Syringe Research Articles

The role of neutrophils-lymphocytes ratio (NLR), lymphocytes-monocytes ratio (LMR), platelets-lymphocytes ratio (PLR) in oral cancer and acute dental infections

Objectives: The present study was a cross-sectional observational study, which was carried out on patients reported to the Department of Oral Medicine and Radiology. This study aims to evaluate the hemogram parameters NLR, LMR, and PLR among 90 Patients. Methods: Patients were divided into 3 groups: Group A consists of 30 patients with histopathological confirmed oral cancer. Group B consists of 30 patients who presenting acute dental infections. Group C consists of 30 patients clinically healthy subjects. The hemogram parameters NLR, LMR and PLR were compared in the 3 groups and we studied their correlation to the clinical prognostic indicators like T stage, to the presence or absence of lymph node metastasis, and to differentiation of cancer. After obtaining personal informed consent, a thorough examination of the oral cavity and the lesion was conducted with an illuminated light and mouth mirror. Blood tests were performed on all the subjects before treatment. Under aseptic conditions, Venous blood (2 ml) was collected by venepuncture of the median cubital vein in the cubital fossa of the forearm using a disposable syringe with a 24-gauge needle. The withdrawn blood was transferred into an EDTA-containing test tube. Haematological parameters were analysed using an automated haematology analyzer. NLR, LMR, and PMR were calculated as the ratio of absolute peripheral neutrophil to lymphocyte, lymphocyte to monocyte, and platelet to lymphocyte count, respectively. Results: The present study revealed that NLR is significantly elevated in oral carcinoma compared to healthy individuals, but is lesser than in patiemts with acute dental infections. LMR is higher in oral carcinoma than in acute dental infections and healthy individuals, but no statisticaly significant difference was detected among the groups. PLR is higher in oral carcinoma than in Acute dental infections and healthy individuals, and it is statistaicaly significant. There are significant correlations in oral carcinoma between NLR, LMR, and PLR. NLR has a positive correlation with PLR and a negative correlation with LMR, which showed clinical significance as determined by the Spearman correlation coefficient. In Acute dental infections and healthy individuals, there is a significant correlation of NLR with LMR and PLR but no significant correlations between LMR and PLR and vice versa. NLR, LMR, and PLR were correlated to clinical prognostic indicators like T stage, presence or absence of lymph node metastasis, and differentiation of cancer. There is no significant difference in NLR, LMR, or PLR ratios concerning Clinical T staging since the p-value is greater than 0.05 for NLR, LMR, and PLR (p= 0.072, 0.446, 0.446, respectively). A statistically significant difference is found in LMR to the clinical presence or absence of Lymph node metastasis since the p-value is less than 0.05 only for LMR (p=0.018). The mean values of LMR in N0, N1, and N2 were 9.49, 5.65, and 4.40, respectively; this implies that the mean value of LMR decreases in advanced oral carcinoma as the nodal stage increases with lymph node metastases. A statically significant difference is found in NLR (p=0.011) and PLR (p =0.013) for differentiation of tumour (p-value is less than 0.05), which implies NLR & PLR values are elevated in moderate differentiated oral carcinomas when compared to well-differentiated oral carcinoma. Conclusions: A significant elevation exists in haematological parameters like NLR, LMR, and PLR in oral carcinoma and acute dental infections.

Automated Vial and Pre-Filled Syringe Counting in the Pharmaceutical Industry Using YOLO and SAHI Techniques

Automated Vial and Pre-Filled Syringe Counting in the Pharmaceutical Industry Using YOLO and SAHI Techniques

Swellable Biopolymer Composite Microneedle Patch for Pain-Free Collection of Interstitial Fluid to Analyze Multiple Biomolecules.

