Vial Size Research Articles

Cost avoidance from dose rounding biologic and cytotoxic antineoplastics.

Background To reduce product wastage, our institution allows automatic dose rounding of biologic and cytotoxic anticancer agents. The purpose of this project was to determine the actual annual cost avoidance due to pharmacist-managed automatic dose rounding of anticancer treatments. Methods Financial impact was assessed within the context of our departmental standard work which supports automatic dose rounding of biologic anticancer agents (±10%) and cytotoxic anticancer agents (±5%) to the nearest vial size for body surface area- or weight-based doses. Exclusions to automatic dose rounding include multiple dose vial products, pediatric orders, clinical trial drugs, and parenteral busulfan. The amount of cost avoidance for each rounded dose was determined using the product acquisition cost of the smallest available product amount. Data were collected from anticancer treatment orders for the fiscal year 1 July 2013 to 30 June 2014. Results A total of 6216 doses of anticancer drugs were checked for dose rounding during the period of data collection. Almost $200,000 in product acquisition cost was avoided with pharmacist-managed automatic dose rounding. Six different biologic products accounted for approximately 7% of the total doses analyzed and 78% of the cost avoidance. Fifteen drugs comprised the array of cytotoxic agents rounded. Approximately, 37% and 4% of the biologic and cytotoxic doses were rounded up to the vial size. Conclusion Routine dose rounding of biologic anticancer agents (±10%) and cytotoxic products (±5%) achieved cost avoidance through reduction of drug wastage at our institution.

Influence of Different Container Closure Systems and Capping Process Parameters on Product Quality and Container Closure Integrity (CCI) in GMP Drug Product Manufacturing.

Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in the literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters contribute to the final capping result.In this study, we used different container closure system configurations from different good manufacturing process drug product fill & finish facilities to investigate the influence of the vial size and the rubber stopper design on the capping process. In addition, we compared two examples of large-scale good manufacturing process capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force.

Total Hip Replacement in a Hemophilia-a Patient with High Titer Inhibitor

BACKGROUNDPatients with hemophilia seldom need joint arthroplasty today, due to decrease of bone and cartilage damage under factor prophylaxis started early childhood. However, hemophilia patients with inhibitors often develop severe joint damage as a result of ongoing bleedings. It is a formidable challenge to manage post-operative bleedings with bypassing agents in such cases. There have been only a few reports of major hip surgery in hemophilia A with inhibitors. Here we report a case of successful total hip replacement in an 18 year old adolescent boy with high titer inhibitor since infancy under recombinant factor VIIa (rVIIa) coverage.PATIENTThe patient has been followed up with high titer inhibitor ranging between 35- 95 BU since he was three years old and received mostly on demand treatment with either rVIIa (NovoSeven®) or activated prothrombin complex concentrate (APCC) (FEIBA®). Prophylaxis with APCC and rVIIa were also given for 3 years and 6 months, respectively. During the last two years, he experienced frequent bleedings in his right hip joint and developed crippling joint damage and assessed as grade IV according to the World Federation of Hemophilia grading system leading to severe chronic pain requiring opiate analgesics, shortened right leg and difficulty in walking and climbing. Preoperative inhibitor titer was 64 BU. Intravenous rVIIa was given in a dose of 270 mcg/kg, 30 minutes before surgery, repeated in 120 mcg/kg dose two hours after the first dose and continued in 90-120 mcg/kg doses during the first 24 hours. Intraoperative hemostasis was excellent and only two units of red cell transfusion was needed. However, he developed severe bleedings at the surgery site in the second day of surgery, which was partially controlled with 270 mcg/kg rVIIa. Four units of red cell transfusion was given and tranexamic acid 4x1 g daily was started. Since 120 mcg/kg rVIIa in every 2-3 hours did not stop bleeding, we added 50IU/kg APCC twice daily, rVIIa was reduced to 90 mcg/kg and tranexamic acid was stopped. No thromboprophlaxis was given. Although bleeding gradually decreased eventually over the next 3 days, he developed high fever with increased CRP level and re-bleeding at the surgery site at the fifth day suggesting wound infection. Broad spectrum antibiotics combined with bypassing agents was continued for 21 days during which no bleeding was noted. At 1 month, he had excellent joint function and clear surgery site. He is still receiving only APCC prophylaxis 50 U/kg three days weekly. Treatment cost was calculated as postoperative changes in rVIIa and APCC doses related to the size of vials and patient weights. Total amount of treatment cost was approximately 610.000 $ US for rVIIa and 66.000 $ US for APCC during hospitalization.CONCLUSIONSTotal hip replacement is rarely performed in young hemophilia patients with high titer inhibitor due to difficulty in management of bleedings and high cost of treatment product. However, it can be unavoidable in severely crippled patients, incapable of doing daily activities and suffering from intense pain. Our experience in the present case is encouraging for performing hip arthroplasty in such cases. No excessive bleeding occurred during surgery under rVIIa treatment. Combined use of rVIIa and APCC for secondary bleedings during post-operative period is safe and effective. High cost of surgery emphasize the need for development of suitable prophylaxis regimes in children with inhibitor to prevent crippling arthropathy. DisclosuresNo relevant conflicts of interest to declare.

