Syringe Research Articles

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.

Trends in the market for drug delivery devices categorized as combination drugs and medical devices and regulatory challenges for autoinjectors in Japan.

Although a variety of drug delivery devices have been launched in recent years, few studies have comprehensively investigated the market trends of combination drugs and medical devices approved or certified in Japan and the regulatory challenges related to their approval. Among the drug delivery devices, autoinjectors are more convenient than traditional prefilled syringes and are designed with safety features to prevent needlestick accidents, allowing self-injection by patients. Therefore, autoinjectors have been incorporated into the treatment of various diseases and have shown significant growth among drug delivery devices. This study aimed to investigate the market trends of combination drugs approved in Japan, especially those with autoinjector formulations, and to explore the challenges in the regulatory aspects of combination drugs. Information on the number of marketed drugs and medical devices was obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) database using specific definitions. We looked at the annual changes in the number of drug delivery devices approved and certified as combination drugs or medical devices and the number of canceled certifications. We also examined the classification and main certification criteria for Japanese medical device nomenclature. The study suggested that the number of combination drugs with autoinjector formulations is increasing, replacing previously approved or certified pen-type medication injectors. Moreover, 53% of all drug products were approved for autoinjector formulations after the initial authorization approval in Japan, and more than half of them obtained approval for additional formulations for autoinjectors within five years of the initial authorization approval, with the largest number of cases obtaining approval for additional formulations two years later. The lack of clear regulatory requirements for autoinjectors may lead to confusion among applicants. Furthermore, there are challenges in filing regulatory applications, thus hindering the rapid launch of combination drug-utilizing devices with superior usability.

Breastfeeding Success With Use of Electric Breast Pump Versus Inverted Syringe Technique in Lactating Women With Inverted Nipple: Open Labelled Randomized Control Trial.

Background Inverted nipple is a commonly encountered impediment to proper attachment and latch establishment. Correction of inversion using a disposable syringe represents the conventional method of management. However, it is understudied, cumbersome, and inconvenient. Using electric breast pump represents a more physiological method to achieve correction of inversion. This open-label, randomized control trial investigated syringing versus electric breast pump both in terms of effectiveness in achieving correction of inversion of nipple and patient satisfaction with the use of the assigned intervention. Objectives The primary objective of this study was to compare breastfeeding success by Day 3 postnatal age (achieving correction of inversion of nipple and establishment of direct breastfeeding) in syringing versus electric breast pump in mothers with inverted or flat nipples. The secondary objective was to compare the two methods for the pain experienced by the mother while using syringing versus an electric breast pump. Methodology/Design This was a single-center, open-label randomized control trial performed at a tertiary care neonatal unit in Eastern India, from December 2022 to September 2023. 60 healthy mothers with inverted nipples were randomly allocated to one of two interventions: Group A (n=30, syringing); or Group B (n=30, electric breast pump). Both groups were compared for the establishment of breastfeeding by Day 3 postnatal age and daily maximum pain scores till Day 3 (visual analogue scale). Multivariable logistic regression was used to look for factors independently associated with establishment of breast feeding by Day 3 postnatal period. Chi square test was used to compare the proportions of different outcomes between the groups. Results The primary outcome of establishment of breastfeeding by Day 3 postnatal period was achieved in 18 (60%) mothers in syringe group vs. 17 (56.67%) in the breast pump group, with no statistically significant difference (p=0.793). In the first two days the pain score differences were not statistically significant, but on Day 3, 28 (93.99%) mothers in the electric breast pump group had no/mild pain compared to 22 (73.33%) mothers in the syringe usage group. This difference was statistically significant (p= 0.038). Conclusion In hospital settings where electric breast pump is easily available, the same may be preferred over inverted syringe technique for achieving establishment of breastfeeding by Day 3 postnatal period with minimal nipple pain in mothers. However, further large scale studies will be required to confirm these findings.