Sampling of interstitial fluid (ISF) using microneedle (MN) patch offers a pain-free minimally invasive alternative to syringe needle-based blood sample collection. However, there is a challenge in the development of MN patch that provides swelling behavior with sufficient mechanical strength for skin penetration. Here, we report fabrication of MN patch made of biopolymer composite containing iota-carrageenan, gelatin, and polyethylene glycol. Calcium chloride was used as a crosslinker to improve mechanical strength. MN patch was characterized for integrity, swelling behavior, mechanical strength, aspiration of fluid from agarose gel, and the excised porcine ear skin. An array of 361 MNs was able to aspirate 36 ± 5 and 14 ± 1 μL fluid after application in agarose gel matrix and the ex vivo porcine skin model, respectively. MN patch applied in vivo rat model for 30 min resulted in the collection of ISF containing 267 ± 128 mg/dL, 24 ± 13 mg/dL, and 0.6 ± 0.4 mIU/mL of glucose, uric acid and thyroid stimulating hormone (TSH), respectively. The concentration of glucose, uric acid, and TSH in rat blood was found to be 199 ± 47 mg/dL, 8.4 ± 6 mg/dL, and 1.1 ± 0.6 mIU/mL at the same time. Furthermore, MN patch applied on the forearm of 10 healthy human volunteers for 30 min was able to aspirate 32 ± 14 μL of ISF. The concentration of glucose, uric acid, and TSH determined from ISF samples of human volunteers was 64 ± 25 mg/dL, 4.2 ± 4.1 mg/dL, and 0.16 ± 0.08 mIU/mL, respectively. The visual analogue scale (VAS) pain score after MN application was lower compared with hypodermic syringe needle insertion. Taken together, biopolymer composite-based swellable MN patch can be developed for collection of ISF for simultaneous determination of multiple biomolecules in a minimally invasive manner.

New prefilled syringe aflibercept design. A cause of symptomatic IOP spike after aflibercept PFS?

To describe ocular hypertension cases after using a new aflibercept prefilled syringe and to assess the main characteristics of these eyes and their possible association with intraocular pressure (IOP) changes. Case series. We reported all the cases of ocular hypertension following aflibercept prefilled syringes (PFS) treatment in our department between April 2021 and December 2023. A total of 4183 eyes were treated with aflibercept PSF. Thirteen transitory IOP elevations were observed immediately after injection (0.3%). Two eyes had an IOP between 30-35 mmHg, five eyes had an IOP between 36-55 mmHg and three eyes had an IOP > 56 mmHg. The mean IOP was 45.5 mmHg±11.33. Only six eyes needed anterior chamber paracentesis (37.5%). The other patients were treated conservatively (ocular massage and/or IOP-lowering drops). The mean IOP after treatment was 15.71 mmHg±7.20. Visual acuity improved after treatment in all the patients. Compared with other injectors, reports have indicated a higher incidence of moderate and severe IOP spikes with aflibercept PSF. The European Medicine Agency (EMA) has associated this significant increase with incorrect syringe handling, leading to higher injection volumes. Although plunger misalignment seems to play a role in the IOP spikes, some other characteristics of this new injector could play a role. Factors such as syringe diameter, plunger alignment, and injection force may contribute to this issue. The reason some authors found no significant differences in IOP elevation after IVI, with aflibercept PFS, could be due to variations in patient characteristics, which may also play an important role in post-IVI pressure changes. Intraocular pressure spikes after aflibercept PFS can be explained by injector characteristics. The PFS of aflibercept has a domed plunger. Incorrect alignment between the base of the plunger and the black dosing line could cause an increase in the injected volume. Furthermore, the wider syringe diameter of aflibercept PFS could imply a larger injection force, increasing the risk of IOP elevation. Patient characteristics, such as previous VPP, axial length, or glaucoma history, may also play a role. Further studies are required to develop an ideal intravitreal syringe.

7483 The Pharmacokinetic Profile of Lanreotide Autogel® Improved Long-Term Arrhythmia Fluctuations in Acromegalic Cardiomyopathy

