Sterile Preparation Research Articles

Preparation and Evaluation of Sulfacetamide Sodium Ocusert for Controlled Drug Delivery

The intent of this research was to formulate and evaluate controlled release ocusert of sulfacetamide sodium for the treatment of bacterial conjunctivitis. Ocusert is a sterile preparation having drug as dispersion or as solution in the polymeric base. Prepared Ocuserts were formulated using hydroxyl propyl methyl cellulose K-15 and Ethyl cellulose as polymers at various concentrations and combinations. Polymeric Films were prepared by mercury casting method using different ratios of polymers. Selected physiochemical properties such as thickness, weight, percentage moisture absorption, and in-vitro release and sterility studies of sulfacetamide sodium ocusert were studied and reported that prepared ocusert resolved the problems of poor bioavailability, frequent dosing and wastage of active ingredient.
 Keywords: Hydroxypropyl methyl cellulose K-15, ocusert, sulfacetamide sodium

Compression of Vectors for Small Interfering RNAs Delivery: Toward Oral Administration of siRNA Lipoplexes in Tablet Forms.

Currently, most nonviral nucleic acid vectors are in the form of colloidal suspensions administered primarily parenterally. This type of formulation and the mode of administration impose strong constraints such as the size of the administered vectors or the production of sterile preparations. The tablet form provides access to easy oral administration, well accepted by patients; As regards nucleic acid vectors, a dry form represents an advance in terms of stability. Using an optimized lipid-based small interfering RNA-delivery system, we studied the tabletability of a liquid suspension of these vectors. We optimized the conditions of freeze-drying by choosing excipients and process, allowing for the conservation of both the gene-silencing efficacy of the formulated siRNAs and the supramolecular structure of the lipid particulate system. Gene-silencing efficacy was assayed on luciferase-expressing cells and the structure of the siRNA vector in freeze-dried and tablet forms was examined using small-angle X-ray scattering (SAXS) synchrotron radiation. The freeze-dried powders were then mixed with excipients necessary for the good progress of the compression by allowing for a regular supply of the matrix and the reduction of friction. The compression was carried out using a rotary press simulator that allows for complete monitoring of the compression conditions. After compression, formulated siRNAs retained more than 60% of their gene-silencing efficacy. Within the tablets, a specific SAXS signal was detectable and the lamellar and cubic phases of the initial liquid suspension were restored after resuspension of siRNA vectors by disintegration of the tablets. These results show that the bilayer lipid structures of the particles were preserved despite the mechanical constraints imposed by the compression. If such a result could be expected after the freeze-drying step, it was never shown, to our knowledge, that siRNA-delivery systems could retain their efficacy and structure after mechanical stress such as compression. This opens promising perspectives to oral administration of siRNA as an alternative to parenteral administration.

Preparation and assessment of ocular inserts containing sulbactum for controlled drug delivery

Ocuserts or Ophthalmic inserts are sterile preparations containing drug as dispersion or as solution in the polymeric support. The sulbactum is highly used as antibacterial agent in combination with other antibacterial agent. This study aims to formulate novel sulbactum ocuserts to enhance patient compliance through providing controlled drugs release from polymeric matrix. Ocuserts were prepared by solvent-casting method using different polymers HPMC, K4M, Polyvinyl alcohol,ethyl cellulose as polymer gelatine and propylene glycol and dibutyl phthalate as plasticizer in different ratios. The prepared ocusters were physic-chemichally evaluated for their weight, thickness, drug content uniformity, surface pH, swelling index (SI) and folding endurance. The viscosity of the polymeric solution used for the formulations was determined using Brookfield viscometer. In-Vitro Drug Release study and Accelerated stability studies were also performed. The prepared ocuserts show uniform weight, thickness and drug content. Their surface pH was in the physiological range and showed acceptable folding endurance. HPMC formulas had higher SI values. Results of in-vitro testing for one of the prepared ocuserts shows slow release of drugs up to 24 hours. One of the prepared ocuserts is promising for once-daily effective and safe drug delivery system of sulbactum for glaucoma treatment.
 Keyword: Ocuserts, sulbactum, viscosity, Ophthalmic

