drug products are important to understand particle formation mechanisms, which can help develop control strategies for particle formation during the formulation development and manufacturing process. However, existing analytical techniques such as microflow imaging and light obscuration measurement lack the sensitivity and resolution to detect particles with sizes smaller than 2 µm. More importantly, these techniques are not able to provide chemical information to determine particle composition. In this work, we overcome these challenges by applying the stimulated Raman scattering (SRS) microscopy technique to monitor the C-H Raman stretching modes of the proteinaceous particles and silicone oil droplets formed in the prefilled syringe barrel. By comparing the relative signal intensity and spectral features of each component, most particles can be classified as protein-silicone oil aggregates. We further show that morphological features are poor indicators of particle composition. Our method has the capability to quantify aggregation in protein therapeutics with chemical and spatial information in a label-free manner, potentially allowing high throughput screening or investigation of aggregation mechanisms.

Assessment of the treating physicians' first-hand experience with handling and satisfaction of ofatumumab therapy: findings from the PERITIA survey conducted in Europe.

BACKGROUND: Real-world evidence on experience and satisfaction of ofatumumab as a treatment option for relapsing multiple sclerosis (RMS) is limited. OBJECTIVE: To present cumulative responses from a questionnaire related to first-hand experience of treating physicians on handling and convenience of ofatumumab therapy along with concerns related to COVID-19. METHODS: PERITIA was a multicentre survey conducted to collect responses from the ASCLEPIOS I/II trial investigators from Europe via an online questionnaire. RESULTS: Forty-six physicians (Germany, n = 14; Spain, n = 12; Portugal, n = 10; Italy, n = 10) completed the survey. Overall, 43% of the physicians considered the benefit-risk ratio of ofatumumab as very good. Over 93% were in favour of ofatumumab self-administration at home and the majority (83%) believed it to be completely true that self-administration of ofatumumab eases the burden for patients in terms of time. All investigators would like to potentially use anti-CD20 therapy as a long-term strategy. Even during the COVID-19 pandemic, physicians were in favour of a self-administration of MS therapy at home over other anti-CD20 therapy infusions. CONCLUSION: European neurologists who were part of this survey considered the benefit-risk-ratio of ofatumumab as favourable and the monthly self-administered subcutaneous injections offering convenience for patients in the clinical practice.

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

OBJECTIVE: 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. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed publications meeting our inclusion criteria underwent rigorous screening, including title, abstract, and full-text article assessments, performed by two reviewers. DATA SYNTHESIS: 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. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: 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. CONCLUSION AND RELEVANCE: 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.

Handling injectable medications in anaesthesia: Guidelines from the Association of Anaesthetists.

Peri-operative medication safety is complex. Avoidance of medication errors is both system- and practitioner-based, and many departments within the hospital contribute to safe and effective systems. For the individual anaesthetist, drawing up, labelling and then the correct administration of medications are key components in a patient's peri-operative journey. These guidelines aim to provide pragmatic safety steps for the practitioner and other individuals within the operative environment, as well as short- to long-term goals for development of a collaborative approach to reducing errors. The aim is that they will be used as a basis for instilling good practice.

Whitening efficacy and tooth sensitivity in a combined in-office and at-home whitening protocol: A randomized controlled clinical trial.

OBJECTIVE: This controlled randomized clinical trial determined the whitening efficacy and the intensity and absolute risk of tooth sensitivity in dual whitening when prefilled at-home whitening trays were used between in-office whitening intervals. MATERIALS AND METHODS: An in-office whitening agent containing 35% hydrogen peroxide was used. A prefilled tray with a whitening agent containing 6% hydrogen peroxide was used for at-home whitening. Sixty-six subjects were randomly assigned to three groups. Group I: at-home whitening was performed 10 times between the in-office whitening treatments. Group II: at-home whitening was performed five times between the in-office whitening treatments. Group III: only in-office whitening was performed. The tooth color changes were evaluated using a spectrophotometer. A visual analog scale was used to express the pain intensity. RESULTS: All the groups showed increased ΔE*ab, ΔE00 , and ΔWID with increased whitening sessions. Group I at the 3rd whitening session showed significantly higher ΔE*ab, ΔE00 , and ΔWID than group III. Tooth sensitivity showed higher values up to 24 h after whitening. CONCLUSIONS: Although dual whitening with the prefilled tray and in-office whitening had higher whitening ability than in-office whitening alone, the intensity and absolute risk of tooth sensitivity was similar. CLINICAL RELEVANCE: The dual whitening might produce faster and stronger whitening effects than in-office whitening alone.