Abstract Disclosure: M. Iwabuchi: None. Background: The prognosis of acromegaly is related to the status of cardiac complications. Ventricular premature contractions (VPC) are frequently observed in acromegaly, and it is very important to suppress fatal arrhythmias to improve long-term prognosis. Somatostatin analogs are widely used as pharmacotherapy for acromegaly, and they have been reported to improve cardiac prognosis. In comparison to LAR, lanreotide Autogel® has a unique property of self-aggregation under favorable conditions, leading to a stable structure of highly organized nanotubules and has a long half-life after subcutaneous injection determined by pseudo-first order kinetics. CASE: 55-year-old man visited a cardiologist for the treatment of PVCs and heart failure. Because of his acromegalic features, endocrinological and image examinations were performed, and diagnosis of acromegaly was confirmed. His GH was 7.17 ng/mL, IGF-1 566 ng/mL (Normal range: 59-215). Concerning excess of GH may cause nonischemic cardiomyopathy, administration of 20 mg of LAR once a month was started. GH and IGF-1 improved to1.52 ng/mL and 217 ng/mL respectively. The dose of LAR was increased to 30mg because of a remaining fluctuation of VPCs. Considering a possibility of the problem of bioavailability due to method of injection and the pharmacokinetics of LAR, administration of lanreotide Autogel® was started instead of LAR, with the result that an improvement of the fluctuation of the symptom was observed without remarkable change in GH and IGF-1. Arrhythmia status was assessed over time using Holter electrocardiography. Pretreatment Holter electrocardiogram showed 18% of total heart rates in PVCs. After LAR injection, the frequency of PVCs decreased to 3%, and 6 years after changing LAR to lanreotide, the frequency of PVCs decreased to 2%. Clinical Lessons: Simulated steady state pharmacokinetic profiles of LAR and lanreotide Autogel® differ significantly. During LAR treatment, serum concentrations of the drug are approximately stable, whereas the characteristic first-order kinetics of lanreotide Autogel® is superimposed on levels just before the next administration. The pharmacokinetic differences indicate that LAR can be better tailored to therapeutic levels, whereas serum levels of lanreotide must be high for part of the interval between injections to be effective in the period before the next administration. Lanreotide Autogel® has similar clinical effects compared to LAR for the treatment of cardiomyopathy of acromegaly and has the advantage of being available in a convenient pre-filled syringe and no necessity of injection by healthcare professionals. It is suggested that the pharmacokinetic profile of Lanreotide Autogel® resulted in decreased arrhythmia fluctuation in acromegalic hearts, which has been maintained for the past 6 years. Presentation: 6/3/2024

Pharmacokinetic comparison of subcutaneously administered CT-P13 (biosimilar of infliximab) via autoinjector and pre-filled syringe in healthy participants.

CT-P13, a biosimilar of infliximab, is used to treat inflammatory diseases that arise from immune system complications, resulting in excessive and persistent inflammation. The subcutaneous (SC) formulation of CT-P13 overcomes the drawback of prolonged administration associated with the intravenous (IV) infliximab biosimilar, necessitating autoinjector (AI) administration. This randomized, open-label, two-arm, parallel-group, single-dose clinical pharmacology study aimed to evaluate the pharmacokinetics (PK) and safety of CT-P13 SC administration via AI compared with the existing pre-filled syringe (PFS) method. A total of 147 healthy participants were randomized into two groups, of which 139 completed the study. Blood samples were collected from before CT-P13 SC administration to 2016 h after the start of the administration. Serum concentrations were analyzed using the Meso Scale Discovery electrochemiluminescence method. Geometric mean ratios (90% confidence interval) of the AUCinf (areas under the concentration-time curve from zero to infinity) and Cmax (The maximum serum concentration) for CT-P13 SC AI versus CT-P13 SC PFS groups, were 94.15% (85.02%-104.26%), 92.48% (84.66%-101.01%), respectively. CT-P13 SC AI and CT-P13 SC PFS achieved comparable PK because the 90% CI was within the predefined equivalence margin. At the end of the study, immunogenicity results revealed that 70 (97.22%) and 73 (98.65%) participants tested positive for anti-drug antibody (ADA) in the CT-P13 SC AI and CT-P13 SC PFS groups, respectively. They were tested positive for neutralizing antibodies. No other significant safety differences were observed between the treatment groups. In conclusion, both administrations demonstrated PK equivalence and were both safe and well-tolerated.

A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study.

To study if galcanezumab is effective for vestibular migraine (VM). There are currently no placebo-controlled trials showing that treatment is effective for VM. Therefore, we performed the first placebo controlled, randomized clinical trial of a calcitonin gene-related peptide-targeted monoclonal antibody for VM. This was a single site, prospective, double-blind placebo controlled randomized clinical trial. Key inclusion criteria were as follows: participants aged 18-75 years with a diagnosis of VM or probable VM per Barany Society criteria. The primary outcome was change in VM-PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) score, and secondary outcomes included change in DHI (Dizziness Handicap Inventory) score, and count of definite dizzy days (DDDs). Participants were randomized 1:1 to 3 months of treatment with galcanezumab or placebo via subcutaneous injection with a pre-filled syringe, 240 mg the first month, and 120 mg for the second and third months. Forty participants were randomized, and 38 participants were in the modified intent to treat analysis. VM-PATHI score was reduced 5.1 points (95% confidence interval [CI] -13.0 to 2.7) for placebo (N = 21), and 14.8 points (95% CI -23.0 to -6.5) for galcanezumab (N = 17), a difference of -9.6 (95% CI -20.7 to 1.5, p = 0.044). DHI dropped 8.3 points in the placebo arm (95% CI -15.0 to 1.6), and 22.0 points in the galcanezumab arm (95% CI -31.9 to -12.1), a difference of -13.7 (95% CI -20.4 to -8.5, p = 0.018). The count of DDDs per month dropped from 18 days (standard deviation [SD] 7.6) in the baseline month to 12.5 days (SD 11.2) in month 4 for those in the placebo arm, and from 17.9 days (SD 7.9) in the baseline month to 6.6 days (SD 7.3) in month 4 for those in the galcanezumab arm, a difference of -5.7 days (95% CI -10.7 to -0.7, p = 0.026). No serious adverse events were observed. In this pilot study, galcanezumab was effective in treating VM.