Uma análise preliminar do desperdício de quimioterapia No tratamento do câncer

ObjectiveChemotherapy is essential for the cancer treatment. Usually, in the preparation process of the chemotherapy, part of the medication must be discarded to achieve the dose prescribed by the doctor. The dose of medication discarded results in toxic waste production. The objective is to analyze the chemotherapy waste in the preparation process of the drug. MethodsIt has been conducted a cross-sectional observational study. The study data were obtained from chemotherapy’s requests by oncologists linked to a health insurance plan. It has been calculated the dose of chemotherapy waste in each application, considering the dose prescribed by the doctor and the drug dosage form. ResultsIt were analyzed 1,289 prescriptions for intravenous chemotherapy of 106 users with cancer. There were a total of 63,824mg of chemotherapy residue produced, with an average of 602mg by user and 49mg by application. The average percentage of chemotherapy waste was 11.96%, between 0 to 50%. ConclusionThe number of applications and the dose used in the treatment protocol, the commercial dosage forms and the no use of dose rounding of medication to the nearest vial size were factors related to increased production of chemotherapy waste.

Modular vaccine packaging increases packing efficiency

BackgroundWithin a typical vaccine supply chain, vaccines are packaged into individual cylindrical vials (each containing one or more doses) that are bundled together in rectangular “inner packs” for transport via even larger groupings such as cold boxes and vaccine carriers. The variability of vaccine inner pack and vial size may hinder efficient vaccine distribution because it constrains packing of cold boxes and vaccine carriers to quantities that are often inappropriate or suboptimal in the context of country-specific vaccination guidelines. MethodsWe developed in Microsoft Excel (Microsoft Corp., Redmond, WA) a spreadsheet model that evaluated the impact of different packing schemes for the Benin routine regimen plus the introduction of the Rotarix vaccine. Specifically, we used the model to compare the current packing scheme to that of a proposed modular packing scheme. ResultsConventional packing of a Dometic RCW25 that aims to maximize fully-immunized children (FICs) results in 123 FICs and a packing efficiency of 81.93% compared to a maximum of 155 FICs and 94.1% efficiency for an alternative modular packaging system. ConclusionsOur analysis suggests that modular packaging systems could offer significant advantages over conventional vaccine packaging systems with respect to space efficiency and potential FICs, when they are stored in standard vaccine carrying devices. This allows for more vaccines to be stored within the same volume while also simplifying the procedures used by field workers to pack storage devices. Ultimately, modular packaging systems could be a simple way to help increase vaccine coverage worldwide.

One size does not fit all: The impact of primary vaccine container size on vaccine distribution and delivery

BackgroundWhile the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. MethodsUsing our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. ResultsReplacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while reducing the total costs by up to $0.25 per dose administered. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. ConclusionsOur results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency.