The silicone depletion in combination products induced by biologics

Silicone oil (SO) migration into the drug product of combination products for biopharmaceuticals during storage is a common challenge. As the inner barrel surface is depleted of SO the extrusion forces can increase compromising the container functionality. In this context we investigated the impact of different formulations on the increase in gliding forces in a spray-on siliconized pre-filled syringe upon storage at 2–8 °C, 25 °C and 40 °C for up to 6 months. We tested the formulation factors such as surfactant type, pH, and ionic strength in the presence of one monoclonal antibody (mAb) as well as compared three mAbs in one formulation. After 1 month at 40 °C, the extrusion forces were significantly increased due to SO detachment dependent on the fill medium. The storage at 40 °C enhanced the SO migration process but it could also be observed at lower storage temperatures. Regarding the formulation factors the tendency for SO migration was predominantly dependent on the presence and type of surfactant. Interestingly, when varying the mAb molecules, one of the proteins showed a rather stabilizing effect on the SO layer resulting into higher container stability. In contrast to the formulation factors, those different stability outcomes could not be explained by interfacial tension (IFT) measurements at the SO interface. Further characterization of the mAb molecules regarding interfacial rheology and conformational stability were not adequately able to explain the observed difference. Solely a hydrophobicity ranking of the molecules correlated to the stability outcome. Further investigations are needed to clarify the role of the protein in the SO detachment process and to understand the cause for the stabilization. However, the study clearly demonstrated that the protein itself plays a critical role in the SO detachment process and underlined the importance to include verum for container stability.

"We only trust each other": A qualitative study exploring the overdose risk environment among persons who inject drugs living with HIV in Nairobi, Kenya.

In Kenya, overdose remains a major public health concern with approximately 40% of persons who inject drugs (PWID) reporting personal overdoses. PWID living with HIV (PWID-LH) are particularly vulnerable to experiencing fatal and non-fatal overdoses because of the surrounding physical, social, economic, and political environments, which are not fully understood in Kenya. Through qualitative inquiry, this study characterizes Kenya's overdose risk environment. Participants were purposively recruited from a larger cohort study from September to December 2018 using the following inclusion criteria: HIV-positive, age ≥18 years, injected drugs in the last year, and completed cohort study visits. Semi-structured interviews explored experiences of personal and observed overdoses, including injection settings, sequence of events (e.g., pre-, during, and post-overdose), safety strategies, and treatment. Interviews were transcribed, translated (Swahili to English), reviewed, and analyzed thematically, applying a risk environment framework. Nearly all participants described personal and/or observed overdose experiences (96%) and heroin was the most frequently reported substance (79%). Overdose precursors included increased consumption, polysubstance use, recent incarceration, and rushed injections. There were also indications of female-specific precursors, including violence and accessing prefilled syringes within occupational settings. Overdose safety strategies included avoiding injecting alone, injecting drugs incrementally, assessing drug quality, and avoiding polysubstance use. Basic first-aid techniques and naloxone use were common treatment strategies; however, naloxone awareness was low (25%). Barriers to treatment included social network abandonment, police discrimination, medical stigma, fatalism/religiosity, medical and transportation costs, and limited access to treatment services. In Kenya, the overdose risk environment highlights the need for comprehensive overdose strategies that address the physical, social, economic, and political environments. Morbidity and mortality from overdose among PWID-LH could be reduced through overdose prevention initiatives that support harm reduction education, naloxone awareness, and access, destigmatization of PWID, and reforming punitive policies that criminalize PWID-LH.

Patterns of daily oral HIV PrEP adherence among people who inject drugs in Ukraine: an analysis of biomarkers.

Daily oral HIV pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) is recommended for people who inject drugs (PWID) but coverage is low. The real-life effectiveness of PrEP among PWID is unknown as previous studies were conducted in controlled settings and mainly relied on self-report. Analysis of PrEP metabolites-tenofovir diphosphate (TFVdp) and emtricitabine triphosphate (FTCtp)-offers an objective measure of adherence. To analyse longitudinal patterns of PrEP adherence among PWID in Ukraine, we used data from a community-based implementation trial conducted in Kyiv between July 2020 and March 2021 to test the efficacy of SMS reminders to improve adherence. Among 199 enrolled participants, 156 (78.4%) were retained through 6 months. Based on TFVdp/FTCtp levels assessed at 3 and 6 months, we identified groups with various adherence patterns (adherent at ≥2 doses/week, improved, worsened, non-adherent). Correlates of adherence were analysed using multinomial logistic regression. Most participants (53.8%, n = 84/156) had no detectable metabolites at both assessments; 7.1% (n = 11/156) were consistently taking ≥2 doses/week; 1.3% (n = 2/156) were consistently taking ≥4 doses/week; 13.5% (n = 21/156) exhibited improved and 21.8% (n = 34/156) had worsened adherence at 6 compared to 3 months. "White coat compliance" (increased dosing prior to assessment) was common. Consistent adherence was associated with SMS reminders, younger age, employment, lower income, longer injection drug use duration, recent high-risk injecting (receptive syringe sharing, using pre-filled syringe, back- or front-loading, container sharing), absence of overdose in the past 6 months, perceived HIV risk through sexual intercourse and higher PrEP self-efficacy. Alcohol consumption was associated with inconsistent PrEP use. Groups with improved and worsened adherence did not differ. Daily oral PrEP may not achieve the desired effectiveness among PWID as a standalone intervention, calling for testing of alternative PrEP formulations and innovative integrated risk reduction strategies, especially in the context of HIV epidemics associated with injection drug use in eastern Europe and central Asia and the public health crisis in Ukraine caused by the war with Russia. SMS reminders may be effective among PWID who prioritize PrEP. Our findings offer practical guidance in identifying PWID who are likely to benefit from PrEP and those who need additional support.

Electroless Ionization Mass Spectrometry Using a Compact Electrokinetic Ionization Source.

We introduce a new ionization technique for compact, portable mass spectrometers. It consists of a syringe with sample liquid capped by a self-ionizing spray nozzle containing a microfabricated nozzle chip. Interaction of the sample liquid with the nozzle wall results in electrical charging without the need for electronics. Elaborate cleaning procedures are redundant when disposable syringes and mass-fabricated spray nozzles are used. This self-named electroless spray ionization (ELI) technique shows comparable performance to conventional ionization techniques. In contrast to commonly used electrospray ionization, ELI exhibits excellent ionization efficiency for low-conductive solutions such as water or acetonitrile. Due to its compact size and the absence of high-voltage electronics, it can also be readily integrated in other ionization sources. Besides reviewing the main properties of ELI, we showcase the technique's potential for two on-site, ambient mass spectroscopy applications: perfume fingerprinting and fast screening of fungicides on citrus fruits.

Vaccine preparation time, errors, satisfaction, and preference of prefilled syringes versus RSV vaccines requiring reconstitution: randomized, time and motion study

Aim The current study compared preparation time, errors, satisfaction, and preference for a prefilled syringe (PFS) versus two RSV vaccines requiring reconstitution (VRR1 and VRR2) in a randomized, single-blinded time and motion study. Methods Pharmacists, nurses, and pharmacy technicians were randomized to a preparation sequence of the three vaccines. Participants read instructions, then consecutively prepared the three vaccines with a 3–5-min washout period in between. Preparations were video recorded and reviewed by a trained pharmacist for preparation time and errors using predefined, vaccine-specific checklists. Participant demographics, satisfaction with vaccine preparation, and vaccine preference were recorded. Within-subjects analysis of variance was used to compare preparation time. Mixed-effects Poisson and ordered logistic regression models were used to compare the number of preparation errors and satisfaction scores, respectively. Results Sixty-three pharmacists (60%), nurses (35%), and pharmacy technicians (5%) participated at four sites in the United States. The least squares mean preparation time per dose for PFS was 141.8 s (95% CI = 156.8–126.7; p <.0001) faster than for VRR1, 103.6 s (95% CI = 118.7–88.5; p <.0001) faster than for VRR2, and 122.7 s (95% CI = 134.2–111.2; p <.0001) faster than the pooled VRRs. Overall satisfaction (combined “Very” and “Extremely”) was 87.3% for PFS, 28.6% for VRR1, and 47.6% for VRR2. Most participants (81.0%) preferred the PFS vaccine. Limitations The study is limited by the inability to completely blind observers. To minimize the effects of order, we utilized a 3-sequence block design; however, the order in which the vaccines were prepared may have affected outcomes. Participants were assessed once, whereas if repeated preparations were performed there may have been trained efficiencies gained for each vaccine. Conclusion PFS vaccines can greatly simplify the vaccine preparation process, allowing administrators to prepare almost four times more doses per hour than with vial and syringe systems.

A Comparative Study on Regulatory Requirements for Pharmaceutical and Biological Product registration in ASEAN and Asia Pacific Region for Parenteral Dosage Form

Regulatory requirements for pharmaceutical and biological product registration varies significantly across different regions impacting availability of critical parenteral dosage form in that market. This thesis provides a comprehensive comparative analysis of regulatory requirements for registration of parenteral dosage form in emerging markets which include ASEAN and Asia – Pacific region. The study majorly examines key regulatory framework, submission requirement, review process and lifecycle management. Focusing on how these factors affect development and market entry of parenteral product. The research explores major difference in documentation, quality requirements and product life cycle management across these markets. Data for the study is gathered from extensive review of official regulatory documents and guidelines. Parenteral means ‘Para’ + ‘Enteral’ which means those products that surpasses the intestine and directly enters into systemic circulation. The pharmaceutical parenteral products are derived from synthetic or plant-based API’s whereas biological parenteral products are derived from organisms. This thesis covers all types of parenteral registration requirements including, branded, generic and biosimilar. It includes vaccines, pre-filled syringes, bottles, vials, bags, ampoules, etc. Aim behind considering RoW market is that they are constantly updating and emerging themselves against regulatory challenges. Some of the countries in these regions have adopted ICH guidelines and others maintain unique regional guidelines. Some countries in region like ASEAN follow ACTD. Few countries like India to reduce the task of handling hard copy have established portals while few have established soft copy submission in CD/DVD or USB form while other still need submission in hard copy.