Linear and Post-Buckling Analysis of Biocompatible Polymer Microneedle for Transdermal Drug Delivery

To facilitate the delivery of drugs into the skin structure, microneedles play a pivotal role. Unlike conventional hypodermic syringes, microneedles penetrate only the dermis layer, avoiding nerve receptors and resulting in a painless injection. However, when a drug is administered into the skin, microneedles may undergo bending and buckling, leading to structural failure. Such failure can cause the drug to remain beneath the skin, potentially creating complications. Preventing the catastrophe of microneedle failure necessitates a close examination of parameters involved in the bending and buckling process. In this paper, we focus on buckling analysis, as the majority of microneedle failures are attributed to the buckling effect. We perform buckling analysis through finite element analysis to predict the critical buckling load (Pcr). This analysis helps determine the maximum load that a microneedle can withstand. We conduct this analysis using two modes: linear and non-linear (post-buckling analysis). By varying the tip diameter of the microneedle (20µm, 40µm, 60µm, 80µm, 100µm), we can identify the safe insertion load.

Usability of the zilucoplan prefilled syringe for the treatment of generalized myasthenia gravis: insights from a human factors validation study

ABSTRACT Background Generalized myasthenia gravis (gMG) is a chronic, autoimmune neuromuscular disease, often accompanied by high treatment burden. The objective of this usability study was to validate that the zilucoplan prefilled syringe (PFS) can be used safely and effectively. Methods The study recruited 75 participants representing five distinct user groups (injection-naïve gMG patients, injection-experienced gMG patients, injection-naïve caregivers, injection-experienced caregivers, and healthcare professionals), who each simulated an injection without being directed to use the instructions for use (IFU). Participants were then asked to repeat the process as directed by the IFU. Participants were assessed and use errors identified using performance-based criteria. Results 73/75 (97.3%) participants were able to safely administer the dose of medication during the first simulated use, with or without the IFU. When utilizing the IFU, all 75 (100.0%) participants were able to administer the medication. The rate of use errors was low, with pass rates for observation-based tasks ranging from 85.3% to 100.0%, and in general, after participants were instructed to refer to the IFU, the rate of use errors was reduced. Conclusions This human factors study demonstrated that the zilucoplan PFS is safe and effective for intended users, including patients with gMG and their caregivers.

Pharmacokinetics of Subcutaneous Itepekimab Injection With an Autoinjector Device and Prefilled Syringe in Healthy Participants

AbstractItepekimab, 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.

Comparison of the quality of three obturation techniques in primary anterior teeth using cone-beam computed tomography: An in vitro study

Background: This study aimed to compare the number of voids of primary anterior teeth obturated with Endoflas by using three different obturation techniques, namely, endodontic pressure syringe, modified disposable syringe, and reamer using cone-beam computed tomography (CBCT). Materials and Methods: Thirty-six single-rooted primary incisors and canines with lengths ranging within 15–22 mm were randomly divided into three groups (12 teeth/group) according to the obturation techniques used. Group A, endodontic pressure syringe; group B, modified disposable syringe; and group C, reamer. A single operator instrumented and obturated all teeth by using Endoflas. An independent evaluator analysed the quality of the obturation techniques by using CBCT imaging to determine the number of voids in the root canals. Fisher's exact test and multiple pairwise comparisons adjusted by the Dunn–Bonferroni method were used to statistically assess the results. Results: All study groups showed no statistically significant difference in the number of voids (P > 0.05). Comparing the thirds of each group, the coronal and middle thirds of group A contained the maximum number of voids, followed by groups B and C, with no statistically significant difference. For the apical third, voids were highly presented in group C followed by group B. Meanwhile, group A was found to have no voids. Conclusion: Within the limitations of the current research, we concluded that voids existed in all techniques used; however, they were the least when using endodontic pressure syringes. Thus, an endodontic pressure syringe used with an Endoflas obturation material may be preferred as an obturation technique.