Vaccine wastage assessment in a primary care setting in rural India

Background: Knowing the wastage rate helps in assessing vaccine wastage and relative magnitude of its various causes helps to target efforts in reduce this wastage. Area specific wastage rate is useful in tailoring the vaccine vial size . Research question: What is the vaccine wastage in a primary care setting in rural India? Methods: A record based descriptive study was carried out in an immunization clinic of rural health centre in South India. All childhood vaccinations between 1 st April 2012 and 31 st March 2013 were included in the study. Number of doses issued and number of children vaccinated were obtained from the registers maintained at the rural health centre. Vaccine wastage rates and wastage factor were calculated. Results: A total of 5013 vaccinations (DPT, OPV, measles, MMR, and pentavalent, hep B, TT) were provided. Wastage rate for liquid vaccines was 3.4% and for lyophilized vaccines 28.2% among vaccines provided under national immunization schedule, wastage was highest for measles (46.5%). Conclusions: All vaccines except measles had wastage within the limits proposed by World Health Organization. Wastage rates have to be calculated routinely and considered during vaccine procurement.

Implementation of pharmacy services in 22 oncology clinics.

145 Background: Our integrated health care system consisted of 15 hospitals and 159 clinics. Since 2011, 22 private practice oncology clinics transitioned to hospital-based clinics. This presented an opportunity to standardize safe and effective pharmacy services at these locations. Methods: Using patient volumes, system leaders determined six pharmacists would serve the 22 new clinics via telepharmacy. Baseline pharmacy services to be offered were prospective order verification, product checking and drug information dissemination. To prepare for the transition, over 25 physicians agreed to standardize electronic order sets and develop one formulary. Vial sizes were consolidated and a uniform way to prepare each chemotherapy agent was designated. Over 75 policies were reviewed and updated. Education was provided to all caregivers prior to the transition. Once baseline services were integrated, additional patient-focused services such as supportive care counseling, follow-up phone calls, medication reconciliation and chemotherapy education were offered. Results: Pharmacists verified over 66,000 physician-ordered chemotherapy prescriptions in 2013, intervening on about 6% by suggesting adjustments for potential organ dysfunction or toxicity. For the past year pharmacists counseled nearly 90 patients a month regarding their supportive care medications. Survey results revealed a consistent increase in overall understanding, although the sample size did not allow for statistical significance. In addition, pharmacists made about 25 follow-up phone calls to patients to assess control of nausea and vomiting, completed medication histories for about 10 patients new to chemotherapy and were consulted for about 5 chemotherapy teachings per month. Conclusions: Integration of pharmacy services in our oncology clinics has allowed for development of a streamlined and safe process for ordering and preparing chemotherapy. It also has increased patient access to pharmacists and education related to supportive care medications.

Correlation between dispensed and prescribed doses of factor products for bleeding disorders: can a small, centre-based pharmacy hit the mark?

The prescribing and dispensing of factor replacement products have come under scrutiny in recent years. Some payers are shunting patients away from local 340B pharmacies anticipating larger pharmacies will be better able to match dispensed antihaemophilic factor vials to the prescribed dose. Our aims were to assess our baseline ability to achieve an aggregate and per patient dispensed to prescribed factor ratio (D:P ratio) of 1 and to evaluate obstacles to achieving unity. We conducted a retrospective review of the factor products dispensed from our 340B pharmacy and the corresponding prescriptions over the 6-month period prior to instituting routine D:P ratio assessment. The mean D:P ratio for all 65 patients was 1.00 (SD = 0.07). The mean paediatric D:P ratio differed from unity (P = 0.017) and from the mean adult D:P ratio (P = 0.003) in favour of a higher dispensed dose. A correlation between lighter patients and a higher dispensed dose was observed. Also, paediatric patients receiving 2 vials per dose had a mean D:P ratio greater than unity (P = 0.002). Pharmacy size does not dictate the ability to achieve a D:P ratio of unity. Ongoing monitoring of D:P ratios and dose ranges prescribed should be performed by all pharmacies to ensure acceptable allocation and cost of factor replacement for each patient. To further improve the D:P ratio metric in the paediatric population manufacturers should strongly consider adding more nominal dose increments within their lower range of vial sizes.

The budget impact of controlling wastage with smaller vials: A data driven model of session sizes in Bangladesh, India (Uttar Pradesh), Mozambique, and Uganda

IntroductionOpen vial vaccine wastage in multi-dose vials is a major contributor to vaccine wastage. Although switching from 10-dose vials to 5-dose vials could reduce wastage, a higher total cost could be triggered because smaller vials cost more to purchase and store. MethodsThis study drew field data of daily session sizes in local vaccination facilities from Bangladesh, India (Uttar Pradesh), Mozambique, and Uganda, and used Akaike Information Criteria to determine the best fit statistical distribution across various clinic types. These distributions were input to estimate the vaccine wastage using Lee's (2010) model. Inactivated polio vaccine (IPV) immunization was simulated to compare the costs over ten years with 10-dose vials versus 5-dose vials. ResultsBy switching from 10- to 5-dose vials, the observed open vial wastage rate due to vial size preference and session size for IPV was reduced from 0.25 to 0.11 in Bangladesh, 0.17 to 0.08 in India (Uttar Pradesh), 0.13 to 0.06 in Mozambique, and 0.09 to 0.04 in Uganda, respectively. The cost savings realized from lower IPV wastage did not offset the higher costs of procurement and storage costs associated with smaller dose presentation. ConclusionWhile our model showed that switching from 10-dose vials to 5-dose vials of IPV reduced open vial wastage, it was not cost-saving.

GC–MS Characterization of Volatile Compounds in Habanero Pepper (Capsicum chinense Jacq.) by Optimization of Headspace Solid-Phase Microextraction Conditions

The habanero pepper (Capsicum chinense Jacq.) is very aromatic and is the hottest pepper in the world. In this study, a headspace solid-phase microextraction/gas chromatography–mass spectrometry (HS-SPME/GC–MS) method was developed to evaluate the volatile compounds that contribute to the aroma of Yucatan habanero pepper. The optimization of the extraction conditions by HS-SPME/GC–MS was carried out by using a fractional factorial design (2 k-2 V) and univariate analysis. Eight factors were evaluated: equilibrium time, extraction temperature, extraction time, salt addition, pH, fibre, vial size and agitation. Optimal results were as follows: 14 min of equilibrium, 53 °C and 46 min of extraction, polydimethylsiloxane/divinylbenzene/carboxen (PDMS/DVB/CAR) fibre and a 15-mL vial. Fifty-three compounds were identified in habanero pepper employing the optimized extraction conditions.

Potential cost savings associated with dose rounding antineoplastic monoclonal agents.

This study explored the potential financial benefits associated with dose rounding three costly cancer agents: bevacizumab, trastuzumab, and cetuximab. Electronic chemotherapy health record software was queried to identify inpatient and outpatient use of bevacizumab, trastuzumab, and cetuximab. Available drug vial sizes were noted. Costs of actual doses prescribed were compared to theoretically reduced doses (5% and 10%) adjusted to the nearest vial size. Only doses resulting in a decrease in the number of vials qualified for dose rounding. New doses were analyzed for potential cost savings considering the percent-change from the original dose. All institutional review board procedures were followed. In all, 425 doses of bevacizumab, trastuzumab, and cetuximab were identified. At a 5% dose reduction, 51 doses (12%) qualified for dose rounding, translating to a potential cost savings of $60,648 ($6,188, $52,640, and $1,820, respectively). Although a 5% limit was set, the average change in dose did not exceed 2.5%. At a 10% dose reduction, 124 doses (29%) qualified for dose rounding, translating to a potential cost savings of $112,585 ($26,520, $80,605, and $5,460, respectively). With the 10% dose reduction, the average change in dose did not surpass 6.1%. Projected annual savings were calculated as $181,944 or $337,755, depending on the rounding limit. Consultation with key physicians regarding the proposed percent reduction resulted in a 10% dose reduction for all cases when utilizing these three agents. Implementation of a dose rounding protocol for bevacizumab, trastuzumab, and cetuximab represents a potentially substantial cost savings at this institution.