KEPATUHAN PELAYANAN FARMASI KLINIK DI RSUP DR. WAHIDIN SUDIROHUSODO

Pelayanan farmasi klinik merupakan salah satu pelayanan kesehatan yang berorientasi kepada pasien sehingga perlu dilakukan kesesuaian standar pelayanan farmasi klinik untuk menciptakan pelayanan yang bermutu dan berkualitas. Tujuan penelitian ini dimaksudkan untuk mengetahui bagaimana kepatuhan Pelayanan Farmasi Klinik di RSUP Dr. Wahidin Sudirohusodo sesuai dengan sebelas indikator pelayanan farmasi klinis berdasarkan Peraturan Menteri Kesehatan Nomor 72 Tahun 2016. Metode penelitian menggunakan pendekatakan kualitatif. Pengumpulan data dilakukan di RSUP Dr. Wahidin Sudirohusodo Makassar dengan Teknik wawancara mendalam, observasi, dan dokumentasi. Informan penelitian adalah Kepala Instalasi Farmasi, penanggung jawab Pelayanan Informasi Obat, penanggung jawab Depo, apoteker, dan pasien. Hasil penelitian menemukan bahwa sebelas indikator pelayanan farmasi klinik yaitu pengkajian dan pelayanan Resep, penelusuran riwayat penggunaan obat, rekonsiliasi obat, Pelayanan Informasi Obat (PIO), konseling, visite, Pemantauan Terapi Obat (PTO), Monitoring Efek Samping Obat (MESO), Evaluasi Penggunaan Obat (EPO), dispensing sediaan steril; dan Pemantauan Kadar Obat dalam Darah (PKOD) sudah dilaksanakan dengan baik walaupun masih ada indikator yang belum optimal. Hanya satu indikator yang belum terlaksana yaitu pemantauan kadar obat dalam darah karena terkendala dengan pembiayaan sarana dan prasarana yang cukup mahal. Kepatuhan Pelayanan Farmasi Klinik di RSUP Dr. Wahidin Sudirohusodo Makassar sudah dilakukan cukup baik tetapi masih terdapat beberapa hal yang perlu dibenahi oleh pihak rumah sakit, diantaranya perlu peningkatan SDM, penjadwalan visite yang lebih intens, penganggaran yang memadai untuk pengadaan alat kesehatan dan produk media edukasi.

Addition of 3% hydrogen peroxide to standard skin preparation reduces Cutibacterium acnes–positive culture rate in shoulder surgery: a prospective randomized controlled trial

Hydrogen peroxide is an inexpensive and effective antimicrobial agent that can be implemented in surgical skin preparations. The purpose of this study was to evaluate the decolonization effect of Cutibacterium acnes when adding hydrogen peroxide to a standard sterile preparation for shoulder surgery. This was a single-institution, prospective, randomized controlled trial of male patients undergoing shoulder arthroscopy (April 2018 and May 2019). Patients were randomized to a standard skin preparation vs. an additional sterile preparation with 3% hydrogen peroxide. After draping, a 3-mm punch biopsy was obtained from the posterior arthroscopic portal site of all patients. Anaerobic and aerobic culture substrates were used and held for 13 days. Seventy male patients were randomized into the hydrogen peroxide group and 70 male patients were in the traditional group. Twelve (17.1%) patients in the hydrogen peroxide group and 24 (34.2%) patients in the traditional group had positive cultures for Cacnes (P = .033). Cultures were positive at a mean of 4.5 days (range 3-7) in the hydrogen peroxide group and 4.1 days (range 3-8) in the traditional group (P = .48). There were no cases of skin reaction to the surgical preparation in either group. The results of this study suggest that the addition of hydrogen peroxide to preoperative surgical site preparation can reduce the Cacnes culture rate. Hydrogen peroxide is inexpensive and can be added to the typical skin preparation used prior to shoulder surgery without substantial risk of skin reactions.