Melt-blown polypropylene nonwoven as an efficient and eco-economic sorbent for pipette tip micro-solid phase extraction for the determination of tyrosine kinase inhibitors

BackgroundThe detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy. ResultsThis study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-μSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 μL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5 % to nearly 100 %. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R2 > 0.993), accuracy (relative recoveries: 86.3%–114.8 %), and precision (relative standard deviation: 3.4%–11.3 %), with detection limits between 0.022 and 0.135 ng mL−1. SignificanceThe introduction of MBPP for PT-μSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings.

Adverse tissue reactions to ORISE gel during endoscopic mucosal resection and dissection

BackgroundSubmucosal injection of lifting agents (LAs) is frequently used to facilitate endoscopic mucosal resection or endoscopic submucosal dissection. ORISE (Boston Scientific Corporation) gel, approved in 2018 by the United States Food and Drug Administration, has been commonly used until recently. Its use proliferated because of its practical prefilled syringe, prolonged lift effect, and ideal coloration. However, it has been noted to cause unexpected tissue reactions, described as “giant cell reaction” (GCR), which can obscure macroscopic and microscopic views, potentially interfering with pathologic evaluation. This study aimed to describe the adverse effects of ORISE gel. MethodsThis retrospective study analyzed pathologic specimens from all consecutive patients who received ORISE injections for attempted polyp removal and subsequently underwent segmental colon resection at our center between 2019 and 2022. A descriptive analysis was performed. ResultsA total of 45 patients were included, of whom 17 (38.0%) were female and the median age was 66 years. The indications for surgery included adenocarcinoma in 14 patients (31%), suspected malignancy in 3 patients (7%) who had benign GCR-induced masses, and other indications in 28 patients, such as large polyps or recurrent polyps after initial endoscopic treatment. Surgical procedures included right hemicolectomy (44%), low anterior resection (13%), left colectomy (11%), sigmoidectomy (7%), and abdominoperineal resection (4%). Histologic evidence of previous LA injection was seen in 31 patients (69%), with 24 patients exhibiting GCR. At final pathology, no residual neoplasm was found in 9 patients (18%); however, 14 patients (31%) had adenocarcinoma (T1 [7], T2 [3], T3 [3], and T4 [1]). ConclusionORISE gel interacts with various tissue layers of the colon, frequently resulting in GCR. This reaction and the potential subsequent mass effect formation can affect decision-making regarding the management of complex colorectal lesions. Further study into the causes and consequences of LA tissue reactions is warranted.

Quantitative Monitoring Maximizes Cost-Saving Strategies When Antagonizing Neuromuscular Block With Sugammadex.

Introduction Weight-based dosing combined with variable patient weights in pediatric anesthesia can lead to significant medication excess and waste from single-use medication vials packaged for dosing in adults. Medication aliquots have been proposed as a strategy to decrease waste and therefore expense when using high-cost medications such as sugammadex. Appropriate dosing of sugammadex to antagonize neuromuscular block is based on the results of quantitative monitoring, though the use of these monitors is not routine. In this quality improvement project, we demonstrate cost savings from aliquoting sugammadex from large, single-use vials and using quantitative monitoring to guide accurate and appropriate dosing. Methods After institutional review and approval, patients receiving rocuronium neuromuscular block during their anesthetic care between October 10 and December 9, 2022, were included for analysis. Sugammadex aliquots were prepared under sterile conditions in the operating room pharmacy according to current compounding guidelines. Quantitative neuromuscular monitoring with electromyography-based monitors was used to guide accurate sugammadex dosing. Cost analysis included the actual savings achieved when aliquots were used instead of single-use vials, the potential savings if aliquots had been used as opposed to single-use vials, and the actual savings achieved when quantitative monitoring indicated that adequate spontaneous recovery was reached and sugammadex administration was not needed. Results A total of 200 patients were included in the analysis. In 73 patients, a 200 mg/2 ml vial of sugammadex was utilized, while 86 patients received sugammadex from pre-filled aliquot syringes of 50 mg/0.5 ml. Forty-one patients did not require sugammadex antagonism as they achieved spontaneous recovery to a train-of-four ratio ≥90%. Conclusion Administration of sugammadex from aliquots rather than manufacturer-packaged single-use vials, with dosing guided by quantitative neuromuscular monitoring, produced a net cost savings of approximately $46 per case and projected net annual cost savings of nearly $370,000 in our institution. Forty percent of the net cost savings came from confirmation by quantitative monitoring of adequate spontaneous recovery to a train-of-four ratio ≥90%.