Detection and Identification of an Unknown Impurity in Ephedrine HCl 5 mg/mL Cyclic Olefin Syringes: Formulation Development.

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already.

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

The Effect of Syringe-Filling Technique on the Risk for Endophthalmitis after Intravitreal Injection of Anti-VEGF Agents.

PURPOSE: This study aimed to compare the risk for post-injection endophthalmitis between different anti-vascular endothelial growth factor (VEGF) agents and syringe preparation techniques. METHODS: A retrospective study of anti-VEGF injections performed in 3 large ophthalmology departments between 2013 and 2019 was conducted. Injections were categorized according to the drug and the syringe-filling technique - prefilling by a hospital pharmacy, prefilling by a good manufacturing practice (GMP) pharmacy, self-drawing from the vial by the injecting physician, and use of a prefilled syringe. Cases of endophthalmitis were identified, and their rates were analyzed. RESULTS: A total of 197,402 injections were included, and 53 cases of endophthalmitis were identified (0.027% risk). The risk of endophthalmitis following injections with syringes that were prefilled by GMP pharmacies or the manufacturers was significantly lower than that following injections which were self-drawn by the physician (0.019% vs. 0.055%, p < 0.0001). For ranibizumab, risk of endophthalmitis decreased since it became available in a prefilled syringe (0.054% vs. 0.014%, p = 0.066), bordering on statistical significance. CONCLUSIONS: The syringe-filling technique is an important factor determining risk of post-injection endophthalmitis. Use of GMP-grade prefilling by professional pharmacies or the manufacturers significantly reduces this risk and should be the technique of choice for all drugs administered by intravitreal injection.

Stability of 4 Intravenous Drug Formulations in Prefilled Syringes Stored Frozen for Up to 60 Days.

Purpose: Prefilled drug syringe use may reduce the cost of routine antibiotic drug delivery. Storage of prefilled syringes frozen (-20°C) or refrigerated (4°C-5°C), can optimize the use of robotic syringe filling systems if acceptable stability data is gathered per USP 797 standards. Methods: Four intravenous (IV) drug formulations were prepared from bulk standard solutions and filled into 10 mL syringes using an Intellifill© IV Robot. Formulations were Piperacillin (2.0 g) and Tazobactam (0.25 g) as 2.25 g in 10 mL; Piperacillin (3.0 g) and Tazobactam (0.375 g) as 3.375 g in 10 mL; Cefuroxime as 1.5 g in 11 mL; and Vancomycin as 1.0 g in 10 mL. Concentrations were assayed at "zero time," and after 21, 45, and 60 days frozen. Syringes were warmed to room temperature (RT) by gently rolling in hands. Three syringes of each formulation were assayed by stability-indicating HPLC per USP procedures. Assay results are the average of 5 injections of samples from each syringe upon return to RT and repeated for 3 separate syringes maintained at RT for 24 hours. Results: All formulations were stable out to 60 days frozen. Both of the piperacillin/tazobactam formulations were also stable when kept at refrigerated temperature for 9 days. Conclusion: Piperacillin/Tazobactam formulations can be stored frozen (-20°C) for up to 60 days with no appreciable loss. Cefuroxime and Vancomycin formulations can be stored frozen for up to 60 days. Both Piperacillin/Tazobactam formulations can be refrigerated for up to 9 days. Implementation of larger batch compounding coupled with frozen syringe storage and delivery could result in enhanced uniformity of composition and significant manpower savings.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results.