Does umbilical contamination correlate with colorectal surgery patient outcomes?

Most preoperative assessment tools to evaluate risk for postoperative complications require multiple data points to be collected and can be logistically burdensome. This study evaluated if umbilical contamination, a simple bedside assessment, correlated with surgical outcomes. A 6-point score to measure umbilical contamination was developed and applied prospectively to patients undergoing colorectal surgery at an academic medical center. There were 200 patients enrolled (mean age 58.1 ± 14.8; 56% female). The mean BMI was 28.6 ± 7.4. Indications for surgery included colon cancer (24%), rectal cancer (18%), diverticulitis (13.5%), and Crohn's disease (12.5%). Umbilical contamination scores were 0 (23%, cleanest), 1 (26%), 2 (21%), 3 (24%), 4 (6%), and 5 (0%, dirtiest). Umbilical contamination did not correlate with preoperative functional status (p > 0.2). Umbilical contamination correlated with increased length of stay (rho = 0.19, p = 0.007) and postoperative complications (OR 1.3, 1.02-1.7, p = 0.04), but not readmission (p = 0.3) or discharge disposition (p > 0.2). Sterile preparation of the abdomen is an important component of proper surgical technique and umbilical contamination correlates with increased postoperative complications.

NADPH Oxidase Controls Neutrophil Infiltration in the Lung in Early Response to Fungal Cell Walls Via LTB4

The leukocyte NADPH oxidase generates superoxide, the precursor to reactive oxygen species important for host defense and immunoregulation. Genetic defects in NADPH oxidase result in chronic granulomatous disease (CGD), characterized by serious bacterial and fungal infections and aberrant inflammation. Aspergillus pneumonia is frequent, and associated with pyogranulomatous inflammation. Of note, even sterile fungal cell walls elicit increased neutrophilic inflammation in CGD mice, demonstrating that that NADPH oxidase can limit inflammation independent of its antimicrobial effects. Leukotriene B4 (LTB4) is a potent inflammatory mediator, acting as a chemoattractant and activating other polymorphonuclear leukocyte (PMN) functions. PMN themselves are prominent source of LTB4, and sense LTB4 through its receptor BLT1, which stimulates additional LTB4 synthesis by autocrine and paracrine routes. This leads to feed forward amplification of LTB4 production locally and formation of PMN clusters. Ca2+ acts as an important second messenger in PMN, including regulation of LTB4 synthesis. Activated human CGD PMN have increased intracellular Ca2+ levels compared to PMN from healthy donors due to electrogenic effects of the NADPH oxidase (Geiszt M. et al JBC 1997). Intracellular Ca2+ overload in PMN is speculated to contribute to increased PMN pro-inflammatory activity, but specific pathways and in vivo relevance are not well defined. Therefore, we therefore investigated the production of LTB4 by murine CGD PMN and the role of LTB4 in PMN recruitment and lung hyperinflammation following pulmonary challenge with zymosan, a sterile fungal cell wall preparation. Zymosan-stimulated PMN from Cybb-null mice, a model for X-linked CGD, produced higher LTB4 in vitro compared to wild type (WT), even in the presence of SOD and catalase to counteract oxidative degradation. Higher LTB4 production correlated with higher levels of intracellular Ca2+ in stimulated X-CGD PMN. The increased LTB4 produced by X-CGD PMN was dependent on cell density and the LTB4 receptor BLT1, consistent with a feed-forward loop that amplified LTB4 production. Zymosan-stimulated X-CGD PMN also formed larger and more numerous clusters in vitro compared to WT PMN. Cluster formation was abrogated by inhibiting LTB4 synthesis with the 5-lipoxygenase (5-LO) inhibitor zileuton or by the BLT1 receptor antagonist U75302, demonstrating that cluster formation was LTB4 and BLT1 dependent. We next examined whether LTB4 regulated the response to zymosan in the lung. Following intranasal administration of zymosan, X-CGD mice had higher PMN numbers in bronchoalveolar lavage (BAL), larger PMN foci by lung histology, and increased lung LTB4 as compared to WT mice. These differences were evident by 8 hr and progressed over the first 24 hr post-challenge, in contrast to WT mice where inflammation plateaued at 8 hr. Treatment with zileuton or U75302 just prior to zymosan significantly reduced lung PMN numbers for both WT and X-CGD mice at 8 hr post challenge, and lung PMN remained substantially reduced in X-CGD mice at 24 hrs. Moreover, delaying administration of zileuton to 8 hr after zymosan challenge also significantly decreased PMN inflammation in X-CGD but not WT mice at 24 hrs, indicating that ongoing synthesis of LTB4 otherwise continued to promote PMN recruitment in CGD mice. These results demonstrate that PMN production of LTB4 in response to fungal cell walls is limited by NADPH oxidase via its effects on intracellular Ca2+. In oxidase-deficient CGD mice, LTB4 plays a major role in driving excessive PMN recruitment to the lung in the early response to zymosan. This study is the first to implicate LTB4 in promoting neutrophilic lung inflammation in response to fungal cell walls in CGD, likely by an amplified feed-forward loop involving increased production of LTB4 by CGD PMN. LTB4 could be a potential therapeutic target to ameliorate CGD hyperinflammation. Disclosures No relevant conflicts of interest to declare.