Sample volume optimization for radon-in-water detection by liquid scintillation counting

Radon is used as environmental tracer in a wide range of applications particularly in aquatic environments. If liquid scintillation counting (LSC) is used as detection method the radon has to be transferred from the water sample into a scintillation cocktail. Whereas the volume of the cocktail is generally given by the size of standard LSC vials (20 ml) the water sample volume is not specified. Aim of the study was an optimization of the water sample volume, i.e. its minimization without risking a significant decrease in LSC count-rate and hence in counting statistics. An equation is introduced, which allows calculating the ²²²Rn concentration that was initially present in a water sample as function of the volumes of water sample, sample flask headspace and scintillation cocktail, the applicable radon partition coefficient, and the detected count-rate value. It was shown that water sample volumes exceeding about 900 ml do not result in a significant increase in count-rate and hence counting statistics. On the other hand, sample volumes that are considerably smaller than about 500 ml lead to noticeably lower count-rates (and poorer counting statistics). Thus water sample volumes of about 500–900 ml should be chosen for LSC radon-in-water detection, if 20 ml vials are applied.

Dynamically optimizing the administration of vaccines from multi-dose vials

Many vaccines are manufactured in large, multi-dose vials that once opened, must be used within a matter of hours. As a result, clinicians (especially those in remote locations) face difficult tradeoffs between opening a vial to satisfy a potentially small immediate demand versus retaining the vial to satisfy a potentially large future demand. This article formulates a Markov decision process model that determines when to conserve vials as a function of time of day, the current vial inventory, and the remaining clinic-days until the next replenishment. The objective is to minimize open-vial waste while administering as many vaccinations as possible. It is analytically established that the optimal policy is of a threshold type. Furthermore, an extensive sensitivity analysis is conducted that speaks to the benefits of consolidating demand, investing in buffer stock, and adopting different vial sizes. Lastly, a practical heuristic is evaluated and shown to perform competitively with the optimal policy.

Evaluation of interferences on measurements of 90Sr/90Y by TDCR Cherenkov counting technique

A study to evaluate conditions affecting the determination of 90Sr/90Y activities in liquid samples by the triple-to-double coincidence ratio (TDCR) Cherenkov counting technique was conducted. The Cherenkov radiation produced by the 90Y beta decay was determined using a commercially available Hidex 300 SL liquid scintillation counter. The interferences of sample geometry, including sample counting vial type and volume composition, and sample colour on the TDCR were investigated. The effects of potentially interfering beta and mixed beta–gamma emitters on the TDCR Cherenkov counting of 90Sr/90Y activities were also examined. The TDCR values were used to quantify counting efficiencies of 90Y under different experimental conditions. The results demonstrated that the Cherenkov counting efficiency of 90Y is independent of sample volume and counting vial size. The effect of colour quenching was examined using yellow and brown food-grade dyes. The TDCR correction for colour quenching was found to be effective. An evaluation of counting efficiency of different beta-emitting radionuclides demonstrated that strong gamma emissions can contribute to the Cherenkov counting efficiency. Overall, measured radioactivity values deviated from reference values by ≤7.5 %, which is acceptable for screening applications in emergency situations.

Dynamic headspace generation and quantitation of triacetone triperoxide vapor

Two methods for quantitation of triacetone triperoxide (TATP) vapor using a programmable temperature vaporization (PTV) inlet coupled to a gas chromatography/mass spectrometer (GC/MS) have been demonstrated. The dynamic headspace of bulk TATP was mixed with clean humid air to produce a TATP vapor stream. Sampling via a heated transfer line to a PTV inlet with a Tenax-TA™ filled liner allowed for direct injection of the vapor stream to a GC/MS for vapor quantitation. TATP was extracted from the vapor stream and subsequently desorbed from the PTV liner for splitless injection on the GC column. Calibration curves were prepared using solution standards with a standard split/splitless GC inlet for quantitation of the TATP vapor. Alternatively, vapor was sampled onto a Tenax-TA™ sample tube and placed into a thermal desorption system. In this instance, vapor was desorbed from the tube and subsequently trapped on a liquid nitrogen cooled PTV inlet. Calibration curves for this method were prepared from direct liquid injection of standards onto samples tube with the caveat that a vacuum is applied to the tube during deposition to ensure that the volatile TATP penetrates into the tube. Vapor concentration measurements, as determined by either GC/MS analysis or mass gravimetry of the bulk TATP, were statistically indistinguishable. Different approaches to broaden the TATP vapor dynamic range, including diluent air flow, sample chamber temperature, sample vial orifice size, and sample size are discussed. Vapor concentrations between 50 and 5400ngL−1 are reported, with stable vapor generation observed for as long as 60 consecutive hours.

463

Introduction: Anticoagulation with warfarin is associated with numerous adverse events and complications, the most significant being intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is recommended for international normalization ratio (INR) reversal, however data regarding its use following ICH is variable with regards to dosing, infusion rate, and product choice. Available evidence supports efficacy of 4-factor PCC when compared to fresh frozen plasma (FFP), yet there are no direct comparisons with 3-factor products. Methods: We conducted a retrospective chart review of all patients receiving 3-factor PCC for reversal of INR following ICH between the dates of January 1, 2012 and August 1, 2013. Patients were excluded if they received PCC for an alternate indication or did not have an available baseline and/or repeat INR following PCC administration. Results: A total of 36 patients were included, one half of which were female. On presentation, the median age was 69 years and the mean INR was 4.1 ± 1.0. Thirty-three of 36 patients (91.7%) achieved an initial goal INR (≤ 1.4) following a single PCC dose, with the mean INR after PCC infusion being 1.2 ± 0.2. The average dose of PCC given after rounding to the nearest vial size was 31 IU/kg. Median time from PCC infusion to INR was 49 minutes. Vitamin K was utilized in 34 (94.4%) patients while FFP was given to only 5 (13.9%). In those with a baseline INR greater than 4.5, there was no difference in the probability of INR reversal, with 8 of 9 patients reaching goal INR after a single dose per our protocol (p<0.99). No patient experienced a documented thrombotic event within 7 days of PCC administration. PCC was infused over a median duration of 14 minutes (198 IU/minute) without any documented infusion reactions. Conclusions: Implementation of a fixed weight-based dosing protocol for 3-factor PCC was effective at providing rapid and complete INR reversal without any adverse events. With the new FDA approval of 4-factor PCC, 3-factor PCC may offer significant cost savings with similar efficacy however direct comparisons are needed.

Adjusting For Drug Wastage In Economic Evaluations Of New Therapies For Hematologic Malignancies: A Systematic Review Of The Literature and Implications

The cost of cancer care is rising to levels that appear unsustainable, in large part driven by a rapid increase in expenditures for novel therapies. In 2005, the direct costs of cancer care in the United States were $74 billion, with a prediction that these figures will double this decade as the population ages and we enter an age of biologically-tailored drug development. Historically, the evaluation of the cost-effectiveness of new drug therapies presumes that every milligram of drug is effectively utilized. With manufacturers dictating the availability of vial sizes for parenteral drugs, however, this may not be the case. A recent single-institution study in Canada estimated that an annual loss of $150 000 ($CDN) could be attributed to drug wastage of a parenteral therapy for myelodysplasia (Walker et al., Can J Hosp Pharm 2012). Whether current economic evaluations routinely model the potential for drug wastage, or the strategies to mitigate wastage, has not previously been determined.We sought to identify the frequency of drug wastage modeling in economic evaluations of modern parenteral therapies for hematologic malignancies. All US Food and Drug Administration (FDA) approved parenteral therapies from 2006-2013 (n=14) were identified for review. A systematic review of published English-language economic evaluations for these therapies was conducted and data on the conduct of the cost-analyses were extracted in duplicate. The primary outcome was the proportion of studies that explicitly modeled drug wastage in the base-case analysis, with results presented descriptively. Where possible, we calculated the impact of wastage on incremental cost-effectiveness ratios (ICERs) and drug acquisition costs.Thirty-three publications were retrieved; five of these studies were excluded (3 were non-English language and 2 were review articles). Of the remaining 27 reports, 3 were publicly-funded health technology assessments (HTAs) to inform funding decisions by the UK National Institute for Health and Care Excellence (NICE) and the remainder (n=24) were peer-reviewed publications. Sixteen economic evaluations were of rituximab-based regimens and 6 were bortezomib-based.Drug wastage was considered in the primary or base-case analysis in one third of the publications (9 of 27; 33%); wastage was considered in 2 of the 3 HTAs (67%) and 7 of the 24 peer-reviewed reports (29%). Of the 9 models that considered wastage in the base-case analysis, 2 completed sensitivity analyses in which no drug wastage occurred (i.e. vial sharing between patients). In both studies, consideration of wastage changed the calculated ICER. In one study, the ICER increased by 32% when wastage was incorporated into drug acquisition costs. In the second study, azacitidine (AZA) was compared to decitabine (DEC) for myelodysplasia, with both drugs provided as single-use vials and subject to substantial wastage. When no drug wastage was modeled, AZA was associated with higher costs than DEC (+$2 655 USD) and yielded an ICER of $15 528/QALY. When wastage for both drugs was considered, AZA was associated with lower costs (-$15 890) and AZA dominated DEC. Of the 18 publications that did not model wastage in the primary analysis, no study went on to model wastage in sensitivity analyses. In 4 of these 18 studies, the potential effect of wastage on drug acquisition costs could be calculated from data provided in the publication. The calculated drug acquisition costs if wastage occurred would potentially be +5-16% higher (mean +9%) than the costs modeled in the base-case analyses of these 4 studies.The potential costs associated with drug wastage are considered in only one third of modern cost-effectiveness models. The impact of wastage on calculated ICERs and drug acquisition costs is potentially substantial. The modeling of wastage in base-case and sensitivity analyses is recommended for future economic evaluations of new intravenous therapies for hematologic malignancies. Disclosures:No relevant conflicts of interest to declare.