OBJECTIVE: We compared the pharmacokinetic exposure following a single subcutaneous dose of benralizumab 30 mg using either autoinjectors (AI) or accessorized prefilled syringes (APFS). APFS and AI functionality and reliability for at-home benralizumab delivery have been demonstrated in the GREGALE and GRECO studies, respectively. METHODS: In the open-label AMES study (NCT02968914), 180 healthy adult men and women were randomized to one of two device (AI or APFS) and three injection site (upper arm, abdomen, or thigh) combinations. Randomization was stratified by weight (<70 kg, 70-84.9 kg, and ≥85 kg). Blood eosinophil counts were measured on Days 1, 8, 29, and 57. RESULTS: Benralizumab pharmacokinetic exposure was similar between AI and APFS. Geometric mean ratios (AI/APFS) (90% CI) were 92.8% (87.4-98.6) and 94.5% (88.2-101.2) for two area under the concentration‒time curve measurements (AUClast and AUCinf). Benralizumab exposure was approximately 15-30% greater for thigh vs. abdomen or upper arm administration. Exposure was slightly greater for APFS vs. AI regardless of injection site or weight class. These differences were unlikely to be clinically relevant, as eosinophil depletion was achieved consistently with both devices at all injection sites. No device malfunctions were reported. No new or unexpected safety findings were observed. CONCLUSION: Benralizumab pharmacokinetic exposure was similar between AI and APFS, with consistent blood eosinophil count depletion observed with both devices. These results support benralizumab administration with either AI or APFS, providing patients and physicians increased choice, flexibility, and convenience for potential at-home delivery.

Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without Human Hyaluronidase and Auto-injector Tolerability in Humans.

Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) delivery of co-administered therapeutic agents by locally and transiently degrading hyaluronan in the SC space, and can be administered with therapeutics using a variety of devices. Two SC delivery studies were carried out to assess auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL (AI2 and sAI2) with different injection speeds and depths (5.5-7.5 mm) and two pre-filled syringe (PFS) devices of 1 and 2 mL. The injection included a placebo buffer with and without rHuPH20 to evaluate the effect of rHuPH20 on SC injection performance. The feasibility of using similar devices to deliver a placebo buffer in humans was investigated. rHuPH20 was not studied in humans. In miniature pigs, postinjection swelling was evident for most PFS/AI injections, particularly 2 mL. Swelling heights and back leakage were typically lower with rHuPH20 co-administration versus placebo for most device configurations (1 or 2 mL PFS or AI). Auto-injections with versus without rHuPH20 also resulted in reduced swelling firmness and faster swelling resolution over time. Slow injections with rHuPH20 had shorter and more consistent injection time versus placebo. In humans, minimal injection site swelling and negligible back leakage were observed for 2-mL injections of placebo, while more erythema was observed in humans versus miniature pigs. Even at high delivery rates with PFS or AI, the addition of rHuPH20 resulted in improved SC injection performance versus placebo in miniature pigs.

Analysis of Silicone Oil in Prefilled Syringes and Biopharmaceutical Drug Products Using High-Performance Liquid Chromatography.

As the packaging of choice for many therapeutic proteins, prefilled syringes have been widely used in biopharmaceutical industry as primary containers, where silicone oil is applied to ensure their proper functionality. Adequate lubrication from sufficient amount of silicone oil and its appropriate distribution across syringe barrels is crucial for successful administration of drug product (DP) from the prefilled syringes; however, silicone oil is also susceptible to leaching from the syringe surface into the formulation with the potential to interact with therapeutic proteins, which could lead to the formation of visible and sub-visible aggregates and/or particles that are potentially immunogenic. Accurate determination and careful control of silicone oil levels in both empty syringes and protein drug products are therefore critical in process development to ensure syringe functionality, drug product quality, and patient safety. On the other hand, analysis of silicone oil can be challenging especially when the analysis is performed on formulated protein drug products, where matrix effects could be significant. It is demonstrated in this study that silicone oil in empty syringes or formulated drug products can be extracted effectively using organic solvents and quantitatively determined using high-performance liquid chromatography (HPLC) coupled with a universal detector. It was also shown that direct extraction of silicone oil from formulated protein drug products can be very challenging, but pretreatment of the protein drug products with pepsin enzymatic digestion facilitated the extraction process, which enabled the analysis of silicone oil in the drug product at low ppm levels.

Changing practice to using pre-filled syringes for flushing IV cannulas.