Clinical Outcomes and Experiences with Prefilled Syringes Versus Vials for Intravitreal Administration of Anti-VEGF Treatments: A Systematic Review.

Anti-vascular endothelial growth factor (VEGF) agents have been the standard treatment for retinal diseases for almost two decades. These treatments are administered via intravitreal injection using single-use vials or prefilled syringes (PFS). In this systematic review, we evaluate health care resource use and clinical outcomes and experiences with PFS for intravitreal injection of anti-VEGF treatments. MEDLINE, EMBASE, and The Cochrane Library were searched from January 1, 2015 to February 8, 2024 to identify literature reporting outcomes regarding procedural efficiency, health care resource use, patient and clinician experiences, and safety for currently approved anti-VEGFs (ranibizumab, aflibercept, brolucizumab) administered using PFS. Comparators were vial-based injections of the same anti-VEGFs. A total of 36 publications met the criteria for inclusion in the systematic literature review; the majority were non-randomized studies, with a small number of reviews, case series, survey studies, and opinion articles. Publications reported that preparation times were significantly shorter for PFS (40.3-57.9s) versus vials (ranibizumab, 62.8-98.0s; aflibercept, 71.9-79.5s), with no differences in product stability between PFS and vials. Clinicians expressed a preference for PFS and thought PFS were faster, easier to use, and had increased safety versus vials. Publications consistently reported significantly lower rates of endophthalmitis per injection with PFS versus vials (ranibizumab PFS, 0-0.02%; aflibercept PFS, 0.01-0.02%; ranibizumab vial, 0.02-0.05%; aflibercept vial, 0.02-0.06%). Four publications reported increased rates of transient vision loss after aflibercept PFS injection versus vial-based injection. No publications reported outcomes regarding health care resource use or patient experiences. The available literature supports the increased procedural efficiency of PFS versus vial-based intravitreal injection of anti-VEGFs. PFS are positively perceived by clinicians and have a safety benefit in the form of a decreased risk of endophthalmitis versus vials.

Case Study: Compatibility Testing of Pre-Filled Syringe Stopper Technology with Vaporized Hydrogen Peroxide Terminal Sterilization Process.

STERIS and W.L. GORE collaborated on a case study testing the compatibility of a new prefilled syringe plunger design with VHP terminal sterilization. VHP chamber conditions require deep vacuum pulsing, which may represent challenges to prefilled syringe container integrity. The growing industry trend toward VHP sterilization is driven by the FDA search for alternative sterilization methods to EO and the recent publication of a VHP specific process standard. The purpose of the study is to test and report compatibility of the new 0.5 mL GORE IMPROJECT plunger, a silicone free syringe solution for ophthalmic application, with VHP sterilization. Various challenges have been reported when using conventional, siliconized, prefilled syringe systems for intravitreal injections such as subvisible particles, inflammation, silicone floaters, and intraocular pressure increases. The GORE plunger eliminates the need for silicone oil as a lubricant on the plunger and barrel, while meeting strict container closure and terminal sterilization requirements of ophthalmic applications. This case study presents successful results of deep vacuum VHP terminal sterilization process compatibility with the GORE plunger design and material composition. Test results include primary container integrity, stopper off-gassing/ingress, and visual inspection. Principles of VHP vacuum sterilization process, test cycle configuration, and its main parameters are presented.

Study of Leachable Compounds in Hospital Pharmacy-Compounded Prefilled Syringes, Infusion Bags and Vials

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

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Impact of dimensional variability of primary packaging materials on the break-loose and gliding forces of prefilled syringes.

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGF) required during injection, certain primary packaging materials (PPM) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory defined silicone oil quantities in certain drug products, such as ophthalmic, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of PPM has an important role in controlling BLGF. The dimensions of PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmic focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of PPM on the BLGF in ophthalmic PFS. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated, were first sampled during aseptic production, and tested for BLGF. Subsequently, defined dimensions of PPM were measured individually. The results showed that the dimensional variability of PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPM is improvable for critical drug products such as ophthalmic. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.

Rapid photothermal assay for ultrasensitive point-of-care detection of tumor markers based on a filter membrane.

Anultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu2-xSe was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0-50 ng mL-1, the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL-1. It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied tothe quantitative determinationof CEA levels in human serum samples with a recovery of 96.2-103.3%. This rapid assay can be performed by "one suction and one push" through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers.