Dose Vials Research Articles

Evaluation of the Most Potent of Three Vaccines in Controlling Newcastle Disease in Pullets using different Vaccination Regimen

Newcastle disease continues to pose serious public health and economic challenges to both small holder and commercial poultry worldwide. The aim of this study was to evaluate the most potent vaccine used in the control of Newcastle disease in pullets using different vaccination regimens. Two hundred- and twenty-five-day-old Isa brown pullets were purchased from a reputable hatchery at Ibadan, Nigeria. The chicks were divided into five groups of 45 chicks each. Groups A, B and C were divided into subgroups 1, 2 and 3 consisting of 15 chicks each. Group D was the negative control group which was neither vaccinated nor challenged while group E was the positive control group which was not vaccinated but challenged with Newcastle disease virus (Kudu 113, genotype XVII). The vaccines (La Sota, VG/GA and La Sota clone) were reconstituted as follows: each 1, 000 dose vial of vaccine was reconstituted with 5 ml of water; 0.1 ml of the dissolved vaccine was diluted in 300 ml of clean drinking water and administered to the birds via the oral route. Blood sampling was carried out using standard procedure and ELISA was carried out according to manufacturer’s instruction. There was presence of high maternally derived ND antibodies in the experimental chicks (12,627±1,806 - 17,722±1,607). The La Sota clone vaccine produced more antibodies (3,508±975) which was significantly different (p< 0.05) compared to VG/GA (737±439.77) vaccines. La Sota clone was able to confer 100% protection (p< 0.05) against Newcastle disease with no morbidity and mortality (0%). Vaccination at week 2 was the most effective (p< 0.05) for La Sota and La Sota clone strains but least for VG/GA strain of Newcastle disease vaccines.

Design and Construction of a Radiochemistry Laboratory and cGMP-Compliant Radiopharmacy Facility.

The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment.

Quality by Design Considerations for Drop-on-Demand Point-of-Care Pharmaceutical Manufacturing of Precision Medicine.

Distributed and point-of-care (POC) manufacturing facilities enable an agile pharmaceutical production paradigm that can respond to localized needs, providing personalized and precision medicine. These capabilities are critical for narrow therapeutic index drugs and pediatric or geriatric dosing, among other specialized needs. Advanced additive manufacturing, three-dimensional (3D) printing, and drop-on-demand (DoD) dispensing technologies have begun to expand into pharmaceutical production. We employed a quality by design (QbD) approach to identify critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs) of a POC pharmaceutical manufacturing paradigm. This theoretical framework encompasses the production of active pharmaceutical ingredient (API) "inks" at a centralized facility, which are distributed to POC sites for DoD dispensing into/onto delivery vehicles (e.g., orodispersible films, capsules, single liquid dose vials). Focusing on the POC dispensing/dosing processes, QbD considerations and cause-and-effect analyses identified the dispensed API quantity and solid-state form (CQAs), as well as the nozzle diameter, system pressure channel, and number of drops dispensed (CPPs) for detailed investigation. Final assay quantification and content uniformity CQAs were measured from demonstrative levothyroxine sodium single-dose liquid vials of glycerin/water, meeting the standard acceptance values. Each POC facility is unlikely to maintain full quality control laboratory capabilities, requiring the development of appropriate atline or inline methods to ensure quality control. We developed control strategies, including atline ultraviolet-visible (UV-vis) verification of the API ink prior to dispensing, inline drop counting during dispensing, intermediate atline-dispensed volume checks, and offline batch confirmation by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following production.

The faces behind vaccination: unpacking the attitudes, knowledge, and practices of staff of Cameroon’s Expanded program on Immunization

BackgroundImmunization is regarded as one of the most cost-effective public health interventions in global health. However, its cost-effectiveness depends greatly on the knowledge and skills of vaccinators. With the growing complexity of immunization programs, the need for a well-trained vaccination workforce cannot be overemphasized. In this study, we assessed the knowledge, attitudes, and practices among vaccination staff in Cameroon.MethodsThrough a descriptive cross-sectional design, we used structured questionnaires and observation guides to collect data from vaccination staff in health facilities that were selected by a multistage sampling method. Data were analyzed using STATA 13 software.ResultsOverall, we collected data from Expanded Program on Immunization focal staff in 265 health facilities across 68 health districts. Over half (53%) of the surveyed facilities were found in rural areas. Nearly two-thirds of health facilities had immunization focal staff with knowledge gaps for each of the four basic immunization indicators assessed. In other words, only 37% of staff knew how to estimate coverages, 36% knew how to inteprete the EPI monitoring curve, 35% knew how to prepare vaccine orders, and 37% knew how to estimate vaccine wastage. In terms of practices, staff waited for more than ten children to be present before opening a 20-dose vaccine vial in 63% of health facilities, and more than five children to be present before opening a 10-dose vaccine vial in 80% of surveyed facilities. Provision of vaccine-specific information (informing caregiver about vaccine received, explanation of benefits and potential side effects) during immunization sessions was suboptimal for the most part.ConclusionThis study suggests marked deficits in immunization knowledge among vaccination staff and exposes common attitudes and practices that could contribute to missed opportunities for vaccination and hinder vaccination coverage and equity in Cameroon. Our findings highlight the urgent need to invest in comprehensive capacity building of vaccination staff in Cameroon, especially now that the immunization program is becoming increasingly complex.

Cost-utility analysis of teduglutide compared to standard care in weaning parenteral nutrition support in children with short bowel syndrome

A growing proportion of children with short bowel syndrome (SBS) remain dependent on long-term parenteral nutrition (PN). Teduglutide offers the potential for more children to decrease PN support and achieve enteral autonomy (EA), but at a significant expense. This study aims to assess the incremental costs of teduglutide plus standard of care compared to standard of care alone in weaning PN support per quality-adjusted life year (QALY) gained in children with SBS. This is a cost-utility analysis comparing teduglutide with standard of care alone in children with SBS. A microsimulation model of children with SBS on PN aged 1-17 years was constructed over a time horizon of six years, with a cycle length of one month. The study adopted the healthcare system and societal payer perspectives in Ontario, Canada. The health outcome measure was QALYs, with results expressed in terms of incremental costs and QALYs. Scenario analyses were performed to examine the effects of different time horizons, timing of teduglutide initiation, and modeling cost of teduglutide based on pediatric weight-dosing. Incremental healthcare system costs for teduglutide compared to standard of care were CAD$441,314 (95% CI, 414,006 to 441,314) and incremental QALYs were 1.80 (95% CI, 1.70 to 1.89) resulting in an incremental cost-effectiveness ratio (ICER) of CAD$285,334 (95% CI, 178,209 to 392,459) per QALY gained. Incremental societal costs were CAD$418,504 (95% CI, 409,487 to 427,522) and incremental societal QALYs were 1.91 (95% CI, 1.85 to 1.98) resulting in an ICER of CAD$261,880 (95% CI, 136,887 to 386,874) per QALY gained. Scenario analysis showed that teduglutide was cost-effective when it was started two years after intestinal resection (ICER CAD$48,741, 95% CI, 17,317 to 80,165) and when its monthly cost was adjusted using weight-based dosing, avoiding wastage of the remaining 5mg dose vial (Teduglutide dominated over SOC as the less costly and most effective strategy). Although teduglutide was not cost-effective in weaning PN support in children with SBS, starting teduglutide once natural intestinal adaptation is reduced and adjusting its monthly cost to reflect cost by volume as dictated by weight-based dosing rendered the intervention cost-effective relative to standard of care. These results indicate the potential for clinicians to re-assess optimal time for initiation of teduglutide after intestinal resection, drug manufacturers to consider the use of multi-dose or paediatric-dose vials, and the opportunity for decision-makers to re-evaluate teduglutide funding.

Dose rounding bevacizumab and its biosimilars to reduce drug waste in the oncology care model in a community oncology network.

1529 Background: The Oncology Care Model (OCM) was a 6-year long Medicare value-based care (VBC) program that rewarded practices for decreasing TCOC compared to a benchmark price, while maintaining high-quality cancer care. Drug waste from partially used single dose vials (SDV) of expensive anti-neoplastic agents is a leading contributor to avoidable Total Cost of Care (TCOC) expenditures for payers. Dose rounding (DR) of biological anti-neoplastic agents, using recommendations (https://www.nccn.org/docs/default-source/clinical/order-templates/hopa.pdf?sfvrsn=3af91118_6) from the Hematology Oncology Pharmacists Association (HOPA) and endorsed by the National Comprehensive Cancer Network (NCCN), is a standard approach to mitigate the impact of drug waste. Many of the practices in The US Oncology Network (The Network) adopted a DR program for biologic agents in 2018 as a strategy to reduce drug waste and TCOC. We studied the impact of a DR initiative targeting bevacizumab and its biosimilars (B+B) on TCOC and drug waste expenditures for The Network practices participating in the OCM. Methods: Claims data for 14 practices in The Network participating in the OCM were assessed. Drug administration data for B+B was used to evaluate drug waste, total dose, TCOC, DR and the financial impact of drug waste reduction on TCOC from 2017 to 2021. Results: In 2017, prior to implementing DR, an average of 5.3% (range 4.6% to 5.5%) of the total dose of B+B was wasted, with ~25% of B+B administrations having waste in excess of 10% of the total dose. Implementation of the initiative led to a reduction of waste on 30% of the total administrations of B+B across 14 OCM participant practices in The Network. As a result of DR, B+B drug waste decreased by 55% to an average of 2.5% (range - 2.3% to 2.7%) of the total dose in 2021. Decreasing drug waste resulted in TCOC reduction of approximately $100 per member episode per month (0.97% of TCOC) for episodes with B+B administrations in the OCM. The highest waste reduction was seen with B+B administered for treatment of gastrointestinal cancers (colon, rectal, anal, gastroesophageal, or pancreatic cancers) compared to other cancer types (lung, brain, ovarian, etc.), and for B+B administrations where drug waste was greater than 10% of the total dose (~50% reduction). Conclusions: Drug waste contributes avoidable expenditures to the TCOC. Implementing strategies such as DR can offset the impact of drug waste and offer meaningful TCOC savings for VBC programs such as the OCM. A similar DR approach may be adopted for other high-cost biologic agents where drug waste results from partial use of SDVs.

Closed System Transfer Devices (CSTDs): Understanding Potential Over- and Under- Dosing of Liquid Vial Drug Products and How to Generally Mitigate

Closed system transfer devices (CSTDs) are a major challenge for drug manufacturers to assess and assure drug compatibility and acceptable dosing accuracy for a range of clinical administration strategies. In this article, we systematically investigate parameters affecting the loss of product during transfer by CSTDs from vials to infusion bags. We show that liquid volume loss increases with vial size, vial neck diameter, and solution viscosity - while dependent on stopper design. We further compared CSTDs’ performance with a traditional syringe transfer and learned that loss is larger for CSTDs than for syringe transfer. Based on experimental data, a statistical model was developed to predict drug loss upon transfer by CSTDs. The model predicted that, for single dose vials with USP<1151> conforming overfill, a complete extraction and transfer of the full dose can be assured for a broad range of CSTDs, product viscosities, and vial types (2R, 6R, 10R, 20R) if a flush (of syringe, syringe adaptor, bag spike) is performed. The model also predicted that complete transfer cannot be achieved for fill volumes ≤ 2.0 mL. For multi-dose vials and pooling of several vials, respectively, the effective dose transfer (i.e., ≥ 95%) for all CSTDs tested was predicted to be achieved if a minimum of 5.0 mL is transferred.

Insights into handling and delivery of Y-90 radioembolization therapies.

The use of Y-90 radioembolization techniques has become a standard tool for the treatment of liver cancer and metastatic diseases that result in liver lesions. As there are only two approved forms of radioembolization therapy, the procedures for use are also fairly standardized even though exact international and interdepartmental procedures can vary. What has been less published over the years are the nuanced differences in delivery techniques and handling of the two available Y90 radioembolization therapies. This paper seeks to examine various aspects of delivery techniques, product handling, and radiation exposure that differ between the available and approved products. Understanding these differences can assist with providing more efficient treatment, confirmation of accurate therapy, more informed handling of the products, and improved training of physicians and other hospital staff. Two commercially available and approved radioembolization devices were compared to assess nuanced, but key differences between the available products regarding therapy delivery, handling of the products, and radiation exposure to patients and staff. This work is broken into two sections: (1) Therapy Delivery, (2) Radiation Safety. Therapy delivery characteristics were assessed by using an external radiation detector system with detectors placed inside of each delivery system facing the dose vial and on the output catheter lines to the patient. Additional detectors were placed near the liver of the patient and on top of the foot to measure extremities. Data were acquired continuously throughout therapy delivery to collect time activity curves (TACs) for the characterization of each therapy. These data were analyzed to assess if (a) real-time monitoring of radiation could be used to provide an accurate assessment of residual dose before the patient leaves the procedure room, and (b) can dose delivery characteristics be observed that enable improved training and quality control. Calculation of residual dose using the external detector TACs was performed by analyzing initial and final activity peaks to determine measured count rate differences. Radiation safety aspects were assessed by monitoring radiation exposure to staff handling each of the available therapy products. Nuclear medicine technologists and interventional radiology physician body and hand doses were measured for each delivered therapy using standard body and ring dosimeters. The TACs noted above collected for the liver and extremities were used to assess if any off-target or leached Y90 activity could be detected for each therapy. Blood was collected at times before, during, and after treatment and then counted on a gamma counter to assess differences in free Y90 circulating in the blood. Each patient in this study also received a post-treatment whole-body PET/CT at 2-4 h post-infusion to assess for any aggregate free Y90 deposition that may have resulted from circulating free Y90 in the subject following therapy. Calculations of residual dose in the vial following therapy using the real-time detection methods resulted in values that were not statistically different from the values calculated by nuclear medicine following the procedure ( ). Real-time collection of dose delivery data enabled observation of key characteristics related to each delivery method. For SIR-spheres procedures, the cycle of pushing the dose and visualizing with fluoro can easily be seen with each push resulting in a smaller and smaller peak with intermittent fluoroscopy pulses. TheraSpheres infusions show a rapid bolus with nearly all of the measurable injected activity being infused in the first push of the dose. Staff radiation exposure assessments showed statistically significant differences between glass and resin spheres for hand doses of physicians and technologists (p > 0.05), but no statistical difference between body doses for both products ( ). Assessments of free Y90 circulating during therapy showed that patients undergoing therapies with resin spheres had post-infusion blood levels that were 120% higher than pre-infusion levels while glass sphere therapy patients only saw a 7% rise in post-infusion blood levels. The coefficients of variation (COVs) across glass sphere measurements pre, during, and post, were only 0.008 while resin sphere measures saw much greater variability with a COV of 0.45. Both glass and resin therapies showed blood levels at 2-4 h post-injection to be similar to levels measured pre-injection. Neither therapy showed any signs of focal aggregation at 2-4 h post-infusion on whole-body PET/CT. Although glass and resin radioembolization therapies are similar, they both have unique characteristics related to their administration and handling by staff. Understanding the nuances can assist in providing more efficient delivery, better staff education, and reducing radiation exposure to everyone involved with these therapies. The use of near real-time monitoring is feasible and can be used to obtain critical information about the delivery success of a therapy and can inform physicians on their techniques to optimize their practice as well as provide more consistent training to residents.

Vaccine Wastage and its Contributing Factors in Public Health Facilities of Oromia Special Zone, Ethiopia: Explanatory Sequential Mixed Method Design

Background: Although the availability of vaccines is crucial to achieve comprehensive and equitable immunization coverage. This study assessed vaccine wastage and its contributing factors in public health facilities in Ethiopia. Methods: A facility-based explanatory sequential mixed method was used. An institutional-based cross-sectional study design used to assess the vaccine wastage and vaccine cold chain management in all (27) health facilities offering consistence vaccination service and assessed the knowledge and attitude of 127 vaccinators and handlers. Finally, a phenomenological study design was employed among key informants and content analysis was performed using NVivo 11 plus. Results: The overall vaccine wastage rate was 22.9% while the wastage factor was 1.4. The vaccine wastage rate was found highest for Bacillus-Calmette-Guerin (55.2%), 20 dose vials (55.2%), lyophilized (44.7%) and injectable vaccine (26.0%). Only 13 (48.1%) facilities were having satisfactory cold chain infrastructure while 17 (63%) had good cold chain practices.. Distance from Woreda health office (p=0.03) and Ethiopian pharmaceutical supply agency (p=0.02), work experience (p=0.04), level of education (p=&lt;0.001), profession (p=0.001), and attitude (p=0.04) of vaccinators and vaccine handlers were determinants of vaccine wastage. Key informants stated that factors related to logistics, immunization practices, health professional and vaccines were contributing to wastage. Conclusion: Vaccine wastage in health care facilities was above the standard. Large dose vials and opened vial policy were resulted higher wastage and hence, recommended to reduce vial size. Improving the availability of cold chain logistics, supportive supervisions and training were recommended to reduce wastage.

Using real-world data to quantify chemotherapy waste at Mayo Clinic.

8 Background: At Mayo Clinic, the implementation of an automated chemotherapy dose rounding program has resulted in significant cost savings when doses are rounded down to a vial size, however, the cost burden from drug waste continues to be a significant issue when rounding to a vial size is not within our 10% rounding allowance. The mismatch between drug doses and the marketed vial sizes, along with the limitations to the use of single dose vials is a recognized problem, resulting in billions of dollars of wasted drugs in the United States.The goal of our study was to quantify the cost of the wasted amount of chemotherapy and biologic drugs after the implementation of an automated dose rounding program. Methods: Using the electronic health record (EHR), data was collected for biologic and oncolytic agents administered from 1/1/2019 through 12/31/2021. Drugs with waste documented during preparation and that were administered to cancer patients were selected for analysis. The % of doses with waste documented was calculated based upon the total number of all doses given. The total cost of the drug administered along with the cost of the amount of drug wasted were calculated based upon costs listed in the EHR at the time of administration. Results: For the 3-year period, 446,832 doses were dispensed with 47,626 (10.7%) of those doses having waste documented. The total cost of the drugs with documented waste was $114,323,203 with 21.9% ($25,086,608) accounting sole for wasted drug. Five drugs accounted for 59% of the total cost of the drug waste (Table). When examining individual drugs with a high % of doses with documented waste, methoxsalen, epirubicin, eribulin, topotecan, &amp; bortezomib each had &gt; 70% of doses with a documented wasted amount. Conclusions: Despite having an aggressive institutional dose rounding policy, drug waste still results in considerable and significant costs to the Mayo Clinic System. Our data likely underestimates the total cost of drugs waste given that waste documentation requires manual entry into the EHR at the time of preparation. Our results support the need to create and develop solutions that could lead to reduced waste costs which include re-examining the weight based dosing of drugs, mandating pharmaceutical companies to have vial sizes that more appropriately meet the range of standard dosing, developing more multi-dose vials that can be shared across multiple patients, utilizing closed-system transfer devices to extend beyond-use-dating time, or requiring pharmaceutical companies to reimburse payers and patients for the cost of the amount wasted. Drug waste is still a considerable issue and one that needs to be addressed at a policy level.[Table: see text]

An assessment of vaccine wastage in the Solomon Islands.

Calculating vaccine wastage rates supports vaccine forecasting and prevents stock outs/over-stock at central and immunisation delivery facilities. Ensuring there are sufficient vaccines on the several small islands of The Solomon Island while minimising waste is a challenge. Twenty-two health facilities were selected randomly from six purposefully identified provinces in the Solomon Islands and across the different levels of the health service. Additional data were obtained from the national medical stores and the Expanded Programme on Immunisation (EPI) monthly reports for 2017 and 2018. All the selected facilities were visited to observe stock management practices. We calculated wastage rates for each vaccine antigen in the EPI and described the type of wastage. We found a wide variation in the average wastage rates at the second level medical stores which may be attributed to the partial availability of wastage data. The overall wastage rate for 20-dose BCG was 38.9% (18.5-59.3), 10-dose OPV was 33.6% (8.1-59.1), and single dose PCV was 4.5% (-4.4-13.5). The data from the two smaller and farthest provinces were incomplete/not available and did not contribute to the overall wastage rates. About 50% of the reported wasted doses at the facility were reported as "damaged" vials. Wastage rates were high for the multidose vials and slightly lower for the single dose vials which were also higher than the indicative rates. There is a need to improve recording of vaccine wastage through continuous monitoring for better forecasting and program effectiveness.

Improvement in the knowledge of health care workers following the structured training sessions under swachhta action plan

Introduction Of the total bio- medical waste generated only 10- 15 % is hazardous. Improper waste management poses hazardous effect on health care workers and patients. Health care workers play pivotal role in waste management. Thus, this training aimed at strengthening the knowledge of participants to improve their practices on Cleanliness, Sanitation &amp; Hygiene and Infection control. Methodology The training was conducted in a tertiary care centre of Patna to assess the improvement in knowledge of nursing officers and sanitary staffs. A total of seven sessions were held for nursing officers and eight sessions for sanitary staffs. The training was attended by 189 nursing staffs and 180 sanitary staffs. Pre and post session assessment of knowledge was done using google forms, different for nursing and sanitary staffs. Results Marked improvement in knowledge related to policy and bio- medical waste segregation was observed in nursing officers except for blood bag and sharp objects. Only 12.8% participants knew about the correct sequence of wearing personal protective equipment (PPE). Also, about 30% of the participants had knowledge of avoiding needle- stick and proper use of multi- dose vial. About 90% of participants knew correct steps of hand- washing following training.

Synthesis of 225Ac-PSMA-617 for Preclinical Use.

The recent approval of radiopharmaceuticals for diagnosis and treatment of cancer is ushering nuclear medicine into a new era of theranostics and alpha therapy using radiopharmaceuticals labeled with 225Ac shows remarkable results in clinical trials. As such, reliable methods for the synthesis and quality control of 225Ac-radiopharmaceuticals are needed. 225Ac-PSMA-617 is being used for targeted alpha therapy in patients with prostate cancer, and we had cause to synthesize the agent for preclinical use. However, technology transfer proved cumbersome owing to the paucity of information available on synthesizing and analyzing 225Ac-radiotherapeutics. To address this need, we describe a straightforward synthesis of 225Ac-PSMA- 617 as well as suitable approaches for quality control analysis using standard equipment in a modern PET Center. PSMA-617 precursor was dissolved in 25 μL metal-free water (0.67 mg/mL) and combined with 500 μL 0.05M Tris buffer, pH 9. Actinium stock solution (~65 μCi in 15 μL) was added and the reaction was heated at 120°C for 40-50 min. The reaction was cooled and 0.6 mL gentisic acid solution (4 mg/mL in 0.2 M NH4OAc) was added. To formulate the dose for injection, sterile saline, USP (8 mL) was added and the pH was adjusted by the addition of 100 μL 0.05 M Tris buffer (pH 9) to give a final pH of ~7.2. The final solution was filtered using a 0.22 μm GV sterile filter into a sterile dose vial. Radiochemical purity was determined by radio-TLC (eluent: 50mM Sodium Citrate, pH 5), and plates were analyzed using an AR2000 scanner. The method provided 225Ac-PSMA-617 in high radiochemical yield (57 ± 3 μCi, >99%) and radiochemical purity (98 ± 1%), formulated for preclinical studies (9 mL, pH = 7.2), n=3. A straightforward synthesis of 225Ac-PSMA-617 is described that will facilitate production for (pre)clinical studies. The approach could also be applicable to the synthesis of other alpha radiotherapeutics incorporating 225Ac.

Impact of electronic vaccine intelligence network application used in immunization sessions in Pune city

Background: Millions of deaths due to various diseases have been reduced globally as well as in India since inception of vaccination programme. In order to avoid the instances of cold chain failure and ensure constant monitoring of temperature of cold chain equipment’s Electronic vaccine intelligence network (eVIN) technology was adopted by Government of India.Methods: A mixed methodology design with both qualitative as well as quantitative components were studied. This study was conducted in 16 immunization centres spread across the metropolitan Pune city in western Maharashtra.Results: Vaccine beneficiaries increased for polio 814 (3.25%), DPT1643 (21.79%), MR 9615 (23.02%) and IPV 2297 (23.58) vaccine after execution of eVIN app. Vaccine availability of BCG (6.04%), Polio (20.02%), MR (64.24%), IPV (11.38%) and hep B had increased as compared to the other vaccines. The vaccine wastage decreased for penta (8.64%), IPV (123.98%), TT (32.63%) and hep B (47%) vaccines post eVIN application compared to the pre eVIN. The qualitative study included in depth interviews, key informants’ interview and focus group discussions. Various themes and subthemes emerged like the user-friendliness of app, difficulties faced by health care workers, their suggestions for improvements in the app.Conclusions: The eVIN system is playing a pivotal role in effective and efficient management of vaccine supply, maintaining stock availability and monitoring. To reduce vaccine wastage usage of small dose vials in immunization sessions would be helpful.

Contributions of village animal health workers to foot-and-mouth disease control in Cambodia.

Local animal health services in rural communities in Cambodia are mainly provided by village animal health workers (VAHWs), although the participation and contribution of VAHWs to livestock disease prevention are uncertain. The participation of the VAHWs as identified by their 'dropout rate' was examined in a desktop review in December 2020 of the national data on VAHWs recorded between 2011 and 2020. The contribution and involvement of VAHWs in disease prevention programmes were examined in a survey conducted between February and March 2014, then analyzed in the context of other surveys of VAHW knowledge, attitudes and practices. The survey involved guided group discussion with VAHWs (n=198) from the two Cambodian provinces of Kampong Cham and Pursat. This study identified that VAHWs generated less than 22% of their annual household incomes from animal health services. Less than one-third had vaccinated livestock against foot-and-mouth disease (FMD), with none having vaccinated cattle every 6 months during the study period, and nearly half of the VAHWs having never vaccinated their own cattle against FMD. As no privately provided FMD vaccination services occurred in these communities, with all vaccines delivered through the government-subsidized programme, the findings confirmed that VAHWs only vaccinated animals against FMD when vaccines were made available by the Government. The desktop review found that the number of VAHWs in 2020 declined by more than 24% since 2017, and the proportion of female VAHWs was consistently low, with a mean of 8.26 (±1.019). These findings confirm findings from previous studies that identified considerable weaknesses in the VAHW system in Cambodia, particularly in contributing to FMD control. Cambodian animal health authorities require more effective policies to strengthen the current VAHW system, improving their services delivery; their retention as 'active'; their development of more sustainable roles with lower 'dropout' rates and the prolonged gender inequity. With the limited availability of government-subsidized FMD vaccination currently, extension programmes that engage VAHWs and farmers in seeking privately funded and delivered FMD vaccination that incorporates appropriate multivalent FMD serotype vaccines of high quality, delivered in small dose vials from a robust cold chain, is suggested. This strategy would assist VAHWs to contribute to the provision of private livestock vaccination services that are likely essential for sustainable FMD prevention and control in Cambodia.

Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response

IntroductionRapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits. MethodsWe developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes. ResultsThe OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases. DiscussionThe OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.

P–587 Highly purified human menopausal gonadotrophin (HP-hMG, Menopur) as a ready-to-use solution for injection in pre-filled pen is bioequivalent to HP-hMG powder for reconstitution

Abstract Study question Are serum FSH levels after single subcutaneous dosing of HP-hMG in a liquid formulation and a powder formulation bioequivalent? Summary answer The 90% CIs for the geometric mean ratios of serum FSH AUCt and Cmax were both within 0.8000–1.2500, thus the two formulations are bioequivalent. What is known already For several decades, HP-hMG (Menopur) has been used for the treatment of infertility; its efficacy and safety compared to other gonadotropins have been consistently demonstrated in several prospective, randomised controlled trials and meta-analyses (Deeks et al 2018; Bordewijk et al 2019). Menopur powder for reconstitution is available in multidose and single dose formulations. Up to 3 single dose vials (each containing 75 IU) may be dissolved into 1 mL solvent for administration. Recently, and for the first time, Menopur has been successfully formulated in a stable, ready-to-use solution for injection, which may be administered by a pre-filled pen. Study design, size, duration This was a randomised, two-way crossover, single dose, bioequivalence trial comparing Menopur liquid injected by pre-filled pen, with Menopur powder injected by conventional syringe and needle. The primary endpoints were AUCt and Cmax of baseline-adjusted FSH. Pituitary-suppressed, healthy women were randomised to receive one treatment sequence including a single subcutaneous injection of 450 IU Menopur liquid (600 IU/0.96 mL) and of 450 IU Menopur powder by two subcutaneous injections of 225 IU in 1 mL. Participants/materials, setting, methods Blood samples were collected pre- and post-dose, until 9 days after each injection. The PK parameters of FSH and hCG were assessed by noncompartmental methods with adjustment for endogenous pre-dose levels. Highly sensitive and specific electrochemiluminescence immunoassays were used for quantification and the LLOQ of the FSH and hCG assays were 1.47 mIU/mL and 0.5 mIU/mL, respectively, and the total validated CV was within 5% for both assays. Main results and the role of chance In total, 76 women were randomised and 56 completed the trial. The main reason for discontinuation was insufficient pituitary suppression prior to the second administration of HP-hMG. The mean FSH and hCG serum concentration-time profiles were comparable between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals of FSH for HP-hMG liquid versus HP-hMG powder were 1.12 [1.0562; 1.1889] for AUCt and 1.17 [1.0946; 1.2490] for Cmax, showing that the two formulations were bioequivalent. Maximal serum FSH concentrations were reached at 18.19 h for HP-HMG liquid and 15.55 h for HP-hMG powder. In addition to FSH, the PK parameters for hCG were compared between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals for HP-hMG liquid versus HP-hMG powder were 0.93 [0.86; 1.01] for AUCt and 0.94 [0.86; 1.02] for Cmax. There was no difference between the two groups in the incidence or severity of adverse events, and both preparations were well tolerated. Mild injection site reactions were less common after administration of HP-hMG liquid by a single injection compared to HP-hMG powder by two injections and were mostly related to pain and erythema after drug administration. Limitations, reasons for caution This bioequivalence study is based on the comparison of single dose administrations in healthy female volunteers of reproductive age. Wider implications of the findings: The new HP-hMG solution for injection in a pre-filled pen will deliver the efficacy and safety of Menopur in a convenient delivery device. Trial registration number NA

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

A successful model of biosimilar adoption in a community oncology practice.

6514 Background: The emergence of biosimilars creates an opportunity for more cost-effective treatment. Utilization of biologics in cancer care has increased and accounts for 70% of oncologic drug spending growth from 2010 to 2015. Biosimilars can play a vital role in controlling this rapid rise in cost. Practices focused on Value Based Care arrangements, such as the Oncology Care Model, can reduce total cost of care by increasing utilization of biosimilars. The process of interchange is complicated by the designation of each biosimilar which prevents simple interchange. Communication with physicians and the healthcare team along with patient education and consent must be performed. We describe a successful model for therapeutic interchange of brand drugs to biosimilars. Methods: Texas Oncology elected to increase utilization of biosimilars in 2020. We collaborated with McKesson Specialty Health to create educational materials for patients and clinical staff. Communication was sent to all personnel about the therapeutic interchange process. A central pharmacy team reviewed all new orders and substituted a biosimilar for brand, unless a payer insisted on origin drug or a biosimilar not in the practice formulary. Additionally, a report was generated weekly of all existing patients who would benefit from switching. The pharmacists, upon consultation with the physician, then substituted a biosimilar for brand drug. Patients were then educated and re-consented. We started with rituximab in 07/2020 followed by bevacizumab in 09/2020 then trastuzumab in 10/2020. Results: The table below shows our conversion rate for all administrations. We were able to increase utilization of biosimilars from January of 2020 to December of 2020 from 5% to 80% for Rituximab, 9% to 88% for bevacizumab and 8% to 74% for trastuzumab. Based on average ASP for a 70 kg patient, the potential savings per administration is $550 for bevacizumab, $850 for trastuzumab, and $1400 for rituximab. In one month alone, this project dramatically reduced cost by $4 million or 21% by conversion to these three biosimilars. Additional savings can be realized with the use of biosimilar multi-dose vials vs single dose vials. Conclusions: Our comprehensive team approach successfully deploys therapeutic interchange of biosimilars for brand drugs in a community oncology practice which leads to substantial cost savings. This has real implications in controlling the total cost of care.[Table: see text]

Sterility testing using a closed system transfer device in oncology medication compounding: a novel method for testing partially used vials

BackgroundThe National Association of Pharmacy Regulatory Authorities (NAPRA) Model Standards for non-hazardous sterile preparations and the model standards for pharmacy compounding of hazardous sterile preparations, calls for partially used single dose vials to be used or discarded within six hours of first access. This may lead to significant wastage, particularly with less utilized and expensive medications like oncology treatments. If demonstrated that sterility of these partially used vials can be maintained through a compounding procedure, there may be an opportunity to consider their re-uses.ObjectiveThe primary objective is to determine the ability of a compounding procedure, including a closed system transfer device (CSTD), to maintain sterility for partially used vials at two compounding centres at Trillium Health Partners. A secondary objective was to evaluate a novel method for verifying sterility.MethodsA CSTD was incorporated into the standard compounding methods at two hazardous compounding centres. Using growth media to detect any bacterial or fungal contamination that might have occurred during compounding, storage, and repeated access, the vials were tested in various growth conditions.ResultsThere was no growth noted in all compounded samples. The CSTD, when used in our environment with certified personnel, maintained sterility for 14 days, even with repeated access.ConclusionsThis study demonstrates that under our local compounding procedure using CSTD we were able to maintain vial sterility when stored under typical conditions and accessed several times for up to 14 days. This method may be considered to assess a facility’s local compounding procedures and provide valuable information regarding storage and utilization of partial vials, which may result in reduced waste and cost avoidance for the health care system.