Charting the Etanercept Journey: Tracing Cost Dynamics in Poland's Off-Patent Market from Reference Drug Rivalry to Biosimilar Monopoly.

To evaluate the pricing of etanercept (ETN) reference and biosimilar drugs in a changing competitive to monopolized market. We conducted a comprehensive, retrospective analysis of ETN market competition, specifically changes in tender price based on shifts in market monopoly, including the effects on cost evolution, in the off-patent market in Poland. We included a total of 473 tenders for ETN purchase in dedicated biologic drug reimbursement programs, covering both pre-filled syringes and automatic injectors. This study covers the timeframe from November 2017 to December 2023, throughout which we evaluated a unique setting of ETN market re-monopolization from the perspective of payer, hospital and patient benefits resulting from changing cost calculations. Between 2017 and 2022, Erelzi was recorded as having the largest total tender volume (59%), with a mean price [per ETN daily defined dose (DDD)] of €7.28, followed by Enbrel (31%, €8.34) and Benepali (10%, €9.45), respectively. Over the last 6 months of waning market competition, the mean price for winning bids was estimated at €5.69. After market re-monopolization by an ETN biosimilar, the mean price of winning bids increased to €8.09, and continued to increase (€9.71) in the last 6 months of available follow-up. In contrast to the competitive era, no significant relationship between tender volume and winning price was recorded after re-monopolization. In the most recent tenders, mean ETN prices increased up to €15.82, nearly tripling the lowest prices of the competitive market period. In the early re-monopolization market, mean annual treatment cost per patient is estimated at over €3800, which exceeds therapy costs in the prior competitive market years, and is expected to increase to over €6200 based on the most recent tenders. On a healthcare system level, this corresponds to over €3.42 million excess costs due to market monopoly. Higher ETN prices resulted in downstream failure of regulatory incentives to promote affordable biologics. Due to higher pricing, hospitals lost over an estimated €2.52 million, with possible risk of treatment restrictions. For the same reason, the public payer achieved comparable savings, allowing for partial coverage of higher reimbursement expenses. This nation-level scenario of market re-monopolization by a biosimilar drug confirms net loss and excess costs for the healthcare payer, as can be expected from economic theory. The upwards drug repricing and restriction of treatment availability occurs much more rapidly than the decrement in a period of market competition.

Diagnostic Accuracy of Fine Needle Aspiration Cytology (FNAC) in Salivary Gland Tumors.

Professor Oral Pathology, Islamabad Dental Hospital, Islamabad 6Demonstrator Oral Pathology Margalla Institute of Health Sciences, Islamabad Author`s Contribution 1Conception and idea acquisition of data, 2Data Analysis, 3Results interpretation, 4Editing and drafting, 5Critical Revision, 6Final approval of the study to be published Funding Source: None Conflict of Interest: None Received: February 02, 2024 Accepted: May 27, 2024 Address of Correspondent Dr. Zainab Niazi Associate Professor Oral Pathology, Islamabad Dental Hospital, Islamabad dr.zainabniazi@gmail.com ABSTRACT Objectives: To evaluate the diagnostic accuracy of fine needle aspiration cytology (FNAC) by comparing its findings with the gold standard histological features of salivary gland lesions. Methodology: This retrospective study was conducted at the Department of Histopathology, Islamabad Medical and Dental Hospital (IMDC), from January 2023 to December 2023, patients presenting with salivary gland swellings. Fifty-seven patients having salivary gland swelling were included on which both histological and cytological evaluation had been done. Twenty cases were excluded because either they had lack of correlation between FNAC and histology or on view of inadequate material. All the patients were clinically evaluated clinically and FNAC was done using 10ml disposable syringe and 23/24-gauge needle without using local anesthesia. The histopathology of the surgical specimens and cytology of the FNAC specimens were compared, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. Results: On FNAC, 37 cases were diagnosed cytologically, as 9 cases identified malignant and 28 as benign. Histopathological examination confirmed 9 malignant cases and 25 benign cases, whereas 3 cases were classified as false positive. The specificity and sensitivity of FNAC were 75% and 94%, respectively. Overlapping cytological features, heterogeneity, and unsampled areas were the primary factors contributing to false-positive. Conclusion: This study showed that salivary gland FNA cytology is a valuable diagnostic technique for salivary gland lesions, however due to great variation in pleomorphic adenoma, the samples must be confirmed by histopathological features.

Localization of the questionnaire about sharps disposal at home among diabetes based on knowledge, attitude, and practice theory, and a cross-sectional survey of current conditions.

Diabetes Mellitus is a long duration disease, and if a person with diabetes is infected with a blood-borne infectious disease and proper syringe disposal practices are not followed, they run the danger of transmitting the infection to others for a very long period. Whereas fewer research has been done in China on the handing of sharp objects at home. Therefore, there is a need to translate and localize the Knowledge-Attitude-Practice Questionnaire regarding sharp disposal for diabetic patients to assess the current level of patient knowledge, attitudes, and practices and to improve the basis for promoting safe sharps handling practices. This investigation was a cross-sectional study. The Knowledge-Attitude-Practice Questionnaire regarding sharp disposal was localized and debugged and tested for reliability and validity, and then 334 patients were investigated by General Characteristics Questionnaire, Knowledge- Attitude-Practice Questionnaire regarding sharp disposal, and the influencing factors of practice level regarding sharp disposal of patients were analyzed. The Cronbach's α value of the attitude section was 0.864 and the content validity index was 0.923. The knowledge and practice sections are in line with continental language conventions and are easy to understand without any ambiguity. The majority (52%) of the participants had poor knowledge and a neutral attitude toward disposing of sharp objects. Sharps disposal practices among diabetes mellitus patients were poor since about 90% of patients dispose of their used sharps directly into the household waste. Furthermore, we found that level of education, knowledge and attitude were the major predictors of practices regarding sharps disposal among diabetic patients (R 2 = 0.573, p < 0.001). The Chinese version of the Knowledge-Attitude-Practice Questionnaire regarding sharp disposal has applicability in China. In China, current practice of disposing used sharps is improper. Additionally, the majority of the subjects had low levels of knowledge and attitudes. To raise awareness and encourage diabetic patients to follow appropriate sharps disposal practices, there needs to be ongoing education and a locally tailored safe sharp disposal alternative accessible.

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY)

Background and AimsCT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC versus placebo as maintenance therapy in patients with Crohn’s disease (CD) and ulcerative colitis (UC). MethodsTwo randomized, placebo-controlled, double-blind studies were conducted in patients with moderately-to-severely active CD or UC and inadequate response/intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks (W) 0, 2, and 6. At W10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until W54 (maintenance phase) using pre-filled syringes. (Co-)primary endpoints were clinical remission and endoscopic response (CD) and clinical remission (UC) at W54 (all-randomized population). ResultsOverall, 396 patients with CD and 548 patients with UC received induction treatment. At W54 in the CD study, statistically significant higher proportions of CT-P13 SC- versus placebo-treated patients achieved clinical remission (62.3% versus 32.1%; P < 0.0001) and endoscopic response (51.1% versus 17.9%; P < 0.0001). In the UC study, clinical remission rates at W54 were statistically significantly higher with CT-P13 SC versus placebo (43.2% versus 20.8%; P < 0.0001). Achievement of key secondary endpoints was significantly higher with CT-P13 SC versus placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. ConclusionCT-P13 SC was more effective than placebo as maintenance therapy and well tolerated in patients with moderately-to-severely active CD or UC who responded to CT-P13 IV induction. ClinicalTrials.gov, NCT03945019 (CD) and NCT04205643 (UC).

Drug-Leachable Interaction Product Evaluation in Prefilled Syringe of Ganirelix Acetate Injection

The concept of extractables and leachable has introduced a new era for identifying potential impurities in drug products. Pharmaceutical packaging materials encompass a variety of polymers due to their appealing properties for storing the drug product. However, numerous chemical species may leach into the drug product from these polymers, posing significant health hazards in the public domain. Identifying such leachable is crucial for assessing safety and addressing toxicological concerns. Acrylic acids are commonly used materials for adhering needles to the barrel in pre-filled syringes. In this study, we identified acrylic acid leachable impurities in ganirelix drug products available in the market using mass spectrometry as an analytical technique. These impurities leached into the drug product during storage conditions. Characterization of the impurities was carried out through data obtained from HRMS and MS/MS analysis, revealing them as polyacrylic acid-ganirelix adduct impurities. This study offers valuable insights into identifying leachable and susceptible sites, providing a foundation for potential modifications in similar classes of drug products, thereby enhancing their safety and efficacy.