Predictions of Vacuum Loss of Evacuated Vials from Initial Air Leak Rates

Container closure integrity is a critical factor for maintaining product sterility and stability. Therefore, closure systems (found in vials, syringes, and cartridges) are designed to provide a seal between rubber stoppers and glass containers. To ensure that the contained product has maintained its sterility and stability at the time of deployment, the seal must remain intact within acceptable limits. To this end, a mathematical model has been developed to describe vacuum loss in evacuated drug vials. The model computes equivalent leak diameter corresponding to initial air leak rate as well as vacuum loss as a function of time and vial size. The theory accounts for three flow regimes that may be encountered. Initial leak rates from 10(-8) to 10(3) sccm (standard cubic centimeters per minute) were investigated for vials ranging from 1 to 100 mL. Corresponding leak diameters of 0.25-173 μm were predicted. The time for a vial to lose half of its vacuum, the T50 value, ranged from many years at the lowest leak rates and largest vials, to fractions of a second at the highest leak rates and smallest vials. These results may be used to determine what level of initial vacuum leak is acceptable for a given product.

Effect of Barcode-assisted Medication Administration on Emergency Department Medication Errors

Barcode-assisted medication administration (BCMA) is technology with demonstrated benefit in reducing medication administration errors in hospitalized patients; however, it is not routinely used in emergency departments (EDs). EDs may benefit from BCMA, because ED medication administration is complex and error-prone. A naïve observational study was conducted at an academic medical center implementing BCMA in the ED. The rate of medication administration errors was measured before and after implementing an integrated electronic medical record (EMR) with BCMA capacity. Errors were classified as wrong drug, wrong dose, wrong route of administration, or a medication administration with no physician order. The error type, severity of error, and medications associated with errors were also quantified. A total of 1,978 medication administrations were observed (996 pre-BCMA and 982 post-BCMA). The baseline medication administration error rate was 6.3%, with wrong dose errors representing 66.7% of observed errors. BCMA was associated with a reduction in the medication administration error rate to 1.2%, a relative rate reduction of 80.7% (p < 0.0001). Wrong dose errors decreased by 90.4% (p < 0.0001), and medication administrations with no physician order decreased by 72.4% (p = 0.057). Most errors discovered were of minor severity. Antihistamine medications were associated with the highest error rate. Implementing BCMA in the ED was associated with significant reductions in the medication administration error rate and specifically wrong dose errors. The results of this study suggest a benefit of BCMA on reducing medication administration errors in the ED.