Potency Analyses Provide Insight Into Student Aseptic Compounding Technique Errors

Objective. To determine whether direct observational scores were predictive of the potency of pharmacy students' compounded sterile preparations (CSPs) and to identify any misunderstandings students had regarding individual aseptic technique steps. Methods. P1 students performed aseptic techniques during three observational encounters separated by two weeks. Students' performances were evaluated using an observation-based rubric and were subject to potency analysis. The encounters were transferring a drug solution from a vial, an ampule, and a reconstituted powder to intravenous (IV) bags. Results. The mean potency of the diphenhydramine (vial) and lidocaine (ampule) met the ±10% goal of expected potency. These results were significantly different from those of the ampicillin (reconstitution) encounter, which was outside the goal. The percentage of students meeting the potency goal was 59.3% for the diphenhydramine, 80.3% for the lidocaine, and 50.4% for the ampicillin encounters. The observation scores were significantly different between all three encounters. There were no correlations between the observational scores and the potency for any encounter regardless of whether or not the student met the goal potency. Although their observation scores were acceptable, up to 50% of students did not meet the potency goal for each of the three encounters. Conclusion. The potency data provided the critical insight that P1 students were not adequately trained to account for pressurization when manipulating vials using aseptic compounding processes. The results suggest that both observation scores and potency analysis should be part of an overall assessment of student ability to compound sterile preparations.

Extemporaneous Compounding: Selective Pharmacists with Separate Skill.

Extemporaneous compounding takes place in community and hospital pharmacies. There are usually specialist compounding pharmacies in major towns and cities, but any pharmacy may undertake compounding as long as they have appropriate facilities according to state-based legislation (e.g. allocated clean bench, specific compounding equipment). Although development is a continuous process, companies are customizing features to meet the majority of patient needs, but the very nature of the process cannot meet all patient needs. The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However, if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no commensurate benefit. Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs. Compounded sterile preparations pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been traced to purportedly 'sterile' steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies. The 2012 outbreak has resulted in intense scrutiny of pharmacy compounding practices and increased recognition of the need to ensure that compounding is limited to appropriate circumstances.