In the UK, the Medicines and Healthcare products Regulatory Agency classifies 'pre-filled syringes' for flushing Intravenous (IV) cannulas and IV access devices as 'borderline' devices and offers some advice on how control measures can help mitigate risks. The Medicines Act (1968) and Medical Device Regulations try to address the legal position of these devices and allow each employer to identify those groups of staff allowed to use them. In turn, this may help address anomalies around the need to prescribe and document their use. This article describes how one large university health board in Wales implemented a change in products and practice and explores the issues around adopting and using CE-marked pre-filled, sterile syringes of 0.9% sodium chloride in place of manually drawing up an IV flush (the CE mark indicates devices that conforms with European legal requirements). Whether the use of individual components or a single pre-filled device can lead to a streamlined and cost-effective way to manage the flushing of IV cannula and vascular access devices was explored. Additional risk factors were identified, and the legal status clarified in line with current guidelines and regulations. As 0.9% sodium chloride in ampoules and vials is classified as a prescription-only medicine, the administration needs control via formal prescription or a patient group direction. Adopting and using these pre-filled syringes as CE-marked medical devices requires careful consideration and sign-off from each employing authority, before implementing them for flushing IV cannulas and IV access devices.

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients.

AIMS: The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. METHODS: A phase 1 study in healthy subjects with 6 devices to administer 2 mL injection volumes was conducted to evaluate the serum PK, safety and tolerability of secukinumab following single s.c. injection of 300 mg in the abdomen (either side) or in the thigh (either leg). Primary PK endpoints were maximum observed serum concentration and area under the serum concentration-time curve. The impact of device, site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 × 1-mL prefilled syringe or 1 × 2-mL prefilled syringe. RESULTS: Mean serum concentration-time profiles for administration as 2 × 1 mL injections or as 1 × 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 × 1 mL injections. A nonclinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a 1-year phase 3 study in patients confirmed PK results observed in the phase 1 study. CONCLUSION: Collective evidence from both studies demonstrated that 2-mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticeable local reactions.

Tissue Resistance during Large-Volume Injections in Subcutaneous Tissue of Minipigs.

PURPOSE: Injection devices for administration of biopharmaceuticals enable subcutaneous self-administration by patients. To meet patient specific capabilities, injection forces need to be characterized. We address the open question of whether tissue resistance significantly contributes to overall injection forces, especially for large injection volumes. METHODS: Subcutaneous tissue resistance was systematically quantified for injection volumes up to 11 mL depending on viscosity (1-20 mPa·s) and injection rates (0.025-0.2 mL/s) using Göttingen Minipigs as the animal model. The contribution of an artificially applied external force at the injection site simulating autoinjector needle cover depression was tested between 2.5-7.5 N. RESULTS: Tissue resistance reached average values of ~120 mbar for injection volumes up to 11 mL independent of viscosity and injection rate, and maximum values of 300 mbar were determined. Artificially applied external forces led to higher values, independent of the absolute applied force - maximum values of 1 bar were obtained when injecting 4.5 mL of the 20 mPa·s solution at an injection rate of 0.1 mL/s with the application of an artificial 5 N force, corresponding to ~450 mbar. All conditions yield defined injection sites suggesting tissue resistance is defined by mechanical properties of the subcutaneous tissue. CONCLUSIONS: We set our results in relation to overall injection forces, concluding that maximum values in tissue resistance may cause challenges during subcutaneous injection when using injection devices. Graphical abstract.

Could pre-filled safety syringes facilitate the adoption of home administration for cancer patients?

Today, healthcare systems around the world are under increasing pressure, not least with the current health crisis. One of the leading efforts to relieve this burden in recent years has been through the promotion and facilitation of self-administration, particularly for patients with chronic illnesses. By relocating certain treatments to patients' homes, hospitals are minimizing the risk of over-crowding and giving patients a more active role in their own medication regime. Fuelled by this trend toward self-care, the prefilled safety syringe market has seen exponential growth in recent years - providing greater ease-of-use and safety for all carers and self-administering patients in non-clinical settings. When looking at the benefit of switching intravenous hospital-based to subcutaneous home-based administration while maintaining the same clinical outcomes, a similar change is also being considered in some areas of oncology. Drawing on the experience of home-treatment for chronic conditions, this article looks at the challenges and considerations of extending this to eligible cancer patients in the future.