AVN 1. Capturing a Migrating Inferior Vena Cava Filter in a Migratory Patient

Mobile patients present special challenges to their medical teams in solving the care puzzle and formulating an optimal treatment plan. This case of a migratory patient and a migrating filter illustrates the challenges of medical management in these medically complex patients. A 65-year-old patient taking warfarin since 2007 for deep venous thrombosis with an implanted inferior vena cava (IVC) filter since 2008 presented for IVC filter removal because of migration. He has an allergy to contrast material. Surgical history includes the following: IVC filter, Florida, 2008; renal transplantation, Michigan, 2008; bilateral hip replacements, Minnesota, 2015; C4-C7 cervical fusion, Minnesota, 2018; IVC removal, Georgia. His vital signs were normal (weight, 85 kg; height, 188 cm; blood pressure, 127/71 mm Hg). Laboratory values were as follows: hematocrit, 32%; platelet count, 172/mL; international normalized ratio, 2.1; blood urea nitrogen, 38 mg/dL; and creatinine, 1.88 μmol/L. Old outside imaging showed the filter tip near the cavoatrial junction. Under general anesthesia and a sterile preparation, the large patent external jugular vein was accessed. A diagnostic catheter was passed over a 0.035-inch Bentson wire (Cook Medical, Bloomington, Ind) into the iliac vein. A normal finding on carbon dioxide cavography was documented. Unsuccessful recovery with Cook retrieval kit caused the filter hook to straighten and the filter to sit higher in the right atrium. A 0.035-inch wire was passed and a 14F sheath placed in the atrium. An SOS-2 catheter (AngioDynamics, Amsterdam, The Netherlands) was passed over a Bentson wire and retracted to cross between the struts of the filter. The wire tip was ensnared and withdrawn through the sheath to form a completed loop between the legs of the filter. The 14F sheath was advanced over the wire and filter, thus disengaging the legs from the cavoatrial junction. The filter was intact. Completion carbon dioxide venography was unremarkable. This filter was placed more than a decade ago. Imaging from the original insertion was not available. An initial high insertion could not be entirely ruled out. However, the current location abutting the atrium precluded further watchful waiting. Initial filter capture was unremarkable, but straightening of the hook increased the technical difficulty. However, the looped wire technique provided a safe and effective alternative to a technically challenging case.

Catheter placement and maintenance

Intravenous catheters are an excellent option for providing short- and long-term fluid or antibiotic therapy. Multiple options for venous access exist. Selection of an access point is multifactorial, but volume to be administered and ease of access are 2 things to consider. While catheter materials and lengths vary, there is not a dramatic difference in overall performance for bovine patients. While a variety of methods exist for placing and securing an intravenous catheter, sterile preparation and regular flushing lay the pathway for longevity of catheter placement.

Development of Guidelines for Accurate Measurement of Small Volume Parenteral Products Using Syringes.

Background: Syringes are commonly used in pharmacy compounding for the measurement of small volumes, especially in the preparation of sterile products for injection and infusion. However, there are no current official guidelines for the proper use of syringes in measuring small volumes. Objective: The purpose of this project was to determine the accuracy and precision of commercially available syringes in measuring small volumes during sterile product preparation to make recommendations for syringe size selection. Methods: To assess precision and accuracy of syringes, 3 separate investigators measured 5%, 10%, or 20% (n = 30 each) of the volume of a 1-, 3-, 5-, 10-, or 20-mL syringe with an attached 18G, 1½" needle by drawing sterile water for injection from a vial. Delivered volumes were measured gravimetrically using an electronic balance and converted to volume using the specific gravity of water (1.0). Accuracy is represented as the mean and standard deviation, while precision is represented as percent relative standard deviation. Differences were assessed using a 1-way analysis of variance with Bonferroni adjustments and significance set at P < .05. Results: Precision and accuracy were highly variable and often significantly (P < .05) different compared to the theoretical volume delivered both within and between investigators. An increased likelihood of unacceptable error (>5%) was observed when less than 20% of the labeled capacity of a syringe was measured. Mean percent error ranged from 1.4% to 18.6%, despite manufacturer specification of ±5% accuracy, suggesting proper technique as a major factor in small-volume measurements. Conclusion: In addition to proper, validated training of syringe users, we recommend that users measure no less than 20% of the indicated volume of the syringe while choosing syringes as close as possible to the desired measurement. When possible, very small volumes should be diluted to meet the minimum volume of the smallest syringe available. Implementation of these recommendations will improve accurate dosing and, ultimately, patient safety.

State and National Organizations Supporting the Profession of Pharmacy

I have the good fortune from where I sit as the chief executive officer for a state pharmacy association of participating in many national conversations about important priorities in the pharmacy profession. Over the past four months there have been a greater level of discussions between the states and national entities on a myriad of subjects that are front-and-center in several areas of pharmacy practice. These subjects have ranged from changes to the international standards for compounding nonsterile and sterile preparations to pharmacy Direct and Indirect Remuneration fees (DIR) imposed by third-party payers and pharmacy benefit managers (PBMs), and many others.The practice of pharmacy is largely a local issue, meaning, activities like scope-of-practice, commercial payment provisions, Medicaid administration, and regulatory oversight are all controlled individually within a state's jurisdiction. And in fact, the state pharmacy associations are often the closest to knowing the political, regulatory, and practice nuances in those areas and the best means for moving priorities forward or otherwise affecting change. The national organizations are tremendous partners in supporting the state efforts, but for the most part defer to the states since, as former Speaker of the United States House of Representatives Tip O'Neill once said, “All politics is local.”However, with recent issues such as those mentioned above gaining national momentum and having a profound impact on the global practice of pharmacy across the U.S., it has provided a renewed opportunity for the states to support the national organizations in their efforts to affect change from the top. This two-way commitment from the state and national organizations to work on the important issues facing the profession – no matter where that lever comes from – is a key to an effective collaboration, and frankly, just getting the work done. At the end of the day, whether the activity originates at a national or state level, at some point it will impact (for better or for worse), the practice of pharmacy at the grassroots level. This constant reminder of the impact that the collective profession and the patients that are served will experience is why the state and national entities work so closely together. We share those values that seek to promote and advance the profession and are always willing to cooperate with one another to ensure that pharmacists and the communities in which they work, live and play, are benefitted from our collaboration.As a pharmacist, researcher, faculty member, student pharmacist, or pharmacy technician reading this Journal, I encourage you to talk to your peers in active practice. Remind them that, while the clinical evidence as demonstrated in this edition's manuscripts will advance patient care, so too will the collaboration and work of the state and national pharmacy organizations. We hope you will participate, belong, and encourage your peers to do so as well in the interest of ensuring that the challenges and opportunities in the practice of pharmacy are dealt with as effectively as possible.

ASHP national survey of pharmacy practice in hospital settings: Monitoring and patient education-2018.

The results of the 2018 ASHP national survey of pharmacy practice in hospital settings are presented. Pharmacy directors at 4,897 general and children's medical-surgical hospitals in the United States were surveyed using a mixed-mode method of contact by mail and email. Survey completion was online using Qualtrics. IMS Health supplied data on hospital characteristics; the survey sample was drawn from IMS's hospital database. The response rate was 16.6%. The percentage of hospitals that routinely have pharmacists assigned to provide drug therapy management has increased. Transitions-of-care processes have generally increased over the last 6 years. The percentage of hospitals with pharmacists in a wide variety of clinic types and clinical practice areas has increased over the last 2 years. Opioid stewardship programs are emerging in many U.S. hospitals, with pharmacists participating or taking the lead in program implementation. Outsourcing of compounded sterile product preparation is common. The proportion of hospitals not using any technology when compounding sterile preparations has declined. Pharmacy departments commonly track and monitor trends for administrative, operational, quality, and outcome metrics. Pharmacists continue to improve drug therapy monitoring for patients in U.S. hospitals. They are also responding to public health issues related to medication use. These advancements include taking an active role in opioid stewardship programs, safe compounding of sterile medications for patients, and reducing the need for hospital-based care.

Evaluation of gravimetric-based technology-assisted workflow for nonhazardous sterile product preparation

The impact of a gravimetric-based technology-assisted workflow (TAWF) system on the nonhazardous compounded sterile product (CSP) error capture rate, production times, and pharmacy staff perceptions of compounding methods was evaluated. For 2 weeks prior to TAWF implementation, staff used a punch clock to document production times with a volumetric method. Preimplementation error data were captured in a previous study; TAWF software captured error and time data in the postimplementation period. An online staff survey was administered before and 90 days after TAWF implementation to evaluate perceptions of the 2 methods. The error capture rates were 0.47% in the preimplementation period and 41.48% in the postimplementation period. The median time to prepare CSPs was significantly shorter in the preimplementation period versus the postimplementation period (p < 0.0001). The median time to check CSPs was significantly shorter at both 90 days (p < 0.0001) and 180 days (p = 0.0006) after TAWF implementation. When asked if the current method was the safest and the most accurate method for preparation, staff members' perceptions improved from neutrality to agreement when the TAWF was implemented. Staff members were in agreement that the volumetric method was faster than the gravimetric TAWF method but were neutral as to whether the latter was the preferred compounding method. The study results indicated that gravimetric-based TAWF preparation of nonhazardous CSPs is slower than manual volumetric preparation but can improve the error capture rate. Staff perceived the gravimetric TAWF method to be the safest and most accurate for producing CSPs.

Freeze drying in the biopharmaceutical industry: An environmental sustainability assessment

Most biopharmaceuticals are produced as sterile parenteral preparations, requiring very strict production conditions. In addition, liquid formulations face stability challenges which is why currently around half of all biologics are freeze dried for preservation. The environmental impact of the fill and finish processes to produce a freeze dried biopharmaceutical (infliximab) was evaluated from two perspectives: (i) considering only process-specific needs and (ii) calculating the overall site needs. An Exergetic Life Cycle Assessment was conducted using both a bottom-up and top-down approach. The process-specific and overall site needs are 6.5 and 39.6MJex/vial, respectively. These results reveal that 84% of the cumulative exergy entering the manufacturing plant is non-process-specific. Electricity consumption is the highest footprint driver (86%), dominated by the Heating, Ventilation and Air Conditioning (HVAC) system running during non-production hours and/or supporting non-production related areas. If resource efficiency is pursued, the focal target might need to shift towards non-process-specific needs which are not essential for the product functionality/quality (e.g. full HVAC regime during non-production hours). It should be kept in mind that Good Manufacturing Practices conditions always have to be maintained. Currently performed energy saving measures addressing HVAC systems could potentially reduce the overall site needs calculated in this study by up to 16.5MJex/vial.

Impact of a chemotherapy workload and productivity dashboard on pharmacy technician turnover.

To describe the methods used in the development of an intravenous chemotherapy workload and productivity dashboard and its impact on symptoms of burnout and technician turnover. In February 2017, chemotherapy sterile preparation pharmacy technicians reported symptoms of burnout as a result of perceived increase in workload. In response, an i.v. chemotherapy workload and productivity dashboard was developed at an academic medical center to validate workload in comparison to the reported job stress of pharmacy technicians. The dashboard provided pharmacy leadership objective data to validate staff concerns and leveraged lean principles to level-load the work prior to requesting additional full-time equivalents (FTEs) to senior leadership. The rate of turnover of i.v. chemotherapy technicians was assessed before (December 2016-June 2017) and after (July 2017-January 2018) dashboard implementation and approval of an additional i.v. chemotherapy technician FTE. The addition of the new FTE resulted in a decrease in productivity from an average of 106% (range 67%-151%) to 84% (range 65%-110%). The interventions allowed for the ability to leverage a staffing-to-demand model, resulting in the observed improvement in technician symptoms of burnout and a notable decrease in the overall turnover rate of i.v. chemotherapy technicians. The i.v. chemotherapy workload and productivity dashboard confirmed frontline staff perception and provided data to support the addition of labor resource and an opportunity to leverage a staffing-to-demand model to decrease symptoms of burnout and technician turnover.

Multicenter study to evaluate the benefits of technology-assisted workflow on i.v. room efficiency, costs, and safety.

The benefits of technology-assisted workflow (TAWF) compared with manual workflow (non-TAWF) on i.v. room efficiency, costs, and safety at hospitals with more than 200 beds are evaluated. Eight hospitals across the United States (4 with TAWF, 4 without) were evaluated, and the characteristics of medication errors and frequency of each error type were measured across the different institutions. The average turnaround time per workflow step and the cost to prepare each compounded sterile preparation (CSP) were also calculated, using descriptive statistics. The TAWF hospital sites detected errors at a significantly higher rate (3.13%) than the non-TAWF hospital sites (0.22%) (p < 0.05). The top error reporting category for the TAWF sites was incorrect medication (63.30%), while the top error reporting category for the non-TAWF sites was incorrect medication volume (18.34%). Use of TAWF was associated with a preparation time decrease of 2.82 min/CSP, a compounding time decrease of 2.94 min/CSP, and a decrease in overall cost to prepare of $1.60/CSP. The use of TAWF in the i.v. room was associated with the detection of 14 times more errors than the use of non-TAWF, demonstrating different frequency of error in the results. TAWF also led to a faster preparation time that had a lower cost for preparation.

Normal Saline and Dextrose 5% in Water Do Not Support Bacterial Growth 24 Hours After Being Spiked in the Perioperative Environment.

The Joint Commission requirement is that the US Pharmacopeia Chapter <797> is followed, which recommends that administration of compounded sterile preparations should begin no later than 1 hour after their preparation. We hypothesized that simply spiking the IV fluid in a nonsterile environment does not pose an increased risk of infection to the patient. Two 1000-mL bags of IV fluid (normal saline and dextrose 5% in water) were spiked and hung in 5 busy perioperative locations, once a week for a 13-week period. A 10-mL sample was drawn from each bag of IV fluid at time zero and 24 hours resulting in 260 samples in total. All samples were inoculated in 2 separate growth media (sheep's blood agar and thioglycollate broth). The primary outcome was growth versus no growth in any of the specimens. If any growth was noted, the sample was marked as positive and further testing to identify the organism was undertaken. A total of 257 samples (normal saline = 127, dextrose 5% in water = 129) were collected over a period of 13 weeks, yielding 514 specimens. Three samples were excluded from the study secondary to the IV bags being discarded accidentally. No growth was identified in any of the specimens. The 97.5% CIs were as follows: normal saline = 127 (0-0.034) and dextrose 5% in water = 129 (0-0.033), correcting for multiple tests. No bacterial growth was noted in any of the 257 samples collected. Normal saline and dextrose 5% in water do not support bacterial growth 24 hours after their preparation using standard sterile techniques in the perioperative space.

Evaluating containment effectiveness of A2 and B2 biological safety cabinets.

This study investigates the use of a canopy-connected recirculating class II type A2 biological safety cabinet (BSC) as an alternative to the B2 when preparing volatile, sterile compounded preparations. Selection of the appropriate BSC for processes that use subgram levels of volatile chemicals is difficult due to a lack of quantitative containment evidence by cabinet type. There is a perception that hazardous compounding must be done in a B2 cabinet due to the potential for vapors, and this study seeks to challenge that perception. In total, 5 tests, 3 prequalification tests and 2 containment capability tests, were conducted on a single cabinet of each type at sterile compounding pharmacies. Prequalification tests were performed to verify that each BSC was operating properly. Each cabinet was certified to NSF-ANSI 49-2016, particle counted per ISO 14644-1:1999, and subjected to a qualitative video smoke study. Once these tests confirmed the expected working conditions, 2 containment capability tests were conducted. The containment testing included tracer gas testing per ASHRAE 110:2016 section 8.1.1 through 8.1.13, and cyclophosphamide sampling during sterile compounding of the drug material. Both cabinets passed all the prequalification tests. During the ASHRAE tracer gas testing the A2 cabinet was able to contain a tracer gas 92% to 160% as effectively as the B2 cabinet depending on the position of the gas ejection. During sterile compounding the airborne cyclophosphamide sampling captured samples of less than 1.0 ng at all locations for both the A2 and B2 cabinets. The data generated from this study demonstrate that use of an A2 for hazardous compounding can provide a comparable level of safety for the environment, users, and product while having less stringent airflow requirements relative to a B2. The simpler requirements for an A2 make them an appealing alternative as they have the potential to reduce the overall operating costs associated with a compounding pharmacy while maintaining safe levels of containment.